DIVIDED LEGACY

A HISTORY OF THE SCHISM IN MEDICAL THOUGHT

Volume IV

TWENTIETH-CENTURY MEDICINE:

THE BACTERIOLOGICAL ERA

Harris L. Coulter

Center for Empirical Medicine Washington, D.C.

North Atlantic Books Berkeley, California

Passages from A. G. Gilman, L. S. Goodman, and A. Gilman, The Pharmacological Basis of Therapeutics (copyright 1980 by Macmillan Publishing Company) used with permission of McGraw-Hill, Inc.

Passages from H. A. Lechevalier and M. Solotorovsky, Three Centuries of Microbiology (copyright 1974 by Dover Publications, Inc.) used with permission of Dover Publications, Inc.

Passages from Eric J. Cassell, “Ideas in Conflict: The Rise and Fall (and Rise and Fall) of New Views of Disease”; from David E. Rogers, “The Early Years: the Medical World in Which Walsh McDermott Trained”; from Paul B. Beeson, “The Changing Role Model and the Shift in Power”; from Robert H. Ebert, “Medical Education at the Peak of the Era of Experimental Medicine”; from Eric J. Cassell, “The Changing Concept of the Ideal Physi cian”; from Stephen R. Graubard, “Preface to the Issue, ‘America’s Doctors, Medical Sci ence, Medical Care’”; and from Lewis Thomas, “Biomedical Science and Human Health the Long-Range Prospect” reprinted by permission of Daedalus, Journal of the American Academy of Arts and Sciences, from the issue entitled, “Discoveries and Interpretations Studies in Contemporary Scholarship, Volume I,” Summer, 1977, Vol. 106, No. 3 Passages from the Wilson Quarterly, Spring, 1980 (copyright 1980 by the Woodrow Wil son International Center for Scholars) used with permission of the Woodrow Wilson Inter national Center for Scholars.

Passages from Tedd Koren, “Retracing, W'hat is It?” (copyright 1990 by Koren Publications, Inc.) used with permission of Koren Publications, Inc.

Passages from Walter I. Wardwell, Chiropractic: History and Evolution of a Mew Profession (copyright 1992 by Mosby-Year Book, Inc.) used with permission of Mosby-Year Book, Inc.

Passages from K. Codell Carter, Essays of Robert Koch (copyright 1987 by K. Codell Carter), an imprint of Greenwood Publishing Group, Inc., Westport, CT, reprinted with permission of Greenwood Publishing Group.

Divided legacy: .4 History of the Schism in Medical Thought, Volume IV

Copyright © 1994 Harris Livermore Coulter. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, or any information storage or retrieval system, without written permission of the publisher. Printed in the United States of America.

Published by

North Atlantic Books    Center for Empirical Medicine

P.O. Box 12327    4221 45th Street, NW

Berkeley, California 94701-9998    Washington, DC 20016

Cover design by Paula Morrison Production by Catherine Campaigne

Divided Legacy: A History of the Schism in Medical Thought is sponsored by The Society for the Study of Native Arts and Sciences, a nonprofit educational corporation whose goals are to develop an educational and crosscultural perspective linking various scientific, social and artistic fields; to nurture a holistic view of arts, sciences, humanities, and healing; and to publish and distribute literature on the relationship of mind, body, and nature.

Library of Congress Cataloging-in-Publication Data

Coulter, Harris L. (Harris Livermore), 1932-Divided Legacy

Vol. 2 has imprint: McGrath Pub. Co.; vol. 4, North Atlantic Books.

Includes bibliographies.

Contents: v. 1. The patterns emerge: Hippocrates to Paracelsus — v. 2. Progress and regress: J. B. Van Helmont to Claude Bernard — [etc.] — v- Twentieth century medicine, the bacteriological era.

1. Medicine—History. 2. Medicine—Philogophy—History. 3. Therapeutic systems—History. I. Title.

R131.C7 610'.9    73-75718

ISBN 1-55643-170-8

1 2 3 4 5 6 7 8 9 / 98 97 96 95 94

for Katya

TWENTIETH-CENTURY MEDICINE: THE BACTERIOLOGICAL ERA

TABLE OF CONTENTS

Page

INTRODUCTION.................................xv

PART ONE:

THE RISE AND DECLINE OF

THE SPECIFIC DISEASE.............................3

Chapter I: The Germ Theory: Infection and Specificity.......5

Predecessors: Trousseau and Virchow.............5

Founders of Bacteriology.......................9

Infection and Contagion......................21

Specific Diseases: Koch and Pasteur.............26

Monomorphism and Pleomorphism.............30

I he Doctrine of “Normality” and

The “Pure Culture” Technique..............34

Socioeconomic Factors

Promoting Monomorphism..................37

Chapter II: Pasteur, Metchnikoff, Behring,

and the Therapeutics of Similars....................44

Attenuation and Pleomorphism................46

Auzias-Turenne and “Syphilization”.............49

Discovery of Attenuation......................52

I he Isopathic Movement in Homoeopathy .......56

Johann Gottfried Rademacher.................60

Ludwig Griesselich and Homoeopathic

Opposition to Isopathy.....................61

Professional Antagonism vs. Public Support.......65

Koch and Homoeopathy: Tuberculin............73

Isopathic Treatment of Tuberculosis.............80

Organotherapy.............................86

Practical Immunology: Emil Behring............88

Discovery of Antitoxin.......................92

Behring and Homoeopathy....................96

Chapter III: Ehrlich, Koch, and the Doctrine of Contraries . . 105

Allopathic Modifications of the Proving.........105

Allopathic Practice.........................109

Ehrlich’s Attack on Pharmacology.............Ill

Ehrlich’s Physiology........................114

Ehrlich and Immunity ......................115

Immunology and Dyestuff Theory.............119

Experimental Chemotherapy.................121

The Doctrine of Contraries...................125

Drug Resistance...........................129

Specific vs. General in Ehrlich’s Thought........130

Ehrlich as Scientist.........................131

Ehrlich as Vitalist..........................133

Reception of Ehrlichism.....................134

Psychological and Socioeconomic Factors .......136

Chapter IV: Host Resistance and Immunity ............144

Empiricism and Host Resistance: Pasteur .......144

Metchnikoff and Phagocytosis ................148

Inflammation and Digestion..................152

Empiricism and Host Resistance: Behring.......155

Rationalism and Host Resistance:

Koch and Ehrlich........................157

The Carrier State. Endogenous Disease.

Pleomorphism...........................161

Koch and Ehrlich on Phagocytosis

and Vaccination.........................165

Metchnikoff and Vaccination.................169

Phagocytosis and Host Resistance in the

Late Twentieth Century...................171

Chapter V: Decline of the Entity: Infectious Diseases.......181

The Koch-Henle Postulates ..................182

The First Postulate.........................183

The Socioeconomic Basis of Pleomorphism......185

Guenther Enderlein........................188

Viruses and Filtrable Forms of Bacteria.........191

Bacterial Classification......................194

Host Resistance: Exogenous and

Endogenous Disease......................197

Adaptation and Pleomorphism................201

The Second Postulate.......................203

The Third Postulate........................203

Empiricism and Rationalism

in the Pleomorphism Controversy ...........204

Chapter VI: Decline of the Entity: Non-Infectious Diseases. . . 212

Human Variety in Disease ...................212

Human Variety in Health....................216

Defining the Entity.........................219

Mental Illness.............................222

Prevalence of LIndiagnosable Disease...........223

The “Controlled Clinical Trial”...............224

Need for Disease Entities....................227

The Internal Cause ........................229

Confusion among Disease, Cause, and Symptom . . 232 Empirical Criticism of Rationalist

Disease Theory..........................235

PART TWO:

EMPIRICISM AND VITALISM IN

TWENTIETH-CENTURY MEDICINE..................243

Chapter VII: Homoeopathy..........................245

The Proving..............................245

Reinterpreting Empiricism:

Primacy of the Visible ....................247

Diseases and Disease Causes..................252

The Three Rules of Practice..................253

Chronic Disease...........................255

Symptoms: Primary and Secondary............256

The Constitutional Type.....................258

Mental Illness.............................259

Symptoms: Classification.....................260

Homoeopathic Opposition to Kent ............269

The Triumph of the Kent Repertory.............274

The Law of Cure ..........................281

The Ultramolecular Dose....................292

Veterinary Homoeopathy....................299

Nosodes in the Twentieth Century.............300

Preventive Vaccination and Homoeopathy.......301

The Bowel Nosodes ........................307

Clinical Trials in Homoeopathy...............311

Allopathic Political Attitudes .................316

LAffaire Benveniste ..........................323

Chapter VIII: Osteopathy and Chiropractic.............331

Physiology ...............................331

Pathology................................334

Therapeutics .............................335

Empiricism vs. Rationalism in

Manipulative Medicine ...................337

The Law of Cure ..........................340

Allopathic Political Attitudes .................343

Clinical Evaluations of Chiropractic ...........348

Wilhelm Reich . . ..........................349

Chapter IX: Naturopathy.........................353

History..................................353

Philosophy...............................355

Physiology and Pathology....................357

Therapeutics .............................358

Chapter X: Vitalism in Allopathy I:

Immunology and Allergy........................366

From Microbe to Antigen....................366

Hay Fever and Allergy......................368

Anaphylaxis ..............................371

Immunity................................372

The Latent Period .........................374

Passive Immunization and Serum Sickness.......374

Preventive Vaccination......................376

Imponderables in Vaccine Design

and Production..........................380

The Balance of Preventive Vaccination .........381

Almroth Wright and Therapeutic

Vaccination ............................390

Non-Specific Therapy. Mixed Vaccines.

Fever Therapy ..........................397

Autohemic Therapy........................403

Tuberculin After Koch......................405

Tuberculin Testing.........................407

Vaccine Therapy and Homoeopathy ...........408

Clinical Ecology and Immunology.............417

•    External vs. Internal....................417

•    Peculiar vs. Common ...................420

•    Similars vs. Contraries...................423

Antibody Formation, Specificity, and

Empiricism.............................427

Chapter XI: Vitalism in Allopathy II: Pharmacology......439

Reactivity of the Organism ..................439

Disease as Reaction ........................442

Symptoms Beneficial .......................446

Cause of Reaction Unknown .................449

Symptoms Prior to Pathology. Function

Prior to Structure........................450

Neo-Hippocratic Tendencies .................452

Reactivity of the Organism to Medicines........454

The Arndt-Schulz Law......................456

The Koetschau Hypothesis and the Wilder Law . . 460

Colloidal and Metal-Salt Therapy.............462

Experimental and Clinical Evidence

for the Arndt-Schulz Law..................464

•    Botanical Research.....................464

•    Bacteriological Research.................464

•    Physiological and Medical Research........466

The Arndt-Schulz Law and Ionizing Radiation ... 471 The Arndt-Schulz Law in Vaccine Therapy:

Dose Size and the Negative Phase ...........473

The Similar Remedy in Allopathy:

The Nineteenth Century ..................475

The Similar Remedy in Allopathy:

The Twentieth Century ...................477

Ultrasensitivity to the Similar: Aggravation......485

The Law of Cure in Allopathy................486

•    Driving the Disease Inward:

From Skin to Internal Organs.............487

•    Driving the Disease Inward:

From One Internal Organ to Another.......492

•    Driving the Disease Inward:

From Physical to Mental.................493

•    Symptoms Disappear in the

Reverse Order of Their Appearance........494

PART THREE:

THE PHARMACOLOGY OF CONTRARIES

AND ITS CONSEQUENCES.........................501

Chapter XII: The Doctrine of Contraries: The Receptor Site. . 503

A. J. Clark and the Law of Mass Action.........503

The Doctrine of Contraries ..................506

Receptor-Site Theory and Practice ............508

Critique of Receptor-Site Theory..............515

The Receptor Site: A Doctrinal and

Economic Necessity......................517

Chapter XIII: The Doctrine of Contraries:

Adverse Reactions............................524

Side Effects and Adverse Reactions ............524

Rebound.................................528

Adverse Reactions in the

Nineteenth Century......................535

Therapeutic Nihilism.......................538

Penicillin and the Antibiotics.................540

The Antibiotic Era.........................543

Overuse of Antibiotics ......................543

Polypharmacy and Polyvalency ...............546

Adverse Reactions in the Twentieth Century.....550

Microorganism or Host? ....................554

Superinfections............................556

Antibiotic Stimulation of Superinfections........559

Veterinary Use of Antibiotics.................561

Morbidity and Mortality from

Adverse Reactions .......................563

Chapter XIV: The Doctrine of Contraries:

Drug Disease and Chronic Disease ................570

Allergy and Hypersensitivity .................573

Hypertension .............................574

Diabetes.................................576

Ulcers...................................579

Deafness.................................580

Asthma..................................581

Heart Disease.............................582

Mental Illness.............................585

Neurologic Disabilities......................586

Cancer .................................. 590

Congenital Defects.........................591

Arthritis and Rheumatism ...................592

Arteriosclerosis and Other Vascular Diseases.....595

Action of Drugs on the Immune System ........596

Autoimmune Diseases and AIDS..............601

PART FOUR:

MEDICAL REFORM .............................609

Chapter XV: The Institutional Ascendancy of Rationalism ..611

A Theoretical Void.........................615

The Meaning of “Scientific Medicine”..........619

I he Search for a Theoretical Structure.........622

Chapter XVI: The Training of Physicians .............627

Overwhelmed by “Facts” ....................627

Specialization vs. General Practice ............631

Research.................................636

Clinical Training ..........................638

Dehumanization...........................641

The Physician as Diagnostician ...............645

Pharmacology and Clinical Pharmacology ......648

Dearth of Nutritional Education ..............652

The Physician as Prescriber..................657

Chapter XVII: Political, Socioeconomic, and Psychological

Dimensions of Therapeutic Systems................666

Empiricism...............................666

Rationalism ..............................670

Indispensability of New Drugs................677

The “Old” ancl “New” Medical-Industrial

Complexes .............................678

Inflation of Costs ..........................680

Incipient Decline of Rationalism ..............684

Restoring the Balance ......................687

Bibliography..................................695

Index of Personal Names..........................739

Subject Index..................................753

Illustration: The Koetschau

Type-Effect Hypothesis...........................461

INTRODUCTION

The volumes of medical history comprising Divided Legacy, of which this is the fourth and last, analyze therapeutic thought in the Western tradition as a philosophical conflict. They tell of a dichotomy in medical speculation, a conflict between two theories known traditionally as Empiricism and Rationalism, which has lasted from ancient times to the present.

Our focus thus differs from that of other contemporary histories of medicine which recount the development of physiology, biophysics, anatomy, and biochemistry—rather than therapeutics and disregard theory. Divided Legacy attempts to restore therapeutics to a central position, the position it occupied in medical historiography before the early nineteenth century.a And since therapeutics is determined by theory, these volumes tell of the emergence, progress, and vicissitudes of therapeutic philosophy.

While this conflict can be discerned in the earliest writings of the Hippocratic Corpus, from the fifth century BC, the names Empirical and Rationalist become current in Rome at the beginning of the Christian era—designating groups of physicians competing writh one another ideologically and economically.

Empirical thinkers analyzed in earlier volumes of Divided Legacy include Theophrastus Paracelsus (1490-1541), Jan

"Kurt Sprengel’s Versuch einer pragmatischen Geschichte der Heilkunde (five volumes, 1792-1803) was the culmination of this older tradition, which went into decline with the nineteenth-century development of the “auxiliary sciences.” Mention should also be made of Julius Petersen’s Hauptmomente in der geschichtlichen Entwick-lung der medicinischen Therapie (1877).

Baptista Van Helmont (1578-1644), Thomas Sydenham (1624-1689), Giorgio Baglivi (1668-1707), and Georg Ernst Stahl (1660-1734).

Pierre Jean-Georges Cabanis (1757-1808), Philippe Pinel (1745-1826), Rene Laennec (1781-1826), Auguste-Frangois Chomel (1788-1858), Pierre Bretonneau (1771-1862), Etienne Pariset (1770-1847), Pierre Louis (1787 1872), Armand Trousseau (1801-1867), and other members of the nineteenth-century Paris “clinical school” also subscribed to a Hippocratic/Empirical doctrine.

The most important Empirical thinker in history, however, was Samuel Hahnemann (1755-1843), the originator of homoeopathy. Discovering a new technique for ascertaining the curative powers of medicinal substances—the “proving”—he reformulated traditional Empirical concepts into a new and intellectually powerful therapeutic doctrine- homoeopathy which has more than withstood the challenge of time and promises to continue its independent and successful existence into the indefinite future.b Today, nearly two centuries after Hahnemann first launched the homoeopathic concept, this school flourishes in all the industrialized countries of the world and in most others as well.

Representative Rationalist medical thinkers discussed in earlier volumes of Divided Legacy include certain Hippocratic writers, Galen (129-199 AD), Rene Descartes (1596-1650), Frederick Hoffmann (1660-1742), Hermann Boerhaave 11668-1 738), and Benjamin Rush (1745-1813).

A subvariety of Rationalism known as Methodism flourished in ancient Rome and was espoused in modern times by William Cullen (1 7 10-1 790), John Brown (1735-1788), F.J.V. Broussais (1772-1838), Francois Magendie (1783-1855), Claude Bernard (1813-1878), and especially Rudolf Virchow (1821-1902).

The dominant medicine of late twentieth-century industrialized society is Rationalist or Rationalist/Methodist in structure and inspiration. Although called “scientific medicine” by

b On Hahnemann’s discovery of the “proving,” see below, pp. 245ff.

its adherents and partisans, this definition cannot be sustained. As the following pages show, the only therapeutic doctrines which can be considered scientific are those found in the Empirical tradition—homoeopathy in particular. Twentieth-cen-tury Rationalism represents an adaptation of the “auxiliary sciences” of medicine to the socioeconomic demands of medical practice in an industrial society.

When “scientific medicine”—meaning the Rationalist or Rationalist/Methodist side of the dichotomy—is examined in and for itself, as is customary in medical historiography, without taking the Empirical side into consideration, the dynamic of medicine’s intellectual development becomes unintelligible.

The earlier volumes of Divided Legacy trace the emergence and historical course of Empiricism and Rationalism from ancient times to the late nineteenth century. The two philosophies are seen to be internally logical and coherent structures of thought as well as radically opposed to one another in all respects. The concepts “disease,” “cause,” and “symptom,” the principles of therapy, the relationship between theory and practice—in a word, all elements of a medical philosophy— have had contrasting and conflicting acceptations in the two traditions.

The elemental dichotomy determining the diverging structures of the two doctrines is the espousal of vitalism by the Empirics vs. Rationalism’s mechanistic or chemical understanding of the living organism.

“Vitalism” has had a variety of meanings throughout history. The Empirical tradition has taken it to signify recognition that the laws governing the living organism differ from those of lifeless matter. I he organism is reactive, at all times coping with, and attempting to overcome, the stresses which impinge upon it from outside. It behaves purposively, the nature and form of its reaction being determined by the specific environmental stress encountered. It responds to challenge, which no aggregate or assembly of non-living substances can ever do.

Homoeopathy accepted this central assumption of Empiricism, characterizing the processes of health and disease in vi-

talist terms and recognizing a “vital force” or “vitality” in the body which causes it to react to external stimuli.

The patterns of this reactive power are made visible in the patient’s symptoms which, however subjectively disagreeable or painful, are nonetheless beneficial manifestations of the organism’s effort to overcome the disease. They are signs of a curative, not a morbific, process.

The laws which the organism renders visible by its patterns of behavior in sickness and health are the laws of vitality. These are the laws which the physician must seek out and apply in therapeutics.

These laws are peculiar to the living organism and cannot be derived from the “auxiliary sciences.” They cannot be known a priori but are only discoverable a posteriori—by observing the organism’s behavior in sickness and in health.

This interpretation of vitalism has never been disproved and cannot be disproved by biochemical or biophysical experimentation. Even less can it be refuted by arguments. It can be confirmed or disproved only by treating patients in accordance with its axioms and postulates and observing the outcome, i.e., only by therapeutic experience.

Rationalist medical thinkers have denied the existence of a “vital force” apart from, and superior to, the organism’s physicochemical constituents. They have assumed the identity of organic and inorganic matter in bringing both within the purview of physics, chemistry, and mechanics:

It is self-evident that only such laws as govern the material world will be found governing material vital phenomena—the laws, that is, which have hitherto been brought to their most exact and most logical development by physics and chemistry, or, more generally speaking, by mechanics. The explanatory principles of vital phenomena must therefore be identical with those of inorganic nature—that is, with the principles of mechanics.

—Encyclopedia Britannic a, 19111

There is no essential difference between the structural chemistry of life and that of inanimate nature.

Fielding H. Garrison, 19222

There is no way to distinguish between something formed in a cell and the same thing formed in a chemical laboratory. On the basis of countless experiments in the fields of medicine, physiology, biology, and chemistry, scientists believe today that life is a series of complex chemical reactions. All these chemical reactions, no matter how complex, obey the laws of science. No new laws of science are yet needed to account for the chemical reactions involved in the process of life. T herefore, there is no special chemistry of the living system, and cells, the basic unit of living systems, must obey the laws of chemistry ... To understand the process of life, you must understand the principles of chemistry.

—George Schmid, 1982s

Traditional Rationalism has ignored the dynamic Empirical understanding of vitalism, misinterpreting it to mean that organic matter possesses unique features differentiating it from inorganic. Hence the 1828 test-tube synthesis of the organic substance urea by Friedrich Woehler (1800-1892) has in modern times been called the “death knell” of vitalism. If a “vital” substance can be synthesized in the laboratory, the argument went, no vitality or “vital force” is needed. In fact, Woehler’s own contemporaries did not regard his achievement as undermining vitalism, and this conclusion was reached some generations later.

In the twentieth century W. T. Astbury applied X-ray crystal-lographic techniques to biological substances and showed them to possess an essentially crystalline orderliness and regularity:

Astbury’s work abolished forever the idea of a hard and fast line of demarcation between physical objects and the substances of the living world—a conceptual revolution of the same kind but far greater than that said (in retrospect) to have been brought about by Woehler’s reputed synthesis of urea in 1828.—P. B. andj. S. Medawar, 19774

If organic matter is not unique and specific to itself. Rationalism avers, its operations can be understood in terms of some corpus of knowledge, some set of categories and concepts, developed outside and apart from the living body.

The Greek and Roman Rationalists relied on formal logic to unlock the secrets of the organism. Their sixteenth- and seventeenth-century descendents looked to chemistry (“iatro-chemistry”) or mathematics (“iatromathematics”). In the eighteenth century these yielded to a neurology-based medicine patterned on the discovery of electricity and involving a presumed excess or deficiency of “excitability” or “excitement.” This was represented by the Methodists, Cullen and Brown. In the early nineteenth century the Methodist Ma-gendie based treatment on a physiopathological theory derived from chemistry and hydraulics in which the movement of blood through the capillaries played the principal role.

Today’s Rationalism has converted “iatrochemistry” into “biochemistry” and “iatrophysics” into “biophysics,” has applied crystallographic techniques and the like, but the aim is still to comprehend the living organism in terms of some external discipline.

But despite Woehler and his urea, vitalism has remained strong, taking delight in puncturing the more extravagant claims of Rationalist materialism. The physicist Niels Bohr (1885-1962) observed that biological phenomena are “irreversible,” that liv ing organisms “utilize past experience for reactions to future stimuli,” and that “quantum phenomena exhibit no feature indicating that an organization of atoms is able to adapt itself to the surroundings in the ways we witness in the maintenance and evolution of living organisms. Furthermore, it must be stressed that an account, exhaustive in the sense of quantum physics, of all the continually exchanged atoms in the organism not only is infeasible but would obviously require observational conditions incompatible with the display of life.”1 And Bohr was not alone:

Vitalism ... makes only the statement that the reduction of

any vital processes exclusively to the laws of physics and

chemistry has up to now not been efficient even in a single case. Such a refutation of the sometimes very aggressive assumptions of mechanism is of course not a theory ... Vitalism in its modern form, often called Neovitalism, does in itself not try to explain dogmatically the vital phenomena ... The modern vitalist will avoid the pretense that he can provide explanations for that which he in fact can only observe as existing.—Bruno Kisch, 19596

We move beyond this purely critical function to propose a more assertive doctrine. Building on the traditional Empirical awareness of the body as a reactive and purposive entity, we aim to reinforce twentieth-century vitalism (or neovitalism) by demonstrating its applicability to the phenomena of sickness and health, to illness and treatment. By resurrecting the all-but-forgotten discipline of therapeutic philosophy we put some flesh on its dry critical bones.

Empiricism holds “illness” to be part of a reactive curative process. All genuine observation, these physicians assert, proves that the living body resists morbific environmental impulses and seeks to ward them off or neutralize them. It is focussed and resolute in its reactions, capable, within limits, of defusing and deactivating most of the noxious environmental impulses and stresses which tend to disease.

I his has two corollaries: stress on the body’s inherent power of resistance, and in diagnosis, emphasis on the uniqueness of the individual.

1. “Sickness as reaction” or “sickness as struggle” leads necessarily to reliance on the patient’s power of resistance, and this factor has always been given more weight by Empirical physicians than by Rationalist ones.

I he body’s technique for coping with morbific influences resembles the process of digestion. Called pepsis by the Hippocratic and other Greek Empirical writers and coctio in the ancient Latin texts, it involves the “coction” (“cooking”), transformation, and excretion of the disease cause.

In the late nineteenth century “coction” was converted to phagocytosis” by the Russian-French biologist Elie Metch-nikoff, illustrating how perennial concepts are redefined and clothed in the scientific vocabulary of the day

“Cooking” the morbific cause requires the application of heat, and fever or inflammation usually accompany the coction process.

2. The pattern of symptoms manifested by the given patient represents the precise manner in which his organism at this moment in time is resisting this particular morbific environmental impulse. I he pattern will differ from one patient to the next in function of his or her genetic makeup and medical history (i.e., the factors responsible for “uniqueness”) and the particular environmental stress at work on the organism; hence the intimate processes within any individual patient cannot be known with precision, and the physician can only be sure of their external manifestations—the symptoms.

Because of their awareness of each patient’s uniqueness, and of the consequent heterogeneity of “disease,” the Empirics stressed the impossibility of reliable knowledge of internal pathophysiological processes and the supreme importance of the visible in medicine, i.e., this patient's visible signs and symptoms.

While conventional (Rationalist) medical science can, of course, obtain knowledge of physiological, biochemical, and other internal processes in general, the information cannot be applied with precision and reliability to any patient in particular. The individual patient will always differ from the norm, and the physician’s task is to treat this particular patient, not patients in general.0

Furthermore, because “sickness as reaction” always takes the form of coction, crisis, and evacuation, the general features of this reaction, meaning those manifested by all patients, are less useful for diagnosis and treatment than those which distin-

c“It is hard to see how a weaver or carpenter will be benefited in regard to his own craft by knowing this ‘good itself,’ or how a man who has viewed the Idea itself will be a better doctor or general thereby For a doctor seems not even to study health in this way, but the health of man or perhaps the health of a particular man; it is individuals that he is healing” (Aristotle, Nicomachean Ethics 1097a 8-14; see Divided Legacy, I, 151).

guish Patient A from Patient B. Empirical therapeutic doctrine is inexorably drawn to emphasizing the features which distinguish patients from one another over those they possess in common.

In ancient medicine this appeared as a preference for “peculiar” symptoms (Latin: propria) over “common” ones (commu-nia). In homoeopathy it is seen in emphasis on the “strange, rare, and peculiar” symptom.

These show precisely how the vital force of this patient is attempting to cure this condition at this moment in time; an accurate understanding of the propria will reveal precisely how the disease is to be combated.

Furthermore, if the peculiar symptoms represent the patient’s unique mode of reacting, the medicine that intensifies this unique reaction will be curative.

The body often externalizes, and rids itself of, the morbific cause through natural discharges: urine, stool, perspiration, and especially skin disorders and eruptions. Suppression of these manifestations has long been known to generate serious systemic disorders. Ancient Empiricism thus advocated the use of medicines which promoted discharges and eruptions.

As always, the physician takes his lead from the patient. He must promote the development of the patient’s very set of symptoms, and the curative medicine is the one which will support and stimulate this incipient healing effort. If correctly selected, it will be that patient’s “specific.”

In the homoeopathic school the ancient “promoting” medicine was converted into the “similar” and had the same function—that of furthering the organism’s own response to the morbific cause.

Rationalist therapeutic doctrine proceeds from different assumptions and arrives at a different mode of diagnosis and treatment.

1 he living organism is not seen as “reactive,” even less as “purposive.” The visible sickness is not “response” but rather the emanation of a morbific causal entity inside the organism. I his “cause” is a structural abnormality, while the visible sickness is a function disturbed by the abnormality.

To the Greek Rationalists the causal entity was a degenerated humor, disrupting the balance of “the hot,” “the cold,” “the wet,” and “the dry.” Today it is a physico-chemical imbalance, often induced by microbial attack, interrupting one of the “mechanisms” of life.d

Rationalism attaches a different meaning to the symptoms. They do not represent a positive curative effort by the organism’s vitality but are an extension or emanation of the noxious “cause” inside. And since the “cause” is by definition harmful, an entity which disturbs the body’s functions, the symptoms must also be morbific. Far from wanting to stimulate or intensify them, the Rationalist physician seeks to neutralize or eliminate the symptoms.

Hence it seems reasonable to the Rationalist mind that cure should result from reversing or contravening this internal “cause” (or one of the ensuing malfunctions). Rejecting “similarity” as illogical, they seek substances which “oppose,” “neutralize,” or “act contrary to” the hypothesized “cause” or malfunction.

The “contrary” medicine has as ancient a lineage as the “similar,” emerging originally among the medical followers of Aristotle and relying for validation upon the latter’s “principle of contradiction”—meaning that a concept or combination of concepts cannot be both affirmed and denied at the same time.e

The curative medicine is “contrary" to the disease in the sense of possessing “opposite” qualities. In early Rationalist doctrine the “hot” remedied the “cold,” the “wet” remedied the “dry,” etc. Sometimes these qualities could be ascertained by sensory observation (honey, for example, is “dry” because it arouses thirst), but most commonly they had to be ascertained by logic.

The modern history of Rationalist therapeutics is largely the story of man’s efforts to analyze in chemical terms the

dSee below, Chapters V and VI. As we demonstrate, such “causes” are largely imaginary and cannot be defined with precision.

'“It is impossible for anyone to believe the same thing to be and not to be” (Aristotle, Metaphysics 1005b 23; see Divided Legacy, I, 131).

workings of medicines and their connections with the pathophysiology of the body. Paul Ehrlich was the major exponent of this trend and gave Rationalist therapeutics a stamp it has not yet lost.

In twentieth-century bacteriology the dominant “contrary” medicines have been those which kill or neutralize the assumed bacterial causes of diseases. Other “contraries” eliminate or block the production of some substance thought to be in excess in a given diseased state—cholesterol in the coronary arteries, sugar in the urine, and the like.

Since the “cause” is the ultimate object of concern to the Rationalist physician, the symptoms interest him only insofar as they indicate this cause. Hence he attributes maximum importance to the “common symptoms” (communia), those manifested by all patients with the “same disease” and which are the least common denominators of this disease, because they can most readily be associated with the internal causal entity. Peculiar symptoms (propria)—not manifested by others with the “same disease”— are disregarded as fleeting and evanescent reflections of the patient’s idiosyncrasy, of little or no significance for therapy.

Whereas Empiricism bases treatment on the patient’s idiosyncrasy, for Rationalism idiosyncrasy is a confounding element in an otherwise logical and well-structured doctrine.

And, just as it cannot find a doctrinal niche for “idiosyncrasy," Rationalism cannot make sense of the “specific” remedy—viewing it as in principle amenable to analysis but not yet analyzed.

I have a conviction ... that the concept of the specific in medicine, whenever it dominates in medical theory, deleteri-ously affects its practice and retards its further development.—Iago Galdston, 1942'

And since the body’s mechanisms and functions are seen as finite, the number of “diseases” accepted by theory is also finite. This is carried to a logical extreme in Methodism which admits only two (sometimes three) possible “diseases” and two (sometimes three) possible remedies. It was carried to an even

greater extreme by the nineteenth-century Methodist Rudolf Virchow, who did not admit “disease” at all, but held it to be merely an extension of normal physiology: “pathology is nothing but physiology with obstacles.”f

This is a polar contrast with Empiricism, which does not recognize categories of “disease” at all. Its stress on “peculiar” features dissolves any “disease” into all the individuals suffering from it. While accepting the names, “malaria,” “syphilis,” “smallpox,” and others on traditional grounds, Empiricism still regards the differences among those stricken by one or the other of these diseases as more significant for treatment than the similarities conferred by the names, “malaria,” “syphilis,” “smallpox,” and the like. The number of “diseases” in the world is coextensive with the number of patients.?

Thus, to summarize the conflict between Empiricism and Rationalism in therapeutics:

•    Empiricism perceives the organism as reactive; the modes of reaction reflect the laws and regularities peculiar to the body as a living organism; they can be ascertained only by observing it in sickness and health. To Rationalism the body is not a reactive entity but a mechanism obeying the laws of such disciplines as chemistry, physics, and mechanics.

•    To Empiricism the symptoms are signs of the body’s reaction, beneficial phenomena which should not be suppressed or eliminated. For Rationalism the symptom is intrinsically harmful, the emanation or external manifestation of a structurally defined disease “cause” buried within the body.

•    Empiricism holds pathophysiological processes to be ultimately unknowable in the sense that their precise nature in the patient at hand can never be ascertained; diagnosis and treatment, therefore, must be based upon

fSee below, pp. 5-7. See also Divided Legacy I, 291-301; II, 606-645. *See below, pp. 252-253.

symptomatic knowledge which, if correctly interpreted, provides the physician with all necessary knowledge about this patient’s reaction. Rationalism holds that pathophysiological processes, being identical with processes observable in chemistry, physics, or other “auxiliary sciences,” are ultimately knowable; the particular case exemplifies a general law.

•    Empiricism sees the patient’s “peculiar” symptoms as more meaningful for treatment than those which he possesses in common with other patients. Rationalism takes the contrary view: the “common” symptoms are more significant because they point to the causal entity inside.

•    It follows that, while Empiricism rejects the concept of '"disease” and sees every patient as unique, for Rationalism the patient is the representative of a larger “disease.”

•    Empiricism is oriented toward the “similar” remedy, which helps to further or promote the body’s vital reaction; Rationalism applies the “contrary” remedy which is thought, as it were, to bypass the host organism and act directly on the internal causal entity.

•    Empirical therapeutics seeks to strengthen the patient’s powers of resistance and compensate for the predisposition to become ill; any remedy which promotes a vital reaction must thereby strengthen the resistance and lessen predisposition to illness. Rationalism is far less interested in the body’s resistance or predisposition because these cannot readily be analyzed in physical or chemical terms and cannot be modelled by one of the “auxiliary sciences.” In general, Rationalism is more concerned with the “disease” than with the host organism.

Volume III of Divided Legacy describes the hostile interaction between Empiricism and Rationalism in the nineteenth century, institutionalized as a conflict between the homoeopathic movement and the American Medical Association. The ideological assault against homoeopathy by the orthodox profes-

sion (known as “allopaths”) was a reprise of the traditional and ongoing Rationalist/Empirical antagonism.11

When the hostility assumed an economic form, it turned so bitter that allopathic physicians were for decades prohibited from professional contact with homoeopaths; even social intercourse could bring down on the head of the offender the full fire and brimstone of the allopathic congregation.

This tension continued from the 1830s to the end of the century. In the early 1900s, however, the homoeopaths largely surrendered their position and accepted fusion with allopathic organizations, leading in short order to disappearance of the separate system of medical education which had been the bulwark of homoeopathic independence. By the 1940s organized homoeopathy had sharply declined in the United States and other countries where it had formerly flourished. It no longer bore responsibility for upholding the Empirical viewpoint in medicine and for almost three decades had no impact outside the ever diminishing circle of homoeopathic adherents.

But in the late 1960s, to the surprise of supporters and opponents alike, homoeopathy and other forms of Empirical medicine, now baptised “natural,” “holistic,” “alternative,” “complementary,” and the like, experienced a powerful resurgence—reasserting themselves the more strongly for having been so thoroughly repressed. This caused soul-searching among those who had interpreted the decline of homoeopathy earlier in the twentieth century as the inevitable supersession of an “unscientific” medicine by “science.”1

Since the cyclical movement of medical thought is a decades-long process, the ongoing renaissance of medical Empiricism promises to continue well into the twenty-first century.

hIn the following pages the words “Rationalist” and “allopathic” are used interchangeably.

‘Thus, the author of a somewhat naive and dismissive account of American homoeopathy (1971), with the subtitle The Rise and Fall of a Medical Heresy, published a second historical survey in 1988 with the subtitle “The Rise and Pall and Persistence of a Medical Heresy” (Martin Kaufman, in Norman Gevitz, ed., Other Healers).

To make sense of these and other doctrinal fluctuations in medicine a more comprehensive philosophy is needed.

The absence of such a philosophy not only inhibits a correct interpretation of twentieth-century Empiricism but has a blighting effect on Rationalist thinking. This is seen in the vast profusion of chaotic and disparate data which is one of its distinguishing characteristics. “Literature” is produced in quantities far exceeding the ability of even the narrowest specialist to stay abreast of the information flow, and yet no ordering principle ensures internal consistency and compatibility with the literature of other medical specialties. If a theory existed for reference, there would be less production of “facts,” and the “facts” generated would have a reasonable life expectancy. A truly scientific discipline does not abandon its received truths every five or ten years. The unending twistings and turnings of allopathic thought, its renunciation of concepts held with dogmatic tenacity a few years earlier, are presented by professional apologists as evidence of medical “progress” but actually reveal scientific hollowness and inconsistency, the absence of any understanding of how the body functions as an integrated whole, and consequent inability to avoid being carried along by new externally-generated scientific paradigms such as molecular biology or genetic manipulation which promise final answers to perennial medical puzzles.

Valuable nuggets of knowledge are buried deep in the detritus. Allopathic medical education is anarchic and wasteful of the student’s time and enthusiasm. The so-called “controlled clinical trial" designed to bring order into this wasteland of fragmentary hypotheses and discarded theories is methodologically grotesque. The vaunted “peer review” system is merely an additional barrier ensuring that ideas departing from received truths will have a rough passage to the pages of scholarly publications.

1 he appeal to “science” in modern Rationalism is an appeal to professional consensus. No objective scientific criteria exist, and the “expert" is merely an expert on his colleagues’ opinions.

Not least important, the absence of a philosophy leaves physicians vulnerable to the officious attentions of the pharmaceutical industry, which has been prompt to use them as sales agents for its wares.

In Western industrial societies the unlicensed practice of medicine, which could be a valuable corrective, is generally barred by law.J The resulting absence of competition has caused a rapid increase in costs which, if the trend continues, will eventually lead to medical services consuming the whole of society’s surplus wealth.

The volumes of Divided Legacy have sought the patterns in this intellectual muddle, providing a guide for the perplexed in their effort to sort out the issues. We have tried to substantiate our belief that the huge volume of data produced by twentieth-century medicine falls into intelligible patterns only when scrutinized from the viewpoint of the conflict and interaction between the two ideologies.

Finally, we have indicated some of the socioeconomic ramifications and corollaries of Empiricism and Rationalism.

NOTES

1.    Encyclopedia Britannica, Eleventh Edition (191 1), XXI, 554.

2.    George Schmid, 1982, 2.

3.    Fielding H. Garrison, 1922, 503.

4.    J. S. and P. B. Medawar, 1977, 53.

5.    Niels Bohr, 1958, 100.

6.    C. M. Brooks and P. F. Cranefield, eds., 1959, 331 332.

7.    Iago Galdston, 1942, 26.

jEngland is a unique exception. There the practice of medicine, with or without a license, is a fundamental liberty of the citizen. One effect has been the lowest per capita cost of medical services in the Western world. See below, p. 686tf.

But it is particularly necessary, in my opinion, for one who discusses this art to discuss things familiar to ordinary folk. For the subject of inquiry and discussion is simply and solely the sufferings of these same ordinary folk when they are sick or in pain.

—Ancient Medicine

PART ONE

THE RISE AND DECLINE OF THE SPECIFIC DISEASE

The twentieth century is called the “bacteriological era” because the discovery of microorganisms and the associated doctrine of “specific diseases” put a stamp on medical thought which seemed to render earlier therapeutic principles obsolete.

The microbe, which ever more powerful microscopes showed to be associated with a multitude of diseased conditions, was the keystone of a new theoretical edifice. Representing the concrete pathological “cause” which had for so many centuries been sought by Rationalist thinkers, it generated an apparently unassailable structure of thought and practice.

This volume of Divided Legacy traces the rise and incipient decline of the bacteriological interpretation of disease, the “germ theory” as it came to be called, which has dominated medicine since its emergence in the 1880s.

THE GERM THEORY:

INFECTION AND SPECIFICITY

I he discovery of infection, and the specificity of many infectious conditions, was the catalyst precipitating the emergence of the germ theory.

Predecessors: Trousseau and Virchow

1 he nineteenth-century Paris clinical school was led by Armand lrousseau, and German “physiological medicine” by Rudolf Virchow.3 The contrast between these two men and their doctrines, exacerbated by Franco-German antagonism, could not have been more absolute. Trousseau was an Empiric and a vitalist, seeking the unknown “specific,” the quid divinum, in disease and defining it in terms of the patient’s symptoms; he mistrusted hypothetical knowledge of physiological or pathological processes, and like Hahnemann-—from whom much of his medical thinking was taken—urged that medicines be “proved” 011 the healthy to ascertain their curative powers. To the “specific” in disease he wanted to oppose the “specific” remedy, and the purpose of the prescription wras to stimulate the diseased organism in the direction of recovery.

Virchow, on the contrary, reduced all the phenomena of life to movement at the cellular level. Not merely rejecting

See Divided Legacy, II, Chapters VI and VII.

“specificity” as an obscurantist concept, he denied any qualitative distinction between sickness and health. In fact, he denied the existence of “disease” altogether, assimilating all of medicine to physiology and characterizing pathology as “the physiology of the diseased organism.” “The ideal we shall strive to realize ... is that practical medicine shall become applied theoretical medicine, and theoretical medicine shall become pathological physiology.”1

Tetanus, for instance, was a mechanical irritation of the nervous system.2 Anemia (“chlorosis”) was due to a “defective structure of the heart and large arteries.”3 Scrofula, tuberculosis, and pellagra were disturbances of nutritional function.4 Gonorrhea was not an infectious disease but an “organic disturbance of a single part,” as were psoriasis, otorrhea, pneumonia, and cystitis.5

Virchow’s obsession with internal pathology, at the expense of the patient’s visible signs and symptoms, is seen in his statement, when told that the French clinicians were developing accurate symptomatic pictures of disease: “Das Kennen ist wichtig, aber das Begreifen ist das Wichtigere und Hoehere!”6b

The enthusiastic advocates of the new movement, in their exaggerated zeal, sought to find in physiology not only the direction of their activities, but also the decisive last word in pathological and especially in clinical questions. T he clinical pictures were only “recognized” insofar as they reflected physiological laws; it was then attempted to read the separate symptoms in the light of these often very distorted physiological images. Often one constructed them oneself instead of finding them by faithful and impartial observation. Of Ludwig Traube [1818-1876] it must be said that he, too, often made clinical medicine the serv ant of physiology, losing himself in petty details and subtleties of symptomatology in order to preserve the most intimate connection possible with physiology, and other clinicians did the same.—Bernard Naunyn, 1908'

The very significant contributions of Pierre Bretonneau and other Paris clinicians were discarded, and therapy especially was

b“Descriptive knowledge is good, but grasping the essence of the phenomena is better.”

set back several decades. One of Virchow’s disciples announced in 1866: “Everything which since Laennec has been designated as infiltrating tuberculosis of the lung is the product of chronic, especially catarrhal, pneumonia.”8 The 1865 demonstration by Jean-Antoine Yillemin (1827-1892) that tuberculosis is inocula-ble, hence infectious, was ignored by German medical thinkers in the mounting political antagonism between the two countries; what had been taken as the initial stages of tuberculosis were said by them to be nonspecific apex and catarrhal pneumonias, apex catarrhs, or various kinds of bronchitis and peribronchitis.9

Bretonneau ... had early come to the conclusion that pharyngeal and laryngeal diphtheria were the manifestations of a single disease entity, but by Virchow they were completely divided and reduced to the category of non-specific and unrelated examples of a membrane-forming order of inflammation, and thus, under the separate names of diphtheria and croup, pharyngeal and laryngeal diphtheria led an artificially divided existence until, in due time, the advent of bacteriology reunited them. Similarly, Laennec’s masterly generalization of the various clinical and pathological features of pulmonary tuberculosis was broken down into many nonspecific and disparate elements that had no meaning for the clinician until Koch, half a century later, restored the validity of Laennec’s concept.—Francis Walshe, 195610

When Claude Bernard, the only Frenchman who agreed with Virchow, died in 1878, the Empirical-vitalist-specificist viewpoint was entirely identified with France, the Rationalist/Metho-dist-mechanistic-antispecificist one with Germany.0

Many have remarked upon the rapidity with which the germ theory was accepted by the profession.11 But this was only to be expected. Nature abhors a vacuum, and so does the physician. Virchow rejected disease entities as “ontology.” Trousseau did not reject them but could not define them: “Diseases are neither

'It would be an exaggeration to hold, with Paul de Kruif, that this helped bring on the First World War, but it was one of many irritants in the Franco-Germanic relationship during those decades (de Kruif, Microbe Hunters, 206).

entities [etres] nor purely accidental modifications of the organism.”d

Lacking was a visible, palpable cause which would both concretize Trousseau’s “specificity” and introduce clinical thinking into the therapeutically sterile Teachings of Virchow. This need was filled by the germ theory. When the visible and palpable microorganism was offered to fill the doctrinal and psychological gap, the response was overwhelming. The association of a “germ” with each new “disease” emanating from laboratories and hospitals in Paris, Berlin, and London made the doctrine irresistible.

The germ theory responded to the physician’s psychological need for a material embodiment of “disease.”

The idea that pathology is merely modified physiology or, to quote Francis Walshe, that “illness was to be thought of only in terms of deviations of bodily functions from a physiological norm,” seems unnatural.12 That “diseases” possess peculiarities which distinguish them from one another seems intuitively right. And physicians every day see confirmation of this intuitive truth. Carl Wunderlich (1815-1877), for instance, was punished for his Methodist foolishness by discovering the existence of “typical” temperature curves associated with what “ontologists” were calling “diseases.” Specificity cast its shadow on his thinking despite all his efforts.13

The Rationalist physician, furthermore, has a marked need for categories as guides to treatment. And the basis for distinguishing “specific diseases” had been created by earlier research in the Paris School. Bretonneau and Louis had themselves described a number of “specific diseases”—especially diphtheria, typhoid, and tuberculosis. Each disease, they said, arises from its own “seed” (le germe). And each has its own specific essence, “ce quelque chose de special, ce quid divinum qui ne peut etre saisi, et qui, de Vaveu d'Hippocrate, echappe a toute explication.”1*’' Other “diseases”

dDivided Legacy, II, 573.

'“This peculiarity, this divine essence, which cannot be grasped and which, as Hippocrates admitted, defies all explanation.”

had long been known to medicine: smallpox, measles, yellow fever, syphilis, and Asiatic cholera. A large part of the medical world believed in specificity and was willing to accept the germ theory long before discovery of Bacillus anthracis, Bacillus tuberculosis, or the Klebs-Loeffler bacillus. Witness the 1875 statement by Carl Thiersch (1822-1895): “My heart inclines me to the bacteria, but my reason says, ‘Wait a little longer.’”15

Even though some of the older physicians held back— the followers of Claude Bernard because le germe meant reintroducing the vital force into medicine, Virchow and his disciples because “specificity” meant “ontological” obscurantism the younger generation accepted the new ideas with enthusiasm, and the “germ theory” of “specific diseases” was erected on the ruins of “physiological medicine.”16

The ever-recurring craving of the clinician for “ontology,” for fixed categories of diseases, was, then, fully justified. The quid dwinum of the diseases referred to by Sydenham and Breton-neau had now taken definite shape.

Knud Faber, 192217

Founders of Bacteriology

I his doctrinal reconstruction was the work of Louis Pasteur (1822-1895), Robert Koch (1843-1910), Elie Metchnikoff (1845-1916), Paul Ehrlich (1854-1915), and Emil Behring (1854-1917).

Pasteur was born in Dole, a small town in eastern France, his father a tanner who had served under Napoleon, his mother a peasant woman. He managed with difficulty to become educated, being awarded the bachelier es sciences in 1842 (with the grade of "mediocre” in chemistry). In 1843 he entered the Lcole Normale in Paris where he remained his whole life despite intermittent academic appointments in Dijon, Strasbourg, and Lille.

He first achieved fame through work on fermentation. Challenged by local distillers’ complaints of setbacks in fermenting alcohol from beets, Pasteur pinpointed accidental contamination

by stray fungi, leading to a major discovery about the role of the fungus Mycoderma in the manufacture of vinegar.

He then studied wine diseases. As with beets, the fermentation process was disturbed by contamination with acid-producing organisms, and he urged heating to eliminate the undesired enzymes. This was roundly condemned by the French soldiers and seamen who had to drink “pasteurized” wine and were said to have preferred plain water, but the procedure was an outstanding success with milk.

Pasteur thereafter appreciated that each type of fermentation has its own specific enzyme (leferment), and he would apply the idea of “specificity” later to his study of diseases.18

As a conservative Catholic, he was an instinctive vitalist, which helped him appreciate that fermentation is the work of a live organism, the yeast globule: “the consequence of life without air.”19 In this, for example, he opposed Claude Bernard who preferred a non-vitalist, physico-chemical explanation of fermentation; he stated in 1865: “I have sometimes heard it said that the property of decomposing sugar was due to the life inherent in a globule of yeast. This vitalistic explanation means nothing and explains nothing about the action of yeast.”20

Pasteur would later give a vitalist explication of microbial diseases.

In the early and mid-1860s he opposed spontaneous generation on the same vitalist grounds, combating the liberals, materialists, and atheists who held that life emanates from matter: “What a victory for materialism if it could be affirmed that it rests on the established fact that matter organizes itself, takes on life itself; matter which has in it already all known forces ... Ah, if we could add to it this other force which is called life ... what would be more natural than to deify such matter? ... What good then would be the idea of a creator God?"-1

In the late 1860s he studied the silkworm industry, decimated by disease, and found the worms to be infected with a microorganism—again the struggle of one life-form against another. Through a technique of isolating the infected worms, he single-handedly saved that important industry.

After France’s defeat in the war with Prussia, Pasteur became

The Germ Theory: Infection and Specificity 1 1

a Germanophobe and turned his energies to beer manufacture, in the hope of producing a French beer the equivalent of the preferred German imports/

The last stage in his life was devoted to the diseases of animals and humans. Casimir Davaine (1812-1882), working from 1850 to 1865 and already influenced by the ideas of Pasteur, had demonstrated that anthrax was caused by the Bacillus anthracis— the first such demonstration of the pathogenic role of a bacterium in the human being and in animals.22 This set Pasteur to thinking of a way to prevent and treat it, and his Germ Theory and its Application to Medicine and Surgery (1878) described a new technique of isolating and cultivating the causal microorganism through “serial cultures.”23 Each fresh culture was inoculated with a drop of culture from the preceding one: “The last culture of the series was able to multiply and act in the body of animals in such a way that the animals developed anthrax with all the symptoms typical of this affection.”24

This same communication urged surgeons to work in sterile conditions to prevent wound infection.

Joseph Lister (1827-1912), the Scotsman who introduced antiseptic surgery in 1867, had earlier acknowledged his indebtedness to Pasteur’s discoveries in the realm of “ferments” and disease microbes.25

In 1880 Pasteur announced a method of protecting fowl against the common and devastating disease, chicken cholera. It was an extension of the “serial culture” technique involving “attenuating" the “virus” (toxic material) and using it as a vaccine.

In 1881 he devised an anthrax vaccine for sheep, “attenuating" it through exposure to air and demonstrating it in a controlled trial. None of the twenty-four sheep, one goat, and six cows in the vaccinated group were affected by exposure to anthrax bacilli, while in the unvaccinated group the goat and all twenty-four sheep died, while the cows became very ill.26

Pasteur crowned his career in 1885 with a treatment for rabies. He “attenuated” the virus by inoculating it in rabbits and

1 Whenever he received a German book or a pamphlet, he would take hold of it with the tip of his fingers and pass it over to me, or he would put it away altogether with an air of disgust” (Elie Metchnikoff, Founders of Modern Medicine, 104).

drying their spinal cords, using this material as the basis for a vaccine.

His great achievements in combating microbial diseases led to a financial outpouring of gratitude from all parts of the world to establish what in 1888 was baptised the Pasteur Institute.27

In 1892 his seventieth birthday was marked by an international celebration in Paris. He died three years later.

Robert Koch, the other great founder of bacteriology, was born in the Harz Mountains of north-central Germany, the third of thirteen children of a mining inspector. He attended the university in neighboring Goettingen, where he was taught anatomy by Jacob Henle (1809-1885). Graduating in 1866 he practiced medicine in Berlin, Hamburg, and finally, the small towns of Rakwitz and Wollstein near Poznan (Posen) in what is now Poland. He served in the army during the Franco-Prussian war, caring for the wounded and the numerous typhoid and dysentery cases.

By 1871 he was back in Wollstein and in 1873 commenced research on the developmental cycle of anthrax, epidemic in the area. Davaine’s research had not explained how the anthrax bacillus could survive the cold when it was seen to perish rapidly merely from contact with air. Koch tackled this issue and by 1876 felt sufficiently confident to request an interview with the prominent bacteriologist Ferdinand Cohn (1828-1898), who expected “little of value from a completely unknown physician from a rural Polish town” (as he wrote later). But Koch’s demonstration was utterly convincing, and Cohn remarked to a colleague: “This man has made a great discovery, all the more amazing in that he has developed simple, precise, and definitive methods entirely on his own. I consider this the greatest discovery in the field of bacteriology and believe that Koch will continue to surprise us and shame us with further discoveries.”28

Koch’s first paper, “The Etiology of Anthrax Based on the Developmental Cycle of Bacillus anthraciswhich revolutionized bacteriological research, appeared in 1877, a year prior to Pasteur’s announcement of the same discovery. It described the spore form of the bacillus, solving the mystery of anthrax hibernation through the Polish winter. “This fact,” Koch wrote, “removes all doubt that Bacillus anthracis is the actual cause and con-tagium of anthrax.”29

He published papers on the rapid air-drying of thin films, their fixation and staining, and the use of photographs to record the results. His methods were of unsurpassable accuracy, and his striving for reproducible results established standards for the first time.

Even working under thoroughly primitive conditions Koch had astonished the world leaders of bacteriology by the simplicity and precision of his procedures. With publication in 1877 of his “Methods for Studying, Preserving, and Photographing Bacteria,” his name became synonymous with the advance of German microbiology.

His staining techniques used the aniline dyes developed and introduced by German industry through the work of Paul Ehrlich.

Koch’s 1878 Investigations into the Etiology of Wound Infections demonstrated that they were caused by microbial infestation justifying the antiseptic surgical technique just being introduced by Lister.30

In 1880 he joined the Imperial Health Office as head of the bacteriology division. There in 1881 he published a theoretical work, “On the Study of Pathogenic Microorganisms,” giving the outlines of what would later be called the “Koch-Henle Postulates” and which have provided researchers in bacteriology with a set of bearings for navigating this ocean of uncertainty.31

Koch’s most important and urgent task in the Imperial Health Office was to prepare pure cultures. He used slices of cooked potato, but some bacteria would not grow on this medium. Then he tried thickening the infusions with gelatin, but it was too easily liquefied. Finally the wife of a colleague suggested agar-agar, a gelatinous substance from seaweed which she had received from a Dutch friend in Java, and this has remained the standard ever since.

In 1881 he studied the etiology of tuberculosis, the leading cause of death during those decades in the industrialized societies of the world, announcing discovery of the bacillus in 1882.32 To achieve this Koch employed all the techniques he had worked so

hard to master: serial cultivation of the bacillus, an appropriate culture medium, fixation, staining, and microscopic examination of specimens.

He concluded that tuberculosis, like anthrax, is “parasitic” and also infectious. In thus identifying the bacillus, Koch advanced beyond the stage reached in the 1868 Etudes sur la Tuhercu-lose by Villemin, itself an original and ground-breaking study which aroused Koch’s decided admiration.33

Koch and his associates thereafter discovered etiological agents associated with relapsing fever (O. Obermaier in 1873), glanders (Friedrich Loeffler in 1882), Asiatic cholera (Koch in 1884), diphtheria (Loeffler in 1884), typhoid (G. Gaflky in 1884), staphylococcal and streptococcal infections (J. Rosenach in 1884), gonorrhea (Ernst Bumm in 1885), pneumococcal pneumonia (Albert Fraenkel in 1886), meningococcal diseases (A. Weichselbaum in 1887), tetanus (S. Kitasato in 1888), plague (S. Kitasato and Albert Yersin in 1894), dysentery (K. Shiga in 1898), syphilis (Fritz Schaudinn in 1905), and others.34

Koch’s relations with Pasteur were worse than hostile. The two scientists disliked one another intensely, due to mutual incomprehension of each other’s languages, to the political antagonism between their countries, and to the fact that they were working somewhat at cross-purposes.*

Called to Egypt in 1883 to investigate Asiatic cholera, Koch succeeded in isolating a vibrio, but it did not produce the disease in a healthy organism. This slight non-fit with the Koch-Henle postulates was overlooked, however, since other evidence seemed convincing, and he received a decoration from the Prussian crown.

In 1890, as professor of hygiene in Berlin, he introduced a remedy for tuberculosis made from the bacillus itself. Clearly bor-

eH. H. Mollaret has shown that the Koch-Pasteur antagonism had much to do with their inability to communicate in any language. The feud came into the open at the 1882 International Conference on Hygiene in Geneva. During a speech by Pasteur, Koch kept trying to interrupt, provoking consternation among those present. Later the Germans found they had simply misunderstood Pasteur’s “recueil Allemand” (“German compilation”), taking it to be “orgueil Allemand” (“German arrogance”), but relations deteriorated from that moment (Mollaret, “Contribution,” 63). The presence of a qualified interpreter might have affected the whole history of bacteriology!

rowed from homoeopathy, Tuberculin had to be employed in homoeopathic doses, which Koch failed to do, causing thousands of deaths and virtually ending the career of the Father of German Bacteriology.

This catastrophe darkened his declining years, which were spent increasingly outside Germany, in travels to tropical areas seeking new diseases to conquer: Egypt in 1891 (cholera), Capetown in 1896 (rinderpest), India and German East Africa that same year (bubonic plague), Egypt again in 1900 (rinderpest), southern Italy the same year (malaria), Rhodesia in 1902 (African Coast Fever), and German East Africa again in 1905, 1906, and 1907 (sleeping sickness, African Coast Fever, and relapsing fever). In 1908 he travelled around the world, being feted especially in Japan and the United States.

In 1905 Koch was awarded the Nobel Prize and addressed the Stockholm audience on the subject of tuberculosis and its treatment by Tuberculin.

He died of a heart attack in 1910, still struggling to perfect Tuberculin.

Elie (Ilya) Metchnikoff, of a moderately affluent Russian landowning family, took up biology while still a child and graduated from the four-year biology program in Kharkov after only two years.

Then commenced a period of wandering.

In 1864, he was in Germany collecting marine specimens and performing research in the Giessen biology laboratory. But when his results were published under the name of the department chairman, he left distraught for Naples, then to St. Petersburg to obtain the doctorate. By age twenty-two he was docent of the university in Odessa.

In 1868 Metchnikoff returned to Naples to study marine fauna, then went back to St. Petersburg, where he married a young woman who died in 1873 of tuberculosis. This induced him to attempt suicide with his wife’s morphine, but in 1875 he found consolation in a very happy second marriage. Even so, Tsarist opposition to liberal trends at the university, and the resulting academic friction, led to another suicide attempt in 1881.

Soon after, his parents-in-law died leaving the young couple enough money for further European travel; in 1882 they departed for Messina (together, in Russian style, with his wife’s five sisters and brothers!) to collect marine specimens and pursue research on the shores of the Mediterranean.

This trip was a fabulous success, as he discovered phagocytosis—the ingestion and digestion of microbes by certain classes of white blood cells—which changed the course of his life and of immunology: “Thus it was in Messina that the great event of my scientific life took place. A zoologist until then, I suddenly became a pathologist.”35

From his earliest years he had focussed on the digestive process and on inflammation. Now he assimilated both of these concepts to phagocytosis—yielding a Hippocratic doctrine of resistance and immunity which has not lost its validity today.

In 1887, after being coldly received by Koch (who did not approve of phagocytosis), Metchnikoff joined Pasteur (who did), remaining at the Institute until the end of his life and becoming its scientific eminence and leader after Pasteur’s death.

He was awarded the Nobel Prize in 1908.

Other than defending and perfecting the theory of phagocytosis, Metchnikoff was passionately interested in the prolongation of life. He concluded that the aging process and differing levels of resistance to disease could be attributed to differences in the intestinal bacteria and urged all to eat yoghurt, with its friendly lac-tobacilli, as the key to good health and long life.

He died in 1916.

As Pasteur and Koch had restructured diagnosis, so treatment was revolutionized by Paul Ehrlich—the son of a distiller, innkeeper, and lottery collector from Prussian Silesia who set a stamp on pharmacology' it has yet to throw off

In high school Ehrlich was talented in mathematics and Latin and notoriously poor at German composition. This was emblematic of his later career: his predilection for mathematics betrayed a mind reveling in abstractions for which he coined plausible and persuasive Latin- and Greek-derived names. I hat Ehrlich was uncomfortable with German is immediately obvious

The Germ Theory: Infection and Specificity 1 7

to those who read his many papers on medical and pharmacological theory, which are lifeless, wearisome, and repetitious.

In the early 1870s he studied natural sciences at Breslau and medicine at Strasbourg, but the truly determining influence on his thought was fascination with the emerging chemistry of aniline dyes. His cousin, the pathologist Carl Weigert (1845-1904), was using them in bacteriology for staining, and Ehrlich here found ready-made a body of theoretical doctrine which he could promptly apply to medicine.1'

Ehrlich’s first paper on dyes appeared in 1877, the year he passed the state medical examination. At this time (he wrote later), “There fell into my hand a work by [Emil] Heubel in which the author believed he demonstrated that the secret of lead poisoning could be revealed by placing segments of liver, heart, and kidney tissues in a dilute solution oflead and determining after a lapse of time how much of the metal each tissue absorbed.

I he thesis of this work was a revelation to me—and a sort of destiny.” 36-'

His 1878 dissertation, Contributions to the Theory and Practice of Histological Staining, suggested that dyes do not adhere physically to animal tissue but establish a chemical bond. His further conclusion that the chemical group on the dye molecule responsible for coloration was usually not the same as the group responsible for the molecule’s binding to animal tissue was crucial to his later pharmacological theorizing.37

All Ehrlich’s medical ideas were generated by this original Hash of inspiration about aniline dyes and his conviction that medicines act through physical contact with their target organs. Julius Morgenroth, his pupil and assistant, stated about the 1878 dissertation: “It is amazing how many germs of later work there are in this paper by the young Ehrlich.”38 A professor of

''Carl Julius Salomonsen later recalled: “Do you remember Ehrlich as a student at Breslau? We laughed at him because he was always running around among us with blue, yellow, red, and green fingers?” (Lewis P. Rubin, “Styles in Scientific Explanation,” 401).

'Emil Heubel, Pathogenese und Sjmptome der chronischen Bleivergiftung: experimentelle L ntersuchungen. Berlin: Hirschwald, 1871.

medical history at Frankfurt wrote in 1929 that the dissertation “contains the germ of Ehrlich’s entire life-work which culminated in the invention of Salvarsan ... It proves that Ehrlich, when leaving the University and before he even became a clinical assistant, was already on the way to becoming the creator of chemotherapy.”39

Ehrlich emerged from medical school with a ready-made set of ideas, which he spent the rest of his life implementing. He saw himself primarily as a chemist and resolved to establish medicine on a chemical basis. His 1898 statement, “Chemistry constitutes the axis about which the most important views in medicine turn,” recalls Claude Bernard’s uLa physiologie, c’est moi/”40

These ambitions were well integrated in a charming and engaging personality:

Never did I ask something of him that he did not with pleasure grant immediately; and a hundred times he bestowed on me, unasked, the most precious kindness. He was the most extraordinary man I have ever met; with his wonderful inspiration, his enormous power of work, his astonishing knowledge, he was the greatest man in the medical world of his time, and more of a genius than any other person. Paul Ehrlich was in his innermost soul modest, sincere, noble-minded, and with the greatest kindness and consideration towards everybody. I am convinced that every one of my countrymen who ever came into contact with him has the same feelings towards him as I do.—W illiam Bulloch, 1938"

However, the good that Ehrlich accomplished must be distinguished from the nonsense. He was, above all, a very good chemist and used this to transform medicine in many ways:

Ehrlich harnessed brilliant talents, a darting intelligence linked to untrammeled imagination, compulsive industriousness, the faculty of stereognostically visualizing benzene rings and structural chemical formulas; technical ingenuity and punctiliousness, and unique virtuosity in “test-tube” chemistry; the capacity to direct several lines of research simultaneously, through a system of daily “blocks” carrying written

instructions to every coworker and the foresight to abandon paths that were unpromising.—Claude Dolman, 197242

He improved and standardized the insights and methods of his contemporaries. In 1882 Ehrlich succeeded in staining the tuberculosis bacillus. In 1897 he discovered how to measure antitoxin, thus establishing the field later called immunochemistry and contributing to the quantitative study of the antigen-anti-body reaction.43

Even his bitter opponent, Max Gruber, called him “a tireless worker, an unsurpassable experimenter and observer” whose “name will survive his theory and remain inseparably linked to the doctrine of immunity which he has enriched with a mass of very important facts.”44

It was for “contributions to immunology” that Ehrlich shared the Nobel Prize with Metchnikoff in 1908.

But his theory was weaker than his practice. His gift for coining words, phrases, and metaphors served merely to embellish a pharmacological theory identical with that of Galen and all other Rationalist thinkers.

He had the luck to come on the scene at a moment of general intellectual hesitation and indecision when his personality, charm, and talent encountered minimal resistance. Relying on a theory of aniline dye manufacture and application, he refurbished the conventional Rationalist paradigm of pharmacological action, basing it upon the laws of structural chemistry.45

In 1910 Ehrlich proposed the arsenic-based medicine Sal-varsan as a treatment for syphilis.

He died in 1915 at age sixty-one; the autopsy showed advanced arteriosclerosis.46

Emil Behring (1854-1917; the “von” was conferred only in 1896 when he was admitted to the nobility) was born to a poor village school teacher in West Prussia, like Koch one of thirteen children. While medicine was always his goal, funds were unavailable, and he was about to enter the university at Koenigsburg to prepare for the ministry when, through intercession at higher levels, he was admitted to the Friedrich-Wilhelm Institute, the medical school of the Prussian army.47

He graduated in 1878, that eventful year he later called the “birth-date of medical bacteriology.”48

After 1889 he worked with Koch at the Institute of Hygiene in Berlin, and in 1891 they moved to the new Institute for Infectious Diseases.

In an 1892 paper Behring assigned the symptoms and pathology of diphtheria and tetanus to bacterial toxins rather than to the microorganisms themselves.49

But he resembled Pasteur in being concerned more with therapy than with causation and in 1892 proposed a technique of treating diphtheria with blood from artificially immunized animals, so-called “passive immunization.” Later he treated tetanus in the same way.

The curative substance in the blood he called “antitoxin,” although there is no “contrariety” involved; “antitoxin” is in reality a protective antibody, i.e., an immunoglobulin or protein molecule. How it neutralizes toxin or antigen remains a mystery today.

By the early 1890s Behring’s fame began to overshadow that of Koch, and he had to move to Halle in 1894, and to Marburg two years later as professor of hygiene. Because he was accused of introducing homoeopathy into medicine, these university appointments were vigorously opposed by the other professors.50

At Marburg he perfected diphtheria and tetanus antitoxins and worked on the riddle of tuberculosis. But he had no better luck than Koch, and an effective tuberculosis preventative (the BCG vaccine) was only developed after World War I by the French.

These discoveries brought Behring world renown. In 1895 he was appointed Geheimmedizinalrat. In 1896 he was admitted to the nobility and made Von Behring. Soon afterwords he became Wirklicher-Geheimmedizinalrat and was referred to as Ekzellenz Von Behring. In 1901 he received the Nobel Prize.

In 1913 he came up with one last triumph, a toxin-antitoxin mixture which he used as a prophylactic vaccination for diphtheria.51

He died in 1917.

Of these five individuals Koch and Ehrlich represent a purely Rationalizing approach to therapeutic problems, while Pasteur,

The Germ Theory: Infection and Specificity 2 1

Metchnikoff, and Behring are strongly oriented toward the Empirical pole. Behring, in fact, was an intermittent propagandist for homoeopathy.

The ideological dimension affected their personal relations. Pasteur and Metchnikoff were intimate friends and hostile to Koch. Koch was belligerent toward Pasteur, arrogant with Metchnikoff, and disputatious with Behring who, in turn, disliked both Ehrlich and Koch while idolizing Pasteur—whose photograph hung in his study beside portraits of Frederick the Great, Napoleon, and Bismarck. Behring visited France often, adored the Institut Pasteur, where he was a welcome guest, and made Metchnikoff and Emile Roux godfathers to two of his sons.52

Infection and Contagion

I he emerging doctrine needed an acceptable understanding of infection and contagion.

Not that infection was unknown prior to the late nineteenth century; Giovanni Baptista Morgagni (1682-1772), for instance, regarded plague, smallpox, acute exanthematous diseases, tuberculosis of the lungs, rabies, and many inflammations as contagious and refused to perform autopsies in such cases.53 I he “itch" (scabies) was also known everywhere to be contagious. French physicians in 1823 showed anthrax to be contagious by inoculating healthy animals with blood from diseased ones.54

I hat contagion and infection were accepted concepts before being officially recognized is seen also in Hahnemann’s observation during the Asiatic cholera epidemic of 1831-1832, that the “contagious matter of the cholera most probably consists ... of an enormous brood of ... excessively minute, invisible, living creatures’’ and his recommendation that camphor be employed as a preventativeJ

1 he cholera epidemics in Western Europe and the United States contributed to general awareness of the fact of contagion, thereby abetting the public infatuation with camphor as a pre-

jSee Divided Legacy, II, 412.

ventative and curative substance. Its price rose ten to twenty times at any rumor of a cholera epidemic.

The cause of camphor was thereafter taken up by the Paris chemist Francois Raspail, who viewed it as the king of the materia medica.55 One of his associates, the physician P. L. Cottereau, absorbed so much camphor in the attempt to ward oil microbial infection that in 1847 he apparently died of it:

At an early age he had been impressed by the idea that parasitic infection by the infinitely small is the cause of nine-tenths of our diseases ... rabies is due to invasion of the tongue by a bug of greater or lesser dimensions ... asthma is an accumulation on the walls of the bronchia and at the base of the tracheal artery of mucosities and parasitic tissue caused by the ticklings of little worms.

—Piedagnel, 1846-184756

Suitably convinced, Cottereau took increasing quantities of camphor: “When he felt well, he took some, he smoked it, he almost always had a piece in his mouth, he never went out without his tobacco pouch and pill-box full; if he felt ill, or even indisposed, he added camphorated rubbings and washings.”

Another contribution to the emerging doctrine was made by Ignaz Philipp Semmelweis (1818-1865), a Hungarian physician working in the obstetrical clinic of the Vienna Allgemeine Krankenhaus, who observed as early as 1846 that women often contracted “childbed fever” (puerperal sepsis) after examination by medical students who also performed autopsies. In an adjoining clinic serviced by nurses and midwives, who did not perform autopsies, the death rate from “childbed fever" was much lower. Convinced that infection was being carried from the autopsy room to the obstetrical ward, Semmelweis forced the students to wash and brush their hands and dip them in chlorine before doing pelvic examinations or delivering babies; the death rate promptly dropped to the level achieved by the nurses and midwives. But when his data were published in 1847, the physicians rose up in outrage, ascribing the lower death rate to a change in the genus epidemicus. Semmelweis returned to Budapest where he died a decade later in obscurity, driven insane by persecution and lack of recognition.57

However, he did not attribute childbed fever to a microorganism, although aware that it was passed through physical contact.

Twenty years would pass before physicians could bring themselves to accept his data the time needed for the older generation, responsible for so many deaths and unwilling to bear the responsibility, to depart the scene.

It was the surgeon Lister who, with help from Pasteur, demonstrated the tie between infection and microbe.

The introduction of anesthesia in the late 1840s had greatly increased the amount of surgery performed, with a consequent rise in deaths from the fearsome “hospital gangrene”:

When it rages in a great hospital, it is like a plague; few who are seized with it can escape. There is no hospital, however small, airy, or well regulated, where this epidemic ulcer is not to be found at times; and then no operation dare be performed. Every cure stands still. Every wound becomes a sore, and every sore is apt to run into gangrene; but in great hospitals it prevails at all times and is a real gangrene.

—John Bell, 180158

[In hospitals of the 1850s] every wound discharged pus freely, and putrefactive changes occurred in the discharges of all, producing in the atmosphere of every ward, no matter how well ventilated, a fetid sickening odor, which tried the student on his first introduction to surgical work just as much as the unaccustomed sights of the operating theater. It is hardly necessary' to add that fatal wound diseases and complications were never absent at any time from the hospitals of that day.—Sir Hector Cameron, 191259

In the Munich Allgemeine Krankenhaus in the 1860s, four-fifths ol all patients contracted hospital gangrene, and the city fathers considered tearing the building down.60

Lister, a Quaker and a physician of strongly vitalist inclinations, turned the tide against “hospital gangrene” by going a step beyond Semmelweis and blaming wound infections on a microorganism.k His 1867 article “On a New Method of Treating Compound Fractures” held microbial infection responsible for the tendency of compound fractures (when the bone ends project through the skin) to suppurate:

We find that a flood of light has been thrown upon this most important subject by the philosophic researches of M. Pasteur, who has demonstrated by thoroughly convincing evidence that it is not to the oxygen or to any of its gaseous constituents that the air owes this property but to minute particles suspended in it, which are the germs of various low forms of life long since revealed by the microscope and regarded as merely accidental contaminants of putrescence, but now shown by Pasteur to be its essential cause, resolving the complex organic compounds ... just as the yeast-plant converts sugar into alcohol and carbonic acid.

—Joseph Lister, 186761

Lister introduced “antiseptic surgery,” employing a carbolic acid solution to disinfect rooms, wound dressings, and bandages (although never going so far as to wash his own hands). This revolutionized the operating room until “antiseptic" surgery was succeeded in the 1890s by “aseptic.62,1

In 1874 Lister wrote Pasteur an expression of gratitude “for hav ing, by your brilliant research, demonstrated to me the truth

kLister’s first writing was on “The Durability of Vitality in the Tissues.” Later in life, when discussing phagocytosis with the vitalist Metchnikoff, whom he greatly admired as a man and scientist, Lister remarked: “It seems to me that these movements, predetermined for a fixed purpose, are another manifestation of something higher than mere chemical affinity” (Elie Metchnikoff, Founders oj Modern Medicine, 110).

‘Carbolic acid was not without its own drawbacks, being useful preventively but not for sterilizing an existing wound. Alexander Fleming wrote: “Lister himself recognized that carbolic acid, which was his standby as an antiseptic, was very poisonous to the tissues ... none of these chemicals had much effect in destroying bacteria once they had invaded the tissues. I commenced medicine in the early years of this century. Then Lister’s methods were rather discredited—asepsis had taken the place of antiseptics ... Carbolic acid, boric acid ... iodine, etc. ... failed in treatment. They were either non-diffusible, or if they were diffusible they poisoned the tissues more than the bacteria. One of the first things I learnt in the casualty room was not to put a carbolic compress on a septic finger or carbolic gangrene was likely to result” (Alexander Fleming, Chemotherapy, 9).

of the germ theory of putrefaction and thus having provided me with the sole principle which can guide the antiseptic system to

success.”63

Pasteur endorsed the idea of microbial contamination of wounds, writing in The Germ Theory and its Applications to Medicine and Surgery (1878) that infection by the anaerobic vibrion septique (Clostridium septicum) is responsible for much wound infection and hospital gangrene. As a preventive measure he urged general implementation of antiseptic—even aseptic—principles and practices in surgery: “The water, the sponge, or the lint with which you wash or cover a wound, deposit germs there which, as you can see, propagate in the tissues with extreme facility and infallibly would bring death to the operated patient in a short time if life in these limbs would not oppose the multiplication of these germs ... The rotten condition of the bandage offers but an insufficient barrier to the invasion of infinitely small organisms with which, unknowingly, you have covered his injured parts. If I had the honor of being a surgeon, imbued as I am with the knowledge of the danger of exposure to the germs spread on the surface of all objects, particularly in hospitals, not only would I use only thoroughly cleansed instruments, but, after having cleaned my hands with the greatest of care, I would subject them to rapid flaming, which is not any more painful than what a smoker feels when he passes a hot coal from one hand to the other. I would use only lint, bandages, and sponges previously exposed to air temperatures of 130 to 150 degrees C.”64

But English surgeons were no more willing than Viennese obstetricians to admit their contribution to the devastations of hospital gangrene; they attributed it to “spontaneous generation” and steadily turned a deaf ear to Lister’s proposals for antisepsis. Students did not dare study with him until after graduation:

After a certain period of deliberate silence, Lister’s colleagues launched an attack against him. The famous [Sir James] Simpson [professor of obstetrics]"1 ... opposed the new

"'Simpson was also the most virulent opponent of homoeopathy in his generation {The Practitioner 57 [1896]: 574).

method very vehemently. Spens, Lister’s colleague at Edinburgh, utilizing statistical facts he had gathered, attacked the antiseptic method and attempted to destroy it once and for all. In other countries, too, the voice of criticism was raised, although not as vociferously as in Great Britain ... many years went by before the great discovery of Lister—the application of the theory of the nonexistence of spontaneous generation of ferments—became a common possession.

—Elie Metchnikoff, 193965

German, French, and Danish surgeons adopted antiseptic surgery before the English.66

Specific Diseases: Koch and Pasteur

In the seminal year 1878, Koch’s Etiology of Wound Infections proposed a theory of specific diseases based upon the distinctions among microorganisms: “The bodies of animals that die of artificial infected wound diseases invariably contain ... many bacteria ... In each case a definite organism corresponds to a distinct disease ... One fact is so prominent that I must regard it as established. This fact helps to remove most of the obstacles to recognizing a contagium ammatum for infected wound diseases ... This is that there are differences among pathogenic bacteria, and each has a constant nature ... each distinct bacterial form corresponds to a specific disease. The form always remains the same, however often the disease is transferred from one animal to another, the kind always remains the same and never changes into other kinds.”67

Each species of microbe causes only the disease associated with it. Streptococci cause streptococcal diseases but not erysipelas, puerperal fever, endocarditis, intestinal mycoses, or hospital gangrene.

Where Pasteur’s views were shaped by his study of fermentation, Koch was affected by his contact with wounded soldiers. He demonstrated with meticulous accuracy that bacteria are not mere concomitants of wound infection but their actual causes. “The infection was produced by such small quantities of blood

serum or pus that the result could not be attributed merely to chemical poisoning ... We come to this conclusion ... that for every individual traumatic infective disease, a morphologically distinguishable microorganism is identified.'’68

Koch’s essay marked the birthdate of the “germ theory."

Pasteur was not unsympathetic to a classification of specific diseases but much less systematic than Koch.69 Where the latter’s thinking was diagnostic, classificatory, and etiological (“only etiology interested me”), Pasteur’s leanings were to therapy. “Specificity" concerned him as a factor in treatment more than diagnosis.

He accepted the Empirical concept that the “cure points to the cause”: “The etiology of anthrax is found, and at the same time the prophylaxis of this disease.”70

While he commenced research on diseases of animals and humans only in the mid-1870s, Pasteur had long been attracted to this area. As early as 1867 he asked Napoleon III to fund a laboratory to study the “causes of putrid or contagious diseases ... gangrene ... viruses ... experimental inoculation.”71

I he dominant theory at this time held disease “causes” to be crystalline structures or chemical toxins.72 Claude Bernard, for instance, in 1865 had wanted to locate the cause of cholera in "mineral elements of the blood.”73 But Pasteur’s work with the “ferments” which turn beer and wine sour convinced him that they were alive and specific, each yielding a particular type of fermentation and a specific product; this led naturally to viewing the agents of “putrid diseases” also as living organisms which invade the body from the outside.

I he whole of Pasteur’s thought is permeated with the distinction between the living and the non-living—what has been called “vegetalism.”74

Pasteur inclined, therefore, logically toward the theory' of germs. It was only a question of proving it by experimentation, and for that he was better equipped than any scientific man of his time. He was familiar with the infinitely small organisms; he knew how to manipulate them. He had a clear field; and he advanced with great strides.—Emile Duclaux, 189675

This is why the anti-vitalist “physiological” school of Virchow was so opposed to the germ theory:

The idea that there could be in the tissues organisms come from the exterior which, by penetrating and developing there, impressed upon them specific modifications, was in disagreement with the general current of anatomical ideas, and yet more with physiological views ... it is plain with what welcome the idea would be received of the intervention under the form of living and parasitic organisms of this proscribed vital force.—Emile Duclaux, 189676

The microbe ... was the sudden reappearance of the vital force in regions from which it was desired to eliminate it. The idea of the microbe brought back in the clearest manner the idea of conflict, of strife for the necessities of life, of the struggle for existence.—Emile Duclaux, 189677

In 1881, as the recently appointed director of the Bacteriological Laboratory of the Imperial Health Office, Koch commenced his own study of the tuberculosis bacillus, presenting his results to the Berlin Physiological Society a year later."

He concluded that infectious diseases are caused by living organisms which reproduce themselves and can be cultivated in the laboratory, identified, and arranged in a typology; further, every disease has its microbial cause; if the bacterial cause is the same, the disease is too, despite differences in clinical symptomatology.78

Here he built on an 1840 exposition of the relations between microbial diseases and their causes by Jacob Henle, his professor of anatomy. Henle had written that to establish the microbial etiology of a disease, (1) the agent must be found regularly in the host during the course of the disease, (2) must be isolated, and (3) must be shown capable of causing the disease.79

"Virchow refused to attend and had recently criticized the “juvenile work” of the “youngsters” at the Imperial Health Office. He changed his views, however, in the end of his life, and a student later recounted hearing him lecture on bacteriol-ogy, with slides of tuberculosis, cholera, typhus, and other microbial causes, in which “the nearsighted old gentleman kept confusing gonococci with tuberculosis bacilli” (H. U. Lammel, “Virchow Contra Koch,” 208).

Thereafter these principles were known as the Koch-Henle Postulates. The microbe became a new organizing principle in medicine, bringing much scattered clinical data together into a series of new specific entities. Koch wrote in the 1880s: “Only this one species of bacteria with specific characteristics always occurs in both phthisis and tuberculosis. In lung cavities, miliary spleen tubercles, tuberculous skin and brain diseases, in fungal joints, in spontaneous tuberculosis, and in experimental animal tuberculosis, one always finds the same bacilli. In anthrax, also without exception, specific large bacilli always appear. In erysipelas there are specific micrococci, and in relapsing fever a spirochete ... Tuberculous bacilli constantly occur among ph-thisics and ... without exception, they are missing in healthy persons.”80 “Among humans anthrax is so variable, both clinically and anatomically, that without considering anthrax bacilli one would form completely different disease pictures.”81 “Because of the identical properties of the bacilli, and of the cultures grown from them, and because of the identity of the inoculation results obtained from these cultures, the various forms of tuberculosis must be regarded as identical.”82

He extended the analysis to cholera: “From the cholera material that I have investigated, I conclude that comma bacilli occur in all cases of cholera. They are specific to the disease.”83

In contrast to the holism of Empiricism, Koch accepted the coexistence of two or more infectious diseases in a single host: “Many pathological processes which once seemed mysterious are now more perfectly understood. This includes the frequent occurrence of combinations of various infectious diseases of which one is to be regarded as the primary infection and the others as secondary.”84

I he bacterial cause, which could exist both inside the body and outside, was accepted with rapidity by the medical profession. It was the living embodiment of the “proximate” disease cause which has figured prominently in Rationalist theory since ancient times, and it released the tension generated by the conflict between Trousseau’s “specificity” and Virchow’s “physiological medicine.”

By tying the given “disease” with all its signs, symptoms, and pathology to a specific concrete causal agent, Koch made it difficult for future generations to vitiate the concept as Virchow had undermined the ideas of Bretonneau and Louis. It would be decades before the connection with the causal microbe was broken and the disease “entity” started to dissolve.

The “germ theory” responded to the Rationalist physician’s profound psychological need for firm ground amid the ocean of data. The entity allows him to select among symptomatic and other data and to give a name to the patient’s condition, keeping them both happy.

Nosography is not an embryonic stage in the growth of modern medicine, but the very root and trunk of medicine upon which all else must be grafted, and by which alone the grafts can become fruitful.—Francis Walshe, 195685

Monomorphism and Pleomorphism

I he “germ theory” was bolstered by the doctrine of “monomorphism”—meaning that microbial genera and species are fixed and eternal, that each microorganism is associated with a specific disease, and that the number of such germs or microorganisms is finite.

This concept was first systematized in Cohn’s 1871 “Unter-suchungen ueber Bacterien” which classified microorganisms into categories according to their shape and their physiological and behavioral characteristics. While he admitted that species were provisional, he believed his six genera—micrococci, bacteria, bacilli, vibrios, spirilli, and spirochetes—to be eternal, i.e., natural.

After Cohn’s fateful meeting with Koch in 1876 the two collaborated in advancing the monomorphist viewpoint. Koch wrote: “There are differences among pathogenic bacteria and ... each has a constant nature ... each distinct bacterial form corresponds to a specific disease. This form always remains the same, however often the disease is transferred from one animal to another.”86 “No bacterial species is known to change into another species.”87

And he was echoed by his assistant, Carl Fraenkel: “Under some circumstances a very careful and precise consideration of all their pecularities is necessary; yet, where this condition has been fulfilled, one species has never been found to merge into another and display its characteristic marks.”88,0

Koch was at pains to distinguish anthrax, for instance, from “malignant edema” and “Rauschbrand.” Anthrax and Rauschbrand are so similar symptomatically “that until recently they were regarded as the same disease”: “Both ... are bacilli diseases. However, Rauschbrand bacilli are slightly shorter and thicker, they remain restricted in local collections, and they produce gas in the tissues. Otherwise, the symptoms and course of Rauschbrand approximate anthrax so closely that they are often confused in veterinary practice.”89

I he main difference between anthrax and “malignant edema” is that “after an anthrax inoculation, the animal dies; with malignant edema it remains alive.”90 Unfortunately, even the bacilli resemble one another greatly: “A very unreliable means of distinguishing between anthrax and edema bacilli is that the latter are mobile. I have often entirely missed this, and even if among many nonmotile bacteria a few can be found that twist, it does not follow that those that do not move are also edema bacilli. It is possible for an animal to have both anthrax and malignant edema. The only certain and decisive way of distinguishing the two species is by means of their form. Anthrax bacilli are slightly wider than edema bacilli and differ from them in their entirely characteristic articulation ... To prevent any misunderstanding I refer to my writings on the subject...” 91,p

An opposed view was held by the adherents of “pleomorphism," first proposed in studies of fungi by the Tulasne brothers in Prance and, in Germany, by the mycologist Anton de Bary (1831-1888).92 Excitement over the possibility that fungi could

11 his work is cited by us throughout as evidence for Koch’s own views, since fraenkel writes: “I have at all limes been assisted by Dr. Koch’s weighty advice, and am thus fortunate enough to know that my views are in complete harmony with those of the master of recent bacteriology” (Carl Fraenkel, Bacteriology, Preface).

p Today anthrax is attributed to Bacteridium anthracis, while Rauschbrand or “septic gangrene” is attributed to Clostridium feseri (also called Bacterium chauvoei).

change their form and attributes led to conjecture that the same was true of bacteria and, indeed, that bacteria themselves were the progeny of fungi. This idea was developed in the 1860s by Ernst Hallier (1831-1904), professor of botany at Jena, who suggested that the bacterial genera known as micrococci, cryptococci, arthrococci, etc., were merely forms (Morphen) of fungi which could be generated by altering environmental conditions.93

The most famous, even notorious, figure in the history of pleomorphism was Hallier’s and Koch’s contemporary Carl Wilhelm von Naegeli (1817-1891), professor of botany at Zurich and Munich, who accepted the fungal theory of bacterial development and concluded that microorganisms of various kinds can be transformed into one another merely by changing the conditions of their environment.94 “I have examined thousands of dividing yeast forms, and I should be unable to maintain ... that there is a need even of a division into two specific forms ... If my view is correct, the same species in the course of generations take different morphological and physiological forms which, in the course of years, bring about sometimes the sourness of milk, or the acid formation of sauerkraut, or the fermentation of wine, or the putrefaction of albuminous substances, or the reddening of foods containing starch; sometimes producing typhus fever, cholera, or intermittent fever.”95

The ghost of von Naegeli’s radical pleomorphism has haunted bacteriology since that time, coming to the fore in the 1920s and 1930s, and again in quite recent times. Some have held that only the species—lowest in the phylogenetic hierarchy- are form-changing. Others allow pleomorphism at higher levels genera, classes, families, even orders.

Monomorphists used young cultures, on the assumption that only these are “legitimate” and “normal.” One German researcher insisted that morphological and cytological studies of bacteria should never be made with cultures older than twenty-four hours, because “the bacteria do not feel well” {die Bakterien anfangen, sich uebel z.u befinden.) after that time.96

Some monomorphists went so far as to refuse the appellation “bacterium” to any microorganism showing pleomorphic ten-

dencies. Cohn had declared that all bacilli multiply by fission, and when the tubercle bacillus was seen to multiply by branching, one German authority declared it to be the “parasitic growth of a pleomorphic organism, probably belonging to the genus of higher fungi.”97

Pleomorphists objected: “It is well known that frequent transfers to the same substrate repeated after a few days tend to keep a strain constant, whereas older cultures are much more liable to furnish either new variants or to exhibit atavistic tendencies.”98 Monomorphists devised culture media which particularly favored bacterial growth, prompting pleomorphists to observe that media favorable to bacterial growth may be “artificial” in the sense of unrelated to the microbe’s normal environment. The bacterial phase or stage most readily cultivated in a medium may not be significant for the disease process. The Swedish bacteriologist Ernst Bernhard Almquist (1852-1946), for instance, grew his cultures in media resembling the microbe’s natural environment.99

In due course the monomorphists retreated somewhat from their ideological bastions, admitting that variety in the behavior of bacteria was “normal,” not “pathological,” but insisting that the forms were unchanged.100

But pleomorphists called this a timid and inconsistent position:

As life is characterized, according to Spencer, by the “continuous adjustment of internal relations to external relations,” it is, indeed, self-evident that variations must occur under changed conditions. That all, morphological as well as physiological, characters of the bacteria may vary has been explicitly stated, probably for the first time, by Naegeli. The following of his sentences is remarkably accurate when we consider that it was written more than thirty-five years ago: “ I he species cannot be defined by absolute characteristics but rather through its ability to manifest certain modifications of its morphological and physiological behavior under certain external constraints, other modifications under other constraints.”—Felix Loehnis, 1922101

The dispute was more than a professorial quarrel over the shapes of microbes. For the pleomorphism/mo no morphism clash was only the symptom of a larger dispute, i.e., between the Empirical and Rationalist philosophies.^

In the particular instance what was involved was the role and importance of the host organism. Microbes altered their forms in response to environmental stress. Disease microbes responded in this way to unfavorable or hostile conditions in the host organism. Pleomorphism meant that the host was an active participant in infection and disease- in contrast to Koch and the monomorphists who held the microbe to be all-powerful, the host organism a passive victim. Pleomorphism meant downgrading the microbe, since the host, by resisting the latter’s onslaught, could alter its characteristics.

The Doctrine of “Normality” and The “Pure Culture” Technique

Supporting monomorphism was the doctrine of “normality” the assumption that a given bacterial form is “normal ' and all others “abnormal,” “degenerated,” “contaminants,” “teratologic,” “sick,” “illegitimate,” “pathological variants,” “involution forms,” “departures from the norm,” “crippled, hypertrophic, or otherwise abnormal growth,” etc.102

Bacterial forms appearing under the conditions, and on the media, accepted by the majority of investigators were said to possess greater legitimacy than forms appearing on other media or under different culture conditions.

If we examine [anthrax] bacilli which have been developed at a low temperature on the surface of a slice of boiled potato, they can scarcely be recognized. It is, therefore, evident that this type of nourishment is unsuited for their development, as we find all sorts of irregularly developed cells and amorphous bodies massed together, with here and there a long cylinder, which reminds one of what the anthrax cell

^See below, pp. 204—208.

should be. We also see numerous distinctly rounded forms of bacteria, which might be mistaken for cocci.

Do such cells, therefore, belong in the circle of development of the anthrax bacilli? Certainly not. For, if we bring them into favorable conditions of nourishment, it will be seen either that they are no more capable of propagation—that we, therefore, have to do with dead substances—or, on the other hand, that they immediately give birth to the described typical forms of growth, the long rods of regular shape. These forms were, indeed, nothing but the expression of degeneration in the bacteria in question. They are degenerative forms ... “involution forms,” malformations which are not to be mistaken for the healthy bacilli.—Carl Fraenkel, 189103

The morphologic nature of the species can be manifested only in conditions which favor its existence. In unfavorable conditions, subjected to harmful influences, there is either a cessation of growth ... or difficult growth accompanied by pathological phenomena.—Serge Winogradsky, 1889104

It would be a mistake to think that every mode of reproduction is normal and should be considered a regular stage in the development of the species ... evidently morphology can never be founded on the teratology of living beings, but only on their normal cycle of evolution proceeding under normal conditions.—Serge Winogradsky, 1939105

The ‘ "normality” concept was supported and justified by the “pure culture” or “serial cultivation” technique discovered by Joseph Schroeter and perfected by Koch, for isolating the sought causal microbe from among the many accompanying contaminants.106

Both Pasteur and Koch published on this technique in 1878.r 1 he former described growing the anthrax bacterium in a series ol cultures: “each fresh culture being inoculated with a droplet from the previous culture.” When “the last culture of the series

'The word “microbe” was introduced by Charles Sedillot in this “first year of the bacteriological era.”

was able to multiply and act in the body of animals in such a way that the animals developed anthrax with all of the symptoms typical of this affection," Pasteur concluded that “anthrax is a disease caused by bacteria.”107

Koch’s 1878 article on wound infections went further than Pasteur. He claimed that the resultant organism is the “true,” in the sense of “legitimate,” form of the bacterium: “In a series of cultures, if the same form of bacterium is always obtained, a special significance must attach to this form; it must be a constant species.”108

In 1881 Koch presented his version of the pure culture technique to the International Medical Congress in London: “A small quantity of the bacilliferous blood is transferred to a solid culture medium, for example, nutrient gelatin or cooked potato. The bacilli multiply profusely while the other blood components, such as the red and white corpuscles and the serum, remain static. After two or three days, when the bacilli have formed a dense mass of spore-bearing filaments, the smallest possible quantity of this mass, which is no longer blood-red but rather white, is conveyed to another cooked potato. The bacilli propagate exactly as in the first culture and form a thick white covering on the potato ... After the third or fourth transfer, the bacilli are free from any original blood constituents. If the transfers are carried out twenty, fifty, or more times, one can assume with full certainty that the bacilli do not retain even the least disease products from the body.”109

When Pasteur saw this demonstration, he turned to the German whom he had never before met and stated: “C’est un grand progres, Monsieur!”110

A “pure culture” could also be obtained by passage through animals, as was done by Koch, serially infecting twenty mice with anthrax and finding that the blood on the twentieth passage showed no organism except anthrax.111

Ultimately, however, the same pure-culture single-cell techniques which gave the initial evidence in favor of monomorphism were seen to reveal an enormous pleomorphic variability if continuedfor a sufficient length of time.n2 But then the results were rejected by monomorphism, provoking the pleomorphist Felix Loehnis to complain: ‘it is difficult to understand why a method which has always been accepted as quite reliable as long as the results obtained with it have been in accordance with the monomorphistic theory, suddenly should become so highly suspicious, as soon as some conflict arises between preconceived ideas and the facts before our eyes.”113

Socioeconomic Factors Promoting Monomorphism

Monomorphism emerged in a context of intense anxiety over the social depredations inflicted in every country of Europe (and in the United States) by a series of diseases whose very names—tuberculosis, diphtheria, typhus, cholera—were chilling reminders of human mortality. In this period of rapid industrialization and urbanization, with newly immigrated rural populations crowding into instant urban slums, diphtheria and tuberculosis were leading causes of death.

Statistics show that one-seventh of all human beings die of tuberculosis and ... if one considers only the productive middle-age groups, tuberculosis carries away one-third and often more.—Robert Koch, 1882114

Behring wrote in 1914 that out of 100,000 cases of diphtheria every year in Germany, 40,000 died—“a frightful death, in the bloom of life.”115

Asiatic cholera, endemic in India, swept through Western and Eastern Europe at ten-year intervals. Typhus epidemics accompanied every military campaign and commonly carried off more lives than the enemy’s swords and bullets.

During these decades half of the children in a city such as Stettin died in the first year of life.116 And in the countryside anthrax caused enormous losses of cattle and sheep:

In one single Prussian district ... losses of sheep amount to 180,000 marks each year. In the Novgorod district from 1867 to 1870 more than 56,000 horses, cattle, and sheep and 528 people died of anthrax.—Robert Koch, 1876117

All parts of France are affected to different degrees, and the losses are well in the millions ... Every farmer considers himself lucky when the death rate does not exceed two to three per cent of the total number of his animals.

—Louis Pasteur, 1880118

The pathogenic bacterial species are an insignificant portion of the world of microorganisms, but it was these that attracted public and governmental support for bacteriology. Investigations took on social and economic weight and importance with awareness that these animalcules were causing the major epidemic and endemic diseases of the times.

The desire to make discoveries has been great, and there is now scarcely a malady which can be supposed due to parasites which has has not been referred to some particular microorganism.—Carl Fraenkel, 1891119

Bacteriology ceased being a mere pastime and became an endeavor of central importance to the welfare of the state. The new official and bureaucratic interest in the discipline could not but affect its very shape and structure. As each “disease," in turn, became the object of scientific investigation and bureaucratic support, a group of individuals was created with a vested interest in maintaining its distinctiveness as a unique “specific” entity. In the political, bureaucratic, and scientific groups combating these social scourges, the suggestion that tuberculosis could turn into cholera, or typhus into diphtheria, would have been deemed frivolous or insane.

And it was psychologically difficult for physicians, confronted with the devastating violence of these dread crowd diseases, to indulge themselves in leisurely searches for multiple bacterial causes.

When a contemporary criticized Koch’s bacterial classes as arbitrary and urged that distinct species be recognized only “when their whole histories of development have been traced by cultivation from spore to spore in different media,” Koch responded that this demand was “... theoretically correct, but it cannot be made a conditio sine qua non in every investigation of pathogenic bacteria. Otherwise, we would be compelled to stop

investigating the etiology of infective diseases until botanists identify all the important species by cultivation and development from spore to spore. It might easily happen that the endless trouble of pure cultivation would be expended on bacteria that finally turn out to be unimportant.”120

Monomorphism was, above all, a practical response to an emergency situation in bacteriology:

The question of classification might be discussed indefinitely, but of what consequence is it? I he bacteria interest medical men principally from an etiological standpoint, because in them we find the exciters of a number of virulent diseases. All the rest, the nomenclature and purely theoretical study, we may safely leave to the proper persons, the botanists.

—Carl Fraenkel, 1891121

The pleomorphism/monomorphism controversy had a socioeconomic dimension in addition to the philosophical one already mentioned. Accepting pleomorphism meant acknowledging the host organism’s capacity to defend itself against, and dominate, the microbe. Monomorphism, on the contrary, enhanced the role of the microbe in disease, and consequently that of the physician who combats the microbe.

This was the principal reason for the instinctive hostility of Koch and the majority of physicians to pleomorphism. Because pleomorphism was a such a threat to the physician/bacteriologist’s socioeconomic position, the monomorphists identified their doctrine with science itself.*

For all of these reasons, monomorphism was at first excessively rigid, even dogmatic. Rene Dubos states that Koch and Pasteur “overestablished” the doctrine of the specificity of disease causes and that “blind acceptance by several generations of bacteriologists of the Cohn-Koch dogma of constancy of cell forms and immutability of cultural characteristics discouraged for many years the study of the problems of morphology, inheritance, and variation in bacteria.”122

!See below, p. 205-206.

Indeed, the “specific disease” formulation which emerged in the late nineteenth century seemed to its devotees an almost unblemished depiction of reality. From the most eminent thinkers to the least common denominator of neighborhood doctors, all believed in the “disease.” The Russian physiologist Ivan Pavlov (1849-1936) expressed the general view when he stated in a 1900 lecture that clinical medicine “in the thousand years of its existence has succeeded in definitely establishing the types of different diseases and in giving a near perfect morphology of pathological conditions.”123

NOTES

1.    Knud Faber, 1922, 21.

2.    Emil Behring, 1915, 3.

3.    Wilhelm Ameke, 1885, 385.

4.    Emil Behring, 1894, 195.

5.    Ibid., 195, 197.

6.    Knud Faber, 1922, 21.

7.    Ibid., 25.

8.    Ibid., 24.

9.    Ibid., 24.

10.    F. M. R. Walshe, 1956, 1060.

11.    Emil Behring, 1894, 210; Rene Dubos, 1953, 92.

12.    F. M. R. Walshe, 1956, 1060.

13.    Knud Faber, 1922, 22.

14.    Ibid., 14; Harris L. Coulter, Divided Legacy, II, 512.

15.    W. Schmitt, 1979, 626.

16.    Knud Faber, 1922, 29.

17.    Ibid., 29.

18.    P. Vallery-Radot, 1954, 140.

19.    Louis Pasteur, Oeuvres, VI, 33.

20.    Claude Bernard, 1957, 201.

21.    Louis Pasteur, Oeuvres, II, 332-333.

22.    J. Theodorides, 1966; I). Wrotnowska, 1978, 13.

23.    Louis Pasteur, Oeuvres, VI, 112-130; Karel B. Absolon et at., 1970.

24.    Louis Pasteur, Oeuvres, VI, 113.

25.    Louis Pasteur, 1940, II, 577.

26.    Louis Pasteur, Oeuvres, VI, 346-347.

27.    Anne Marie Moulin, 1991, 123.

28.    H. A. Lechevalier and M. Solotorovsky, 1974, 69.

29.    Robert Koch, 1987, 2, 12, 13.

30.    H. A. Lechevalier and M. Solotorovsky, 1974, 80; Robert Koch, 1987, 80.

31.    H. A. Lechevalier and M. Solotorovsky, 1974, 83.

32.    Robert Koch, 1987, 83-96.

33.    Ibid., 95, 130.

34.    H. A. Lechevalier and M. Solotorovsky, 1974, 108-109; William Bulloch, 1938, 237.

35.    Elie MetchnikofT, 1905, xxi.

36.    Cited in I. Galdston, ed., 1958, 51.

37.    J. Parascandola, 1974b, 201.

38.    M. Marquardt, 1949, 17.

39.    Ibid., 17.

40.    Paul Ehrlich, 1956-1960,1, 595; T. S. Work, 1954, 100.

41.    Claude Dolman, 1968, 68.

42.    Claude Dolman, 1972, 302.

43.    A. M. Silverstein, 1982, 401.

44.    Max Gruber, 1901, 1884.

45.    A. M. Silverstein, 1982, 401.

46.    Claude Dolman, 1968, 83.

47.    E. Schadewalt, 1975.

48.    H. A. Lechevalier and M. Solotorovsky, 1974, 217.

49.    Ibid., 219.

50.    Ibid., 225; H. Schadewalt, 1975, 2176-2177.

51.    H. A. Lechevalier and M. Solotorovskv, 1974, 229.

52.    Ibid., 226; Claude Dolman, 1968, 81. '

53.    Emil Behring, 1894, 205.

54.    Jean Theodorides, 1966, 157.

55.    Jacques Baur, 1985, I, 79.

56.    Piedagnel, 1846-1847; Paul Triare, 1892, I, 526.

57.    W. Schmitt, 1979.

58.    “Obituary of Lord Lister,” 1912, 399.

59.    Ibid., 397.

60.    Elie Metchnikoff, 1939, 48.

61.    H. A. Lechevalier and M. Solotorovskv, 1974, 45.

62.    W. Schmitt, 1979.

63.    I,ouis Pasteur, 1940, II, 577.

64.    Karel B. Absolon et at., 1970, 254; Louis Pasteur, Oeuvres, VI, 123 124.

65.    Elie Metchnikoff, 1939,48.

66.    William Bulloch, 1938, 183; A. H. Murken, 1976.

67.    Robert Koch, 1987, 48-49.

68.    Ibid., 29, 48.

69.    Adrien Loir, 1938, 22.

70.    Louis Pasteur, Oeuvres, VI, 254.

71.    Louis Pasteur, 1940, II, 345.

72.    Robert Koch, 1987, 179.

73.    D. Wrotnowska, 1979, 32.

74.    Nils Roll-Hansen, 1972, 349.

75.    Emile Duclaux, 1920, 93.

76.    Ibid., 231.

77.    Ibid., 301.

78.    E. Freerksen, 1982, 123.

79.    Ibid., 122.

80.    Robert Koch, 1987, 122-123.

81.    Ibid., 121.

82.    Ibid., 148.

83.    Ibid., 158.

84.    Ibid., 183.

85.    F. M. R. Walshe, 1956, 1059.

86.    Robert Koch, 1987, 49.

87.    Ibid., 159.

88.    Carl Fraenkel, 1891, 138.

89.    Robert Koch, 1987, 59.

90.    Ibid., 61.

91.    Ibid., 62.

92.    Serge Winogradsky, 1949, 137, 139.

93.    William Bulloch, 1938, 88, 91, 178.

94.    Ibid., 200, 201.

95.    Carl von Naegeli, 1877, 20.

96.    F. IiOehnis, 1922, 24.

97.    Ibid., 21.

98.    Ibid., 29-30.

99.    Ibid., 40.

100.    Ibid., 6.

101.    Ibid., 30.

102.    Ibid., 24-29; Serge Winogradsky, 1949, 145, 148.

103.    Carl Fraenkel, 1891, 4; see, also, 290.

104.    Serge Winogradsky, 1949, 130.

105.    Ibid., 144.

106.    William Bulloch, 1938, 217ff.

107.    Karel Absolon et at., 1970, 247; Louis Pasteur, Oeuvres, VI, 1 13.

108.    Robert Koch, 1987, 50.

109.    Ibid., 131.

110.    W'illiam Bulloch, 1938, 228.

111.    Ibid., 225-226.

112.    Harry Rubin, 1987.

113.    F. IiOehnis, 1922, 39.

114.    Robert Koch, 1987, 83.

115.    Emil Behring, 1915, 32, 36.

116.    Ibid., 228.

117.    Robert Koch, 1987, 14.

118.    Louis Pasteur, Oeuvres, VI, 254.

119.    Carl Fraenkel, 1891, 197.

120.    Robert Koch, 1987, 49.

121.    Carl Fraenkel, 1891, 5.

122.    Paul Talalay, 1964, 87; Rene Dubos, 1946, 135.

123.    Knud Faber, 1922, 27.

PASTEUR, METCHNIKOFF, BEHRING, AND THE THERAPEUTICS OF SIMILARS

Already world-renowned for his investigations of molecular dissymmetry, the fermentation of beer, wine, and vinegar, and for his successful prophylactic measures against the silkworm disease, Pasteur in 1880 made his first contribution to therapeutics in two articles on chicken cholera.

The virulence of infectious diseases (he wrote) changes from one visitation to another, from one locality to the next: ‘it is logical to suspect that variable virulence is probably a common property of the causative agents of various infectious diseases ... For example, do we not witness extremely serious epidemics of smallpox as well as very mild ones? Do we not see the great epidemics disappear slowly only to reappear later and vanish anew?”13 What is more, the conviction of some that disease viruses are inanimate is a mistake; in fact, although some viruses may be inanimate, others are like ferments (lesferments), alive and functioning as living organisms, suggesting that their virulence can be somehow weakened or “attenuated.”2

This live infectious agent can be cultivated serially by seeding “a, so to say, infinitely small quantity, for example, the

aThe French word, “virus " used so commonly in these decades, means “poison” or “poisonous causal principle.” Only in 1898 did the word take on its later meaning of “disease causal agent smaller than a bacterium.” In this communication Pasteur uses virus and “infectious principle,” “virulence” and “infectiousness,” interchangeably

amount that adheres to a needle when dipped into the culture.” And “by a particular change in the culture mode one can diminish the virulence of the infectious microbe. This is the heart [le point vif] of my exposition.”3

He called this process “attenuation.”

i he reduced virulence is seen in the slower growth of the microbe. It can still be cultivated, but its virulence remains weak. Ultimately, the unattenuated and attenuated microbes are identical in all respects except that the former kills twenty chickens out of twenty, while the latter merely renders them sick; and after recovering, they are preservedfrom further infection,4

In 1881 he wrote that this explains the action of “virulent” diseases (maladies virulentes) which confer protection against further infection. The cowpox vaccination of Edward Jenner (1749-1823) is an example: “Would we not be justified in thinking that the same transformations are undergone by the anthrax microbe? Experimentation confirms this hypothesis. Before the extinction of virulence, the anthrax microbe passes through various degrees of attenuation and ... each one of these states of attenuated virulence can be reproduced by cultivation. Each one of our attenuated anthrax microbes constitutes a suitable vaccine for protection against a less attenuated strain.”5

“Attenuation” was applied extensively by Pasteur to vaccine production, usually by passing the virus through a series of cultures, exposing them at each stage to air: “In other terms, by a simple change in the mode of cultivation of the parasite, by a mere increase in the length of time elapsing between the successive transfers of the virus, we can obtain a true vaccinal virus which does not kill, but gives a benign form of the disease and protects from the fatal disease.”6

In 1885 he was able to prevent and treat rabies using dried spinal cords of rabbits who had died of this disease (however, the vaccine was extremely reactive and itself caused numerous deaths). Again, the longer the exposure to oxygen, the lower the virulence.7

Since 1878 Pasteur and Koch had been using the serial cultivation technique to, as it were, separate “legitimate” monomor-phic bacteria from contaminant forms. Now Pasteur was using this same procedure to modify the microbe’s characteristics—merely by altering the conditions of cultivation! The consequences of this twofold idea—preventive vaccination by an attenuated sample of the causal microorganism—were immense. They revolutionized school medicine, creating the disciplines of preventive vaccination and serum therapy.

Attenuation and Pleomorphism

Attenuation had a shattering effect upon monomorphist doctrine, converting Pasteur overnight into a pleomorphist. Koch followed after some years—showing his usual reluctance whenever obliged to defer to the Frenchman.

At the outset of his work in bacteriology Pasteur had been a monomorphist. In working on fermentation, whenever it appeared that the forms were altering, he simply concluded that he was dealing with a different “microphyte,” and he regarded bacterial species in the same way.8

He believed that the bacterial species were nearly constant in form and possessed immutable properties. Transferred from medium to medium, they would always cause the same reaction ... Transferred in the same way to a living creature they would produce a definite disease, that is, one which was always the same when the avenue of entrance was the same, and which became thereby a sort of morbid entity.

—Emile Duclaux, 18969

But after discovering attenuation Pasteur realized that a microbial species can invest itself with such different characteristics as to become unrecognizably different from its original form.10b

bSome have suggested that Pasteur’s change of position was dictated by politics. Thus, his 1864 lecture on spontaneous generation had charged the Liberal opposition with denying the Creator and, ipso facto, the fixity of species; therefore (the argument goes), under the conserv ative Second Empire Pasteur was monomorphist. And with the Third Republic in 1875, Liberalism being in fashion, Pasteur accepted pleomorphism and even made gestures in support of spontaneous generation. It seems to us, however, that the discovery of attenuation was for him more important than changes of political regime (see John Farley, “Social, Political, and Religious Background,” 145, 152).

Attenuation had a similar impact on Koch, when he could finally bring himself to change his mind.

His 1881 “Etiology of Anthrax” rejected pleomorphism with all its works and pomps, hinting that Pasteur’s attenuation was a fabrication, and referring with disdain to “Naegeli’s theory that, within a relatively short time, microorganisms adapt to strange conditions by changing from one form to another ... I often completed as many as fifty transfers using a gelatin culture with aqueous humor. The anthrax bacilli never changed their shape or became non-pathological.”11

But he hedged his bet: “I would like to mention explicitly that I do not, in principle, oppose the theory that one species can be transformed into another closely related species. I do not regard it as impossible that a pathogenic organism could be converted into a harmless one or vice versa.”12

In 1882 he admitted having attenuated anthrax bacilli by serial passage: “Finally we obtained a pure culture of anthrax bacilli from which even mice could be inoculated without harm. These harmless anthrax bacilli were morphologically the same as the virulent bacilli.”13 But he salved his monomorphist conscience by insisting that this was not a general law: “In Pasteur’s opinion ... one can assume the operation of a universal law of attenuation ... In my opinion one cannot go this far. As yet, only the attenuation of anthrax is an uncontested fact ... Before one can talk of a law of transformation for pathogenic microorganisms, one must transform many of them.”14

Koch might equally well have concluded that pleomorphic change is the general law, while monomorphic non-change is the sort of instance which must be determined case by case. Such is the power of unconscious assumptions.

And the tuberculosis bacillus, in any case, did not come under the law of attenuation:

Another question is whether or not ordinary bacteria that are widely distributed and that often enter the body can, in favorable conditions, become tuberculosis bacilli through adaptation and mutation. And also, conversely, whether or not tuberculosis bacilli, either in the body itself or after they have escaped from it, could become harmless. Then no invasion of specific bacteria would be necessary to cause tuberculosis. Everything would depend on the conditions necessary for changing non-pathogenic bacteria into pathogenic bacteria. ... At this time this is no more than a purely hypothetical possibility. No facts support this opinion and many count against it. As yet, there is not one confirmed case in which harmless bacteria have been transformed into harmful ones, and there is no reason to ascribe this capacity specifically to tuberculosis bacilli ... The situation is different with respect to the gradual weakening of tuberculosis bacilli. The attenuation of anthrax bacilli shows that such a process is possible. However, one must recall that anthrax bacilli are weakened under artificial conditions but not under ordinary ones. Normally this does not happen in the body or outside it. Moreover, tuberculosis bacilli in cultures outside the body sometimes live for as long as two years on a dead medium. Their properties, including their virulence, never change. —Robert Koch, 188415

If tuberculosis bacilli could take a non-pathogenic form, “invasion by the specific bacterium would not be required to produce tuberculosis,” and tuberculosis would no longer be a microbial disease.16

But he finally accepted Pasteur’s attenuation, in a somewhat grudging way, while resisting inter-species variation: “No bacterial species is known to change into another species.”1 “Under conditions unfavorable to development a species of bacteria can produce atrophied forms. Certain characteristics ... may be temporarily or ... totally lost. These are only changes within certain limits. They never involve such departures from type as would be necessaryr for a new species to be created or for one species to be converted into another, for example, for anthrax bacilli to be converted into hay bacilli.”18

Paradoxically, when serial cultivation was employed to 'purify” a bacterial culture, it bolstered the monomorphist viewpoint, but when used for attenuation, it encouraged pleomorphism. The significance of attenuation for the emergence of bacteri-

ology and immunology can hardly be overestimated. Whence did Pasteur derive this concept?

Auzias-Turenne and “Syphilization”

Pasteur cited Edward Jenner as his inspiration for preventive vaccination, and this has been echoed by his biographers:

ihe careful reading of the works of Jenner and his followers

had left a profound impression on the mind of the master.

Emile Duclaux, 189619

Inoculation against smallpox by administering the matter from pustules has been known since antiquity and in most cultures of the world. The technique was introduced into England in 1721 by Lady Mary Wortley Montagu, wife of the British ambassador to the Ottoman Empire/ However, it was excessively risky, involving possible infection with syphilis and other diseases of the donor. In 1 778, following the advice of a Gloucestershire milkmaid who told him that those who contracted cowpox from the cows they were milking possessed immunity to smallpox, Jenner started collecting observations; in 1796 he inoculated a boy with matter from the arm of a milkmaid who had contracted cowpox in this way.

Subsequently, lymph from the cow itself was used, and this was the beginning of the mass smallpox vaccination campaigns which, by the end of the twentieth century, seemed to have eradicated this disease from the world.

John Hunter (1728-1793), the great eighteenth-century British vitalist physician and medical thinker, had demonstrated that the “morbific principle” of a disease resides in the pus and other secretions which it produces. He inoculated himself with syphilitic pus to study the development of the disease and concluded: (1) that every disease is “specific,” (2) that every disease is ol the whole person, so that two different “diseases” cannot coexist in the same individual, and (3) that medicines act by their

“stimulating” power on the organism, not by producing evacuation or by neutralizing toxins.

Before undertaking his cowpox investigations, Jenner consulted Hunter, his friend and mentor, who gave him the characteristically Empirical advice: “Don’t think, try; be patient, be accurate.”20

Hahnemann was himself a passionate admirer of John Hunter and incorporated all three of his ideas into the emerging doctrine of homoeopathy. He also welcomed Jennerian vaccination as an example of the Law of Similars.d

But Hunter had yet another admirer in the person ofJ.-A. Auzias-Turenne, a Montpellier physician practicing in nineteenth-century Paris, who, while less well known than Jenner and Hahnemann, should not be overlooked as an influence on Pasteur.

Like Jenner himself, Auzias-Turenne proceeded from Hunter’s idea that diseased matter contains the “morbific principle” to the further idea that inoculating this morbific matter confers protection.

In the 1840s he was studying the development of syphilis in monkeys by inoculating them with syphilitic pus when, to his surprise, the monkeys were seen to resist reinfection while remaining in good health. He called this condition “syphilization,” inoculated himself in the same way, and urged that the technique be extended to prostitutes and others at risk for syphilis.21

Specifically, the soft chancre was an attenuated form of syphilis, which could be used for preventive vaccination just as cowpox was for smallpox. Auzias-Turenne even called it “syphilis vaccination,” but denied that it was inspired by Jenner: “Syphilization was discovered directly by experience and observation.”22

He lectured and wrote on syphilization and vaccination sporadically in the 1850s and 1860s. While his views were congee Divided Legacy, II, 356fT., 374. The pus, unfortunately, contained both syphilis and gonorrhea microorganisms, complicating research into these diseases but not affecting Hunter’s conclusions.

cThis phenomenon is today called “premunition” (Rene Dubos, Man Adapting, 183).

demned by the Academy of Medicine and by specialists in the treatment of syphilis, “syphilization” was practiced in France, Italy, and other countries.23

Auzias-Turenne died in 1870, and in 1878 the various pamphlets and articles he had been writing since the 1850s were published in a book entitled La Syphilisation. His chief Italian follower, Gasimir Sperino, had already published a major work on the subject (in French) in 1853.24

These authors held the disease “virus” to be a morbific principle incorporated in the humors whose existence could be determined only by its effects. It is neither parasite, poison, nor miasm, but something different. It can live inside the host organism or outside it, is transmissible by touch or inhalation, and can reproduce itself after incubation in an appropriate organism.25

Viruses differ from parasites in their ability to impress specific changes on the organism. They differ from venoms by their ability to reproduce and multiply in the organism they attack. And they differ from miasms by their ability to confer immunity.—J.-A. Auzias-Turenne, 186526

Once introduced into the host organism, after incubation this virus causes local symptoms and ultimately constitutional ones. It multiplies inside the host, causes specific changes, and confers immunity. While the mechanism of immunity is not explicable in the present state of science, they argued, the virus seems to exhaust the nutritional possibilities of the given terrain (le terrain):

I he chancre virus is one, just like vaccine or the smallpox virus. It is a seed (une graine) which germinates more or less wrell depending on the terrain; it would weaken and decline, and ultimately perish, if it could never change terrain.

—Casimir Sperino, 185327

Of signal importance was Auzias-Turenne’s observation that viruses” differ in force and intensity: “Viruses are capable of different modalities ... Viruses and infectious diseases are of variable intensity ... since man cannot destroy viruses, let us try to subjugate and utilize them.”28 “Gold seems to attenuate the cholera

virus. The same virus can present varying modalities, i.e., different forms or varying ways of being. Viruses degenerate and weaken; this reciprocal property is fundamental.”29

These ideas offer “brilliant prospects for a medicine of specific diseases,” and Sperino treated constitutional syphilis in humans by this technique in the early 1850s.30

Pasteur was completely fascinated by Auzias-Turenne’s ideas and sought introductions to persons who had known him. Adrien Loir, Pasteur’s nephew who worked in his laboratory from 1882 to 1888 and who, coincidentally, was also a friend of the executor of Auzias-Turenne’s estate, brought the two together:

After having dinner with M. d’Andecy, I spoke with Pasteur about Dr. Auzias-Turenne and brought him the latter’s book as a present from M. d’Andecy. After reading it, the Master told me to ask M. d’Andecy to come and visit. They remained in tete-a-tete for more than two hours. Pasteur kept the book at home, not in the laboratory. It was in a special drawer in a nearby bureau, and he read it often over a period of several years. Many ideas were suggested to him by it. He even copied out whole sentences. He never mentioned the book, Im Syphilisation, as people would have made fun of him. Those matters were not talked about.—Adrien Loir, 193811

But Auzias-Turenne remained in the realm of generalities. And although he used the term “attenuation,” he nowhere suggested a procedure for modifying or “attenuating” the syphilitic pus w'hich he was employing so widely. In any case (according to Adrien Loir) Pasteur only knew of his writings after 1882, while he first reported on “attenuation” two years earlier, in 1880.

Discovery of Attenuation

Pasteur’s initial communication on attenuation, in February 1880, did not explain how this was done, only citing “a certain change in the method of culturing.”32 Nor did he indicate the origin of the idea—other than the reference to Jenner.

And despite exhortations from his colleagues and from the Academy of Medicine, he refused to give further details. I his

caused a scandal, since many in the Academy already held Pasteur in low esteem. In August he went so far as to write a letter of resignation, which was never sent.33 In October, Academician Jules Guerin, 79 years old, tried to assault Pasteur physically at a convocation: “the meeting was adjourned in tumult.” The next day Guerin challenged Pasteur to a duel!34

Koch reflected prevailing opinion when he wrote (1882): “In industry it may be permissible or even necessary to keep secret the procedures that lead to a discovery. However, in science different customs prevail. Anyone who expects to be accepted in the scientific community must publish his methods.”35

Later in October 1880, Pasteur revealed that attenuation was performed by exposing the culture to the ambient air but did not elaborate further on this in his lifetime.36

Even when asked by Lister for further details, Pasteur demurred, despite his enormous admiration for the Scottish surgeon, citing “circumstances which I cannot understand.”37 According to Duclaux, writing in 1896, the discovery was made early in the autumn of 1879 when Pasteur and his laboratory workers returned from vacation to find that most of the cultures left over the summer had died. For reasons not revealed by Duclaux they proceeded to inject these cultures into chickens, with no perceptible effect. Then Pasteur, again with no reason given, decided to reinject the same chickens with a fresh virulent culture:

To the surprise of all, perhaps even of Pasteur himself, who did not expect such a success, almost all of these chickens resisted, whereas new chickens, just brought from the market, succumbed in the ordinary length of time, thus showing that the culture used for the inoculation was very active. With one blow, chicken cholera passed to the list of virus diseases and vaccination was discovered! What secret instinct, what spirit of divination impelled Pasteur to knock at this door, which was only waiting to be opened? Here we see clearly the part played by his readings and his former studies, by the incessant ponderings which had been going on in his mind, and by the intervention, in the midst of these obscurities, of this faculty of imagination.—Emile Duclaux, 189638

An “attenuated” culture was seen to protect the host animal against exposure to a fresh and highly virulent one, and Pasteur w'as said to have exclaimed: “But these animals have been vaccinated!!”39

Rene Vallery-Radot, Pasteur’s son-in-law and biographer, also writing well after the event (1900), attributed the discovery to “chance.”40 Fifty years later, W. I. B. Beveridge used it to illustrate his theory of the constructive role of “chance” in scientific research.41 Geoffrey Edsall in 1971 called it an “intuitive discovery.”42

But research since 1979, when Pasteur's descendents donated his laboratory manuals to the Bibliotheque Nationale, reveals the above account to be pure myth. The manuals show that Emile Roux (1853-1933), not Pasteur, discovered how to attenuate bacterial cultures by exposing them to air, and that “chance” had nothing to do with it: Roux was deliberately testing this technique.43

Since “attenuation” exploded previous bacteriologic and immunologic ideas and is at the heart of twentieth-century immunology, precisely how it entered Rationalist medicine is of considerable moment, and the hundred-year-old mystery of its discovery seems puzzling. Why did Pasteur, his son-in-law, and his associates conceal the circumstances surrounding attenuation, even to the extent of arousing the hostility of the Academy of Medicine and charges of unethical behavior? Why did they insist that it was due to “chance”? Why, after Pasteur’s death, was an elaborate myth concocted?

Roux later told his niece and biographer, Mary Gressac, that in the end of 1878 Pasteur was obsessed with Jennerian vaccination, “how to subdue \asservir\ virulent microbes and render them harmless,” why it was an isolated fact in medicine, and why other vaccinations could not be found.44

This points to another mystery: why Roux himself, the first physician selected by Pasteur to work with him in the laboratory, who remained with him until the end, who was Pasteur’s closest associate and “scientific conscience,” famous for his critical manner and rigid probity, never wrote his memoirs.1

rLike Conan Doyle’s “dog that did not bark.”

Charles Nicolle, who worked under Roux and knew him well, held this to be deliberate: “What illumination we would have received from an intelligence as penetrating as Roux’s. But he did not want to be accused of an assault against a god [attentat contre le dieu\, for Pasteur had become a sort of idol. My dear Master, how wrong you were to remain silent! Only an occasional comment escaped your lips!”45

What did Roux know whose divulgation would have tarnished the image of Pasteur?

In all of this one fact is certain: Roux did not happen upon attenuation by chance and develop an explanation later. He had a technique in mind—exposure to air—and was trying to implement it in practice. But why should this rather innocent procedure have been surrounded by so much mystery and intrigue?

Antonio Caddedu, who has written on this extensively, was himself mystified: “One still wonders what prevented Pasteur, amidst the general hullabaloo, from admitting what really occurred in this matter of the change in culture technique.”46

Most probably, “attenuation” was inspired by, and borrowed from, homoeopathy, which is why Pasteur and Roux kept its origins secret. I'oo much explaining would have disclosed the relationship with a doctrine viewed as heresy by the Academy, and with a group of physicians seen as “untouchables.”

Everyone in those years knew that “attenuating” morbific substances was a standard homoeopathic procedure, in use for decades. And it was accomplished by serial dilution. The very word (Fr. attenuation) was and is a homoeopathic term of art, denoting both the technique and the resulting products Pasteur and Roux did not need any “secret instinct,” any “spirit of divination,” any “incessant ponderings,” or even a “faculty of imagination.” They had only to peer out the window of the laboratory

?It involves serial dilution of the remedy, on a scale of 1:10 or 1:100, with vigorous shaking (“succussion”) at each stage of dilution. The greater the degree of attenuation” in homoeopathy, the more powerful the remedy (Divided Legacy, II, 401). In his October 1880 communication to the Academy Pasteur made the cryptic remark: “One should not assume that attenuation proceeds with mathematical regularity” (Louis Pasteur, Oeuvres, VI, 326). See below, pp. 292ff.

on Rue cTUlm and observe the homoeopath down the street, which is undoubtedly what they did.

The Isopathic Movement in Homoeopathy

The element of homoeopathic doctrine closest to Pasteur’s interests was “isopathy”—the idea that the disease substance itself is the best preventative and cure.

Isopathy figures in every folk tradition (“Hair of the Dog!”) and was part of Western medical culture long before its crystallization in homoeopathy.47 Smallpox inoculation was know'n in most cultures of the world for centuries before its introduction in England in 1721 .h But smallpox was not the only disease subject to immunization. As early as 1820 French and German farmers were protecting pigs against swine typhus by impregnating a piece of cotton with the nasal secretions of diseased animals and inserting it under the skin of healthy ones.48 In Constantinople, during the 1835 epidemic of bubonic plague, nurses removed the scabs from patients and hawked them on the street corners; when reduced to powder and suspended around the neck, they were thought to act as a preventative.49

In 1845 a Hungarian landowner whose cattle were sick with typhus followed the isopathic example, took their saliva, and inserted it into an incision between the hide and the flesh; this caused an “artificial disease” which protected them from the typhus.50

In 1855 a communication to the Paris Academy of Sciences described a similar procedure for sheep pox (la clavelee des moutons) and pneumonia of cattle. Nature protects animals in this way, states the writer, and man should follow suit by “inoculating the preservative virus specific to each disease.”51

Isopathy entered homoeopathy through the experimentation of Constantine Hering (1800-1880) with snake venoms. In 1831, while collecting specimens in Surinam for the King of Saxony, he “proved” the venom of the bushmaster snake (Lachesis trigono-

cephalus), and it subsequently became a major component of the homoeopathic materia medica.'

Hering’s 1837 Wirkungen des Schlangengiftes, zum aertzlichen Ge-brauche vergleichend, zusammengestellt, published in Allentown, Pennsylvania, and one of the first works of the emerging American homoeopathic movement, described the symptomatology of the bushmaster (Ijichesis trigonocephalus), rattlesnake (Crotalus horridus), cobra (Naja tripudians), and viper (Bothrops lanciolatus), drawing information both from descriptions of snakebites and from prov-ings of the potentized venoms.52

During the nineteenth century homoeopaths investigated many other serpent and insect venoms in this way: krait (Bun-garus), toad (Bufo), black-widow spider (Latrodectus mactans), Cuban black spider (Mygale lasiodora), Cuban tarantula (Tarentula cubensis), Spanish tarantula (Tarentula hispania), stinging jelly-fish (Medusa), wasp (Vespa crabro), copperhead snake (Cenchris contortrix), honey bee (Apis rnellijica), and others.53 These were used isopathically, to treat the respective bites and stings, but also as remedies in any states of disease to w'hich they were homoeopathic.

Hering reasoned that venom is a living poison which “acts on the life force with an irresistible power and a lightning rapidity. The saliva of the rabid dog has an analogous action, but slow ... Could one not infer that the saliva of the rabid dog, properly prepared by trituration, would likewise manifest remarkable pathogenetic effects?”54 And just as one vaccinates against smallpox by introducing cowpox through the skin, perhaps snake venom introduced in the same way would be equally protective.55 1 his, Hering observes, would be especially valuable in view of the serious illnesses, often incurable and sometimes fatal, caused by existing vaccination procedures.56

He concludes that the causal agent in smallpox scabs, and the morbific matter of other diseases, could be prepared in the same way as snake venoms and used to treat the corresponding

See Divided Legacy, II, 413fT. The homoeopathic “prov ing” is the technique of administering a medicinal substance in small doses to healthy individuals. The symptom-complex thus produced is the guide to using the substance in the sick (according to the “law of similars”). For more on the “proving,” see below, PP. 245-247.

conditions. In a rush of enthusiasm he announced in 1833: “The plague and anthrax would cease being terrifying, and regardless of whatever scourge arrives from the Orient, the remedy will reach us at the same time.”57

Cholera patients should swallow the matters they ejected potentized; and yellow-fever patients should be treated in like manner; the scales of scarlatina convalescents should be used as a prophylactic against that disease; and typhus patients should have milk-sugar laid on their skin to catch the typhus virus, which was to be used as an antityphus remedy.

British Journal of Homoeopathy, 184958

The first remedy from diseased matter (known later as the “nosode”) to be investigated systematically by homoeopathy was Psorinum from scabies (the “itch”). Hering suggested it in 1831, and the first proving symptoms, including several submitted by Hahnemann himself, appeared in 1833.59 Hering published a lengthy article on it a year later, and Psorinum remains in use today.60

The Viennese homoeopath (and priest) J. E. Veith advocated “autopsorin,” to avoid conveying the donor’s other possible diseases to the recipient.61 He was thus the forerunner of the twentieth-century “autogenous vaccine.”J

Isopathy opened an unimaginably vast field to therapeutic research, encompassing disease products and all insect and reptile venoms. The former, especially, were thought to “exteriorize” an internal condition, making it more amenable to treatment: “11 a disease is latent in the system, the potentized product may bring it to the surface.”62,k

Some treated allopathic medicinal diseases caused by the abuse of quinine, arsenic, mercury, and other drugs by administering the same substances in homoeopathic potency.63

JSee below, pp. 390ff. Gustav Wilhelm Gross (1794-1847), one of Hahnemann’s first associates, potentized his own blood and claimed that, taken sublingually, it relieved his hypertension, but he still died at fifty-three (British Journal of Homoeopathy VII [1849], 337).

kSee discussion of the Law of Cure, below, pp. 281-292.

Homoeopaths continued this work during the decade of the 1830s, stressing the particular applicability of isopathy to contagious diseases. Johan Ernst Stapf (1788-1860) wrote in 1834: “The discovery of the effectiveness of contagious substances against the diseases which produce them is one of the most important discoveries to be noted since the birth of our method.”64 J. W. Arnold, in the same year: “Theory and much practice favor the idea of isopathy in those infectious diseases whose contagium is in the form of a carrier which can be used for healing purposes.”65 Another homoeopath called the morbific principle a “living germ” [lebensfaehige Keime\,66 The homoeopathic physician and veterinarian Johan Joseph Lux (1777-1849), in his 1833 Isopathik der Contagionen, claimed: “If we potentize every contagium and use it in the same way as a homoeopathic medicine, we shall be able to heal all these diseases.” He particularly urged the isopathic treatment of anthrax but warned that with peasants the medicines must be mixed with flour and coloring material, since they do not trust the very small homoeopathic pills.67

Anthrax was always a favored area of investigation. In 1830 Hering gave directions for preparing the homoeopathic remedy Anthracinum from an alcoholic tincture of diseased spleen.68 In 1835 Pierre Dufresne reported on his treatment of anthrax (pustule maligne) with Anthracinum internally; the patient was an agricultural laborer.69 His ideas were soon implemented by the homoeopathic veterinarian Georg Adolph Weber, who in 1836 aborted an anthrax epidemic in cattle isopathically: following Hering’s directions, he took liquid from the spleen of a cow with the disease, attenuated it to the 30th centesimal dilution, prepared a homoeopathic remedy in the usual way, and, by administering four or five pills daily to the cows, kept them immune Irom anthrax. The curative dose was ten to twenty pills every hour or so until twenty doses had been administered. In trials supervised by county health authorities W'eber claimed a recovery rate of eighty percent—as against twenty percent under the normal treatment of the time.70 Dufresne in 1837 made Anthracinum from a peasant sick with the disease, giving it to him and also to his sheep. There were no further deaths, and the flock was removed from quarantine.71

The treatment of measles with Morbillinum was reported in 1834 and 1835.72

Another focus of concern was rabies. In 1833 Hering mixed saliva from a rabid dog with milk sugar and potentized it to the 30th centesimal; he proved it on himself, family and friends and called it Lyssin or Hydrophobinum,73 This medicine entered the homoeopathic textbooks soon afterwards.74 Lux in the same year urged treatment of rabies with attenuations of the liquid from the Marochetti vesicles under the tongue, and this mode of preparing Hydrophobinum became standard.75

The allopaths reacted with predictable indignation at the homoeopaths for prescribing “poisonous saliva of the boa constrictor [sic] ... spiders, worms, bugs, lice ... scab of the smallpox.”76

“Lachesis, the poison of the rattlesnake____To such an extent is

the doctrine similia similibus curentur carried out that ‘syphiline’ is administered to patients suffering under secondary syphilis and ‘blenorrhin,’ which is gonorrheal matter manipulated according to the rules of the homoeopathic confectionary, is mentioned ... as a remedy for gonorrhea or gleet.”77

Johann Gottfried Rademacher

A writer and physician who, while not himself a homoeopath, influenced the debate about isopathy was Johann Gottfried Rademacher (1772-1850), a younger contemporary of Hahnemann. His 1841 Rechtfertigung der von den Gelehrten misskanten, ver-standsrechten Erfahrungsheillehre der alien scheidekuenstigen Geheimaerzte, usually called Rademacher’s Erfahrunsheillehre (Medicine of Experience), endeavored to resurrect the Paracelsan alchemical tradition:

Every organ of the body has its counterpart in nature, for there is an external liver, an external brain, external lungs, etc. By giving the external lungs (Sulphur) to one afflicted w ith a disease of the lungs, the physiological balance w ill be reestablished. If the physician understands well the external man, then he can practice medicine, and employ the external man for the internal, and recognize the internal in the

external. It thus follows that the prescription must be so made that organ comes to organ, the heart to the heart, lung to lung, spleen to spleen. The herbs are the organs; one is the heart, another the spleen, etc. Not that the (external) heart is visible to the eye, but rather it is a spiritual force, and a virtue similar to the heart.—-J. G. Rademacher, 1841781

Rademacher invoked Thomas Sydenham’s “epidemic constitution” to explain why organ remedies sometimes worked and sometimes did not.m He rejected Hahnemann’s formulation of the law of similars as well as dynamization, although speaking well of Hahnemann otherwise. He proposed three “universal remedies” saltpeter (Natron nitricum), iron (Ferrum), and copper (Cuprum) for three “fundamental affections of the whole organism” corresponding roughly to the Paracelsan “salt, sulphur, and mercury” and to Hahnemann’s three chronic diseases: psora, sycosis, and syphilis. He also proposed a series of “organ remedies”—acting on the liver, the spleen, the liver and spleen together, the pancreas, the celiac plexus, the stomach, intestines, urinary organs, uterus, thorax, heart, lungs, trachea, esophagus, eyes, nose, mouth, skin, muscles, and brain.79

Ludwig Griesselich and Homoeopathic Opposition to Isopathy

Another important contribution to the isopathy debate was Ludwig Griesselich’s 1848 Handbuch zur Kenntnis der homoeopathischen oder specifischen Heilkunst. The author himself was wrorthy of note, not only as a homoeopathic pioneer but also as a writer of

... uncommon vigor and insight. A man of pronounced individuality and acute mentality, full of unintimidated courage, with a passionate impulse toward independence of thought and action ... endowed with a rare agility of tongue, he contrived by the fresh, and at times pungent nature of his

'See Divided Legacy, I, Chapter XV.

"See Divided Legacy, II, Chapter III.

literary presentations to attract the widest attention, retaining it until his death.—Richard Haehl, 192280

Griesselich was the son of a district physician w ho graduated in medicine at Heidelberg and promptly commenced duty as regimental physician to the artillery brigade of the Grand Duke of Baden, stationed in Karlsruhe. He was soon drawn to homoeopathy and in 1832 spent some weeks with Hahnemann in Koethen. Returning to Baden he announced formation of a Homoeopathic Society. In 1834 he started a homoeopathic journal, Hygeia.

He was both a devoted admirer of Hahnemann and an unreasonably sharp critic, belonging heart and soul to the trend which rejected pure individualization and sought a therapeutics of “specific diseases.” In Griesselich’s case, as in others, this took the form of a search for “specific remedies.”11

His masterpiece was the above-mentioned Handbuch which appeared just as the author, riding north to join his unit fighting Danish rule over Schleswig-Holstein, was killed by a fall from his horse.

The Handbuch devoted almost twenty pages to the evolution of isopathy and contributed greatly to its popularization. The author himself, however, had reservations about the more extreme isopathic manifestations which he called “drivel” (Spuck).R{

Griesselich’s criticism found much support within homoeopathy:

There is almost no end to the extravagances of the isopathists; the person mentioned above as having potentized his blood, did the same by his tears, and let his son smell the preparation, who forthwith was affected with pain in his lacrymal gland. The evacuations both upwards and downwards of cholera patients have been “potentized” ... According to Attomyr “potentized” itch matter (psorin) developed lice in the head of a healthy person who proved it. Teeth affected with caries and the matter from fistulous ulcers were

"This represented an incipient Rationalization of Hahnemannian homoeopathy (see Divided Legacy, III, Chapter VI).

potentized and termed Caries dentium and Fistulin ... Other curious matters that have been “potentized” by our isopathists are ... the expectorations of phthisical patients, etc. [!!]— British Journal of Homoeopathy, 184982

But others thought differently. In 1861 Hans Hermann Hager’s Medicamenta homoeopathica et isopathica omnia ad id tempus a medicis aut examinata aut usu recepta introduced over sixty new isopathic remedies prepared from organs, parts, secretions, and excretions of humans and animals, as well as twelve made from animal and insect poisons, to the German and world public.83

Isopathy provoked endless arguments in the homoeopathic ranks. Many disapproved because the isopathic substances were rarely subjected to proving and were not prescribed on the basis of symptom similarity. Some objected to giving the morbid products of one patient to another, others on sanitary grounds.

It seems as though the idea was to ... search for medicines amongst all kinds of matter, sometimes too foul to mention, while there are plenty of well-known and “respectable” drugs which, if properly proved, would furnish all that is required for the removal of disease.

American Homoeopathist, 187884

A more general dispute within homoeopathy was over the relationship between the homoeopathic simile and the isopathic idem. Moritz Mueller (1784-1849), one of Hahnemann’s early adherents, claimed in 1834 that das Idem is better than the simile: “Has it ever happened that a homoeopathic remedy did not help when its [proving] symptoms were not only similar but identical to those of the illness?”85 J. A. Veith stated two years later: “The similar is the most solid principle we possess up until now; isopathy is an exaggeration of this therapeutic law. However, I can affirm that I have seen the best effects from the administration of exanthematous products excreted by the individual himself ... W hat one gains is often to accelerate the cure and to provoke into action certain disease states which remain rebellious and stationary under the indicated homoeopathic remedies. Not that

the latter are useless; but they are effective only in certain cases when they have been seconded by the isopathic remedy.”86 Homoeopaths were (and are) no less vulnerable than allopaths to the desire for simplification. Many saw in isopathy a direct relationship between remedy and disease, thus leaning in the direction of the allopathic “entity.” But hopes of curing a given infectious disease merely by administering its causal agent were in due course seen to be exaggerated. Thus, a Hungarian physician wrote in 1845 that if medicines heal on the principle of identity, the isopathic remedy should be effective in every single case; since it is not, similarity to the patient’s symptoms must be the operative principle.87 The British homoeopath E. W. Berridge echoed this idea in 1884: “T he homoeopath treats the individual patient. The isopath treats the disease. The homoeopath individualizes. The isopath generalizes. The homoeopath prescribes for the totality of the symptoms. The isopath prescribes for one, the chief objective symptom ... If isopathy means that every case of syphilis is to be treated and cured by potentized Syphilinum, then Hahnemann never taught it ... But if isopathy means that potentized Syphilinum will cure certain cases of syphilis when the symptoms correspond, then that is what Hahnemann taught ... The fact is that Lux ... taught the former, which is a departure from Hahnemann ... It should not be forgotten that even diseases resulting from specific contagious poisons are very often complicated, and therefore to say that Syphilinum will cure uncomplicated syphilis is very different from saying that it will cure every case in which syphilis exists. How, then, are we to discriminate? Simply by prov-ings on the healthy organism.”88

“Nosodes” eventually entered the homoeopathic pharmacopoeia as valued remedies: Syphilinum, Gonorrhoinum (later called Medorrhinum), Diphtherinum, Carcinomatin (later called Carcinosin), Coqueluchin, Morbillinum, Lyssin (also called Hydrophobinum), and many others. Some underwent provings, but most were employed on the basis of clinical experience and tradition. They took their place as one more class of medicines which promoted cure by virtue of “similarity,” not “identity.”

Smallpox was a special case, since homoeopathy possessed nosodes made both from smallpox matter (Yariolinum) and from cowpox (Vaccininum). This led to much discussion of the relationship between the two. Hering noted that Vaccininum could be considered a “similar,” being the smallpox virus altered by passage through a cow’s body.89 Ultimately Vaccininum was used as a smallpox preventive, while Variolinum counteracted the deleterious sequelae of vaccination.90

The clinical symptomatology of more than forty of these remedies was published in H. G. Allen’s 1910 Materia Medica of the Nosodes.91 Over seventy are described in O. A. Julian’s 1977 Traite de Micro-Immunotherapie Dynamisee.92

Professional Antagonism vs. Public Support

The isopathic movement, viewed by the allopaths and some homoeopaths at mid-century as a medieval throwback, was retroactively justified by bacteriology and immunology. This was later recognized by some allopathic leaders:

The medical world in general considered Isopathy as the acme of homoeopathic nonsense. Such a position is no longer tenable since isopathic treatment has been introduced and scientifically entrenched by the anti-rabies vaccination of Pasteur and the tuberculosis therapy of Koch. The nonsense has changed into a far-seeing heroic hypothesis.

—August Bier, 192593

But the isopathic stamp on immunology could not be admitted by the allopathic rank and file, in view of the ban on professional association with homoeopaths and the unrelenting campaign against them:

1 he warfare against homoeopathy [in Great Britain] was not confined to literature. The power of the majority was exerted against the heterodox minority in other ways. Black was refused the fellowship of the Edinburgh College of Physicians, [William] Henderson was forced to resign his Clinical Professorship; Horner and Rieth were turned out of their hospitals; coroners’ inquests (presided over by allopathic medical coroners) were used oppressively against homoeopathic practitioners. Colleges and universities fulminated anathemas against any of their members who should practice the hated system. Candidates were rejected by examiners if they w'ould not abjure homoeopathy. Societies expelled homoeopathic members, and even their own allopathic members who met homoeopathists professionally. Articles against homoeopathy were frequent in the medical periodicals, but no reply was allowed.... Every place and post of honor and emolument was withheld from homoeopathists.

—Alfred E. Drysdale, 188594

In 1851 the Universities of St. Andrews and Edinburgh, as well as the Royal College of Physicians of Edinburgh, determined not to confer the degree of doctor on any candidate who did not pledge himself solemnly never, during his whole life, to practice homoeopathy.95

If Great Britain, w ith its traditional liberalism, accepted such treatment of the homoeopaths, in other countries it was far worse. Nowhere, in those years, could a “regular physician” admit any benefit from homoeopathic treatment. Only physicians at the summit of the profession—the August Biers, the Emil Behrings, the Almroth Wrights—and then only if more than ordinarily courageous, could make public avowals of support for Hahnemannism.0

France in the late nineteenth century was a battleground of pro- and anti-homoeopathic sentiment, which could not have passed unobserved by Pasteur. As in other countries, the intense hostility of the allopathic profession was offset by strong support for homoeopathy among the population.p

Homoeopathy was introduced into France in the late 1820s simultaneously by J. Mabit in Bordeaux and Count Sebastien Des

°On Behring, Bier, and Wright, see below, pp. 90fT, 390ff, 453fT.

pA striking feature of homoeopathy from its earliest years has been fervent backing by the lay public, which has often rejected the dismissive views of school medicine. The educated, well-born, and well-to-do classes have been particularly zealous in sustaining homoeopathy, and Hahnemann, in fact, was criticized by the allopaths for accepting this support (“lack of professional solidarity”). See Divided Legacy, III, passim-, and Wilhelm Ameke, History of Homoeopathy, 340, 346.

Guidi (an aristocratic refugee from Naples) in Lyons. In Geneva it was established in 1832 by Des Guidi’s first disciple, Pierre Dufresne (who also founded Bibliotheque Homeopathique).^ Hahnemann himself came to Paris in 1835 with his beautiful and aristocratic French wife, Melanie d’Hervilly, forty-five years his junior, and died there in 1843. His presence had a galvanizing effect: in the latter decades of the century France could boast of 150 to 200 homoeopaths.97

I he allopaths hated the new doctrine with a passion. Bre-tonneau, who admitted that the theory possessed validity but held the practice to be “quackery” (charlatanisme) and who said, “In the interest of the medical art it is better that a major fact be forgotten than perverted,” was considered a liberal.98

I he same measures of exclusion and expulsion were adopted against French homoeopaths as in England. In one notorious instance, a group of homoeopaths was charged with “scientific immorality.”99

Melanie Hahnemann, although not a physician, treated patients homoeopathically until her death in 1878, despite being brought to trial and given a token fine in 1847.100 Her noble lineage and connections in the upper reaches of Paris society and politics contributed to the rapid spread of this new doctrine among the aristocracy and haute bourgeoisie.

Of great significance w'as the benevolent attitude of the Empress Eugenie and other members of the Imperial family, provoking anguished exclamations from the allopathic press:

Homoeopathy is gaining ground. The wave is rising from

moment to moment. There it is with the young and beautiful

Empress [Eugenie] in Caesar’s palace ... Oh, what sacrilege!

Oh, medical dignity, what has happened to you?

—VUnion Medicate, 1853101

There was a sensation in 1861 when the Emperor’s niece, Bathilde Bonaparte, died of an ovarian cyst at age twenty-one. Two years earlier, when the cyst was first diagnosed, the dispute over treatment pitted her husband and several members of the Imperial family, who sought homoeopathic intervention, against the Lmperor and other members of the Imperial family, w'ho preferred to rely onjean Cruveilhier (1 791-1874), Jean-Baptiste Bouillaud

(1796-1881), Gabriel Andral (1797-1876), Armand Velpeau (1795-1867), and other notables of the Academy of Medicine.4' According to testimony by the husband and other family members, homoeopathic treatment by a certain Dr. Courtois had greatly helped the patient, preventing the buildup of liquid in the tissues, but the Emperor and other members of the court insisted on allopathy. Bathilde’s husband never recovered from the loss, writing seven years later in his will that “miserable assassins known as physicians” had killed his wife.102

Homoeopathy had an influential spokesman in the person of Jean-Paul Tessier, a socially and medically prominent doctor who had been the favorite student of Andral and adopted homoeopathy because of its success in treating cholera.103 He conducted a homoeopathic service in a Paris hospital from 1848 until his death in 1862.104

Since there were no other public homoeopathic clinics in Paris, a group of 2000 working men and women appealed, in 1865, to the Senate to have homoeopathic services established in the public hospitals. The debate revealed that homoeopathy had the support of one-tenth of the country’s population and one-eighth of the eminent Senators themselves.105

Trousseau in 1862 charged that twenty members of the Academy of Sciences were attended by “quacks,” i.e., homoeopaths. The doctrine had particular support in the medical faculty of Montpellier/

Tessier founded a journal, L Art Medical, which sought unifi-. cation of homoeopathy and allopathy and preached a doctrine of “specific” diseases and “specific” remedies very similar to that of Trousseau. He maintained that “Hahnemann’s theories embody two different hemispheres, his pathology corresponding to his mistakes and his therapy amounting to truth.”106 He rejected the doctrine of chronic disease, denied dynamization, used only the lowest potencies, mixed his remedies, and the like.10'

iOn these and other members of the Paris Clinical School see Divided Legacy, II, Chapter VII.

rDivided Legacy, II, 558-561.

That this was not well regarded by the more severe French Hahnemannians only made Tessier more lethally attractive to the allopaths. Although the hierarchs held aloof from him and his pupils, expelling them from the medical societies, and denying them positions in the hospitals, the military medical services, and the public health service, the idea of homoeopathic “specificity” gained ground in the ranks every year.108

The spirit of Tessier and the “specificist,” disease-oriented, tendency which he represented dominates French homoeopathy to this day.8

While Pasteur and Koch may have been estranged by incomprehension of each other’s language, this was not the case with Pasteur and homoeopathy. The whole development of isopathy was published in French in Dufresne’s Bibliotheque Homeopathique, issued from 1832 to 1837. Further information became available in the 1849 French translation of Griesselich’s Handbuch. Sixteen homoeopathic lay and professional journals were published in France between 1834 and 1890.109 The ongoing debates between homoeopaths and allopaths were reported in the press and followed eagerly by the public at large.

Pasteur would have been torn in two directions. His vitalist and specificist inclinations would have made homoeopathy an attractive idea, as would his occasional visits to, and tete-a-tetes with, the Empress Eugenie.110 As a non-physician, moreover, he would not have felt the visceral hostility which marked the majority of allopaths. But again as a non-physician, however politically adept, imposing his views on a recalcitrant and often frankly hostile medical profession, some of whom were calling him “Paracelsus 11” and violently resenting his seeming condescension, Pasteur could not possibly risk being tarred with the homoeopathic brush.1111 Just as Auzias-Turenne’s La Syphilisation

'His descendent, J. P. Tessier, was a founder of the International Homoeopathic League (Liga Medicorum Homoeopathica Internationalis) in 1925.

'Koch’s 1882 taunt—"After all, Pasteur is not a physician, and one cannot expect him to make sound judgments about pathological processes and the symptoms of disease”—was echoed by many French physicians (Robert Koch, “Ueber die Milzbrandimpfung,” 100).

remained in his bedroom, not in the laboratory, just as Pasteur could not discuss this subject with anyone, a fortiori he could not talk about homoeopathy with colleagues. Because he w;as forcing treatment with “similars” down the throat of school medicine, he had to keep his distance from the followers of Hahnemann.

In the 1870s, as Pasteur achieved renown and was seen to be advocating medicinal concepts, and even substances, that had decades earlier been employed in isopathy, the French homoeopaths, who had tended to view isopathy as a heterodox Germanic offshoot of their discipline, took a renewed interest in it.112

And they became increasingly critical of their illustrious countryman’s borrowings.

H. Krueger’s Pasteurisme, Isopathie, et Homeopathie (1883) first set forth homoeopathy’s claims vis-a-vis the man who was creating the science of immunology. He made a case for isopathy and homoeopathy, commencing with Hering, Lux, Weber, and the other founding fathers.

Pasteur, who (let it not be forgotten) is not a physician himself, wants to throw on the scrap heap the work of several generations of physicians ... Even the allopaths recognize that Pasteur’s aim of “taming the viruses” has already been achieved by Hahnemann ... But Pasteur and his followers only do harm with their impure and insufficiently attenuated vaccines ... The bacterial cause is seductive to the homoeopathic mind, as it reintroduces vitalism into medicine. In this sense [Antoine] Bechamp was correct in stating: “Nothing is the victim of death. Everything is the victim of life!”u But Pasteur is in error thinking he can treat through “identity” with this cause. There is no “identity” in medicine, only “similarity,” and Pasteur’s vaccination procedures are merely an application of the homoeopathic law of similars.

His vaccines are sometimes badly prepared. When a veterinarian whose sheep had all died after being vaccinated com-

uOn Antoine Bechamp (1816-1895) see below, p. 190, 201.

plained to Pasteur, he admitted this. He even suggested setting up an insurance company to indemnify farmers who had suffered losses. Sometimes the vaccines become weak from sitting too long on the shelf.

Hering invented Anthracinum, and homoeopaths have for years been preventing anthrax better than Pasteur can do today. What is more, homoeopaths can treat with this remedy, while Pasteur can only prevent. Nor can he treat anthrax in humans.

In general, Pasteur would do better to follow the homoeopathic example and administer his vaccines orally. The homoeopathic preparations last indefinitely, and, given orally, obviate the danger of infecting the recipient with syphilis and other diseases.

Pasteur has a sort of homoeopathic intuition, but his views are superficial both philosophically and therapeutically. The germs have arrested him half way in a stage of groping and hesitation.113

Krueger notes further that germs do not always take the same form: “Does Mr. Pasteur really know what he is doing in defining his viruses with such mathematical precision?”114 Sometimes a vaccine against one disease will confer protection against several others, suggesting a more general effect on the host organism. Krueger also doubted that the bacteria must be physically present to confer immunity.

When a mother sheep is vaccinated, her fetus is immunized

at the same time, but bacteria cannot pass through the placenta. How does Pasteur explain this?

Pasteur admits that the virulence of a culture is not a function of the number of bacteria in it; in this his cultures resemble homoeopathic remedies, which operate through quality, not quantity.

At a recent medical congress in London the head of Pasteur was depicted in a fireworks display. But “you will never eclipse the radiant star [i.e., Hahnemann!] to whom you owe your borrowed luster.”

In 1884 Jean-Paul Tessier (son of the earlier Tessier) penned a lengthy critique: “Les Precurseurs Medicaux de M. Pasteur.”115

Many rightly accused Pasteur of homoeopathy when he announced recently in the Academy of Sciences the great fact of the variable virulence of certain viruses, and of protecting from one virulence by using another of weaker intensity.... And, indeed, Pasteur’s ideas stem from those of isopathy, specifically, research on rabies, anthrax, syphilis, cholera, and plague. Hering told us long ago that attenuated rabies virus is a powerful remedy in hydrophobia.

Pasteur is following the same course as Trousseau, who could not give a satisfactory answer when accused of practicing homoeopathy. But Pasteur not only applies the law of similars; he also employs medicines in infinitesimally small amounts to treat diseases due to tiny causal organisms. Of course, if he admitted he was practicing homoeopathy, this word which has already led to so much ostracism would provoke the Academy to an explosion of anger capable of blowing up the cupola of the Institute.

Pasteur neglects the factor of resistance. Not everyone bitten by a rabid dog falls ill, as there must be predisposition. In the De-partement de la Seine 268 persons were bitten by rabid dogs from 1881-1883, but only thirty-four developed rabies. In 1883 forty-five were bitten, while only five became rabid. The real cause, the only necessary cause, in the philosophical meaning of the word, is this predisposition. All other causes are merely occasional.

His new theories leave us unmoved, but we follow with the greatest interest his demonstration of the power of infinitesimal doses and of successive dilutions of virulent liquids.116

A final contribution to the homoeopathic critique of Pasteur was T. J. M. Collet’s Isopathie, Methode Pasteur par Voie Interne, Demon-strant la Certitude et VUnite de la Science Medicale (1898), containing a forthright statement of Hippocratic/Empirical/homoeopathic principles and a new defense of isopathy.11'

Disease is the body’s reaction to a morbific agent, and the symptoms are the signs of that reaction. But this reaction is often insufficient to overcome the morbific cause. The “similar” remedy endows the body with the reactive power which it lacks, thus promoting response along the lines which the

organism itself has selected. But it must be given in small doses to “promote a reaction without causing alteration.’'

Pasteur’s “immunity” is not a chemical change, since it must be preceded by a latent period and persists after the vaccine has been eliminated from the body. Vaccination effects a permanent modification of the nutrition, developing in the organism a new reactive capacity capable of dominating toxic agents and eliminating them. It is like a long-term cure, an “habituation” (accou-tumance) to the illness.

Pasteur would do better to treat rabies with the nosode Hydrophobinum than the long series of injections he advocates. But in any case, he has accepted the homoeopathic principle of attenuation.

Isopathy is an improvement and perfection of homoeopathy, having the advantage of simplifying the science and art of cure. Medicines made from the microbial causes of infectious diseases are of isopathic inspiration and a clear development of homoeopathic principles.—T. J. M. Collet, 1898'18

Thus Pasteur’s homoeopathic contemporaries saw the evident parallels between homoeopathy and the emerging doctrines of immunology, and some went so far as to think that Hahnemann and the Hippocratic/Empirical therapeutic tradition were his source of inspiration. While some praised him for it, others castigated him for not acknowledging the debt.119

Koch and Homoeopathy: Tuberculin

Pasteur was not the only bacteriological eminence to adopt homoeopathic ideas and procedures. The most blatant and far-reaching attempt to appropriate a homoeopathic remedy was Koch’s misadventure with “Tuberculin”—for w'hich he, and especially his patients, paid a high price. And like Pasteur, Koch never admitted his indebtedness.

In the late nineteenth century, Germany, Austria, and German Switzerland had upwards of four hundred homoeopathic physicians, four or five homoeopathic hospitals, and four medical journals, the oldest of which (Allgemeine homoeopathische /jitung) had appeared uninterruptedly since 1832.120

These successes had been achieved over ferocious opposition:

Any doctor who expressed a favorable opinion of homoeopathy was at once looked upon as a heretic; anyone who practiced it was a pariah, was expelled from professional association, and persecuted with relentless hatred. It made no difference whether he had formerly given ample evidence of earnest endeavors after truth or whether his character was blameless he was a heretic and as such he was branded and under a moral ban. Why? Because his scientific views differed from those of the allopaths. The same is the case today. Men in distinguished positions who dared to defend publicly what they recognized as truth were persecuted in every possible way.—Wilhelm Ameke, 1885121

In 1854 W. Rapp, Professor of Clinical Medicine at Tuebingen, was forced to resign his position for praising homoeopathy, and he became physician-in-ordinary to the King of Wurttem-berg; as a professor he had drawn more students than Carl Wunderlich.122 In 1876 another Tuebingen professor wrote a scurrilous attack belaboring homoeopathy for refusing to administer quinine and chloral hydrate in one-dram and two-dram doses to patients with fever, concluding that “science does not permit” allopaths to coexist under the same roof with homoeopaths.123’'’

One of the deadliest weapons of German allopathy was the legal stipulation that only apothecaries could compound and dispense homoeopathic preparations (in all other countries physicians themselves dispensed them). But homoeopathy was unpopular with this professional class because the remedies were inexpensive, and the markup was small:

Allopathic apothecaries are the natural enemies of homoeopathy; they have given proof upon proof that they ar-

vHe made the revealing comment that physicians must learn what homoeopathic doctrine is; otherwise, “if he knows nothing more than that it consists in giving infinitely small doses, he will hardly be a match for those laymen who are acquainted with Hahnemann’s system. A doctor’s reputation will certainly not be increased by such ignorance, nor will his position be better assured’ (Wilhelm Ameke, History of Homoeopathy, 330).

dently wish for the overthrow of this system, which they openly denounce as quackery; some even cheat the public who want homoeopathic medicines, and hold it no sin to give their customers simple spirit instead of medicine ... who look upon it as a matter of no importance whether they are prepared well or ill.—Wilhelm Ameke, 1885124

And as a pharmaceutical industry took shape in the latter decades of the century, seeking to market substances which could be patented and sold at a premium, the unpatented and non-patentable homoeopathic preparations came to be held in even lower esteem.w

The 1882 pamphlet, Homoeopathy and its Importance to the General Welfare by Johannes Rigler, after stating in the Preface “I have taken infinite pains to avoid all bitterness and harshness,” called Hahnemann a “dealer in secret remedies,” “quack of the basest kind,” “medical vagabond,” “adventurer,” “liar,” “cheat,” “pickpocket,” “braggart,” “old rat-catcher,” “sly and unprincipled liar and deceiver,” “most shameless of the shameless,” “grand master of lying,” “prince of lies,” “most miserable of all charlatans and swindlers,” “false idol on a beggar’s throne,” “pitiable wretch,” and “arch-father of lies.”

Homoeopathy itself was qualified by the author as a “castle in the sand,” “deception,” “absurdity,” “pretended system founded on the most absurd hypotheses and cleverly invented lies,” “demon that is a disgrace to our century,” “child’s play made up of lies and folly,” “tissue of absurdity and lies,” “miserable trash and nonsense,” “pest,” “refuge for rogues and charlatans,” “impudent miserable crime,” “repulsive and absurd rubbish,” and “miserable filth of the most pitiable superstition.”125

I he homoeopathic physicians were described as “traitors to science,” “fools, rogues, quacks, lunatics, mountebanks.” “The whole lot transcends the master in infamy and trickery.” “There are patients who lack common sense, and there are doctors who

I he American Medical Association’s victory over homoeopathy in the early 1900s was due, not least of all, to abundant financial support from the burgeoning pharmaceutical industry (Divided Legacy, III, Chapter VII). This factor has not lost relevance even today.

are homoeopaths.” “They drag the science of medicine through the dirty mud of the most pitiful superstition.”126

Rigler reserves particular contempt for the lay practice of homoeopathy: “the height of homoeopathic harmfulness in all its viciousness,” “shameful deception,” “system of lies, “homoeopathic imposture,” “disgrace of the age,” and “dishonor to the medical profession.”127

The Berliner klinische Wochenschrift covered the book and its author with fulsome praise, in this fully reflecting the views of its readership:

Dr. Rigler ... draws in this work from authentic homoeopathic sources, viz., the works of Hahnemann and his disciples, a picture of the inept absurdities which this monstrosity, begotten of filth and milk sugar, has produced. We must express our thanks to the author who ... has presented his sum-total in a form which makes its perusal a real pleasure ... We recommend it to be circulated as widely as possible, and hope it may open the eyes of the public.

Quoted by Wilhelm Ameke, 1885128

In this atmosphere Koch, at the Tenth International Medical Congress in 1890, proclaimed discovery of a substance (later shown to be homoeopathic) which exerted a “specific action on tuberculous processes” without side-effects on the host organism.129

His 1884 discovery of the causal agent of tuberculosis had aroused unreasonable expectations of treatment and cure. But morbidity and mortality from the White Plague continued to rise, and no patient had yet benefited from this knowledge. Hence his 1890 revelation had an earth-shaking impact—the Congress members celebrated the event with a massive binge laid on by the Berlin Rathaus.1301 His authority was so unquestioned that all expected the sanitoria to close, and tuberculosis to disappear.

For the next three months Koch held to his laboratory. In November he published a “Further Communication on a Tuberculosis Remedy” (in an unprecedented “extra" issue of the Deutsche medizinische Wochenschrift), giving the results of guinea-pig experiments and also some positive clinical experience (these extra issues, entitled “Results Obtained with the Koch Therapy,” continued for a year).

Although Koch did not so state, the clinical experience consisted in trials on himself and his seventeen-year-old mistress, Hedwig Freiberger (1873-1945), later Frau Koch. Both reacted very violently, the young lady, in particular, carrying the scars of the Tuberculin injections on her back for the rest of her life.131

Like Pasteur, he refused to divulge the origin or composition of his remedy, allowing only that it was a “clear brownish liquid.” But this did not prevent him from indicating, at the bottom of the page, the address where it could be purchased.132

And while Pasteur worked with chickens, Koch prescribed Tuberculin to thousands of men, women, and children. His earlier (1882) sneer that Jenner’s discovery benefited humans, while Pasteur’s only helped sheep, may have come back to haunt him.133

The question of dosage would turn out to be crucial for the ensuing half-century employment of Tuberculin.

Koch announced that the healthy individual will react to 0.25 cc of undiluted Tuberculin. The lower limit of Tuberculin’s action on the healthy individual, “as numerous experiments have shown, is about 0.01 cc of the tincture (equal to one cc of the hundredth attenuation [ Verduennung])”134

A precise description of the process of attenuation was provided in a Prussian ministerial decree of April 17, 1902. It specified that the undiluted tincture was to be mixed 1:10 with water to which 0.5 percent carbolic acid had been added. This ten percent Tuberculin solution was the “stock solution”: “Further dilutions must be prepared by taking one part of the stock solution and nine parts of 0.5 percent carbolic acid solution, and of the solution thus obtained one part is to be mixed with nine parts of 0.5 percent carbolic solution and so forth [emphasis added].”135 Thus the “stock solution” equalled the homoeopathic IX di-

lution; the next level of dilution represented the homoeopathic 2X dilution, and so on. Koch recommended the 2X as the lowest level which could still affect a healthy person.

But the tuberculous one reacted very vigorously indeed to this same dose level:

The generalized reaction consists of an attack of fever which, usually accompanied by chills, raises the body temperature over 39 degrees C [103 degrees F], often as high as 40 [104 F], and even 41 [106 F], accompanied by pain in the limbs, coughing, lassitude, and often nausea and vomiting. Occasionally there is a slight icterus and a measles-like exanthem on the chest and neck. The reaction begins, as a rule, four to five hours after the injection and lasts twelve to fifteen hours.—Robert Koch, 1890136

The remedy ... does not kill the tuberculosis bacilli ... it is only capable of influencing living tuberculous tissue; dead caseous masses, necrotizing bones, and the like, are not affected.—Robert Koch, 1890137

In a patient with pulmonary tuberculosis:

We had to reduce the initial dose of 0.01 cc, and we found that patients almost always reacted violently to doses of 0.002 cc [i.e., homoeopathic 3X] and even 0.001 cc. [also homoeopathic 3X] ... We then initiated treatment of phthisic cases with 0.001 cc and then, after the rise in temperature, continued daily with this dose until no further reaction was observed. The dose was then raised in increments of

0.001 cc to 0.01 cc or more, continuing at each stage until no further reaction was observed.... In phthisis the treatment first resulted in increased coughing and expectoration. Coughing and expectoration then decreased progressively and were entirely eliminated in favorable cases, [emphasis added]

—Robert Koch, 1890 138>y

The November article evoked a new paroxysm of hysteria

yIn homoeopathic prescribing the degree of dilution is important, not the quantity of medicine (number of pills, 0.001 or 0.002 cc of the liquid, etc.).

(known to medical historians as the Tuberkulinsturm), as thousands came from all over the world to the new Mecca. The British Medical Journal reported that excitement was “at white heat.” The price of Tuberculin rose to 1000 marks per dose, and pilgrims often found they could not afford to purchase what they had journeyed so far to obtain.

More than 1500 physicians came to Berlin as well to learn about this new' treatment, among them Joseph Lister with his tuberculous niece.139 One of Koch’s assistants had eight consulting rooms scattered around the city and crowded with patients night and day.140

Although Koch had “strongly advised” against using Tuberculin “schematically and without distinguishing among patients,” counseling “careful individualization,” this was, of course, impossible in the circumstances.141

In the end of 1890 Koch advised the Minister of Education that he was not prepared to yield the Tuberculin patent to the state but proposed to keep it for himself and his associates. They had estimated the potential sale of the remedy at 4.5 million marks per year—a more than astronomical sum. The Minister offered 1.5 million, but Koch stood firm, noting that he could always sell it for more in the United States. Ultimately they reached agreement on three million marks, half to be retained by the state as guarantee of the treatment’s success.

Reichskanzler Leo von Caprivi commented about the deal: “It would not look well if we were to let a German thinker appear so greedy in an area in which Germany until now has been viewed as motivated by idealistic considerations. Could Dr. Koch not take the position, as a matter of raison d’etat, that this arrangement not be revealed to the public?”142

But the persuading of Koch to behave like a statesman dropped from the agenda, and his negotiating position crumbled, when the first clinical results became known. Patients complained of feeling “as sick as dogs—much sicker than before starting treatment," and then, unreasonably, died in increasing numbers.

Virchow, who disliked Koch anyway, published an account of the ongoing trial early in January, 1891. Twenty-one had already

died, and another six or seven were probables. While the bacilli themselves seem unaffected by the remedy (Virchow wrote), it sets up “a very acute irritation in the affected parts, with intense redness and great swelling.” Some patients developed fresh tubercles in the lungs where none had been before.143 A German physician later wrote:

I remember from my daily walks that every day hearses stopped in front of the former coffee house [converted into a tuberculin treatment center]. No sooner had the sanatorium been established and outfitted than it was completely emptied out by death [voellig ausgestorben].—Theodor Brugsch, 1969144

But Koch denied that anything was amiss and in January 1891 promised to reveal the remedy, although conceding ignorance of its precise composition and the basis for its “undeniably beneficial” action on the organism.1452 The identity of Tuberculin was divulged by him only in April, when others had already subjected it to chemical analysis.146 It was prepared by heating the bacilli for some hours in their growth medium, removing the bacterial residue, and evaporating the liquid to one tenth its volume.147

Isopathic Treatment of Tuberculosis

The first recorded isopathic treatment of tuberculosis was in the seventeenth century by the Paracelsan, Robert Fludd (1574—1637): “Sputum rejectum a pulmonica post debitam praeparatiden-em curat phthisin,”l48-aa He was followed by Constantine Hering, always an admirer of Paracelsus, who in the 1830s fabricated Phthisin from the sputum of tuberculous patients.149 In the 1850s Eugene Curie, a homoeopathic physician established in London (and the father of Pierre Curie), undertook “an investigation upon inoculation for tuberculosis,” although precisely what he meant is not known.150

'In a precise parallel to Pasteur’s admission to Lister that he did not understand the mode of action of the attenuated vaccine.

"““Lung sputum, if properly prepared, cures phthisis.”

Hager’s 1861 Medicamenta homoeopathica et isopathica mentioned two isopathic tuberculosis remedies: Laryngophthisinum (from tracheal pus) and Pneumophthisinum (from tuberculous expectoration).151

Samuel Swan in New York brought the tuberculosis nosode to the center of professional and public attention in 1877 when he treated a patient with Tuberculinum from tuberculous sputum.152 He advertised four tuberculosis nosodes in his 1886 Catalogue of Morbific Products, Nosodes, and Other Remedies in High Potencies.153

Willis Alonzo Dewey employed it starting in 1880 at the Ward’s Island Homoeopathic Hospital in New York City.154

Pure Hahnemannians were incensed by Swan’s claim that Tuberculinum would “cure the disease which produced it if given in high potency, even to the person from whom it was obtained.”

Dr. Swan will continue to advocate this empiricism, for he believes himself to be a great discoverer, and to be persecuted as many really great men have been persecuted for their discoveries. Dr. Swan has not discovered anything, but has taken up the ideas of others, and has gone wild over them, a veritable Don Quixote ... We assert that Dr. Swan must leave the International Hahnemannian Association and his opinions must be condemned, or the IHA will become a caricature.—Homoeopathic Physician, 1887155

In his own defense Swan insisted that Hahnemann himself had employed isopathic remedies and that “potentization of the isopathic product makes it homoeopathic to the disease which produces it ... it cannot have any effect on that disease till potentized.”156

Tuberculinum was by this time in common homoeopathic use. In mid-1890, provoked by Koch’s Tuberculin claims, the London homoeopath, James Compton-Burnett (1840-1901), published a short booklet, The New Cure of Consumption by its Own Virus describing fifty-four cases treated over the space of five years with the '‘virus of consumption” prepared from tuberculous sputum and called by him Bacillinum.

[But] the leaders of the dominant sect of the medical profession raised a hue and cry against those of the homoeopaths who were so unspeakable as to use the virus of consumption against the disease itself; and for fear of an unbearable amount of opposition and ignorant prejudice, the practice wras discountenanced and almost discontinued.

—James Compton-Burnett, 1890 157>bb

That objection, Burnett continued, had been eliminated by Koch’s recommendation of what is nothing but a homoeopathic substance in the form of a crude dilution:

The difference between our old friend Tuberculinum or Bacillinum and that of Koch lies in the way it is obtained; ours is the virus of the natural disease itself, while Koch’s is the same virus artificially obtained in an incubator from colonies of bacilli thriving on beef-jelly; ours is the chick hatched under the hen, Koch’s is the chick hatched in an incubator.—James Compton-Burnett, 1890158

The “increased coughing and expectoration” observed by Koch following Tuberculin administration, as well as the reddening around the edges of the tuberculous lesions, were (and are) known in homoeopathy as the “initial aggravation of symptoms” provoked by the similar remedy, part of the curative reaction by the vital force.159,cc

Homoeopaths everywhere recognized Koch’s Tuberculin as nothing more than Tuberculinum in allopathic form. Homoeopathis-che Monatsblaetter commented on the 1902 ministerial decree prescribing the Tuberculin dose range:

By this our homoeopathic doctrine of dosage receives official recognition ... It is particularly noteworthy in this Decree that the dilution of the Tuberculin is termed “necessary,” and that its activity is not only found in the first, second, and

“’Indeed, in 1890 the A\1A Journal observed with disgust that in homoeopathy “the sputum of phthisis [is given] to consumptives ... renal albumen, diphtherine, syphilineum [sic], vomit from a yellow-fever patient” (J.A.M.A., 1890, 365, 367).

"See below, pp. 485-486.

third decimal solution, but from the additional words, “and so forth,” it can be deduced that the higher dilutions are considered effective.160

But where the homoeopaths administered the remedy in high dilutions, repeating it rarely, Koch’s colleagues treated Tuberculin like an allopathic drug: patients were receiving 500 mg and more in the space of a few weeks.161 To the homoeopaths these doses seemed stupefyingly large, and the unending repetitions, as often as every day—which did not allow the patient’s reaction to become established—lethally dangerous:

Mortality tables are now showing the harm that results from using indiscriminately a substance which has such pathogenetic power as all nosodes are now known to possess.

Homoeopathic Physician, 1891162

In February, 1891, Koch left abruptly for Egypt to evade the impending therapeutic disaster and accompanying scandal. He relinquished any honorarium for Tuberculin in favor of a donation to the building fund of the Institute for Infectious Diseases to which he was soon after appointed Director.

An example of the dose range used by homoeopaths in treating tuberculosis was given in 1893. A seventy-year-old woman with incipient tuberculosis w'as given medicine made from her own sputum in the 100th potency—prepared by decimal dilutions (1:10) to the 50th, then in centesimal dilutions (1:100) to the 100th—the dose being one drop in 100 drops of distilled water, a teaspoonful taken four times a day.163

Burnett used “high potencies” in his treatment and mentions 30C and 100C.164 “I use the remedy in high potency, which is not fraught with the palpable dangers of Koch’s method of injecting material quantities under the skin, or, in other words, straight into the blood. Of course, if Dr. Koch’s dosage or mode of administration should give better results than we have obtained, then Koch’s method will have to be adopted. But my present opinion tends to the opposite conclusion.”165

Koch's allopathic colleagues in due course also understood that he was practicing an approximation of homoeopathy.

Behring, for instance, admitted that Tuberculin “falls under the isopathic healing principle.”166 And, across the Atlantic, the Boston allopath Richard Cabot wrote in 1906: “The use of Tuberculin is a form of vaccination which illustrates better than any example known to me the approval of homoeopathic principles in our School.... The poison of tuberculosis, which can produce some of the symptoms of tuberculosis, is here applied for the cure of tuberculosis, through the production of immunity or resisting power in the tissues. Surely this is a case of Similia Similibus Curentur as homoeopathic writers have pointed out.”167

But while Cabot and Behring approved, others were enraged at this imposition of a homoeopathic remedy in what appeared to be infinitesimal doses.dd

That Tuberculin was a “secret remedy”—prohibited by medical codes of ethics—did not improve things:

The fates have not been propitious. The secret is, partly, out, but many believers in it, w'hilst it was a secret, shrug their shoulders now.... Ah! if they had but known that the remedy was a poison, administered in infinitesimal proportions, they would have left it for the homoeopaths to manipulate, according to their dogma and their heresy! And here are the homoeopaths laughing actually at us of the school of legitimate physic, because we have been caught vulgarly swallowing their dogma, admitting even the effect of the infinitesimal dose, and they themselves keeping out of all danger within their own lines. Incredible humiliation!

—Benjamin Ward Richardson, 1891168

From the other end of the medical spectrum, Koch was criticized by behind-the-times followers of Virchow who, still unconvinced of the identity of tuberculosis, phthisis, and scrofula, called Tuberculin a “swindle” on that basis.169

Burnett’s warning about dose size was very apropos, as the results of Tuberculin treatment were catastrophic. Some died from

ddAt the 1890 medical congress Koch had announced discovery of compounds which retarded the growth of tuberculosis bacilli in vitro, “even diluted to one to two parts per million” (Robert Koch, “Zur Aetiologie des Milzbrandes, 186).

“systemic shock” (anaphylactic shock, “delayed hypersensitivity reaction”). Other uncounted thousands died from reactivation of the tuberculous lesions and focal inflammatory reactions, leading to general toxemia.170 The whole episode was soon recognized as a major iatrogenic disaster.171

Koch was forced to admit that he had not even performed autopsies on the test animals he thought had been cured by Tuberculin but had merely concluded from symptomatic improvement that they were on the way to health.172

Although he continued to work on Tuberculin until the end of his life, devising new methods of deriving a medicine from the bacilli, he apparently never contemplated the possibility of merely reducing the dose, as was done later by others.ee

Historians have wondered at the “enigma of Koch’s unwillingness to divulge the nature of Tuberculin.”173 “It is difficult to unravel the history of this phase of Koch’s work because of the secrecy with which he, for some reason, surrounded it.”174 Dubos ascribed it to the desire of the Prussian government to retain a monopoly 011 its manufacture, but commercial rights could have been protected in the ordinary way—by patents and licensing arrangements.175 The reason was simply that Koch did not want to be branded a homoeopath when about to cure the world of tuberculosis (and enrich himself in the process).

The parallel with Pasteur’s reticence about the origins of “attenuation" is striking, as is the inability of both to comprehend how their new discoveries actually worked!

Koch died in the conviction of failure:

That Koch’s greatest achievement, the discovery of Tuberculin, did not fulfill all expectations, is by many still held against him as a crime against the honor of the German nation.—Emil Behring, 1914176

Tuberculin became clinically useful only when the dose was reduced drastically. Koch’s recommended dose of 0.01 cc had to be diluted a million times.177 The American, Edward L. Trudeau

"See below, pp. 405-407.

(1848 1915), who for years conducted a tuberculosis sanatorium at Saranac Lake, New York, used Tuberculin in doses of 1/100,000 milligram (0.00000001 gram).178

The Master of Recent Bacteriology never suspected that each of his 0.1 cc vials of “brownish liquid” contained enough medicine to treat every tuberculosis patient in Germany!

Organotherapy

A particular aspect of isopathy was organotherapy—using organ and tissue extracts to treat conditions centered upon the particular organ or tissue.

Rademacher’s organotherapy had employed ordinary medicinal substances for their impact on a particular organ. The new “organotherapy,” using the organs themselves as medicines, had been suggested by Hering in the 1830s and then popularized by Griesselich’s Handbuch.179 An Austrian physician near Salzburg, for instance, chopped up the lungs of a fox, let them soak for a week in rectified spirits, and used this Hepatin, when strained, to treat boils, hardening of the liver, jaundice, and constipation.11

The good doctor gave it straight, without attenuation or po-tentization.

Against rabies he prescribed the liver of a healthy or a rabid dog or fox. He also prepared Pulmonin (lung tissue) and Lienin (spleen).

This procedure was attacked by homoeopaths for bypassing the proving process and for treating the affected organ rather than the whole person. How, asked Griesselich, can one know that rabies is localized in the liver? He concludes, “JVichts Neues unter der Sonne!” Dioscurides told us 2000 years ago that rabies w as cured by the liver of the rabid dog. “Here the lungs, there the liver, that’s the whole difference!”180

^Griesselich, who was not impressed by everything he described, observed with malevolent sarcasm: “This has turned out to be infallibly effective, as he says— Yes, there is no substance, even Karlsbad water, which can compare with it (L. Griesselich, Handbuch, 66).

“Organic isopathy” was taken up in France by Charles-Edouard Brown-Sequard (1817-1894) and his colleague, Arsene d’Arsonval.

Brown-Sequard was born on Mauritius of a French mother and an American sea-captain father who perished in a shipwreck before the future professor was born. He taught both at Harvard and Paris, where in 1878 he succeeded Claude Bernard at the College de France.

Where isopathy had administered the idem to stimulate the organism in a particular direction, Brown-Sequard’s “organic isopathy” used it more as a vitamin or food supplement: “The morbid manifestations resulting from the internal secretion of one of the organs must be combated by injecting the liquid extract of this organ taken from an animal in good health.”181

Following in the steps of Theophile Bordeu, who first elucidated the role of the ductless glands and the endocrine system, Brown-Sequard used testicular, thyroid, pancreatic, adrenal, cerebral, and other extracts (prepared usually from sheep but also from human organs) to treat a variety of conditions.On the hypothesis that each organ and gland releases substances within the body as well as to the outside, he claimed therapeutic powers for all of them. Testicular extract, for instance, heightens resistance to tuberculosis or anthrax infection.182 He used it also in treating diabetes, Parkinson’s disease, locomotor ataxia, multiple sclerosis, tuberculosis, cancer, and heart, kidney, and brain disease. Adrenal extract he used in Addison's disease, spleen extract in malaria, thyroid extract in goiter, and extract of bone marrow to reconstitute the blood after a hemorrhage. He used juice extracted from rabbit brain and spinal cord to treat insanity, tabes dorsalis, and epilepsy, claiming some rather limited benefit.183

Pasteur, in the last years of his life, treated epilepsy with injections of cerebral emulsion. Therapeutic success eluded him, however, and according to Metchnikoff, “these experiments worried and disturbed him so much that he fell prey to severe insom-

ilia, and his family, and those of his colleagues who, like myself, were close to him had to persuade him to abandon the project. This he did with a heavy heart, for he was oppressed with the feeling that he had not achieved all he might have done.”184

In these same years the Surgeon-General of the United States was advocating Cerebrine—an extract of healthy sheep brain—to treat neurasthenia, hysteria, paralysis, and even insomnia.185 Another professor in New York used thyroid extract as well as Cerebrine to treat paralysis, progressive muscular atrophy, epilepsy, and tuberculous tumor of the brain.186

Organotherapy was developed in the twentieth century by the Viennese Julius Wagner-Jauregg (1857-1940), who investigated the role and function of the thyroid, parathyroid, thymus, pituitary, pineal, adrenals, pancreas, liver, sexual organs, and others in a large variety of disease conditions.1871111

Practical Immunology: Emil Behring

After Pasteur, Emil Behring is the individual most responsible for the therapeutic application of immunology, restoring to honor Pasteur’s initial vitalist formulation which had been shaken by incipient chemical interpretations of immmunologic phenomena.

Several developments in the 1880s undercut Pasteur’s assumption that immunity came from the struggle of “life against life.” In 1883-1884 Theodore Klebs (1834-1913) and Friedrich Loeffler (1852-1915), discoverers of the diphtheria bacillus, were startled to find that it remained localized on the mucous membrane of the throat without penetrating into the bodily fluids and tissues; often bacilli could not be recovered from the patient at all, and the symptoms and pathology were due to an inanimate substance—the toxin which they excreted.188 These conclusions w'ere reinforced in 1889 when Emile Roux and Alexandre Yersin (1863-1943) of the Institut Pasteur also announced discovery of the diphtheria bacillus and published a description of it.IK<*

hhThe “fresh cell” therapy of the Swiss, Paul Niehans, was a later development of organotherapy He received recognition for this in 1954 when appointed to succeed Alexander Fleming as professor at the V atican’s Pontifical Academy (Harald Gaier, Encyclopedic Dictionary, 303).

That same year Shibasaburo Kitasato (1852-1931) and Knud Faber (1862-1956) demonstrated tetanus also to be a toxin-mediated disease.190

In 1886 two Americans working in Germany, D. E. Salmon (1850 1914) and Theobald Smith (1859-1914), followed up on the discovery of Klebs and loeffler and showed that killed bacterial cultures were as capable of conferring immunity as the live ones employed by Pasteur.191 They wrote, “Immunity is the result of exposure of the bioplasm of the animal body to the chemical products of the growth of the specific microbe, which constitute the virus of contagious fevers.”192

In 1887 Henry Sewall (1855-1936), physician and professor of physiology at the University of Michigan, demonstrated that pigeons can be immunized against rattlesnake venom through repeated exposure to “subminimal” doses of the venom—this being due to the “inexplicable tendency of living matter to adjust itself to its environment.”193 He diluted six drops of venom in 88 of glycerine, then carried the dilution process further with distilled water.194 Like Constantine Hering five decades earlier, Sewall assumed an analogy between snake venom and bacterial toxins, writing: “We may suspect that the same sort of resistance against germ disease might follow the inoculation of the appropriate ptomaine, provided it is through the products of their metabolism that bacteria produce their fatal effects.”195’*'

These discoveries tended to transform vaccination into a chemically mediated process, with the vitality playing an ever smaller part. Lifeless bacterial toxins and serpent venoms were capable of conferring immunity when injected in small doses over a period of time.

“The parallel with Hering was perhaps not accidental, as the latter’s 1837 Wirkungen des Schlangengiftes gave copious information on the symptomatology and pathology of rattlesnake bites, and homoeopaths for decades had used these venoms therapeutically Sewall had every opportunity for contact with homoeopathy at the University of Michigan, where a homoeopathic medical school had existed since 1875, and he must have known about Hering’s earlier book (Divided Legacy,

III, 207ff). Furthermore, he had worked in Germany for a year and even published in German, so the language would not have been a problem. That he nowhere mentions Hering is, for the usual reasons, not surprising (even though Sewall was known as an iconoclast).

The vitalist “cellular” theory of Pasteur and Metchnikoff was reconciled with the emerging chemical theory by Behring.^ He was a Hippocratic and an Empiric, who felt a marked kinship with homoeopathy. He satirized medical Rationalism for being governed by empty theory rather than experience, for attributing qualities to medicines they do not possess, and for promising more than it can ever deliver:

We ask, how could it claim any status as a science? Any attempt to dress up this pedestrian routine [Schlendrian\ in new clothes must surely fail, and no unprejudiced physician whose conscience has not been hardened by years of humdrum plodding could write a prescription today relying on these doctrines without an inner feeling of shame.

—Emil Behring, 1915196

Instead, Behring turned to Hippocrates and Thomas Sydenham (1624-1689), the “English Hippocrates,” whom he reckoned “one of the greatest physicians of all time.”l97kk The Hippocratic physician “relies on the activity of a vis medicatrix naturae which struggles against the morbific forces in the organism.”198 “The healing of a sick individual must ultimately be ascribed to the organism’s vital functions."199 To this end the vis medicatrix naturae employs a process of digestion or cooking, which the Greeks called pepsis, followed by expulsion of the transformed morbific product.200 Fever, rapid pulse, oppressed breathing, sweating, diarrhea, and the other manifestations of illness are the weapons used by the vis medicatrix naturae, and the physician’s healing procedures must support those of the body’s natural healing power.201

The symptoms are signs of this power’s effort to overcome the morbific cause: “the signs of a reactive activity by the organ-

i>For this accomplishment, and for his therapeutic contributions generally, Behring should be much better known to the English-speaking world. No English-language biography exists, and virtually nothing from his pen has been translated into English. This is perhaps due to his vitalist orientation, which was unfashionable during his lifetime and became more so after his death.

ism which, even though following the laws of physics or chemistry, reveal themselves as so well adapted to their end result as to raise the question of purposiveness, of conscious aiming at a

goal.”202

The physician observes carefully and remains subordinate to the natural course of the disease, only intervening when necessary: “Hippocrates, as a convinced adherent of the doctrine of the purposive activity of the vital force, only after conscientious testing and thorough reflection, considered himself prepared to intervene.”203

The medical art over the centuries has discovered so many remedies, some of which are truly effective, that we tend to forget that the vital forces of the living organism, which tend to healing and restitution, can do it alone.

-Emil Behring, 1894204

Here the crisis is important, and the physician must note the “critical days.” If the crisis, with subsequent evacuation, is incomplete, the acute disease may become a chronic one.

Knowledge of medicines arises out of experience and practice, not out of theory. The physician prescribes iron and other fortifying remedies for hysteria and avoids cathartics, not as an application of “contraries,” not because this disease reveals weakened or oppressed vitality, but because years of observation and experience have convinced him that cathartics are harmful in this condition, while cordials and tonics are of benefit.205

How the vital force achieves its ends is largely outside the physician’s ken. While anatomical knowledge has its uses, all acute diseases, and most chronic ones, contain a specific and un-definable element which cannot be discovered by dissection, but only by zealous and attentive observation of the patient.206 Behring quotes Sydenham: “Much observation has convinced me that in medicine the philosopher stumbles along behind the empiric. For when I have started with a hypothesis, my treatment has been senseless, like someone trying to build the upper stories and the roof of a house before laying the foundations.”207

Behring’s doctrine of infectious diseases was fitted into this framework. I he living organism reacts to infectious matter just

as it does to other offending substances in the environment, “not only with incubation, crisis, and evacuation, but also with relapse.”208 The disease essence is an abnormal vital activity, a living manifestation of the organized vital parts, of which the symptoms are a reflection. They cannot be explained mechanically, only as purposive manifestations.209 They are not, as Koch thought, local reactions to the presence of bacteria but must be understood as part of the w^hole organism’s reaction.210

Pasteur and Koch had thought that only the live bacterium is capable of provoking a vital reaction by the organism.211 Newer research shows that bacterial and other toxins are capable of doing the same, giving rise to a chemical interpretation of immunity. But the basis of immunity is still the body’s reaction; the production of chemical substances is still the work of the vital force.

Discovery of Antitoxin

In a series of papers in the early 1890s Behring proceeded to identify and define what it was in the blood that neutralized or killed bacteria, and how it could be produced.

He found that medicines such as iodine trichloride and sodium chloroaurate were therapeutic in experimental diphtheria or tetanus even though the bacteria remained present in the host organism and were unaffected: “The treated animal had acquired immunity that could be demonstrated by subsequent challenge. However, the blood of the immunized animal was not bactericidal for the specific organism. The deduction to be drawn was that the blood had acquired the property of rendering the diphtheria or tetanus toxin harmless. ... The high level of antitoxic activity that Kitasato and I observed for the blood of rabbits rendered immune to tetanus immediately suggested the use of such blood as a therapeutic agent for tetanus-susceptible rabbits. The results with tetanus exceeded our most optimistic expectations.”212

In 1894 he published similar research on diphtheria: “We first developed a method for producing a high level of immunity in rabbits and guinea pigs and have used the immune blood for highly successful therapy in susceptible animals.”213

The immunizing substance could be isolated from cell-free serum, and this technique came to be called “serum therapy.'1'214 Behring saw it as a universally applicable method for obtaining antitoxins to diseases.215

The first trials of diphtheria antitoxin are said to have commenced on Christmas night, 1891, although this may be a myth.216 In any case, antitoxin was an immediate success, as the death rate in diphtheria fell from forty percent of cases to eight percent.217

I he advent of antitoxin was welcomed with enthusiasm not least because it displaced the earlier treatment of diphtheria—repeated cauterization of the throat with the caustic, silver nitrate.11

Tetanus antitoxin was an equally spectacular success. This disease in the pre-bacteriological era had a mortality of up to eighty percent; in the British army during World War I antitoxin cut the death rate from tetanus in half.218 In Wbrld War II, when British and American troops were immunized preventively, there were only thirty-five cases of tetanus in the British army, twelve in the American.219

Preventive vaccination and antitoxin therapy for diphtheria and tetanus were among the signal achievements of the bacteriological era.

But how did antitoxin work?

Here Behring was torn between his own Hippocratic-Empir-ical leanings (not uninfluenced by homoeopathy) and Paul Ehrlich’s prompt announcement that antitoxin was governed by the laws of chemistry, bonding with the toxins in the patient’s blood and fluids and neutralizing them precisely as acids neutralize alkalis. To emphasize that the patient’s vitality had no role to play, Ehrlich baptised the technique “passive immunization.”mm

"A contemporary homoeopath commented: “How irrational is it to apply caustics. We think it necessary to preserve from mental excitement patients who are dangerously ill, as its injurious effect is well known; and yet a wretched child who does not understand the object of the treatment is thrown into a paroxysm of terror two or three times a day, so that it cowers in its bed and regards with apprehension everyone who approaches it ... Again we ask: Is it a crime to reject such ‘science’?” (Wilhelm Ameke, History of Homoeopathy, 423).

mmSee below, pp. 97, 1 18.

Behring’s writings contain comments reflecting Ehrlich’s approach, but he ultimately rejects it.220

How antitoxin worked could not be understood apart from how it was produced. To decipher this secret Behring adopted the typically Empirical recourse to history. The Persian emperor Mithradates had fed poison to ducks and drunk their blood to counter the regicidal plans of his courtiers.221 Pliny and other ancients told of tribes living on the Black Sea who ate such plant poisons as Colchicum, Atropa belladonna, and Aconitum napellus “to induce immunity isopathically, meaning, in other words, to induce the formation of antibodies.”222

Snake poisons and their action are “very closely connected with the immunity doctrine.”223 Quinine could also be said to act in malaria by arousing the immunity, by making the affected parts more resistant; other “specifics” whose mechanism of action is a mystery may operate in the same way.224

In a word, the immunized animal produces antitoxin isopathically.225 Like Pasteur’s immunization, it is a vital reaction of the organism; the onset offever is a significant feature, and antitoxin is a by-product of this reaction.226 “Effective immunizing doses of toxin treated with iodine trichloride cause local and generalized reactions. In the absence of a reaction, only a slight rise in immunity is obtained, and too severe a reaction leads to progressive emaciation of the test animals.... The blood of animals so immunized produces unusually good therapeutic effects.”227 “The essential is to bring on certain reactions with which the living organism responds to the poison. These consist of a rise in temperature, change in the heart rate, digestive disturbances, changes in the condition of the blood, etc.; since the typical infectious disease is nothing other than a complex of reactions to a specific disease poison, antitoxin production occurs.”228

Once generated, the antitoxin behaves like any other “specific.”

The blood acquires the capacity to neutralize diphtheria toxin, without killing the bacillus, in the same way that Tuberculin neutralizes the tuberculous process without killing the bacilli in the patient’s tissues. The toxins are chemically modi-lied (“weakened”), leading to an increase in molecule size and less effect on the “toxin-sensitive vital elements of the body.”229’"" Behring also described antitoxin production as “habituation” (Gewoehnung), a concept which had been much employed by Breton-neau and other Paris physicians to explain natural immunity.23000

But, Empiric that he is, Behring urges a practical approach—“One should take the old and tried point of view, ‘By its fruits shall you judge.’”231 And he warns against undue zeal in theorizing about antitoxin production: “It is not for scientific research but rather for philosophical speculation to explain whence the living organism acquires the ability not only to react defensively to morbific influences but then to achieve an even better defense than before, and even to bequeath this inherited characteristic to its descendents.”232

As to how antitoxin “neutralizes” toxin, Behring asks if the effect is “direct” or “indirect,” if the toxin is rendered harmless “by direct contact with the antitoxin or in some other way.”233 Ultimately, he decides that it is indirect: “the definitive neutralization of toxin takes place only with the cooperation in vivo of a complementary corporeal element.”234 It is certainly not a “neutralization” in Ehrlich’s sense of acids “neutralizing” alkalies and vice-versa.235 No chemical analysis of the toxin-antitoxin reaction is available, and this would, in any case, conflict with the fact of their specificity, which does not lend itself to chemical reduction.236’PP Noting that natural recovery’ from an infectious disease like diphtheria is marked by the appearance of antitoxins in the blood, Behring observes that the “natural healing power makes broad use of this disinfectant” as it

""In 1895 Albert Calmette (1863-1933) extended Behring’s antitoxin technique by injecting snake poison into horses and treating snakebite with the defibrinated blood (W. T. Vaughan, Story of Allergy, 50).

°°See Divided Legacy, II, 508fT.

ppBehring credited Koch’s Tuberculin with reintroducing “specificity” into school medicine: “Diphtheria toxin was at hand long before Tuberculin. Why, then, did the gentlemen of Pasteur’s institute not immunize animals with it? Simply because their preconceived views made the thing quite invisible to them.... We should feel ourselves lucky that Koch in the search for a cure for tuberculosis gave us a glimpse into a completely newr world, the study of which brought us a mighty step forward in the search for specific treatments and their preparation” (Pauline Mazumdar, “Immunity in 1890,” 323).

does many other kinds of curative instrumentalities, and that this curative process cannot be understood “mechanically.”237

For instance, diphtheria antitoxin is effective even when applied topically to the nose or throat.238

Part of the action of antitoxins, furthermore, consists in the stimulation of phagocytosis—that “powerful weapon of the vital force.”239

All in all, Behring concludes, we probably understand as much about the toxin-antitoxin reaction as we do about the healing process generally, meaning, not very much.240

Behring and Homoeopathy

Behring’s view of the toxin-antitoxin reaction becomes clearer in the light of his attitude toward homoeopathy. What he writes is highly laudatory, and he might have been even more venturesome if not for the usual socio-political limitations and inhibitions—which applied to the most exalted physicians in the land, as well as to the undifferentiated mass.

In 1897 he observed that “Hahnemann was right when he took his starting-point in the symptoms of the patient. In the simil-la similibus principle modern etiological therapy is at one with homoeopathy.”241 In 1898 he stated: “Similia similibus is the fundamental homoeopathic principle, meaning that a disease is generated which is similar (the homoion, the simile) to the one being

combatted. Aequalia aequalibus is the isopathic healing principle----

Koch’s Tuberculin for tuberculosis falls under this principle, as do Pasteur’s rabies therapy and Jenner’s smallpox vaccination.”242 He wrote in 1912: “Hahnemann’s principle, according to our present way of thinking, was not bad at all.” Cowpox vaccination led Hahnemann to the assumption that a morbific substance, in the correct dose, is curative for the disease which it provokes. “But the concept that the sick person reacts differently to medications than the healthy one, which had to be established empirically by therapeutic trials, also played a role in Hahnemann’s thinking.” 243-fw

<wHe was, of course, aware that the tuberculous person or animal reacts more vigorously to Tuberculin than the healthy one (Emil Behring, Gesammelte Abhandlungen, 147).

If Hahnemann had confined himself to that (Behring continues), his reputation would have been better than it is. He could have performed Pasteur’s mission at the beginning of the nineteenth century. But he did not possess Pasteur’s scientific conscience and allowed himself to be carried away by theory. Homoeopathy is also reminiscent of the ideas of Paracelsus. “What is more, they hypothesize a specific relationship between the remedy and the disease to be combated; but that might well be considered a service at a time when medical science under Virchow put a ban on ‘specifics and everything specific.’”244 Homoeopathic pharmacology, especially its specificity, and even the infinitesimal dose appealed greatly to Behring. He could be quoting Hahnemann directly when he states that many of the best medicines (quinine, digitalis, morphium, and others) are also poisons—the only difference being that of dose—or when he observes that the most powerful poisons make the best antitoxins.245’"

He urges that antitoxin be produced using an aqueous dilution of toxin, this being analogous to Pasteur’s attenuated virus.246 And since antitoxin works by stimulating a reaction, he urges that it be employed in very small, even infinitesimal, doses:

I am touching here upon a subject anathematized till very recently by medical pedantry, but if I am to present these problems by historical illumination, dogmatic imprecations must not deter me. They must deter me no more now than they did thirteen years ago [1892] when I demonstrated before the Berlin Physiological Society the immunizing action of my tetanus antitoxin in infinitesimal solution, [emphasis added] On this occasion I also spoke of the production of the serum by treating the animals with a poison which acted better, the more it was diluted, and a clinician who is still living remonstrated with me, saying that such a remark ought not to be made publicly since it was grist for the mill of homoeopathy.—Emil Behring, 1905247

Hahnemann is to be preferred to Ehrlich when it comes to elucidating the nature of the toxin-antitoxin reaction:

The principles of my antitoxin serum therapy remain to be explained, notwithstanding the assertion by many authors that the therapeutic action of my diphtheria and tetanus antitoxins are clearly understood since the promulgation of Ehrlich’s side chain theory. For speculative minds the new curative substance will undoubtedly become a most interesting object of scientific investigation, but I do not believe that medicine will profit much by it. In spite of all scientific speculations and experiments regarding smallpox vaccination, Jenner’s discovery remained an erratic boulder in medicine, until biochemically thinking Pasteur, devoid of all classroom knowledge, traced the origin of this therapeutic boulder to a principle which cannot be better characterized than by Hahnemann’s word, “homoeopathic.”

Indeed, what else causes the epidemiological immunity in sheep vaccinated against anthrax than the influence previously exerted by a virus similar in character to that of a fatal anthrax virus? And by what technical term could we more appropriately speak of this influence, exerted by a similar virus, than by Hahnemann’s word, “homoeopathy.” ... If I were confronted with a hitherto incurable disease and could see no way to treat it other than with homoeopathy, I can assure you that I would not be deterred from following this course by dogmatic considerations.—Emil Behring, 1905248

The presence of Hahnemann and isopathy, as of Hering’s work on snake poisons, is felt at every stage in the emergence of immunology. Warren T. Vaughan described a visit by Albert Cal-mette, near the end of his life, to the University of Michigan:

There was only one place he really wished to see. This was the laboratory in which Sewall had performed his memorable experiments on snake venoms. As he stood in the small, poorly lighted room he said, “It was here that diphtheria antitoxin was made possible.”—W. T. Vaughan, 1943 '4''

NOTES

1.    Louis Pasteur, Oeuvres, VI, 324.

2.    Ibid., VI, 291-303, at 298, 300.

3.    Ibid., VI, 298.

4.    Loc. cit.

5.    Ibid., VI, 334-335.

6.    Ibid., VI, 326.

7.    Ibid., VI, 604 605; Emile Duclaux, 1896, 298.

8.    William Bulloch, 1938, 188.

9.    Emile Duclaux, 1896, 301 302; see also Louis Pasteur, 1940, II, 579.

10.    Ibid., 302.

11.    Robert Koch, 1987, 72, 75, 76.

12.    Ibid., 76.

13.    Ibid., 104.

14.    Ibid., 113-114.

15.    Ibid., 143.

16.    Loc. cit.

17.    Ibid., 159.

18.    Ibid., 180.

19.    Emile Duclaux, 1896, 274.

20.    F. H. Garrison, 1922, 387.

21.    J.-A. Auzias-Turenne, 1878, viii-ix, 281 fF., 291.

22.    J.-A. Auzias-Turenne, 1862, 12; A. Loir, 1938, 102.

23.    C. Sperino, 1853, 40; J.-A. Auzias-Turenne, 1878, xii.

24.    C. Sperino, 1853. J.-A. Auzias-Turenne, 1878.

25.    J.-A. Auzias-Turenne, 1865-1866a, 9-10.

26.    Ibid., 9-10.

27.    C. Sperino, 1853, 686.

28.    J.-A. Auzias-Turenne, 1865-1866a, 9 10.

29.    Ibid.

30.    Ibid.

31.    Adrien Loir, 1938, 102.

32.    Louis Pasteur, 1940, III, 149; Ixniis Pasteur, Oeuvres, VI, 298.

33.    Louis Pasteur, 1940, III, 148.

34.    Ibid., Ill, 173; Antonio Cadeddu, 1985, 103.

35.    Robert Koch, 1987, 101.

36.    Antonio Cadeddu, 1985, 103.

37.    Louis Pasteur, 1940, III, 156.

38.    Emile Duclaux, 1896, 281.

39.    Antonio Cadeddu, 1985, 89.

40.    Ibid., 90.

41.    W. I. B. Beveridge, 1957, 37.

42.    Pan American Health Organization, 1971, 17.

43.    Antonio Cadeddu, 1985, 101.

44.    Mary Cressac, 1951,62.

45.    Antonio Cadeddu, 1985, 98.

46.    Ibid., 104.

47.    Harald Gaier, 1991, 298fT.

48.    J.-A. Auzias-Turenne, 1865-1866b, 343-345.

49.    H. Krueger, 1883, 62.

50.    J. P. Tessier, 1884-1885, 186.

51.    H. H. Bourguignon, 1855.

52.    C. Hering, 1837.

53.    Loc. cit; William Boericke, 1927, passim.

54.    Bibliotheque Homeopathique II (1833), 101.

55.    Ibid., 103.

56.    Ibid., 105.

57.    Ibid., 107.

58.    Bnt. J. Horn. VII29 (1849), 337.

59.    O. A. Julian, 1977, II, 384fT.

60.    Bibliotheque Homeopathique III (1834), 257 270, 348-362; Catherine Coulter, 1988.

61.    L. Griesselich, 1848,64.

62.    Samuel Swan, 1886, 31.

63.    Bnt.J. Horn. 17/29 (1849), 336; A. R. Morgan, 1898.

64.    Auguste Rapou, 1847, II, 186.

65.    Rudolf Tischner, III, 603.

66.    Ibid.

67.    Bibliotheque Homeopathique III (1834), 125\ Brit. J. Horn. VII 29 (1849), 336.

68.    H. C. Allen, 1910, 21 \ Brit. J. Horn. VII29 (1849), 338.

69.    Bibliotheque Homeopathique I7 (1835), 19-46.

70.    Georg Adolph Weber, 1836, 85 93.

71.    Bibliotheque Homeopathique 17/7(1837), 280, 283.

72.    Ibid., ///(1834), 370; 7F(1835), 5.

73.    Ibid., //(1834), 101; H. C. Allen, 1910, 141-142.

74.    G. H. G.Jahr, 1849, 214.

75.    J. P. Tessier, 1884-1885, 106; Homoeopathic Physician VI (1886), 57 58,

217.

76.    D. King, 1858, 155.

77.    Boston Medical and Surgical Journal XLIV (1851), 406.

78.    A. A. Ramseyer, 1909, 4.

79.    Ibid., passim.

80.    Richard Haehl, 1922, I, 402.

81.    L. Griesselich, 1848, 60.

82.    Bnt.J. Horn. VII29 (1849), 339.

83.    Hans Hermann Hager, 1861.

84.    American Homoeopathist II(1878), 109.

85.    Allg. hom. £eitung 3 22 (1834), 169.

86.    Auguste Rapou, 1847, II, 190.

87.    Ibid., II, 202.

88.    Homoeopathic Physician III(1883), 35; IV(1884), 37.

89.    Bibliotheque Homeopathique II(1833), 106-107.

90.    Ibid., IV(1835), 295; F(1835), 235; Allg. hom. Zeitung VIII8 (1836), 114; Homoeopathic Physician XII(1892), 468-472.

91.    H. G.Allen, 1910.

92.    O. A. Julian, 1977.

93.    August Bier, 1925, 26.

94.    Wiihelm Ameke, 1885, 375.

95.    Ibid., 323.

96.    Charles Janot, 1940, 1-55; Jacques Baur, 1985, 1986.

97.    Charles Janot, 1940, 120, 171, 205; Wilhelm Ameke, 1885, 277.

98.    Emil Behring, 1915, 140.

99.    Charles Janot, 1940, 115; Ludovic de Parseval, 1856, 30; Wilhelm Ameke, 1885, 376.

100.    Compte-Rendu du Proces de Mme. Hahnemann, 1847; Rima Handley, 1990, passim.

101.    L'Union Medicate VII5 (1853); Harris L. Coulter, 1977, 558.

102.    Jacques Poulet, 1968.

103.    Charles Janot, 1940, 110-111.

104.    L’Homeopathie dans les Hopitaux, 1865.

105.    Loc. cit.\ Charles Janot, 1940, 143.

106.    Richard Haehl, 1922, I, 295.

107.    Auguste Rapou, 1847, II, 618.

108.    Charles Janot, 1940, 1 13-1 14; Wilhelm Ameke, 1885, 376; Ludovic de Parseval, 1856, 30.

109.    L. Griesselich, 1848.

1 10. John Farley, 1978, 151.

111.    Louis Pasteur, 1940, I, 144.

112.    Charles Janot, 1940, 184; T.J. M. Collet, 1898, 180-194.

113.    H. Krueger, 1883, passim.

114.    Ibid., 44.^

115.    Jean-Paul Tessier, 1884-1885.

116.    Ibid., 106-107.

117.    T.J. M. Collet, 1898.

118.    Ibid., 195.

1 19. J. Amer. Inst. Hom. 7/(1910), 191; Homoeopathic Physician //(l 882), 121; VI (1886), 57.

120.    Wilhelm Ameke, 1885, 277, 352.

121.    Ibid., 322.

122.    Ibid., 323.

123.    Ibid., 330.

124.    Ibid., 431.

125.    Ibid., 358.

126.    Ibid., 359.

127.    Ibid., 358.

128.    Ibid., 361.

129.    Robert Koch, 1987, 186; T. Gorsboth and B. Wagner, 1988, 130.

130.    T. Gorsboth and B. Wagner, 1988, 132.

131.    Josef M. Schmidt, 1991, 778.

132.    Robert Koch, 1890, 1029.

133.    Robert Koch, 1987, 114.

134.    Robert Koch, 1890, 1030.

135.    R. Haehl, 1922, II, 432.

136.    Robert Koch, 1890, 1030.

137.    Ibid., 1031.

138.    Loc. cit.

139.    Emil Behring, 1915, 34.

140.    W. D. Foster," 1970, 61.

141.    Josef M. Schmidt, 1991, 779.

142.    T. Gorsboth and B. Wagner, 1988, 132.

143.    R. Virchow, 1891, 128; E. R. Long, 1965, 124.

144.    T. Gorsboth and B. Wagner, 1988, 133.

145.    Loc. cit.

146.    Henry Stuart Willis, 1940, 574; T. Gorsboth and B. Wagner, 1988, 133.

147.    Edward Shapiro, 1983, 20; Rene Dubos, ed., 1958, 177.

148.    O. A. Julian, 1977, II, 476.

149.    Bnt.J. Homoeopathy 17/29 (1849), 337.

150.    Marie Curie, 1963, 11.

151.    Hans Hermann Hager, 1861, 107, 132.

152.    The Mw Organon (1879), 342, 439, 449; O. A. Julian, 1977, II, 476; Homoeopathic Physician XI (1891), 187.

153.    Samuel Swan, 1886.

154.    Ibid., 31; Homoeopathic Physician /I7(1884), 57.

155.    Homoeopathic Physician VII (1887), 176.

156.    Ibid., IV{1884), 57-58.

157.    J. Compton-Burnett, 1891, xii.

158.    Ibid.,xiv.

159.    Edward Shapiro, 1983, 20.

160.    R. Haehl, 1922, II, 432.

161.    Josef M. Schmidt, 1991, 779.

162.    Homoeopathic Physician XI(1891), 185.

163.    Ibid., XIII(1893), 373.

164.    J. Compton-Burnett, 1891, 20, 35.

165.    Ibid., xv.

166.    Emil Behring, 1898, 65, 67.

167.    Richard C. Cabot, 1906, 590.

168.    Homoeopathic Physician XI (1891), 192.

169.    Josef M. Schmidt, 1991, 780.

170.    Rene Dubos, ed., 1958, 177; Homoeopathic Physician XI (1891), 186.

171.    T. Gorsboth and B. Wagner, 1988, 134.

172.    Edward Shapiro, 1983,21.

173.    Ibid., 21.

174.    W. D. Foster, 1970, 60.

175.    Edward Shapiro, 1983, 22.

176.    Emil Behring, 1915, 36.

177.    H. A. Hare, 1918, 518.

178.    Richard Cabot, 1906,590.

179.    British J. Homoeopathy VII29 (1849), 337.

180.    L. Griesselich, 1848, 67.

181.    Julius Wagner-Jauregg and Gustav Bayer, 1914, 183.

182.    Charles Eloy, i 893, 52.

183.    Ibid., 134fT., 255-275.

184.    Xaver Schaffgotsch, 1965, 110.

185.    Homoeopathic Physician XIII (1893), 515.

186.    Ibid., 513.

187.    Julius Wagner-Jauregg and Gustav Bayer, 1914.

188.    H. A. Lechevalier and M. Solotorovsky, 1974, 122.

189.    Ibid., 138-141.

190.    William Bulloch, 1938, 260.

191.    H. A. Lechevalier and M. Solotorovsky, 1974, 210-211.

192.    Ibid., 210.

193.    Henry Sewall, 1887, 203.

194.    Ibid., 205; Warren P. IiOmbard, 1909.

195.    Henry Sewall, 1887, 203; Warren T. Vaughan, 1943, 47fT.

196.    Emil Behring, 1915, 5.

197.    Ibid., 131.

198.    Loc. cit.

199.    Emil Behring, 1894, 7.

200.    Emil Behring, 1915, 131.

201.    Ibid., 132.

202.    Emil Behring, 1894, 225.

203.    Emil Behring, 1915, 137.

204.    Emil Behring, 1894, 8.

205.    Emil Behring, 1915, 137.

206.    Ibid., 136.

207.    Ibid., 136-137.

208.    Emil Behring, 1894, 217.

209.    Ibid., 225-226.

210.    Ibid., 230; Emil Behring, 1915, 37.

211.    Emil Behring, 1894, 211-212.

212.    H. A. Lechevalier and M. Solotorovsky, 1974, 219; see also Emil Behring, 1915, 149.

213.    H. A. Lechevalier and M. Solotorovsky, 1974, 220.

214.    Ibid., 222.

215.    Emil Behring, 1915, 34.

216.    H. Schadewaldt, 1975, 2176.

217.    E. Lagrange, 1965, 68; Pauline Mazumdar, 1972, 323.

218.    E P. Gay, 1935, 880.

219.    Rene Dubos, ed., 1958, 358.

220.    Emil Behring, 1915, 159, 163.

221.    Ibid., 145.

222.    Ibid., 144.

223.    Ibid., 145.

224.    Emil Behring, 1894, 8.

225.    Emil Behring, 1915, 144, 148, 161, 183.

226.    Ibid., 33; Emil Behring, 1894, 223, 230, 231.

227.    H. A. Lechevalier and M. Solotorovsky, 1974, 221.

228.    Emil Behring, 1894, 230.

229.    Emil Behring, 1915, 163.

230.    Emil Behring, 1894,8.

231.    H. A. Lechevalier and M. Solotorovsky, 1974, 218.

232.    Emil Behring, 1894, 9.

233.    Ibid., 248-249.

234.    Emil Behring, 1915, 160.

235.    Ibid., 33.

236.    Emil Behring, 1894, 220, 221, 241.

237.    Ibid., 6-7, 10.

238.    Emil Behring, 1915, xiv, 39.

239.    Ibid., 158.

240.    Emil Behring, 1894, 241.

241.    Deutsche med. Wochenschrift XXIII (1897), Vereinsbeilage, 122.

242.    Emil Behring, 1898, 65-66.

243.    Emil Behring, 1915, 140.

244.    Ibid., 140.

245.    Ibid., 169. Emil Behring, 1894, 219; 1898, 66.

246.    Emil Behring, 1915, 162.

247.    Emil Behring, 1905, xxvii.

248.    Ibid., xxvi-xxvii.

249.    W. T. Vaughan, 1943, 50; W. T. Vaughan and J. H. Black, 1954, 9.

EHRLICH, KOCH, AND THE DOCTRINE OF CONTRARIES

While Pasteur, Metchnikoff, and Behring were developing the theory of cure through “similars,” Paul Ehrlich was elaborating a therapeutics of “contrariety.”

“Contrariety” is no less ancient a concept in medicine than “similarity,” being mentioned in the Hippocratic Corpus, but it had to be reformulated in bacteriological terms. If microbes were thenceforth to be the causes of most diseases, therapeutic activity had to be directed against them. “Contrariety” had to mean opposition between microbe and antimicrobial drug.

But to erect a new therapeutic method, Ehrlich first had to tear down the existing one oriented toward the “physiological action” of medicines on healthy individuals. Attention was to be focused not on the host organism, but on the peccant microbe.

Allopathic Modifications of the Proving

Hahnemann’s prov ing, with its documentation of symptoms both physical and mental, and from each of the body’s organs and systems, was premised upon the idea that any drug acts on the whole body, presumably through the nervous system.3 By midnineteenth century Rationalist medicine had accepted this as-

aHence he urged that homoeopathic medicines not be swallowed but allowed to dissolve in the mouth, where they contact the nerve endings under the tongue (Samuel Hahnemann, Organon, 184—, Sec. 284).

sumption, together with its corollary that the action of a medicine in the sick can be ascertained by observing its effects in the healthy. It was assumed that any drug produced a generalized reaction in the body, with each organ responding in its own peculiar manner.1

The “physiological action” of remedies in the healthy was first studied by Johan Joerg and others in the 1820s, and these investigations culminated in the therapeutics of Trousseau.b In the latter decades of the century the discussion of a medicine’s therapeutic application was always prefaced by an analysis of its “physiological action.”2

But while accepting in principle that “experiments made with medicaments upon ... healthy human beings [are the] only rational scientific groundwork for the treatment of disease,” allopathy at the same time pursued a parallel line of research, veering away from “healthy human beings” to a more intrusive type of experimentation on the “lower animals.”3

Instead of administering the remedy orally to humans and noting the ensuing symptomatic changes, hoping to achieve a higher degree of precision, these physicians injected the drug into animals and observed the pathological alterations visible upon autopsy. This represented an incipient Rationalizing of Hahnemann’s Empirical procedure and exemplified the instinctive Rationalist preference for data from inside the body as opposed to symptoms. The procedure was felt to be more “scientific” than merely describing changes in symptoms.

Magendie was the first to tinker in this way with Hahnemann’s proving. In the second decade of the century he mixed medicines with guinea-pig blood in vitro to ascertain the impact upon coagulability, in accordance with his theory that “diseases” could be reduced to disturbances in the movement of blood through the capillaries.c

In the 1830s his student, the Anglo-American James Blake (1815-1893), carried the project forward by injecting drugs into

bOn Joerg and others who tested drugs on the healthy, see Divided Legacy, II, 565fT., Ill, 254fT. On Armand Trousseau, see Divided Legacy, II, 569fT.

the bloodstream of living animals.4 He analyzed drugs for molecular weight, crystalline structure, chemical composition, and the like and in 1841 announced discovery of a “law of isomorphism”: compounds which crystallize in the same form have the same physiological action: “There exists some intimate connection between the chemical properties of substances and their physiological action ... the physiological action of these substances depends upon some property they possess in connection with these isomorphous relations.”5

He was followed in Germany by Rudolph Buchheim (1820- 1879) and Carl Mitscherlich (1805-1871), who introduced a new element of doctrine. Hahnemann, they alleged, had confused the medicine’s “physiological effect” with the patient’s symptoms. The former is manifested by “signs,” while the “symptoms” are due to “idiosyncrasy” and not essential to understanding a medicine’s action. By injecting medicines into animals they hoped to elicit information on “physiological effect” without contamination by “symptoms.”d

This yielded a two-tier doctrine of diagnosis and therapeutics. The patient’s “signs” revealed the disease “cause” and also the “physiological action” of the medicine; this was the substance of “general pathology” and seen as “scientific.” The “symptoms,” on the other hand, being produced by the patient’s idiosyncrasy, fall under “special pathology” and are not “scientific.” Between 1864 and 1870 the Englishman Benjamin Ward Richardson (1828 1896) injected methane, ethane, butane, and pentane compounds into the bloodstream of experimental animals, to see what would happen. The study of remedies, he held, must henceforth be based on these “structure-activity” considerations: “I am certain that the time must soon come when the books we call ‘Pharmacopoeias’ will be everywhere constructed on this basis of thought, and when the chemist and physician will become one and one.”6

The chemist, Alexander Crum Brown (1838-1922), and the Edinburgh physician, Thomas R. Fraser (1841-1920), formed a

team to investigate this new area and commenced their first published paper in 1869 with a declaration of faith: “There can be no reasonable doubt that a relation exists between the physiological action of a substance and its chemical composition and constitution, understanding by the latter term the mutual relations of the atoms in the substance.”7

The identical declaration of faith was made by Thomas Huxley (1825-1895), physician and biologist, some years later in 1881: “There surely can be no ground for doubting that, sooner or later, the pharmacologist will supply the physician with the means of affecting, in any desired sense, the functions of any physiological element of the body. It will, in short, become possible to introduce into the economy a molecular mechanism w'hich, like a very cunningly contrived torpedo, shall find its way to some particular group of living elements and cause an explosion among them, leaving the rest untouched.”8

Thomas Lauder Brunton (1844-1916), whose 1885 Textbook of Pharmacology, Therapeutics, and Materia Aledica contained numerous and unacknowledged borrowings from the contemporary homoeopathic materia medica, also expressed the hope that therapeutics would soon be placed on a completely rational basis: “The prospects of therapeutics appear to me very bright ... I think it is highly probable that before long we shall have a series of drugs which w ill stimulate the biliary secretion of the liver or modify its glycogenic function, arranged in order of comparative strength, in much the same way we have now the class of antipyretics. We may also look for a series of remedies which w ill modify the circulation by dilating the blood vessels not only temporarily but more or less permanently [jw:/].”9

But the search for a structure-function relationship enabling physiological or therapeutic effect to be adjusted by manipulating the medicine’s molecules turned into yet another will o’ the wisp. Crum Brown and Fraser soon bogged down in generalities irrelevant to therapeutics. Although methylation of strychnine, codeine, nicotine, and some other drugs reduced their ability to cause convulsions and diminished their narcotic properties w'hile imparting a paralyzing, curare-like action; and while the quaternary ammonium salts of atropine and other

compounds were also seen to be associated with paralyzing action, these findings were at best of marginal value for treatment.10 A decade later (1901), F. Gowland Hopkins wrote: “It is a matter for some disappointment, and perhaps for surprise, that we should, today, after thirty years, be able to point to very few general relations bearing the stamp of such definiteness and simplicity as are found in the [work of Crum Brown and Fraser]; and that even now the results obtained by these investigators may be quoted as the most satisfactory instance, to hand, of the obvious relation between chemical constitution and physiological action.”11

Fifty-eight years later May’s Chemistry of Synthetic Drugs reproduced the above quotation and commented: “Over half a century has elapsed, and these remarks still remain true.”12 And, indeed, in the end of the twentieth century the structure-function relationship remains a mystery still. None of the myriad investigations by legions of pharmacologists from Ehrlich to the present have enabled physicians to predict with any degree of precision the effect of a change in molecular structure on the physiological or therapeutic action of a medicinal drug.

Allopathic Practice

Late nineteenth-century Rationalist medical practice was oriented toward combating such general manifestations as fever, inflammation, headache, neuralgia, intestinal pain, arthritic and rheumatic disorders, etc.—i.e., the typical phenomena of every disease.

Fever, and the felt need for “antipyretic” therapy, were at the forefront of attention.

Quinine and digitalis, the polyvalent fever medicines par excellence in the early decades of the century, by 1880 had been largely replaced by salicylic acid, synthesized by Hermann Kolbe (1818-1884) and introduced for its fever-reducing properties in the early 1870s.13 Especially in the form of acetylsalicylic acid (aspirin) it became wildly popular, being used in typhoid fever, diphtheria, eruptive fevers, headaches, relapsing fever, pyemia, septicemia, puerperal fever, malaria, acute rheumatism, gout, chronic rheumatism, lumbago, myalgias, tonsillitis, fetid perspiration, eczema, neuralgia pains, even diabetes. It was applied topically to inflamed tonsils and in powder form to cancers and gangrene.14

Chloral hydrate was introduced in 1868 by Oscar Liebreich (1838-1908) and soon became the great nineteenth-century sleeping-pill and tranquilizer; it is the parent substance of chloroform, into which it decomposes in a strong alkaline solution, and Liebreich assumed that it would have a chloroform-like effect when exposed to the alkalinity of the body.15e

Antipyrine (phenazone), aminopyrine (amidopyrine), and Kairin (oxychinolin-ethyl hydrochloride) were also major antipyretics and pain relievers, synthesized by investigators seeking substitutes for quinine.16

I he “coal-tar analgesics” comprised a vast family of related substances, all employed as fever-reducers and pain relievers. The parent substance, acetanalid, introduced into medicine in 1886 as “antifebrin,” was later found to be excessively toxic and replaced in 1887 by phenacetin.17 The latter’s metabolite, acetaminophen (paracetamol), was first used in medicine in 1893 but was considered too toxic and left on the shelf until after World War II when it was resurrected by Yale University researchers worried about the side effects of aspirin. Soon it was being promoted to the American public generally as Tylenol, a supposedly safe substitute for aspirin.18

At an 1882 German congress on internal medicine, the principal topic was “antipyretic methods of treatment." The leading speaker stated that he would not waste words on “the evidence in favor of an antipyretic treatment of fever’’ because he was sure that the audience was already convinced. Fever was to be combated by cold baths, quinine, or salicylic acid.19f

One physician asked if antipyretic treatment is truly

cLiebreich’s theory exemplifies the Rationalist inclination to suppose the existence of “mechanisms” within the body because they seem to be operative outside it. Chloral hydrate did not function in the way assumed, as the body's alkalinity is insufficient for the purpose. Chloral hydrate mixed with alcohol constitutes the “Mickey Finn” so well known to readers of detective fiction.

fAnother physician, unsure of the value of salicylic acid in severe typhus, gave instead, “light Bordeaux wine, up to two liters a day” (Wilhelm Ameke, History of Homoeopathy, 415).

“causal,” i.e., if it kills the “fever-poison” in the organism, and concluded that, in view of the rapid reduction of fever in rheumatic arthritis treated with salicylic acid—taking as many days as it formerly took weeks—one must assume that the fever-poison is destroyed.20

Yet another speaker criticized the antipyretic method for encouraging routine practice: “This has had an injurious effect on our scientific position which it should be our task to regain.”21 But others noted the lack of anything better. Physicians would prefer to treat typhus, scarlet fever, and other diseases with “specifics,” “but for the present that is, alas, only a pious wish.”22 At another German medical congress in 1883 a speaker announced emphatically that “the antipyretic method has justly been called one of the greatest advances w hich have been made in therapeutics in recent times” but characterized it as “expectant—symptomatic.”23

Reacting to this chaos, Virchow and his followers rejected therapeutics altogether, deriding it as a purely “empirical” art. Clinical observation had no function, stated Carl Wunderlich in 1842, being merely the frivolous pastime of “ontology ... which takes abstract concepts for things, implying their actual existence and at once treating them as entities ... To the most widespread and the most dangerous consequences of ontology belongs the practice of setting up species of diseases which have been grouped in classes in the same way as plants. By raising them to the dignity of species, these ontological personifications received, as it were, the sanction of natural history.”24

Virchow suggested hydropathic applications for most conditions and dismissed “specific” medications.25 But his proposals were resented and rejected. A German medical congress in 1878 resolved that “the most important task of medicine, therapeutics, is not advanced by cellular pathology.” Behring called Virchow’s doctrine “therapeutic sterility.”26

Ehrlich’s Attack on Pharmacology

1 his was the background of Ehrlich’s pharmacologic speculations. Practice was dominated by medicines which physicians recog-nizecl as “symptomatic.” And the urge to describe and define the “physiological action” of drugs was becoming exhausted, since, even when this knowledge was available, pharmacologists and physicians did not know how to use it. Rejecting Hahnemann’s rule of similars (the medicine is administered to the patient whose symptoms most closely resemble those of the medicine’s physiological action), they had to fall back on a crude “contrariety” between “physiological action” and disease manifestations or an equally crude and intellectually unsatisfying appeal to “experience” as guides to the drug’s therapeutic application.^

A new paradigm was needed, and Ehrlich’s function was to cobble together the hesitating insights and formulations of Crum Brown, Fraser, and Richardson into a new doctrine of the relationship between medicine and disease, guided by the ready-to-hand technology of aniline-dye manufacture.

Ehrlich undermined research into “physiological action" in the classic way—redefining the field to enhance the value of his own contributions and to diminish that of “physiological action.” Henceforth research on the “physiological action” of medicines fell under traditional “pharmacology”—a “purely biological” or “purely theoretical” science “without any concern for practical application.” Research on healthy animals (he claimed) may reveal the toxic effects of medicinal substances but never their curative powers.27

The medicines elaborated by conventional pharmacology, i.e., most of those in use prior to Ehrlich’s arrival on the scene aspirin, antipyrin, phenacetin, anesthetics, and the like—are not “effective drugs” (wirkliche Heilmittel), not “true curative agents,” but are limited to the relief of symptoms. 28 h

We should never forget the initiative of the chemical enterprises, with their wonderful installations, which, along with many worthless medicines, have produced a large number of very good ones.—Paul Ehrlich, 190829

*See Divided Legacy, II, 636ff.

hThis is probably the first voicing of the allopathic claim, so often repeated in later decades, that “Medicine did not have any truly effective drugs before

Such “symptomatic” drugs are not effective against disease causes, which are mostly microbial.30 Finding “specifics” against “causes” is the task of “experimental chemotherapy.”31 It is accomplished by infecting experimental animals with microbial diseases and then ascertaining which medicine will cure.32

Ehrlich’s “specific experimental chemotherapy” made use of, and reinterpreted, the traditional distinction in medicine between “general” and “specific” remedies, reinforced by enzyme research. In 1892 the biochemist Emil Fischer (1852-1919) had announced that “enzyme and glucoside must join one another as lock and key, in order to be able to exert a chemical effect,” and this idea w'as picked up with enthusiasm by Ehrlich.33 “General” remedies were now identified with thoroughly old-fashioned “pharmacology,” “specific” ones with the thoroughly modern “experimental chemotherapy.” The traditional “specifics”—quinine in malaria, mercury in syphilis, and iodine in goiter—would now be supplemented by a host of new ones through the enterprise and inventiveness of the German chemical industry.34 While Koch and his collaborators were defining a series of new “specific diseases,” mostly of microbial origin, Ehrlich and his followers were seeking for each such “specific disease” its own “specific remedy.”

As will become evident, Ehrlich was completely successful in reformulating pharmacology. While twentieth-century Rationalism has dropped some of his w ilder embellishments, his categories still remain in place. There is the same specious distinction between “signs” and “symptoms”—the former, as it were, generated by the “basic” pathophysiological process, hence “objective” and even “scientific,” the latter merely reflecting the patient’s (subjective) idiosyncrasy, hence not falling in the realm of “science.” There is the same attempt to differentiate medicines which act on “symptoms” from those which act on the “cause,” even though the “cause” cannot be defined or identified and cannot be distinguished from the symptoms.' There is the same groundless distinction between substances that are “toxic” and those that are

not “toxic,” as if this were an essential attribute of substances rather than a function of the quantity administered. There is the same dominant assumption that cure is through “contrariety,” meaning the interruption of some ongoing pathophysiological process, even though the curative value of “interrupting” a pathophysiological process has never been demonstrated.

Ehrlich’s Physiology

Ehrlich followed Virchow in situating vital activity at the cellular level—the “living cell membrane”—and accepting a chemical interpretation of vital processes. “Everything that happens in the cell is essentially chemical in nature.”35

Living “protoplasm” (protein) was thought by Ehrlich to be a uniform and undifferentiated cellular substance, with all vital activity—reproduction, assimilation, growth, multiplication, perception, thought, will—the work of this substance. 36J

To be more precise, he saw “protoplasm” as a chemical nucleus interacting with its surroundings through “receptors” or “side chains” (Seitenketten),37

The latter perform “general” (rather than “specific”) functions such as, first and foremost, oxidation and reduction.38 “Life” is a “vital combustion process,” a “physiological process of combustion.”39

Everything goes to show that it is precisely the indifferent side chains which represent the sites of initiation, or of attack, for the physiological process of combustion, in that some of them bring about combustion by donation of oxygen, while others are consumed in the process.

—Paul Ehrlich, 188540

The other principal function of the side chain is to mediate the cell’s nutrition by anchoring nutrient material and making it

'Only in the 1930s were proteins understood to be discrete molecular entities and hundreds of thousands of varieties recognized. Until then all “protein’ was thought to be a nonspecific uniform aggregate of smaller molecules, and no distinction was made among the different kinds (A. M. Silverstein, “The Concept of Immunologic Specificity,” 699).

available to the “nucleus.”41 Hence Ehrlich sometimes calls the side chain “nutriceptor.”

Nutrient material is assimilated through chemical combination with the “nutriceptor,” inactivating the latter and inducing the “nucleus” to generate additional “nutriceptors” in such superabundance as to be cast of! in profusion into the bodily fluids.42

Ehrlich’s physiology is modeled on that of Justus Liebig (1803 1873), a great and influential organic and physiological chemist who was also a vitalist. The differences between them, however, exemplify the opposite ways in which the vitalist and mechanist minds interpret the same observations.

Liebig had also ascribed major importance to oxidation-re-duction processes in the organism but never equated them with the vitality.43 To him the vital force was “that peculiar cause which must be considered as the ultimate source of the phenomena which characterize vegetable and animal life.”44 But “we shall never learn what life is.”45 It is more powerful than a mere chemical force. During digestion, for example, the life force can overcome the chemical forces which bind together the food needed for nutrition.46

Ehrlich turned Liebig upside down: to him, chemical affinities govern vital processes.47

Ehrlich and Immunity

He first used the side-chain theory in immunology and then in “experimental chemotherapy,” to provide a chemical interpretation of pharmacological processes and to exclude the undefinable vital force, i.e., host resistance, from any role.

Diphtheria or tetanus infection was known to proceed in two stages. The microorganism gains a foothold in the tissues and generates a toxin which causes the disease symptoms and induces the host to produce antitoxins. The latter then combine with the toxin to neutralize it.

Neutralized toxin was named “toxoid” by Ehrlich.48

Thereafter he had to explain how this came about. In an initial communication (1897) he criticized the prevailing interpreta-

tion of antitoxin production. “Most investigators probably accept Behring’s view that the antibodies are products of the living organism ... This explanation, however, presents serious difficulties.’”49 “To attribute what could be called inventive capacity to the body or its cells, enabling them to produce new groups of atoms as required, would involve a return to the concepts current in the days of Naturphilosophie. Our knowledge of cell function and especially of synthetic processes would lead us rather to assume that in the formation of antibodies we are dealing with the enhancement of normal cell function, and not with the creation at need of new groups of atoms.” 50 k

I he key to this riddle is the side chain or “nutriceptor,” which is part of “normal cell function.” By pure coincidence (!!) the “nutriceptor” is also “toxophile,” i.e., possesses the capacity to combine with toxin:

It is coincidental and without relation to the normal activity of the cell if it, at the same time, possesses the property of combining with certain poisons (diphtheria and tetanus toxins, snake venom, abrin, ricin, crotin).—Paul Ehrlich, 189751

The “toxophile” character of “nutriceptors” is “the necessary preliminary and cause of the poisonous action of the toxin.”52 In other words, poisons are poisonous because the body’s cells possess “nutriceptors” for poisons!

When the toxin unites with the “toxophile"’ nutriceptor, it blocks the latter from performing its normal nutritive functions, “from participating, in the physiological sense, in the life of the cell.” The cell is stimulated to regenerate itself, producing, and overproducing, newr nutriceptor side chains which are pushed of! into the blood, forming “antitoxins.” “The cells become, so to say, educated or trained to reproduce the necessary7 side chains in ever-increasing quantity.... This, however, does not take place as a simple replacement of the defect; the compensation proceeds

kjXaturphilosophie was an interpretation of physiology drawing on the philosophy of Hegel, Fichte, and Schelling—neo-Platonic and mystical in inspiration (Divided Legacy, II, 327, 329).

far beyond the necessary limit; indeed, over-compensation is the rule.” It is carried so far that: “to use a trivial expression, [the side chains] will become too much for the cell itself and will be discharged into the blood, like an excretion, as unwanted ballast.”53 Like “magic bullets” (Zjiuberkugeln), these then combine with and neutralize the specific toxin which has generated them.

Antitoxins and “nutriceptors” eventually came to be known as “antibodies” (Antikoerper). Found in abundance in the blood of humans and animals, they represent “side chains of the cell protoplasm which have been produced in excess and therefore thrust off.” 54>‘

Two comments may be made about Ehrlich’s theory of antitoxin formation. In the first place, the view that extra “nutriceptors” are generated by the “nucleus” was the application of a supposed general biological principle enunciated by Ehrlich’s cousin, teacher, and close friend and advisor, Carl Weigert (1845-1904), according to which a damaged cell or tissue will hvperregenerate a missing part.55

Secondly, by assimilating “nutriceptors” to “antibodies” Ehrlich assimilated immunity to the “normal” functioning of the body, to “general physiology.” Immunity is not a defensive reaction, not a vital effort of the whole organism, but a local mechanical f unction: “I think myself warranted in concluding that the formation of antitoxin lacks all the characters of that purposeful, intelligently directed, and remarkable process which it at first seemed to be, and that it is to be regarded merely as a process analogous to those constituting an essential portion of the normal metabolism of the organism.”56

In particular, the symptoms produced by the actions of the tox-ophore group play no part in the production of antitoxins: “On the contrary, we may consider that the severe symptoms, which indicate injury to the cell life, disturb the regenerative functions, and thus hinder or entirely frustrate the course of the immunization process.”57

'At one point Ehrlich used the word “amboceptor” instead of “nutriceptor.” But they both transform into “antitoxins,” i.e., “antibodies.”

He attributes the antitoxin-forming capacity of nutriceptors to the fact that toxins, being of animal origin, are molecularly similar to foodstuffs of animal origin: “It is, therefore, not surprising if they possess a haptophore group corresponding to that of a foodstuff.” 58 m

How, then, does antitoxin (antibody) neutralize toxin? Ehrlich held the process to be chemical, not “vital,” and attacked Behring on this point: “A certain high authority said that antitoxins act after the manner of specific forces (in a physical sense). If this theory of ‘forces’ were to be upheld, every possibility of bridging the contradictions would be completely lost, for then every tertium comparationis would be lacking.”59

What Ehrlich is trying to state is that acceptance of Behring’s “specific forces” would preclude a chemistry-based physiology. “Toxin and its antitoxin influence one another by a direct chemical interaction ... in which biological processes have no share.”60 “This ability to combine with antitoxin is attributable to the presence in the toxin complex of a specific group of atoms with a maximum specific affinity to another group of atoms in the antitoxin complex, the first fitting the second easily, as a key does a lock, to quote Emil Fischer’s well-known simile.”61

Working with guinea pigs, which are highly susceptible to diphtheria toxin, he found that the “action of toxin and antitoxin took place quantitatively,” in that one volumetric unit of antitoxin always neutralizes exactly one unit of toxin.

Later he found that toxic bouillon sitting on the shelf became less and less toxic, so that the same volume represented fewer and fewer lethal doses. And yet antitoxin could still neutralize only the same volume of bouillon: “From this it was evident that the toxic action on animals and the combining capacity with antitoxin represented two different functions of the toxin, and that the former of these had become weakened, while the latter had remained constant.”62

He explained this by “assuming that the toxin was characterized by possession of two different combining groups: one, which may be

mOn the “haptophore,” see below, p. 119. Ehrlich’s assimilation of poisons to foods doubtless reflects Virchow’s assimilation of pathology to physiology and demonstrates Virchow’s residual influence on him.

designated haptophore, conditions the union with antitoxin, while the other group, which may be designated toxophore, is the cause of the toxic action.”63 The haptophore groups of the toxins “unite not only with the antitoxins but also with the side-chains of the cells.”64 “This conception of the constitution of diphtheria toxin, after more extensive, very exact, and much varied experimentation, ... has been confirmed in the completest manner possible.”65

Thus the “toxoid” is a toxin whose haptophore group remains vigorous and active but whose toxophore group has been weakened or destroyed.66 Since it can still generate antitoxins/ antibodies if injected, this proved to Ehrlich that antitoxin is produced by the haptophore group.67

Happily, foodstuffs do not possess toxophores, only hap-tophores. But injections of milk or of blood can generate antimilk or anti-blood antibodies which later unite specifically with these substances and precipitate them.68

Immunology and DyestufT Theory

I he “haptophores” and “toxophores” represent the transfer into immunology of ideas developed in Ehrlich’s 1878 dissertation, Contributions to the Theory and Practice of Histological Staining, which concluded that the chemical group yielding the dye molecule’s distinctive color differs from the one binding the molecule to the tissue sample.69 Furthermore, the dye molecule is “fixed” to the tissue by an oxidation process binding an atomic group of the dye to a “side chain” of a cloth fiber.70

This was neither the first nor the last time Rationalist medicine has been structured by an imported explanatory paradigm."

"It is startling that such a procedure does not even meet with disapproval! “[Emil Fischer’s] investigations of the enzymes show that they are specific in action, affecting only certain chemical substances to which, as he puts it, they are related as a key to a lock or a glove to a hand, an analogy which Ehrlich has cleverly applied in his side-chain theory” (Fielding Garrison, History of Medicine, 737). “Ehrlich ... made out of staining and the theory of dyes, which had seemed little more than a hobby to his Breslau associates, a foundation broad enough to support several new and major sciences, including hematology, immunology, and chemotherapy ... He was a fertile chemist with a capacity for bold generalizations” (Esmond R. Long, History of Pathology, 165). Why, one may ask, is it assumed that dyestuff theory has any application to pharmacology?

Here a problem arose which even today awaits a solution. Organisms can synthesize antibodies to an infinite variety of antigens, and, since Ehrlich rejected the possibility of an “inventive capacity” to synthesize these antibodies, as it were, ex nihilo, he had to maintain that antibodies, or their “physiological analogues,” are already there, preformed in the antibody-producing cells of the host organism.71 And since it would be unnatural for side chains to remain unemployed until the cell is assaulted by a toxin, they had to work in the meantime as “nutriceptors,” executing the ordinary functions of oxidation and reduction: “It would not be reasonable to suppose that there were present in the organism many hundreds of atom groups destined to unite with toxins when the latter appeared, but in function really playing no part in the processes of normal life, and only arbitrarily brought into relation with them by the will of the investigator ... One may therefore rightly assume that these toxophile protoplasmic groups in reality serve normal functions in the animal organism, and that they only incidentally and by pure chance possess the capacity to anchor themselves to this or that toxin." J

This interpretation of antibody formation may have possessed some plausibility for physiologists who assumed that “protein" was a single undifferentiated substance. But when in the 1930s, proteins were found to exist in a virtually infinite variety, Ehrlich’s theory had to be abandoned. In no way could the antibody-forming cells of the organism accommodate such a variety of possible antigens.0

To recapitulate, according to Ehrlich, when a “toxin” acts upon the organism, its “haptophore” combining group interacts w ith a “toxophile nutriceptor” on one of the cells of the organism, while its “toxophore” group exerts a toxic action. In tetanus, for instance, the process occurs at the level of the “nutriceptors” of brain cells: “There are present in the brain, i.e., in the ganglion cells, tetanophile protoplasmic groups, which unite themselves with the toxin. The presence of such groups is the necessary preliminary and cause of the poisonous action of the tetanus toxin in the living animal.”73

"On theories of antibody formation see below, pp. 427—431.

This in due course liberates “antitoxins” or “antibodies” into the bloodstream which promptly combine with the “haptophore” group on the toxin to neutralize it: “the groups must be adapted to each other, e.g., as male and female screw ... or as lock and key.”74

“Natural immunity” exists when “the organs essential to life are lacking in those haptophore groups which seize upon definite toxins.”75

In the 1890s Ehrlich replaced the appellation “side chains” by “receptive side chains” and in 1900 first used the wrord “receptor.”76

Experimental Chemotherapy

Having solved the toxin-antitoxin mystery, Ehrlich turned his questing mind to the problem of how chemical substances act curatively, employing the new approach which he called “experimental” or “specific chemotherapy.” 77 p

It involved inducing an artificial disease in a laboratory animal and finding a medicine which extinguished that disease; this was easiest to accomplish with microbial diseases, and Ehrlich had a fondness for trypanosomiasis w'hose microbes (the try-panosomes) were readily cultivated in the laboratory. But the method could also be employed in non-microbial conditions, treatment being directed at the diseased organ.78

Thus, in contrast to Hahnemann and Behring, for whom all substances were indifferently “poisons” or “medicines” in function of dose, Ehrlich established a special category of substances which are “poisons” and can be used to kill microbes; he employed many aniline dyes in this way, for their toxicity.79

In 1903 the widow of a German aniline-dye industrialist made the family residence available to Ehrlich, and thereafter the Georg-Speyer Haus in Frankfort-am-Main was the center of chemotherapeutic research. “Here we shall ... be concerned with the problem of curing organisms infected by certain para-

pEhrlich was also partial to “organotherapy” but did not theorize about it (J. Parascandola, “Theoretical Basis of Paul Ehrlich’s Chemotherapy,” 21).

sites in such a way that the parasites are exterminated within the living organism, so that the organism is disinfected ... by the use of substances which have had their origin in the chemist’s retort. Thus the task of the new institute will be a specific chemotherapy of infectious diseases.”80

Before 1906 he was reluctant to apply the side-chain theory to the action of drugs on the organism, because drug action can be transitory and because alkaloids, aromatic amines, aniline dyes, and other artificial substances introduced into the animal body can often be removed from the tissues with water, acetone, or some other solvent; indeed, aniline dyes could sometimes simply be shaken out of nerve or fatty tissue, which seemed to preclude the possibility of a “haptophore-nutriceptor” bond.81

Furthermore, since the capacity to produce antibody is “in inseparable connection with the presence of a haptophore atom group,” “alkaloids, antipyretics, antiseptics, etc.,” which do not possess haptophores, could not (in Ehrlich’s view) produce antibodies.82 While the drug-cell interaction may involve “chemical affinities in the widest meaning of the term,” drugs do not enter into a “chemical union” with the “protoplasmic molecule.”83 Cells bond only with foods (producing nutrition) and toxins (producing antibodies/antitoxins), not with pharmacological agents.84

Here Ehrlich relied on other paradigms from dyestuff technology: the formation of “lakes” or of “solid solutions,” neither of which involved a chemical combination between an atom gioup of the drug and an atom group of a cell receptor.”1

While toxins and foodstuffs are distributed through the body in function of their haptophores, and of the relations between these haptophores and the various organs, the distribution of pharmacologically active “specific” agents is through “the entire constitution of the substance.”86^ Such distribution is the “link between chemical constitution and pharmacodynamic action”: "In this we are dealing with a principle which has long been known and

^Here, as elsewhere, Ehrlich’s thinking was identical with Galen’s, who also held that medicines which could not be readily analyzed in terms of hot, cold, wet, and dry (i.e., those later known as “specifics”) operated by their “whole substance.” See Divided Legacy, I, 314—315.

which, I might say, is almost self-evident but which nevertheless is clearly expounded in only a few textbooks on therapeutics.”87 This last truth had dawned on Ehrlich in 1873 when, a dye-stained eighteen-year-old coloring histological preparations in Strasbourg, he came across Emil Heubel’s 1871 work on lead poisoning: Pathogenese und Symptome der chronischen Bleivergiftung.m

In order to elucidate the nature of this poisoning, the author had estimated quantitatively the lead content of the liver, the kidney, and the heart, and had discovered that there were remarkable differences in the amount of lead to be found in the various organs ... This experiment seemed to me, at that time, a revelation. The possibility emerged that this technique might be used to ascertain the sites of action of poisons.—Paul Ehrlich, 190689

Ehrlich called it the “storage axiom”: “This seems at once to be self-evident—to be, as I might express it, part of man’s inborn inheritance ... Conclusions such as this ... can be traced back into antiquity and have assumed importance in several of the bypaths of medicine. They appear quite clearly, for example, in the statement of a medieval physician who thought that drugs must possess spicules by the aid of which they are able to anchor themselves in the various organs.”90

He applied the new insight in his 1885 Habilitationsschrift, “The Requirement of the Organism for Oxygen.” Going beyond the mere staining of histological specimens on slides, Ehrlich developed “vital staining”—injecting dyes into the veins of animals and then killing them to ascertain which organs and tissues had been penetrated by the dye.91 Using dyes that oxidized at different rates he classified organs into three categories according to their avidity for oxygen and proved that different dyes had different patterns of distribution.92 “If a very small quantity of methylene blue is injected into a frog, and a small piece of the tongue is excised and examined, one sees the finest twigs of the nerves beautifully stained, a magnificent dark blue against a colorless background.”93

Rationalist doctrine assumes that the drug must be physically present at the part of the body where its effect is to be exerted (just as bacteria had to be physically present at the locus of the symptoms). Hence it seemed self-evident to Ehrlich that a knowledge of distributional patterns, i.e., of “selective affinities,” was indispensable for a scientific pharmacology. Failure to consider “questions concerning localization" made many newly synthesized drugs purely “symptomatic” and not causal.94

In 1891 he administered methylene blue to two malaria patients with “apparent success.”95 He reasoned that since methylene blue colors the nerves, it must be a “neurotropic substance” with an “affinity” for nerve tissue.96 And from there he leapt to the conclusion that “affinity” implied therapeutic action: “I was able, knowing its distribution in the body, to anticipate for it certain anti-neuralgic and anti-malarial properties which were both established by subsequent investigation. It may be permitted to me to call to mind that in malaria methylene blue is especially of service in the case of persons who, on account of susceptibility, cannot be treated with quinine, and that in the hands of Koch it has shown itself of eminent value in hemoglobinuric fever, since, as opposed to quinine, it exercises no destructive action on the erythrocytes.”97 To explain the differential distribution of drugs Ehrlich invented a new type of cellular side chain (eventually called “chemoreceptors”), in this way assimilating drug action to toxins and antitoxins: “I have now formed the opinion that some of the chemically defined substances are attached to the cell by atom groupings that are analogous to toxin-receptors; these atom groupings I will distinguish from the toxin-receptors by the name of chemoreceptors.”98

It was the “brilliant investigations by Langley on the effects of alkaloids which caused my doubts to disappear and made the existence of chemoreceptors seem possible to me.”99

He decided that microbes also possess chemoreceptors, enabling medicines to act upon them. This contact is mediated by the drug’s selective affinity, and Ehrlich resolved that “the whole field is governed by a simple, I might even say natural, principle”: “If the law is true in chemistry that corpora non agunt nisi liqui-da, then for chemotherapy the principle is true that corpora non agunt nisi fixata. When applied to the special case in point, this means that parasites are killed only by those substances for which

they have a certain affinity, by virtue of which they are fixed by the parasites. I call such substances parasitotropic.”100

Initially he maintained that the cellular chemoreceptor for drugs has a simpler structure than that for bacterial toxins; nor does it break off and enter the bloodstream as an antibody. He introduced the new concepts of “selective group” (of atoms) and “pharmacophore group”—as equivalents for “haptophore” and “toxophore.”101 But finally, in 1907, he equated drugs with toxins, resolving that a drug forms a true chemical bond with the cell of the organism or microorganism.102

The Doctrine of Contraries

Having announced a program of “specific chemotherapy,” Ehrlich had to make good on his promise—designing drugs to perform specific functions within the body. And this function was always to “block,” “oppose,” or “reverse” some physiological process or to “kill” or “neutralize” some supposed microbial disease cause.

The doctrine of “contraries” is the inescapable corollary of the Rationalist dream that the physician can fashion medicinal substances to carry out his will and desire; it is so instinctive as rarely to be subjected to criticism or analysis.

The content of “contrariety” had been enlarged by J. N. Langley in 1878 to include “antagonism” between drugs. Finding atropine and pilocarpine to be mutually “antagonistic” in their action on secretion of saliva by the submaxillary gland, he explained the phenomenon in Darwinian fashion as competition for a specific substance at the level of the submaxillary. 103r The doctrine that medicines “compete” “antagonistically” for a “site” on the wall of a cell of the host organism is the child of Darwinism and of Rationalist confidence that the action of medicines can be determined otherwise than by testing on healthy humans.

“Antagonism” or “contrariety” in its various forms remains to this day the guiding principle of Rationalist-allopathic medicine.

In bacterial diseases Ehrlich urged “extermination” of the parasites.104 Cure is achieved “by means of one or, at most, two injections [whereby] the body is freed from the parasites.” He advised the physician to: “frapperfort etfrapper vite.”% “It is obvious that the dose required must be the greater the more advanced the disease ... Therefore, it is necessary ... to bring therapeutic measures into action as early as possible.”105

The medicine acts on the microorganism directly, not via the vital force of the body:

The natural powers of the organism are in this case not called into requisition; but an artificial aid, to which they stood in no relation previously, is offered to them.

—Carl Fraenkel, 1891106

Since the medicine must make physical contact with the microbe, it must be distributed in the same pattern. While this rule might have exceptions, it is “safest and best for the development of chemotherapy [!!] not to build on the basis of exceptions, but to start with substances that destroy the parasites directly by uniting with them.”107

The proposed medicine must demonstrate antibacterial action in vitro:

One should first experiment with isolated parasites in pure culture ... [seeking] substances that prevent the growth of tuberculosis bacilli.—Robert Koch, 1890108

Then it is tested in animals and in humans “to determine whether observations made in the test tube also hold within living organisms.”109 But efficacy in vitro does not automatically equate with efficacy in vivo, as Koch had noted in 1890: “Some of the so-called animal dyes such as fuchsin, gentian violet, methyl blue, quinoline yellow, aniline yellow, auramine ... even diluted to one to two parts per million ... retard the growth of tuberculosis bacilli. Yet all of these substances remain entirely without effect when employed within tuberculous animals.”110

’“Strike hard and promptly!”

This theoretical gremlin would bedevil Rationalist pharmacology for generations to come.

Ehrlich had an unquenchable preference for drugs of broad application, “the principle of a therapia sterilisans magna.”ul He sought “disinfecting” substances which kill bacteria across the board: “Certain chemoreceptors are present in quite different kinds of parasites—not merely in one alone ... medicines which are made to fit them will kill a very large number of widely different pathogenetic agents.”112

Thus his arsenic-based anti-syphilis drug, Salvarsan (or “606”), was also prescribed in “quinine-resistant forms of malaria,” “blastomycosis,” “Aleppo boil,” “two cases of variola,” “anthrax,” “swine erysipelas in experimental animals and even occasionally in man,” and “lymphangiitis epizootica, the African glanders of horses”: “From these brief indications it will be evident that the agent, which was originally designed to act on spirochetes and trypanosomes, is able, according to the above findings, to register hits, as it were, on other important groups of diseases, which come within the expanding range of its effectiveness.”113 But this broad-spectrum approach was found to be causing “side effects.” “In human trials various side-effects have occurred, making it desirable to improve Atoxyl.' It was particularly obvious that with the use of larger doses, side-efYects—especially blindness [!!]—were not infrequent, and it was generally felt that new medicines in this series should be developed which would be more curative or less toxic.”114

Lord Horder of Ashcroft stated in 1933: “The arrival of '606' was heralded by the hope of a sterilisatio magna. But with the reluctant relinquishing of this ideal, and the resentment shown in many patients by certain organs, and especially the liver, to a mass attack, a less vigorous onslaught has been made ... the modern equivalents of the drug ... are much less toxic than was the original.”115

Diminished toxicity w^as sought by tailoring the drug molecule to, as it were, bypass the host while acting on the microbe,

‘A compound of arsenic and aniline, used in dermatology and sleeping-sickness. The trade-name Atoxyl, of course, suggested absence of toxicity!

to have “only a small affinity for the organs of the diseased body and maximal affinity for the receptors of the parasites.”116

Parasites possess a whole series of chemoreceptors which differ specifically from each other. Now, if we were to succeed in discovering among these a receptor which was not represented in the organs of the host, we would have the possibility of constructing an ideal medicament by selecting a haptophore group which fits exclusively this particular receptor of the parasites. A medicine provided with such a haptophore group would be entirely innocuous, because it is not anchored by the organs; it would, however, strike the parasite with full force and, in this sense, correspond to the immune-substances, the antibodies discovered by Behring which, in the manner of magic bullets, seek out the enemy. Let us hope that it will also be possible, chemotherapeutically, to score bull’s-eyes in this way. I do not consider this at all improbable.—Paul Ehrlich, 1913117

In this way Ehrlich advanced the idea of the “therapeutic ratio” (later called “risk-benefit ratio”) which has ever since remained a mainstay of allopathic pharmacology.118 In trypanosomiasis, for example, the drug’s “trypanotropic” force must exceed its “organotropic” force.119 “Only substances with a favorable ratio of organotropism to parasitotropism w ill act as therapeutic agents, and this ratio is easily ascertained experimentally by comparing the dosis toxica with the dosis tolerata.”120

He hoped his chemotherapeutic drugs would approach the precision of the specific antibodies which, “like magic bullets” (dauberhuge In), were exclusively “parasitotropic” and not “organotropic” at all: “We must learn to aim, through chemical modifications.”121

Koch found that “bacteristatic” drugs could be as useful as the “bactericidal” ones. In tuberculosis “it would be sufficient to retard development; it is not necessary, as is often assumed, actually to destroy the bacteria in the body. To make them harmless, it is sufficient to prevent their growth or reproduction.”122

Diseases not of bacterial origin were treated according to the same principles:

That chemical substances are only able to exercise an action on the tissue elements with which they are able to establish an intimate chemical relationship is a conception of a general nature which has been entertained since the birth of scientific medicine. Paul Ehrlich, 1900123

It is “astonishing, almost astounding,” states Ehrlich, that this principle “should have played in the building up and furtherance of scientific pharmacology a role so insignificant in proportion to its great importance”:

In glancing through the modern textbooks of pharmacology, with rare exceptions ... one finds absolutely no mention of the distribution of drugs in the organism, a matter which is of so much moment for arriving at a true comprehension of the relations existing between pharmacological action, location in the organism, and chemical constitution.

Paul Ehrlich, 1900 124

A drug can sometimes be brought into physical contact with the target organ by combining it with another drug possessing an affinity for that organ: “Having found such substances, one could then use them, so to speak, as a vehicle with which to bring therapeutically active groups to the organ in question.”125

The idea that the drug acts on the “whole body” via the nervous system, affecting every organ and part, was to Ehrlich merely old-fashioned vitalism.11

Drug Resistance

A puzzling feature of anti-bacterial therapy which emerged in Ehrlich’s time and still plagues pharmacology today is the appearance of “resistant strains” or “relapse strains.” Try-panosome-infected animals were seemingly cured, only to have

“However, in the end of his life he recognized that some medicines act via the nervous system (Paul Ehrlich, Collected Papers, I, 598; II, 183).

the microbes reappear with modified drug receptors which rendered them invulnerable.126 Doses were steadily increased but eventually proved ineffective.127 And when the given strain of try-panosome was injected into another animal, it remained drug-resistant: “One is forced, therefore, to make an all-out effort to destroy at the very beginning every single parasite by means of chemicals, as a single surviving germ, owing to the great power of adaptation, may cause the infection to break out afresh.”128 The w'ay to handle this problem is through “combination therapy”—“with therapeutic agents of which each attacks an entirely different chemoreceptor on the parasite ... in accordance with the military maxim, march in detachments, fight as a unit. For all these reasons, I think that, in the future, combination therapy will capture an ever-increasing field.”129

Drug resistance appeared to reside in the microbe, not in the host organism, and Ehrlich resolved that the microbe’s chemoreceptor for that particular drug was impaired. This suggested that the microbial cell actually combined with the drug.130 Even so, he could not explain drug resistance coherently: “The phenomena observed in experiments with drug-resistant strains can be readily explained by the fact that the chemoreceptors, under the influence of drug resistance [??], suffer an impairment of their affinity, which should be regarded as purely chemical ...[??]”'51 Ehrlich cannot really be faulted, however, as pharmacologists ninety years later were still seeking a theoretical explanation of drug resistance.v

Specific vs. General in Ehrlich’s Thought

Ehrlich reinterpreted the doctrinal categories, “general" and “specific” (or “peculiar”). Medicine had traditionally distinguished the symptoms “common” to many different patients from those “peculiar” to a particular patient, not found in others. Ehrlich nullified this distinction in proclaiming that side chains performing the “common” functions of nutrition are (by coinci-

dence!) available as points of attachment for “specific” pharmaceutical substances.132

This formulation violated logic and ran counter to 2000 years of tradition. For if the side chains discharging the commonplace functions of nutrition serve also as points of attachment for “specific” drugs, the whole concept of “specificity” loses its meaning.

Drugs were traditionally designated “specific” when medical (Rationalist) science could not understand how their effects were produced. When the modus operandi was known (or thought to be known), the drug was no longer viewed as a “specific.” But with Ehrlich the “specific” drug is man-made and designed for a particular application, hence known in all of its ramifications.

His immunological theory is marked by the same disregard for logic, as he wants the “specific” tetanus and diphtheria antitoxins to be generated by the same “nutriceptors which perform the ordinary everyday drudgery of feeding the cell and supplying it with oxygen.”,33'w

The influence of Virchow’s assimilation of pathology to physiology pervades all of Ehrlich’s thought: “The complete and exhaustive knowledge of all the different chemoreceptors of a certain parasite I should like to designate as the therapeutic physiology of the parasite c^//.”134 As stated by a contemporary authority, “In effect, a toxin acts as a poisonous foodstuff, and, consequently, the study of immunity becomes a department of general physiology.”135

Ehrlich as Scientist

Ehrlich’s scheme of a series of “specific” medicines, each tailor-made for a specific “disease,” has proven impossible to implement. While the molecular structure of a medicine may well determine its impact on the organism, the nature of this relationship has yet to be discovered, and the effect of a change in mole-

wBut he does make the intriguing suggestion that immunity in some cases might result from the administration of particular foodstuffs (Paul Ehrlich, Collected Works, II, 189).

cular structure on the medicine’s physiological or therapeutic action cannot be predicted/ Drugs cannot be “designed” with the precision Ehrlich anticipated.

Although Ehrlich thought he was reestablishing medicine as a science, his thinking is really a study in the power of unexamined assumptions. And his formulations were not really new. What passed for a pioneering contribution to medical thought was only garden-variety Rationalism decked out in late nineteenth-century language. Ehrlich updated and refurbished seventeenth-century iatrochemistry, reformulating it in the vocabulary and concepts of the dyestuff industry. Thenceforth the relationship between remedy and patient was patterned on that between dyes and the materials they color.

Ehrlich is a clinical case of Rationalism’s impulse to explicate therapeutic problems using paradigms developed in other areas of human thought and endeavor.

His system, therefore, suffered from the theoretical confusion intrinsic to medical Rationalism. His “explanations” of the operations of medicines, toxins, antitoxins, and the like in the body cannot be presented coherently. When confronted with a new problem, he simply posited the existence of new haptophores, often with exclamations of amazement at the “wonderful multiplicity of organic matter.”136 Svante Arrhenius (1859-1927), the Swedish physical chemist, stated that “nearly every new phenomenon led Ehrlich and his school to invoke the presence of a new substance.”137 F. W. Andrewes (1923) charged that Ehrlich “loaded the new science of immunology with a burden of names under which it staggers to this day.”138 Lewis P. Rubin (1980) mentions his “veritable zoo of pro to toxoids, syntoxoids, epitox-oids, toxins, etc.,” which “tangled his theory in Gordian complexity.”139

As early as the turn of the century the Austrian Max Gruber described the haptophores and toxophores as a “ Weichselzopf of hypotheses” and a “harmless amusement.”> He called Ehrlich’s

xSee below, pp. 508-515.

yThe term, Weichselzopf, literally “Vistula Braid,” referred to the Polish peasants’ habit of allowing their unclean and unkempt hair to become so matted that it could not be combed or even washed.

Ehrlich arid Koch 133

doctrines an “attempt to substitute a structure of thought for the missing facts,” but flexible enough to be applied to every conceivable new phenomenon.140

A good example was Ehrlich’s paper, “The Evaluation of Diphtheria Antitoxin and its Theoretical Foundations,” generally thought to have given his career the impetus that led ten years later to the Nobel Prize. Although described by William Bulloch (Ehrlich’s close personal friend) as “a classic in the bacteriological literature,” Claude Dolman (1968) calls it “famous but largely incomprehensible,” while Lewis P. Rubin (1980) charges it with being “as unfortunate for its lack of coherent development as for its cumbersome prose.”141

When Carl Weigert confessed his inability to grasp the argument presented in this paper, Ehrlich responded that the last section is “most difficult to understand” because he was in a terrible rush and “could not find the necessary time for the finishing touches.”142

Theoretical contradictions and inconsistencies abound throughout Ehrlich’s writings, papered over by gratuitous assumptions. His arbitrary ascription of “affinities,” “toxophile” tendencies, etc., to cells of the organism as well as to medicines and immunologic products, greatly resembles the virtus dormitiva of Moliere’s degraded Galenism and was generated by the same Rationalist need to reify the elements of therapeutic theory and method; indeed, it has remained a permanent feature of Rationalist pharmacological speculation.2

While this systematic fantasy provided post facto explanations for almost anything that occurred in pharmacotherapy and immunology, it lacked predictive value and, as science, was worthless.

Ehrlich as Vitalist

Ehrlich hoped to banish the organism’s vitality from medical thought altogether, subordinating it to physics and chemistry, but he unconsciously accepted vitalism at the key point in the argument, the overproduction of side chains in response to a morbific stimulus.

Wlien scrutinized more closely, this doctrinal element is seen to be a reincarnation of the organism’s reactivity. Where traditional vitalism associated reactivity with the whole organism, Ehrlich reduced it to the cellular level. But the supposed tendency of cells to regenerate side-chains and to produce them in excess, so that the reaction is greater than the initial stimulus, cannot be explained chemically, as Ehrlich wanted to do, only biologically or vitalistically. It is reinforced by the evident fact that immunity is often long-lasting:

By the act of immunization, certain cells of the organism become converted into cells secreting antitoxin at the same rate as this is excreted. New quantities of antitoxin are constantly produced, and so throughout a long period the antitoxin content of the serum remains nearly constant.

-Paul Ehrlich, 1900143

The source of this theory, Carl Weigert’s doctrine that loss of tissue through trauma or disease leads to overrepair and overgrowth, had been bitterly contested by Virchow on this very ground because it was an implicit recognition of the organism’s reactivity and vitality. Virchow himself insisted that cell growth occurs only as a result of direct stimulus.144

Despite his most strenuous exertions, therefore, Ehrlich was forced to admit surreptitiously the same vitalism which he otherwise anathematized. This confusion contributes heavily to his doctrine’s overall theoretical incoherence.

Reception of Ehrlichism

Ehrlich’s professional colleagues and equals were highly critical of his theories, especially in France:

By the abuse that [the Ehrlich theory] has made of quite puerile graphical representations which merely translate the exterior aspect of the phenomena without in any way penetrating to their inner meaning, it has extended the deceptive use of explanations that are facile but illusory.—Jules Bordet, 1920l43aa

uLes Allemands et la Science, an anti-German tract published in Paris during World War I, selected Ehrlich as the main object of derision (Lewis P. Rubin, “Styles in Scientific Explanation,” 422).

The leader of British pharmacology, Henry Dale, was equally scathing: “It is impossible to feel confidence as to the general and permanent validity of Ehrlich’s method of interpreting the facts ... It is hardly likely that it will retain permanent status as an exact scientific theory ... Few of the successful results hitherto obtained have been obtained by a consistent application of the theory. Some of them seem, indeed, to be the result of experiments which a serious acceptance of the theory would have discouraged ... It is difficult to resist the conclusion that a new theoretical foundation is required for further orderly building, and that this wall have to take fuller account of the great complexity of the therapeutic process, and especially of the cooperation therein of the infected host [emphasis added].”146

Dale called the side-chain theory “diagrammatic in its simplicity” and pointed to a number of logical and methodical fallacies. When a toxic drug is given to an infected animal, its effect on the tissues should be lessened by diversion of its action to the infecting bacteria; the effects on a healthy animal, by the same token, should be greater, since its action is not deflected to the bacteria. However, the opposite is true, as the infected animal is much more sensitive to the drug.bb Dale also notes that the failure of drugs to act in vivo the way they do in vitro is “not by itself consistent with the simple conception that its curative action is due to chemical affinity for the parasite.”147 “When a certain substance is found to cause the disappearance of, say, a particular species of trypanosome from the blood of an infected mouse, without harming the mouse, and fails to remove a similar infection from the rat ... these observations are taken to indicate that the ratio of its parasitotropic to its organotropic properties is more favorable in the mouse than in the rat. Essentially, however, this is a mere restatement of the observed fact that the mouse can be cured but the rat cannot. The supposition that the result is determined by the distribution of the substance between the cells of the host and the parasites is not based on independent evidence.”148

F. Macfarlane Burnet remarked in 1976: “In the light of our present knowledge, the Ehrlich hypothesis is meaningless and

bbSee below, pp. 485-486, for discussion of hypersensitivity of the diseased organism.

cannot be regarded as the prototype of modern selection theories.”149 But in German-speaking Europe Ehrlichism was triumphant:

Ludwig Aschoff wrote an immensely popular exposition of the theory in 1905, and Ehrlich’s Frankfurt institute turned out scores of workers versed in its Byzantine complexities. Testimonials such as August Wasserman’s claim that he drew inspiration for his diagnostic test for syphilis from the side-chain theory no doubt enhanced its standing. Prior to the First World War the theory and its peculiar terminology were entrenched as medical orthodoxy, as a paradigm, if you will, especially in Central and Eastern Europe. Its defense became something of a cottage industry, and in German-speaking lands, at least, to challenge its foundations could endanger one’s career. Outside the German Sprachgebiet, however, Ehrlich’s detractors were numerous.—Lewis P. Rubin, 1980150

Even more important, since American allopathy was heavily influenced by German in these decades, Ehrlich’s influence was felt especially across the Atlantic.

The Ehrlich theory was promptly endorsed by the medical profession as a whole. For three decades it has had a prominent place in elementary text-books in bacteriology and clinical pathology and has been the generally accepted basis for immunological deduction and clinical interpretation.

—W. H. Man waring, 1927151cc

Psychological and Socioeconomic Factors

Ehrlich was an intellectual primitive with a few strongly held views dating from his student years—specifically, that the action of medicines in the body could be explicated in terms of dyestufl theory.

"Manwaring himself declared: “I believe there is hardly an element of truth in a single one of the dozen or more basic hypotheses incorporated in this theory” and noted “the almost universal failure of therapeutic methods based on these concepts” (W. H. Manwaring, “The Enzyme Theory of Antibody Formation,” 366).

His appeal like that of the Galenism on which his thought was patterned is not to be sought in the scientific force of his doctrine but in the psychological and economic boost he gave the practicing physician, for whom this theory explained the phenomena and thereby provided verbal justifications for therapeutic procedures.

The contrast with the Empirical tradition is instructive. These physicians, specifically Paracelsus and Hahnemann, urged the physician to learn what the medicine is capable of doing and then use it in this way. The physician must use medicines as they want to be used, not as he wants to use them. Francis Bacon formulated the same idea in his apothegm: “Nature is subdued by submission.”dd

Hence the Empirical tradition subordinates the physician to the remedy. Ehrlich did the opposite: proposing medicines devised for specific purposes, he elevated the physician above the remedy, appealing to the former’s vanity and urge to power.

The Rationalist physician needs the assurance that he understands internal pathophysiological processes and also the “mechanism of action” of his medicines. The very diagrams criticized by Jules Bordet—“male” and “female” connections like pipe joints of different sizes and shapes which fitted nicely into one another—made this doctrine irresistible to primitive minds.

Ehrlich had an overweening self-confidence which impelled him to demolish whatever stood in the way of his new formulations. His writings are dotted with statements of the type: “I am convinced,” “seems at once to be self-evident,” “I have now formed the opinion,” etc. He was willing to admit the existence of physiological mysteries as an abstract proposition: “Our actual knowledge concerning the relation between constitution and action is still in its very infancy. Hence the expectation to be able to construct new drugs of predetermined action on the basis of theoretical conceptions will probably have to be deferred for a long time.”152 But this did not bar him from attempting to implement his utopian vision. After stating: “All this endless study has

brought forth is the conviction that we are dealing with atomic groups of the utmost complexity, w hich for the present are beyond our chemical abilities and which, so far as we can see, will long remain so,” he promptly announced his “conviction” that medicinal substances “exert their power by purely chemical means.”153

But, if the phenomena are so complex as to be “beyond our chemical abilities” for the foreseeable future, he did not have the right to conviction that they are ultimately explicable in chemical terms.

The economic and industrial dimensions of the side-chain theory should also be borne in mind. Ehrlich’s far-fetched notion that dyestufTs possess valuable medicinal properties because they form chemical bonds with human tissue and with bacteria hugely benefited the emerging German coal-tar, aniline-dye, and pharmaceutical industries, specifically the firms I. G. Farben and Hoechst.

Until the 1850s coal-tar had been an unwelcome and almost unusable by-product of the processing of natural gas for illuminating and other purposes. Aniline was isolated in 1843 by August Wilhelm Hofmann, leading to research on the amines. In 1856 William Henry Perkin, a British student of Hofmann, discovered that some oxidizing agents act on crude aniline oil and convert it into a dye; he went on to found the British coal-tar industry. The azo-dyes were discovered by Peter Griess, another associate of Hofmann, and after this the German coal-tar industry branched out into perfumes, explosives, and last but not least, medicines.

While Ehrlich cannot be accused of fabricating his theories for commercial reasons, their reception by physicians went pan passu with the expansion of the German drug industry.154

He would hardly be worth criticizing if not for the fact that today, while his vocabulary is quaint, his categories of thought and analysis remain unchanged. Such concepts as drug “distribution” within the organism, the need for “physical contact” with the diseased organ or tissue, the “therapeutic-toxic” or “risk-ben-efit” ratio, the use of large doses of combined drugs to prevent drug “resistance,” and the failure to recognize the body’s reactivity and its effect on pharmacotherapy remain integral parts of Rationalist pharmacological theory and practice.155,ee

And twentieth-century immunology has followed Ehrlich’s lead in inventing (“discovering”) new protein substances in the blood and fluids—globulins of various kinds, T-cells, and the like—to “explain” every new immunological phenomenon.

Another feature which late twentieth-century Rationalism will immediately recognize in Ehrlich is confidence that errors of theory and practice will be corrected by future research:

Even if in the immediate future no great practical success is attained, we must remember that we are only at the very beginning of a rational investigation of the properties of cells, which hitherto have been far too lightly regarded.

Paul Ehrlich, 1900156

Unfortunately, patients are treated in the here and now and are not benefited by future research. Generations of physicians and pharmacologists have been stimulated by Ehrlich to push ahead with an unachievable program and have disregarded or rejected much existing and serviceable pharmacological knowledge in the process.

While nineteenth-century bacteriological doctrine seemed so revolutionary as to demand an overhaul of therapeutics, and Ehrlich can hardly be blamed for responding to this challenge, another might have done it with more insight, subtlety, and sophistication, and thereby with less damage to the patients (one thinks of those blinded by Salvarsan) who always pay the price of therapeutic “revolutions.”

NOTES

1.    John Parascandola, 1981, 22-23; M. P. Earles, 1961 and 1972.

2.    See for example H. C. Wood, 1894, passim: R. Bartholow, 1900, passim.

3.    H. C. Wood, 1894, ix.

4.    John Parascandola, 1971, 3.

5.    Ibid., 4.

6.    Ibid., 5, 8.

7.    Ibid., 5.

8.    Ibid., 8.

9.    Ibid.

10.    Ibid., 8-9.

11.    Ibid., 9.

12.    Ibid.

13.    Wilhelm Ameke, 1885, 395.

14.    R. Bartholow, 1900, 397 400; H. A. Hare, 1918, 134.

15.    John Parascandola, 1971, 9.

16.    A. G. Gilman et at., 1980, 701; Wilhelm Ameke, 1885, 395.

17.    A. G. Gilman et al., 1980, 701.

18.    Ibid.

19.    Wilhelm Ameke, 1885,414.

20.    Ibid., 416.

21.    Ibid.

22.    Ibid., 417.

23.    Ibid., 416.

24.    Knud Faber, 1922, 20.

25.    Ibid., 21.

26.    Wilhelm Ameke, 1885, 426; Emil Behring, 1915, 4.

27.    Paul Ehrlich, 1956-1960, III, 150-151.

28.    Ibid., I, 599, 602; III, 150-151.

29.    Ibid., Ill, 150.

30.    Ibid., Ill, 150.

31.    John Parascandola, 1981, 21.

32.    Paul Ehrlich, 1956-1960, III, 151.

33.    Ibid., II, 114, 184-185.

34.    Ibid., Ill, 151.

35.    Ibid., Ill, 183.

36.    Ibid., I, 436.

37.    Ibid., I, 436; II, 185.

38.    Ibid., I, 435.

39.    Ibid.. I, 436, 438, 495.

40.    Ibid., I, 436.

41.    Ibid., II, 185.

42.    Ibid., Ill, 185.

43.    Thomas S. Hall, 1969, II, 266; Justus Liebig, 1964, 32.

44.    Justus Liebig, 1964, 185.

45.    Ibid., 7.

46.    Ibid., 186, 188.

47.    T. S. Work, 1954, 100.

48.    Paul Ehrlich, 1956-1960, III, 184.

49.    Ibid., II, 114.

50.    Ibid.

51.    Ibid., II, 115. Also, III, 185.

52.    Ibid., II, 186.

53.    Ibid., II, 115; III, 185.

54.    Ibid., II, 114, 115, 187, 189; III, 185, 187.

55.    Ibid., II, 115; Ernest Witebsky, 1954, 169.

56.

Paul

Ehrlich, 1956—

1960, II, 189.

57.

Ibid.,

II, 188.

58.

Ibid.,

II, 185.

59.

Ibid.,

I, 596.

60.

Ibid.,

I, 596; II, 113

-114, 180, 183; III, 184.

61.

Ibid.,

II, 114.

62.

Ibid.,

II, 181.

63.

Ibid.

64.

Ibid.,

II, 185.

65.

Ib,d..

II, 181.

66.

Ibid.,

II, 181, 188; L

,ewis P. Rubin, 1980, 404.

67.

Paul

Ehrlich, 1956

1960, II, 188.

68.

Ibid.

69.

John

Parascandola,

1974, 201.

70.

Paul

Ehrlich, 1956

1960, I, 482-485.

71.

Ibid.,

II, 114; III, 186; T. S. Work, 1954, 110-112.

72.

Paul

Ehrlich, 1956—

1960, II. 184-185; III, 185.

73.

Ibid.,

II, 186.

74.

Ibid.,

II, 184-185.

75.

Ibid.,

II, 186.

76.

Ibid.,

II, 115; III, 184; John Parascandola, 1981, note 29.

77.

Paul

Ehrlich, 1956

1960, III, 60;John Parascandola, 1981, 20

78.

Paul

Ehrlich, 1956

1960, III, 151.

79.

Ibid.,

III, 151, 153.

80.

Ibid.,

Ill, 60.

81.

Ibid.,

II, 184.

82.

Ibid.,

II, 187-188.

83.

Ibid.,

I, 608, 614-616.

84.

Ibid.,

II, 184-185.

85.

Ibid.,

II, 184.

86.

Ibid.,

I, 618.

87.

Ibid.,

, I, 602.

88.

Emil

1 Heubel, 1871.

89.

Paul

Ehrlich, 1956-

1960, III, 54.

90.

Ibid.,

, III, 54.

91.

Ibid.

. Ill, 55.

92.

Ibid.

, HI, 57.

93.

Ibid.

. Ill, 55.

94.    Ibid., I, 599, 602.

95.    Claude E. Dolman, 1972, 296.

96.    John Parascandola, 1981, 8; Paul Ehrlich, 1956-1960, I, 555 558.

97.    Paul Ehrlich, 1956-1960, II, 182.

98.    Ibid., Ill, 132, 509.

99.    Ibid., Ill, 507.

100.    Ibid., Ill, 505-506.

101.    Ibid., Ill, 54-58.

102.    Ibid., I, 596.

103.    John Parascandola, 1974, 200.

104.    Paul Ehrlich, 1956-1960, III, 60.

105.    Ibid., Ill, 512.

106.    Carl Fraenkel, 1891, 148.

107.    Paul Ehrlich, 1956-1960,506.

108.    Robert Koch, 1987, 185-186.

109.    Ibid.

110.    Ibid.

111.    Paul Ehrlich, 1956-1960, III, 308, 512.

112.    Ibid., Ill, 507.

113.    Ibid., Ill, 308. Also, III, 516, 517.

114.    Ibid., Ill, 153.

115.    Lord Horder of Ashcroft, 1933, 267. See also Patricia Spain Ward, 1981.

116.    Paul Ehrlich, 1956-1960, III, 510.

117.    Ibid., Ill, 510.

118.    Joseph D. Cooper, ed., 1971a, 45.

119.    Paul Ehrlich, 1956-1960,111, 121.

120.    Ibid., Ill, 509.

121.    Ibid., Ill, 141.

122.    Robert Koch, 1987, 186.

123.    Paul Ehrlich, 1956-1960, II, 182.

124.    Ibid.

125.    Ibid., I, 618.

126.    Ibid., Ill, 513.

127.    Ibid., Ill, 81-93; T. S. Work, 1954, 107.

128.    Paul Ehrlich, 1956-1960, III, 513.

129.    Ibid., Ill, 514-515.

130.    Ibid., Ill, 507-508.

131.    Ibid., Ill, 507.

132.    Ibid., II, 185.

133.    Ibid., Ill, 187.

134.    Ibid., Ill, 507.

135.    Lewis P. Rubin, 1980, 406.

136.    Ibid., 1980, 417; Paul Ehrlich, 1956-1960, II, 192-194.

137.    Lewis P. Rubin, 1980, 414.

138.    F. W. Andrewes, 1923, 128.

139.    Lewis P. Rubin, 1980, 415.

140.    Max Gruber, 1901, 1884.

141.    William Bulloch, 1938, 262; Claude Dolman, 1968, 70; Lewis P. Rubin, 1980, 404.

142.    Claude Dolman, 1968, 72.

143.    Paul Ehrlich, 1956-1960,11, 187.

144.    E. R. Long, 1965, 135.

145.    Arthur M. Silverstein, 1982, 403.

146.    H. H. Dale, 1923, 390.

147.    Ibid., 361.

148.    Ibid., 360.

149.    F. M. Burnet, 1976, 17.

150.    Lewis P. Rubin, 1980, 422.

151.    YV. H. Manwaring, 1927, 366.

152.    Paul Ehrlich, 1956-1960, I, 599.

153.    Ibid., I, 596.

154.    T. S. Work, 1954, 105; Claude Dolman, 1972, 299-300.

155.    T. S. Work, 1954, 107.

156.    Paul Ehrlich, 1956-1960, II, 195.

HOST RESISTANCE AND IMMUNITY

The emerging doctrine of immunity added structure and substance to the ill-defined concept of “host resistance.” And, as was to be expected, the Empirics and Rationalists interpreted the findings differently, according to their differing assumptions about “disease,” “cause,” and “cure.”

I he physician’s regard for host resistance is the reciprocal of his view of the disease “cause.” Rationalism exaggerated the potency of bacterial causes and underrated host resistance, while the Empirics, whose therapeutics aimed to enhance host resistance, were less impressed by bacterial causes.

Since twentieth-century medicine has been dominated by Rationalism, little systematic attention has been given to factors and mechanisms of host resistance.

Empiricism and Host Resistance: Pasteur

Pasteur’s early studies on fermentation revealed to him that each enzyme (ferment) needs its specific milieu.1 He found also that silkworms inherit a predisposition to the silkworm disease, a “terrain.”2 Thus he was from an early stage attuned to the significance of the milieu. And his discovery, at age sixty, that the microbial cause could be “attenuated” was further proof that disease is a dynamic interplay between causal organism and host resistance. As his biographer, Emile Duclaux, wrote in 1896: “He could henceforth take up again his old idea of conflict, no longer

that brutal strife where the only possible means of intervention consisted in the suppression of one of the adversaries, but a gentle strife which one might attempt to direct by augmenting or diminishing the forces of one of the contestants.”3

In the beginning we ascribed variations in virulence to the microbe ... we have been obliged to add to it those which come from the variation of the living organisms in which the microbes establish themselves, and the virulence which we see results from an infinite number of combinations of these two causes of variation. Emile Duclaux, 18964

Here Pasteur was merely returning to an instinctive vitalism which, indeed, was a part of his profound Catholicism. In 1862, before ever embarking on medical research, he disclosed these leanings in a letter to the Minister of Education: “If God had not so designed things that the organic laws which preside over the changes of tissues and liquids in the bodies of animals constituted an obstacle to [microbial] propagation, at least in conditions of normal life and health, we would be exposed at every moment to being invaded by them. But as soon as the breath of life is extinguished, there is no part of the vegetable or animal organism which does not serve them as food.”5

Later in life Pasteur found support for this idea in the Darwinian “struggle for existence” (the Origin of Species was translated into French in 1862).6

While giving biochemical mechanisms their due, he subordinated them to the organism’s v itality and the concept of “struggle.” He seemed at times to be reclaiming for vitalist biology territory which had already fallen under the sway of bio-chemistry.-*

Oxygenation of the blood, for example, is an important factor of resistance. Birds are refractory to anthrax because “the

a“Thus the development of biological science [under Pasteur] can hardly be seen as a progressive reduction of more and more biological phenomena to physical and chemical theories. Pasteur helped to convert important branches of the study of nature from physico-chemical into biological disciplines.... It is hard to see why the situation need be fundamentally different today. In other words, there seems to be no reason to rule out the possibility of an actual reversal of the physical reductionist programme in biology” (Nils Roll-Hansen, “Louis Pasteur,” 361).

living blood in full circulation is filled with an infinite number of corpuscles which, in order to live and perform their physiological function, need free oxygen ... When, therefore, the anthrax bac-teridium enters normal blood, it meets there an enormous number of organic individualities ready, figuratively speaking, for what one sometimes calls the struggle for existence, ready, in other w'ords, to seize for their own use the oxygen necessary for the existence of the bacteridium.”7

Where Koch ascribed resistance to anthrax to a high level of alkalinity in the blood, Pasteur saw a struggle with the red corpuscles. They are strong when well oxygenated, and the blood is well oxygenated when supported by the organism’s vitality:

The microbes ... disappear—vanquished by what I called a while back life’s vital resistance, Natura medicatrix ... It is particularly interesting to observe the ease with which nature, taking the upper hand, gets rid of the purulent centers of infection that sometimes profusely involve the entire lobe of the liver.—Louis Pasteur, 18788

What a startling ... demonstration of vital resistance ... it demonstrates the potential of living matter to combat the so often disastrous consequences of surgical wounds. I he water, the sponge, the lint with which you wash or cover a wound deposits germs that ... propagate in the tissues with extreme facility and infallibly would bring death to the operated patient in a short time if life in these limbs would not be opposing the multiplication of these germs. But alas! How often is this vital resistance powerless, due to the constitution of the wounded [man]—his weakened condition, or mental state.—Louis Pasteur, 18789

Pasteur’s famous experiment inducing anthrax in chickens, whose high temperature ordinarily kills these bacilli, by attaching their feet to a board immersed in cold water and thus lowering their temperature, was another demonstration of the importance of the terrain for the multiplication of germs in the organism.10

From the outset, therefore, he gave full credit to the concept of the “terrain,” the inherent predisposition or resistance of the host organism. After his death the fabrication was circulated by a contemporary novelist that in his last hours Pasteur stated: “I was wrong. The microbe counts for nothing, the terrain is everything,” or words to that effect. This still has currency, sometimes taking the form, “Claude Bernard was right ...” or even “Antoine Bechamp was right ..But Pasteur never underestimated the significance of the terrain and had no need to admit any such error.

Vaccination was for Pasteur a means of enhancing host resistance, although its precise mechanism remained a mystery to him:

On what depends that immunity which vaccinated animals possess, which is also possessed by animals naturally resistant to certain diseases fatal to other species? ... Here were questions which, yesterday premature and audacious, could now be stated and become the object of experimental study. In a word, it was not alone the mechanism of the disease which ought to be the subject matter for experiment, but also the mechanism of health, that is to say, the entire physiology of the living creature.—Emile Duclaux, 189612

This vitalist aspect of Pasteur’s thought has been overshadowed by his technical virtuosity in laboratory science and his work with microbial causes. It has been neglected by generations of commentators and historians; even Rene Dubos underestimated the vitalist side of his hero: “By the skillful selection of their experimental models, Pasteur and Koch could eliminate from their studies the factors other than the parasite which are necessary to demonstrate that infection can result in symptoms and pathological alterations ... Useful as this artificial system has been for the study of some of the properties of microparasites, it has led to the neglect, and indeed has often delayed recognition of the many other factors which are essential to the causation of disease under circumstances prevailing in the natural world— namely the physiological characteristics of the host and the physico-chemical as well as social environment.”13

Initially Pasteur favored the “depletion theory” of immunity: the bacterial infestation depletes the body of specific nutrititive

substances, preventing the microbe from getting a second foothold.14 But this could not explain the duration of immunity. New chemical substances are added to the blood every day, while immunity can last a lifetime. Hence he sought a “cellular” theory of immunity and welcomed phagocytosis when proposed by Metchnikoff:

A chemical action, whatever it may be, cannot be lasting in an organism in which all the chemical elements are constantly being renewed. There is only the cell which lasts, because it lives.—Emile Duclaux, 189615

Metchnikoff and Phagocytosis

The Russian bacteriologist’s oft-quoted description of this discovery is still compelling:

One day, as the whole family was at the circus to see some trained apes, I remained home along with my microscope and was observing the activity of the motile cells of a transparent starfish larva, when a new thought suddenly dawned on me.

It occurred to me that similar cells must function to protect the organism against harmful intruders____

I thought that if my guess was correct, a splinter introduced into the larva of a starfish should soon be surrounded by motile cells much as can be observed in a man with a splinter in his finger. No sooner said than done.

In the small garden of our home ... I took several rose thorns that I immediately introduced under the skin of some beautiful starfish larva which were as transparent as water.

Very nervous, I did not sleep during the night, as I was waiting for the results of my experiment. The next morning, very early, I found with joy that it had been most successful.

This experiment was the basis of the phagocytic theory, to w hich I devoted the next twenty-five years of my life.

—Elie Metchnikoff, 192116

Phagocytosis had been observed by others in the 1860s and 1870s: Koch’s 1878 treatise on wound infection had called attention to bacteria within white blood cells.17 But the transport of virulent microbes by phagocytes was interpreted by Rationalist thinkers either as a waste-removal process or as a technique for spreading infection, in accordance with their doctrine of the non-reactive host organism.18

Metchnikoff came to the opposite, Empirical, conclusion that phagocytosis is a vitally determined defensive and curative reaction. The migrating cells, baptised “phagocytes” (Greek for “cell-eaters,” Fresszellen), he postulated to be guardians of health against bacterial invasion.

In 1887, on vacation in Paris, he paid Pasteur a visit: “On arriving at the laboratory ... I saw an old man, rather undersized, with a left hemiplegia, very piercing grey eyes, a short beard and moustache, and slightly grey hair covered by a black skullcap. His pale and sickly complexion and tired look betokened a man who was not likely to live many years. He received me very kindly and immediately spoke to me of the body’s power of resistance to microbes, a topic which interested me greatly. Although my young colleagues are still very sceptical about your theories,’ he told me, ‘I at once placed myself on your side, for I have for many years been struck by the struggle for life among the divers microorganisms which I have had occasion to observe. I believe you are on the right track.’”19

Pasteur took him into the Institute and published a commendatory notice of his work in the first issue of the Annales.20 Metchnikoff remained there for twenty-eight years.

Pasteur saw phagocytosis as remedying the defects of his own pathology and therapeutics, carrying them forward along Empirical and Hippocratic lines to their logical conclusion. Indeed, the German zoologist Nicolaus Kleinenberg called phagocytosis a "Hippocratic thought,” and it gave new' scientific respectability to the traditional Hippocratic concept of “disease as struggle.”21

Like Pasteur, Metchnikoff was a vitalist, locating the vitality, inter alia, in the phagocytes:

I he theory of phagocytosis ... maintains that the vital manifestations of the phagocytes, irritability, mobility, and voraci-

ty, constitute an essential factor in ridding the animal of micro-organisms.—Elie Metchnikofl', 190522

The phagocytes manifest phenomena which are purely biological, such as the perception of chemiotactic and other sensations, the migration towrards menaced situations, the ingestion of microorganisms, and the absorption of toxins, and finally the secretion of substances to be utilized in intracellular digestion.—Elie Metchnikoff, 190523

Thenceforth the “struggle” was not between the whole organism and the morbific cause, but between microbial causes and phagocytes. It was removed to the cellular level and made bacteriologically respectable.

Phagocytosis is exhibited not only by the macrophages but also, in a high degree, by the microphages which stand out as the defensive cells par excellence against microorganisms. Their action is divided into a series of vital physiological acts, such as sensitiveness to the microorganisms and their products, amoeboid movements which serve to ingest the microorganisms, and chemical and physico-chemical processes, such as the destruction and digestion of the devoured organisms.

—Elie Metchnikoff, 190524

To make graphic his conviction that disease always involves the host organism, Metchnikoff and two assistants drank cultures of cholera vibrios; while he and one assistant were unaffected, the second assistant suffered a severe diarrhea.25 b

Metchnikoff’s “biological” approach appealed very greatly to Pasteur:

It was by a struggle between the red blood corpuscles and the bacteridium that [Pasteur] explained in 1878 the resistance of the living fowl to anthrax, and we see him at every instance, in that period, hav ing recourse to vital resistance, and saying, “Among the lower forms of life, still more than in the higher species of plants and animals, life prevents life—”

hIn this MetchnikofT imitated Max PettenkofTer. See below, p. 203.

Pasteur, however, was conscious of not having laid hold of the vital point of the mechanism of the resistance of the organism, and it is perhaps for that reason that when he heard of the researches of Metchnikoff on phagocytosis, he gave immediate attention to them ... The simplicity of this conception was striking. These white corpuscles of the blood and of the tissues, playing the role of gendarmes in the organism, constantly in circulation, always ready to throw themselves on everything foreign appearing there, and consequently upon enemies living or dead, surrounding by virtue of this general property the cells of the microbes, digesting them and making them disappear—all that could not fail to captivate him! The idea was that of a biologist and of a naturalist; it had not occurred to Pasteur, but that did not prevent him from welcoming it with deference. As long as he lived, he wished to keep in touch with its progress.

Emile Duclaux, 189626

The Hippocratic “struggle” is waged on a smaller scale, and the victor emerges stronger for the experience:

When it is the host which succumbs, the microbe seems to emerge more inured to the struggle, capable of secreting in greater abundance the products which have rendered it victorious. We explain this fact by saying that it has become more virulent.—Emile Duclaux, 189627

By the same token, a microbial species is rendered more potent by serial passage through animals “which, without being absolutely immune, can resist it a long time and enable it to acquire a new vigor.” But:

When it is the microbe which succumbs in the struggle, the leukocytes in their turn issue from the conflict stronger, more sensitive to the chemiotaxis of the microbes w'hich they have killed, and more accustomed to their toxins, and the animal consequently has a power of resistance, an immunity, which it did not formerly possess.—Emile Duclaux, 189628

Inflammation and Digestion

The role of digestion and inflammation in phagocytosis is a further parallel with the classic Hippocratic doctrine.

After his original discovery, Metchnikoff performed other experiments on the shores of the Strait of Messina and became convinced that the accumulation of phagocytes at the point of lesion was part and parcel of a primitive type of inflammation, available to animals at all levels of the phylogenetic hierarchy.29

I selected ... the large Bipennaria larvae of starfish, so abundant at Messina, and inserted prickles of roses into their bodies. Very shortly these prickles were found to be surrounded by a mass of ameboid cells such as we see in human exudation as the result of the introduction of a spine or other foreign body. The whole process took place under my eyes in a transparent animal possessing neither blood nor other vessels, nor a nervous system. The first point was settled. The inflammatory exudation must be considered as a reaction against all kinds of lesions, the exudation being a more primitive and more ancient phenomenon in inflammation than are the functions of the nervous system or of the vessels. —Elie Metchnikoff, 190530

Because inflammatory' processes and the associated phagocytosis can also take place in animals devoid of a nervous system, Metchnikoff held them to be cellular reactions.31 And since they are part of the organism’s effort to defend itself from attack, they must be interpreted as aspects of a curative response. In an 1883 paper, “Curative Forces in the Organism,’' he set forth his “new” interpretation of inflammation, reviving the older Empirical viewr and popularizing its role as a healing response.32

This aroused Metchnikoff’s Rationalist contemporaries who sawr fever and inflammation as invariably harmful (in those decades, after all, a large proportion of the physician’s prescriptions were for “antifebrile” and “antiinflammatory” substances).

Visiting Metchnikoff in Messina in 1883, Virchow urged caution in declaring inflammation beneficial, since “in pathology just the opposite was invariably taught.” Lister, naturally, was

supportive, writing in 1896: “If there ever was a romantic chapter in pathology, it has surely been the story of phagocytosis.”33

The digestive process was always at the center of Metch-nikoff’s concerns. Two of his earliest papers were on digestion, the second on “intracellular digestion.”34 In the end of his life he concluded that differing levels of resistance to disease can be accounted for by differences in the intestinal bacteria.

The discovery of phagocytosis was entirely in line with this lifelong interest: “The microorganisms are absorbed into the refractory organisms [phagocytes] as the result of a true act of digestion.”35

But this is not digestion in the stomach. Most of the common pathogenic organisms are not dissolved by pepsin, trypsin, and other components of the gastric juices. Phagocytosis is an intracellular digestion within the white corpuscles themselves which hurry to the locus of invasion and ingest the pathogenic organisms.36

Metchnikoff thus accepts the existence of two digestive processes in the body, in a precise parallel to the Empirical School in the first century, A.D.C

Intracellular digestion is probably accomplished by “cytases” (enzymes) within these cells and by other “soluble ferments.”37 Metchnikoff admitted that much here was not yet know^n, but remained to be discovered.

In 1891 he delivered a series of lectures on the “Comparative Pathology of Inflammation” at the Pasteur Institute, calling it a new theory of inflammation and crediting Darwin with the inspiration.38^

I have endeavored to apply to pathology the principles of

evolution which we owe to the genius of English philoso-

cSee Divided Legacy, I, 240-247.

dGert Brieger notes that “for Metchnikoff the phagocytic theory was more than a favorite brain child to be defended at all costs. It was, he felt, a way of understanding immunity and hence led to the cure of disease. Its implications, as his later work clearly showed, were in the direction of an amelioration of the human condition. Phagocytosis, then, can be tied to his later concept of orthobiosis” (Elie Metchnikoff, Immunity in Infectious Diseases, Introduction, p. xxvi).

phers. I have indeed dared to put forward a new theory of inflammation only because I felt that I had Darwin’s great conception as a solid foundation to build upon, supported as it is by the doctrine of natural selection.

—Elie Metchnikoff, 189339

His 1905 Immunity in Infectious Diseases describes phagocytosis in Darwinian terms combined with Hippocratic coction:

The most simple and the most primitive organisms have constantly to struggle for their existence ... When the aggressor in this struggle is much smaller than its adversary, the result is that the former introduces himself into the body of the latter and destroys it by means of infection ... But infection also has its counter. The attacked organism defends itself against the little aggressor. It ... uses all the means at its disposal to destroy the invader. As a very large number of organisms, in order to obtain nourishment, are obliged to submit their food to digestion by various chemical substances, they utilize these substances in the struggle against the infective agents. They digest them whenever they are able to do so.

—Elie Metchnikoff, 190540

Accepting a major role for the host organism in illness suggests sympathy for pleomorphism. And Metchnikoff, indeed, unafraid that the structure of medical science would collapse, published numerous articles favorable to pleomorphism while at the Pasteur Institute, holding that the doctrine was gaining ground and would soon dominate bacteriology.41 Many of these articles appeared in Pasteur’s lifetime, and the Master may be assumed to have concurred; it did not, after all, contradict attenuation but rather buttressed it. French bacteriology has been furtively pleomorphist since that time.42

“Resistance” is the equivalent of immunity:

Immunity against infective diseases should be understood as the group of phenomena in virtue of which an organism is able to resist the attack of the microorganisms that produce these diseases. ... Some have thought it necessary to distinguish between immunity properly so called, that is to say, a

permanent refractory state, and “resistance,” or a very transient property of opposing the invasion of certain infective microorganisms. It is not possible to maintain this distinction, for in reality the limits between these two groups of phenomena are far from being constant. Immunity may be inborn or acquired ... as the result of the spontaneous cure of an infective disease ... [or] the result of direct human intervention as in the practice of vaccination.

Elie Metchnikoff, 190543

Empiricism and Host Resistance: Behring

Behring’s interest in host resistance is seen in his close analysis of the concepts “idiosyncrasy,” “anaphylaxis,” “toxin-hypersensitivi-ty,” “disposition,” and “diathesis.”44

“Idiosyncrasy” is an inborn neurologic tendency to react with symptoms of distress to substances which are harmless to others: iodoform, chloral hydrate, phenacetin, cow’s milk, raw eggs, and certain fish and crustaceans.45 Goethe, for example, was so intolerant of the smell of rotten apples that it made him faint. Schiller, on the other hand, could not work at his desk unless a bowl of rotten apples was in the room!

Idiosyncratic reactions, especially to medicines, are manifested dermatologically, but also in the form of fever, delirium, somnolence, albuminuria, heart symptoms, diarrhoea, constipation, swelling of the mucous membranes, neuralgias, myalgias, and arthritis of the knees and ankles.46

“Anaphylaxis” means the organism’s idiosyncratic reaction to a second exposure to some irritant substance. It must be causally related to isopathically generated antibodies, although the mechanism of the anaphylactic reaction is a mystery. The “serum sickness" of Bela Schick (1877-1967) and Clemens von Pirquet (1874-1929) must be ascribed to idiosyncrasy if it occurs after the first injection, to anaphylaxis if it occurs after the second.476 “Toxin-hypersensitivity” resembles the anaphylactic state.

Once injected with a substance, the animal is far more reactive to a second injection. However, it is not antibody-determined, like anaphylaxis, but due to “a histogenous alteration caused by a Mithradatic poison-exposure.”48

“Disposition” means the organism’s vulnerability to one or another disease. Some are sensitive to cold, others not. Some can carry pneumonia virus in their system without becoming ill:

Pneumonia requires a number of causal factors, which we can divide into exogenous and endogenous; the endogenous disease determinant, also known as “disposition,” can be elevated or depressed in function of time and place, age, and physiopathological factors. Neither disposition alone, nor viral exposure, is sufficient for the disease to arise. The disposed organism must be exposed to the virus; “disposition” and “exposition” together constitute the disease cause.

—Emil Behring, 191549

Virchow was right to insist that the living substrate on which the morbid functions are manifested not be ignored.50

We speak of a “disposition” to tuberculosis, consumption, pneumonia, and the like. “Diathesis,” a subcategory of “disposition,” is used in the sense of lymphatic, arthritic, exudative, and the like.51

Behring associates immunity with resistance, echoing Pasteur in noting that immunity is a “relative concept,” a balance between the virulence of the microbe and the phagocytic and other defenses of the host.52 Habituation plays an important part.5/1 The disposition of the host organism to infection can be lessened by vaccination or by a previous frank or subclinical infection.54 It is also lessened by antitoxins.55

Immunity is called “constitutional” when so enhanced that the infectious agent can find no point of assault in the vital parts of the body.56

Behring describes phagocytosis as a “powerful weapon of the vital force” and incorporates it fully into his theory of immunity.57 It is a Hippocratic concept: the invading bacteria are digested by the phagocytes and expelled from the body through the secretions or through pus-formation.58

Rationalism and Host Resistance: Koch and Ehrlich

Where Behring and Metchnikoff were vitalist, Koch and Ehrlich were mechanistic, and from this stem their differences in the matter of host resistance.

Koch’s philosophical position on vitalism is reflected in Carl Fraenkel’s statement: “The revelations of physical science in general ... exhibit life of all kinds as depending on processes, physical and chemical, which obey the simplest laws.”59 Koch did not view disease as a struggle but followed his master, Jacob Henle, wrho (in the words of the historian, Max Neuburger) “with the greatest tenacity attacked the expression, Reaction, in a medical sense, and the old thought that a fight is unleashed between the organism and the cause of disease. He ... rejected any teleologic suggestions. Spontaneous healing did not ensue from the organism’s purposive defense against the disease stimulus, but only from reappearance of the conditions which made return to normal life possible.”60

Koch was instinctively hostile to “adaptation,” “mutation,” and even “disposition,” regarding them as opening the door to pleomorphism: “[The concept of bacterial] adaptation conforms entirely to the currently dominant and seriously exaggerated opinion of the mutability of bacteria. This conception has numerous adherents. At this time this is no more than a purely hypothetical possibility. No facts support this opinion, and many count against it.”61

Some people, he notes, ascribe to “different dispositions” the “significant differences in the course of tuberculosis among different individuals of the same species, and differences in their resistance to infection ... Of course, this does not even appear to explain these differences. In the case of tuberculosis, many of these differences can be explained simply by variations in the infection site. The quantity of original infection material is also significant.”62

Koch was unwilling to take into consideration the impact of environmental causes on predisposition to disease/Tuberculosis

is not a manifestation of “social ills,” i.e., of low levels of resistance, but is caused by a “tangible parasite.”63

And when compelled to accept the fact of resistance, Koch endeavored to explain it in physico-chemical terms. Some animal species resist anthrax because of a high level of alkalinity in the fluids.64 Individuals recently recovered from measles are more likely to become infected with tuberculosis than those whose lungs are in their pristine condition, because measles “temporarily strips the epithelium from the respiratory mucous membrane or provides stagnating secretions in which bacilli can settle.”65

It has also been claimed, with some justice, that adhesions in the lungs or defects in the chest cavity, which hinder the full movement of the lungs and which may cause unusual collections of bronchial secretions, favor the establishment of tuberculosis bacilli. Once the necessity of such auxiliary causes is clear, it ceases to be so remarkable that many persons who have repeated contact with phthisics do not become infected, while others become infected on the first exposure. Still others, after many exposures that did not take effect, finally fall victim. In the first case, tuberculosis bacilli, which have certainly been inhaled often enough, find no assistance, and they are removed from the respiratory organs. In the second case, there was some defect in the respiratory organs which the bacilli could exploit, and the infectious germ happened to be deposited precisely there. In the last case, such a defect developed later, and so the person lost his or her relative immunity.—Robert Koch, 188466

Every phthisic sw'allows secretion from her or his lungs, and this contains tuberculosis bacilli. Thus it is strange that they do not all reveal intestinal lesions. I explain this as follows: first, in comparison to the lungs, the intestine is a relatively unfavorable invasion site for the slowly growing tuberculosis bacilli.—Robert Koch, 188467

“Disposition” can often “be traced to simple and easily explained conditions.” But not always:

Several facts remain that are difficult or impossible to explain. These facts force us, temporarily at least, to retain the assumption of a disposition. First, there are striking differences in the course of [tuberculosis] between children and adults; there is also the unmistakable predisposition of many families for tuberculosis. Perhaps much of what is ascribed to predisposition can more readily be traced to opportunity for infection. A particular family resemblance can also provide such predisposing moments as a disposition to catarrh of the respiratory organs, or defective construction of the chest cavity. But many observations remain that cannot be accounted for by such explanations. Moreover, individual case histories often show that a given person is not always equally susceptible to development of the parasite. Often, a tuberculosis focus that has expanded significantly begins to shrink, to scar over, and to heal. This means, however, that a body that provided a suitable medium for invasion by tuberculosis bacilli gradually lost the properties that favored the bacilli and changed into an unsuitable medium. In this way limits were placed on the growth of the bacilli. T hus, an individual may be disposed to tuberculosis at one time and not at another. I he basis of this change, however, which may be in the chemical composition of body fluids or in physical conditions, remains to be discovered ... Hereditary tuberculosis is best explained by assuming that ... certain properties are inherited that favor germs that subsequently invade the body.—Robert Koch, 188468

Koch's willingness to recognize facts which ran counter to his Rationalist presuppositions is one of the traits that make him a great figure in medical thought. But, as is typical of Rationalist thinkers generally, he resists “disposition” and “resistance” until logical ingenuity has exhausted itself. To him they are still confounding variables obscuring an otherwise clear and consistent theory: “Acquired and inherited dispositions undoubtedly play a significant role in the etiology of tuberculosis. However, it would be too speculative to discuss these conditions. More thorough studies are required before one can reach conclusions in this area.”69

To Ehrlich diseases were discrete monomorphic entities caused by microbial assault on the passive host organism. He was impervious to the charms of Hippocratic doctrine, never even mentioning it in his writings. And, in a peculiar twist, host resistance to disease is converted by him into resistance to the medicine!!

Underestimating resistance generally, he and Koch viewed the symptoms as signs of damage by the bacterial “cause,” not as part of the host reaction.70 As already noted, the processes generating symptoms do not participate in the production of antitoxin.s Symptoms to them were caused by the presence of bacteria, the patient as usual being a passive victim. 71h

Proof [that bacteria cause diseases] would require that we find the parasitic microorganisms in all cases of the disease [and] that their presence is in such numbers and distribution that all the symptoms of the disease can be explained.

—Robert Koch, 187872

The bodies of animals that die of artificial infected wound diseases invariably contain so many bacteria that the symptoms and death of the animals are sufficiently explained.

—Robert Koch, 187873

The first step ... is the conscientious examination of all those body parts that are altered by the disease. In this way one can establish the presence of the parasites, their distribution in the diseased organs, and their relation to the body tissues ... Only then can one begin to demonstrate that the microorganisms are pathogenic and that they cause the disease.—Robert Koch, 188274

Chronic miliary tuberculosis includes those processes that occur at places in the body that would not ordinarily be accessible to an invasion of bacilli and that appear to develop

*See above, p. 117.

hHomoeopaths did not agree with this: “The extent and intensity of a morbid process are not always proportional to the number of bacteria present” (Wilhelm Ameke, History of Homoeopathy, 391).

into localized tuberculosis without a focus that promotes further infection ... Their origin can only be explained on the assumption that a single bacillus was deposited by the bloodstream in the affected site. Robert Koch, 188475

The microorganisms having once effected an entrance, multiply rapidly and thus cause the group of symptoms appearing in the course of the affection.

—Carl Fraenkel, 189176

A specific microorganism must occur in such quantities, and so distributed within the tissues, that all symptoms of the disease may be clearly attributed to it.—Carl Fraenkel, 189177

Koch and Ehrlich later modified their view that symptoms are caused by the physical presence of bacteria in favor of a toxin theory: “Poisonous proteins, the so-called toxic albumins, which can be obtained from anthrax, diphtheria, and tetanus cultures ... may have an influence, perhaps the most important influence, on the symptoms of infectious diseases.”78

The different bacteria do not, as a rule, form only one definite substance, but always produce several, which by their common joint effects produce the physiological complex of symptoms which we regard the microorganism in question as responsible for.—Carl Fraenkel, 189179

After it had been established ... that the toxin molecule was possessed of a definite haptophore group, which accounted for its capacity to enter into combination with other bodies, it was immediately necessary to inquire into the question whether, and if so to w hat degree, this group entered into the causation of the symptoms of illness.

Paul Ehrlich, 190080

The Carrier State. Endogenous Disease. Pleomorphism

Recognizing the carrier state and the possibility of endogenous disease means accepting the primacy of host resistance vis-a-vis

the microbe. It also indicates sympathy for pleomorphism—i.e., that microbes can assume a less pathogenic form.

The “carrier” state first came to medical attention in Hahnemann’s 1831 observation that “healthy miasm-bearers,” i.e., physicians and nurses, were spreading Asiatic cholera among their patients. Through repeated exposure to the contagium they are “at last ... completely hardened against even the most poisonous cholera miasm at the bedside and rendered quite unin-fectible by this pestilence.” But they can give it to others: “Thus the cholera physicians and nurses are the most certain and frequent propagators and communicators of the contagion far and wide.”'

This was one factor, among many, which turned the allopathic profession against him.

The Munich professor of hygiene, Max von PettenkofTer (1818-1901), suggested the possibility of a healthy “carrier” in 1855.81

Auzias-Turenne alluded to “portateurs des germes” who carry the disease “poisons” even though themselves appearing to be in good health.82

When Pasteur discovered that guinea pigs can harbor the fowl cholera microbe in abscesses without becoming infected, he also understood the importance of the “carrier” concept for epidemiology.83 In 1880 he found a diplococcus in the mouth of a healthy child; later this same organism, now called the pneumococcus, was seen to cause typical inflammations of the lungs, as well as certain forms of brain fever and heart disease.84 And he wrote in 1881, “An epidemic which has been extinguished when its virus has been weakened can recommence if the virus is reinforced ... The plague is a viral disease peculiar to certain countries. In all of them the attenuated virus must subsist, ready to spring to life whenever conditions—climate, famine, misery are propitious. There are other viral diseases which appear spontaneously in all countries, such as the typhus of the camps. Without any doubt the germs of the microbes causing these diseases are everywhere. Humans carry them on their skin or in the intestinal

canal without suffering greatly, but they are ready to become dangerous as soon as their virulence is progressively reinforced by host weakness or by a wound.”85

Metchnikoff states the same: “As soon as he is born, man becomes the habitat of a very rich microbial flora. The skin, the mucous membranes ... the intestines, and the genital organs offer a feeding ground for bacteria and inferior fungi of various kinds. For long it was thought that in healthy individuals all these microorganisms were inoffensive and sometimes even useful. It w'as supposed that when an infective malady was set up, a specific pathogenic microbe was added to this benign flora. Exact bacteriological researches have, however, clearly demonstrated that as a matter of fact the varied vegetation in healthy persons often includes representatives of noxious species of bacteria. Besides the diphtheria bacillus and the cholera vibrio, which have repeatedly been found in a virulent form in perfectly healthy individuals, it has been demonstrated that certain pathogenic microorganisms, e.g., the Pneumococcus, staphylococci, streptococci, and the Bacillus coli, are always, or almost constantly, found among the microbial flora of healthy persons.”86

He even recognized the possibility that virulent bacteria ingested by phagocytes could resist digestion and remain alive until some disturbance of the host environment provoked them into renew'ed multiplication and “egestion” back into the host environment.87 This was a possible source of what came later to be called "latent" or “attenuated” infection.

Koch was initially unreceptive to the idea of the carrier, writing in 1878, “Bacteria do not occur in healthy human or animal tissues.”88 Recognizing endogenous disease meant allocating too great a role to host resistance. While noting without comment in 1882 that “... saliva from healthy persons contains pathogenic bacteria,” he w?as still unwilling to admit that tuberculosis bacilli could be found in the healthy.89 “Without exception, they are missing in healthy persons.”90 When an opponent claimed to have discovered these bacilli in the feces of twenty healthy persons, as proven by Ehrlich’s staining procedure, Koch held the staining method to have been defective. Furthermore, “Even if intestinal bacilli react to stains like tuberculosis bacilli, and even

if they are the same size and shape, nothing is changed. First, one must prove that they possess the same pathogenic properties as tuberculosis bacilli.”91

He even claimed that professional enemies were seeking healthy carriers of the tuberculosis bacillus as evidence that his bacillus was not the cause of TB: “What joy would be occasioned by the news that the tuberculosis bacillus had been found in the intestines of healthy persons or in a single case of bronchiectasis. One hopes to be free from this undesired guest, but unfortunately the hope is unrealized.”92

About anthrax bacilli, “We cannot imagine that they would sometimes appear in an organism as harmless saprophytes and, on other occasions, as the parasitic cause of disease.”93

He recognized the threat the carrier state represented to monomorphism: “Many investigators claim that normal blood and tissues from humans and test animals always contain microorganisms. Some claim that these organisms do not cause disease, but that a morbid process causes them to become abnormally abundant. This is supposedly because the fluids of the animal body, when altered by disease, provide conditions favorable for their development. One can safely ignore these opinions; they have never been confirmed experimentally and are adv anced on theoretical grounds alone. However, suppose bacteria did occur in normal blood, and that increased numbers of the same bacteria ... were found in organs altered by disease. Then it would be much more difficult, perhaps impossible, to prove that these micrococci were the cause of the disease.”94

Research in Zurich in the early 1900s found that every indiv idual in a sample of persons older than thirty had signs of tuberculosis infection; for those eighteen to thirty years of age the figure was ninety-six percent infected; between fourteen and eighteen it was fifty percent, and, between five and fourteen, thirty-three percent.95

In 1882, when Koch first presented his report on tuberculosis, almost every adult individual in Europe must have been infected with virulent tubercle bacilli; Koch himself certainly was, as evidenced by the violence of his reaction to Tuberculin in 1891.96

Koch changed his mind about the carrier state in 1884 when Loeffler found virulent diphtheria bacilli in the mouth of a healthy child, and when he himself discovered that healthy persons can excrete cholera vibrios.97 Earlier he had denied it, stating that the comma bacilli .. do not occur in persons suffering from other diseases or in the healthy.”98 He recognized the carrier in his 1893 studies on cholera and in a 1902 report on typhoid fever. 99-J

Koch and Ehrlich on Phagocytosis and Vaccination

Emblematic of Koch-Ehrlich Rationalism was their attitude toward phagocytosis. The phagocyte performs actions which seem physiologically impossible: it sticks to the wall of a blood vessel and moves through it into the tissues, then senses where to travel, and finally moves through the tissues to its intended victim. This is eminently Empirical, a striking manifestation of the body’s purposive and teleological response to invasion by an enemy. I he actions performed are determined by the end to be achieved.

For this reason phagocytosis was and is difficult for Rationalist medicine to “explain” in reductionist language. Both Koch and Ehrlich disliked phagocytosis as in principle antagonistic to the side-chain theory.100

It cannot be denied that Metchnikoff’s theory agrees ill with the revelations of physical science in general, which exhibits life of all kinds as depending on processes, physical and chemical, which obey the simplest laws ... It contents itself with stating the fact, and does not attempt an explanation ... It w'ould ... be more comprehensible if we could see the cells in a less immediate strife with the bacteria and if both were represented to us as the special exciters of definite processes, chiefly of a chemical nature ... This hypothesis ... presup-

'YVhile the vibrio is recognized today as the “cause” of cholera, it is endemic to the water supply of many countries where it is steadily ingested without giving rise to this disease (Lancet, [November 8, 1947], 695; Rene Dubos, ed., Bacterial and Mycotic Infections, 468).

poses an extraordinary docility in the protoplasm of the white blood corpuscles, to which it attributes something like feeling, thinking, and acting—a sort of mental perception.

—Carl Fraenkel, 1891101

Koch rejected phagocytosis until nearly the end of his life, insisting that the whole phenomenon could be explained chemically.102 He wrote in 1890 that immunity is not “... a purely cellular matter, a kind of battle between the invading parasites and the phagocytes that defend the body ... this view is losing ground; it is becoming apparent that here, too, chemistry plays the main role.”103

He adhered steadily to the mid-nineteenth-century view of phagocytosis as a waste-removal process or technique for transporting microbes around the organism.k

The phagocytes ... did not form an active and dangerous weapon of defence for the organism, did not stand in the foremost rows in the battle against the invading parasites, but were the open graves behind the line of battle, destined to receive the fallen enemies ... Nothing ... compelled us to believe that these cells possessed a peculiar devouring and digesting power: they were, on the contrary, nothing but buriers of the dead, removers of decaying matter.

—Carl Fraenkel, 1891104

Ehrlich as late as 1900 called Metchnikoff’s theory “inconclusive.”105 He himself offered a chemical interpretation—in terms of oxygen deprivation—of the destruction of microbes engulfed by phagocytes: “... without the necessity of first ascribing to the cells any peculiar and specialized activities, such as the formation of special poisons or ferments.”106

The associated inflammation is merely a condition caused by bacterial infection, in no way the sign of the body’s incipient resistance.107

kBut Virchow (possibly to spite his enemy, Koch) published two articles by Metch-nikofT in 1884. In 1885 he himself praised phagocytosis in the first contribution to volume Cl of the Archiv—a jubilee number marking its second century (Elie Metchnikoff, Immunity in Infectious Diseases, xxv).

The Koch-Ehrlich opposition to phagocytosis was somewhat attenuated by the discovery of chemiotaxis, which finally provided a biochemical figleaf for this vitalist phenomenon.1 Even Duclaux at the Institut Pasteur was relieved:

Obedient to what mysterious call do the white cells come from all parts of the organism, filtering through vessels, and penetrating to the region where they will be useful? The living cells have no emotion, not even that of well-being, they have only needs, and obey only physical or chemical actions. The discovery of chemiotaxis ... has taken away from the theory of M. Metchnikoff a little of its mysterious aspect, and with the same stroke has brought back into the field of chemistry the question which had been referred to the cellular field.—Emile Duclaux, 1896108

The denigration of host reactivity was extended by Koch and Ehrlich to vaccination.

Koch had difficulty with vaccination from the outset, not only because it was proposed by Pasteur but because “attenuation" smacked of pleomorphism, and he only accepted it after long hesitation.1091"

When Pasteur introduced rabies vaccination in 1885, Koch at first refused to employ it.110 But he recognized Tuberculin as a type of immunization.111

And when he finally accepted vaccination, he interpreted it differently from Pasteur’s “life against life.” Immunity arises through excretion by microorganisms of chemical substances which remain in the body after the first invasion, inhibiting return of the same bacterial species. According to this “retention theory” of immunity,

'On “chemotaxis” or “chemiotaxis” see below, pp. 172-173.

““Members of the Koch intellectual family did not want to have recourse to attenuated strains of pathogens to produce immunity, since that would have been in contradiction to the ‘law’ set up by the master himself on the fixity of species. ‘Once a pathogen, always a pathogen,’ could be one way of expressing this ‘principle,' which, as important as it was for Koch’s disciples, was ignored by bacteria” (H. A. Lechevalier and M. Solotorovsky, Three Centuries of Microbiology, 216).

... the accumulated products offer an enduring resistance to after-attacks from the same kind of bacteria. The hypothesis of retention agrees with our views, in that it regards the action of chemical substances as the chief factor.

—Carl Fraenkel, 1891112

It followed that active immunization is accomplished simply by injecting these same excretions:

If we remove the microorganisms by careful filtration or cautious application of heat, their excretions remain, which do not multiply in the animal, but, on the contrary, are diluted by mixture with the blood and the tissue-juices, and their effects being thus diminished, they are able to produce immunity.—Carl Fraenkel, 1891113

The theory was attractive not only for introducing a chemical mode of reasoning and depriving the host organism of a role in generating immunity, but because vaccination could thereby be interpreted in terms of “contraries” rather than “similars.” While it was hard to explain how chemical substances could stay for a lifetime in the blood, writes Fraenkel in 1891, “there exist no convincing proofs that such cannot be the case.”114 Hence the German school initially minimized the host’s contribution to immunization: this state was due to the microbe’s impact on the host’s humors, to its contribution of substances hostile to further microbial growth.

Support for the “retention theory” was found in the fact that vaccination does not “take” immediately,

... but that days or even weeks must elapse before the former has been developed to its full extent; that is, the time required for the solution of a requisite quantity of the chemical substances introduced. That this process is not accomplished without difficulty is evident from the considerable increase in the temperature of the body—the “inoculation fever”— which generally occurs, and the importance of which for the production of immunity has recently been insisted upon.

—Carl Fraenkel, 1891115

Behring’s serum therapy presented a new challenge to the Rationalist interpretative urge. Ehrlich was willing to accept the fact of antitoxin production but denied that it constituted a reaction, since, as already noted, antitoxins and other antibodies represented “nothing more than the cell receptors produced in excess under the influence of the toxin and thrust off.”116 And Carl Fraenkel dismissed as outlandish the supposition “that the reception of attenuated germs acts upon the cells as a specific stimulant, to which they answer by a functional reaction, and that this stimulating power exists in the same degree and works in the same manner also in the bacterial products.”117

The intensity of the Rationalist rejection of host reactivity is seen in Fraenkel’s comment on “inoculation fever.” The very phenomenon which to the Empirical mind best exemplified struggle and reaction was given a chemical interpretation (resembling Ehrlich’s denial that the symptoms in disease are associated with antibody production).

In any case, antitoxin put an end to the “retention” theory.118 Ehrlich in 1908 attempted to resurrect Pasteur’s discredited “depletion” theory, integrating it with his “side chains” and “haptophores.”119 But neither “depletion” nor “retention,” as came to be recognized, could explain the lasting nature of immunity. If due to a mere chemical change in the blood, it would necessarily disappear from the circulation in hours or days.

Metchnikoff and Vaccination

The German attempt to chemicalize phagocytosis was unacceptable to Metchnikoff. Out of general charitableness toward his colleagues, he tried hard to show that phagocytosis was compatible with Ehrlich’s side-chain concept, but his efforts are not convincing.120 Ultimately he described Ehrlich’s humoral theory of neutralization of toxin by antitoxin as an “ingenious idea [w hich] cannot be subjected to rigorous experimental test.” “Many well-established facts” are “not in complete accord with this hypothesis.” In particular, it could not account for acquired cellular immunity.121

Metchnikoff saw readily that both vaccination and Behring’s antitoxin stimulate and potentiate phagocytosis, simulating the

natural disease process. By reaction of the “vital elements” to microbial toxin, the phagocytes synthesize antitoxin (which he called “fixative”), the bearer of specificity, which adheres to microbial cells and renders them more vulnerable to phagocytosis; this is “not a chemical action in the proper sense of the word” but sensitizes the microbial intruder to the fermentative action of the substance within the phagocytes.122 “Fixatives ... fix themselves with avidity upon the microorganisms. These organisms may become a more ready prey to the phagocytes and be destroyed very rapidly.”123 " Fixatives can also remain inside phagocytes without being excreted and prepare the bacteria for phagocytosis.124

Here, as always, Metchnikoff refers back to digestion: “Certain elements of the animal, capable of acting on the complex molecules of microbial toxins and their allies, produce special soluble ferments which digest the toxins.”125

Preventive vaccination parallels natural infection: “The phagocytes, which have a very imperfect antimicrobial function or none at all, become, as the result of vaccination, much more active ... [and] exhibit a very marked positive chemiotaxis ... The microorganisms that can be deeply injured by the direct action of the specific serum are few in number. In most cases this action is a feeble one and needs, for its completion, effective cooperation on the part of the phagocyte.”126

I he fluids of the immunized animal or human “very probably possess other properties which must have a greater or lesser function in acquired immunity.”127

Even “passive” immunization requires participation by the phagocytes, stimulated to react by the antitoxin. The host which cannot mount a reaction because weakened by narcotics or some other factor, will not be benefited by antitoxin: “and the animal falls victim to the pathogenic microrganism in spite of more than sufficient amount of fixatives [antitoxin] that was introduced.”128

"“The concept of a specific interaction between antibody and the bacterial surface with resulting increase in susceptibility to phagocytosis has explained definitively one important role of antibodies in host resistance ... Metchnikoff’s statement that specific antiserum does not exert a direct bactericidal action remains uncontroverted” (James G. Hirsch, “Immunity to Infectious Diseases,” 58).

Metchnikoff agreed with Behring that habituation—which diminishes susceptibility to microbial assault—is a large part of immunity: “We can become habituated more or less easily to all kinds of violent sensations ... All cells are able, by modifying their function under the direction of susceptibility, to adapt themselves to changes in the surrounding conditions. All living beings are able, therefore, to acquire a certain degree of immunity.”129

Thus, while he tried to be kind to Koch and Ehrlich, Metchnikoff held participation of the phagocytes to be the central phenomenon in immunity. And he rejected the “retention" and “depletion” theories: “The great majority of pathogenic microorganisms ... readily adapt themselves to all kinds of culture media ... This, therefore, is not the cause of the immunity in such organisms. The cause must be sought amongst factors more closely connected with life.”130 “The phagocytes enter into a struggle against the microorganisms and rid the animal organism of them without requiring any previous help on the part of the body fluids.”131

If immunity resided exclusively in the fluids, it would be impossible for microorganisms to become adapted to a toxic milieu: “A plasmodium, which becomes adapted to all kinds of toxic substances, acquires an immunity against them, and this is due to changes taking place in the living elements; it is not the result of modifications in the toxic fluids which bathe them.”132

Phagocytosis and Host Resistance in the Late Twentieth Century

Since only Empirical thinkers give systematic consideration to host resistance, Rationalist domination of medical speculation throughout the twentieth century has meant hostility to phagocytosis for more than fifty years and neglect of host resistance generally:

The precise mechanisms of host resistance ... remain as ill-defined today as they were at the turn of the century ... Although many studies have been made ... our knowledge

remains grossly incomplete of the precise antimicrobial substances of phagocytes and of how these substances act. James G. Hirsch, 1959133

It is certain ... that many nonspecific stresses increase the vulnerability of the host, but there is little, if any, understanding of the mechanisms through which these effects are exerted.—Rene Dubos, 1973134

The late twentieth century’s understanding of phagocytosis hardly differs from that of Metchnikoff himself. Phagocytic cells are produced in the bone marrow, taking about three days to mature. They are then discharged into the bloodstream, where they remain a few hours and disappear. Of the more than thirty-five billion phagocytes swimming there, and the many more in the bone marrow and tissues, two kinds are recognized, both subv arieties of white blood cells: “polymorphonuclear phagocytes” found in the blood and certain tissues (also called “neutrophils,” “heterophils,” or “eosinophils,” depending upon their staining properties), and “mononuclear phagocytes” found in the liver, spleen, and lymph glands.135

The phagocytes in the liver, spleen, and lymph nodes are fixed to the walls of the passages in these organs (“margination”) to trap any circulating particles that pass by. And when these particles become lodged in the tissues, the phagocytes themselves move from the bloodstream to the particular site. This involves “diapedesis” (migration through the wall of the blood vessel into the cavities and tissues of the body), then “locomotion” to the underlying tissue.

This ability to sense where the potential victim is located and to move in that direction (“chemotaxis” or “chemiotaxis”) is a mystery: “We still have no explanation, and in fact no good hypothesis, to explain this action at a distance.”136

In his experiments on keratitis produced by a crystalline substance extracted from cultures of Staphylococcus aureus, Theodor Leber [ 1840-1917] showed that the leukocytes at a distance were attracted toward the point where this substance had been introduced. On putting some small glass tubes filled with this substance into the anterior chamber of the eye, they became filled with a mass of leukocytes, although the tubes were so placed that the cells had to move against gravity in order to effect an entry into them.

Elie Metchnikoff, 1893137

Furthermore, although phagocytes move quite long distances through tissue to reach their prey, using a sort of ameboid motion, “no one has yet succeeded in discovering the fundamental mechanism by which movement takes place.”138

Once beside its prey, the phagocyte attempts to swallow and digest it. Certain features on the victim’s surface will affect this process. Microbes whose surface is smooth (“encapsulated ") can often resist phagocytosis, despite repeated contact. But if the surface is rough, so that the phagocyte can corner it, even encapsulated ones can sometimes be engulfed. Other forces or features on the victim’s surface making it more or less attractive to the phagocyte may yet be discovered.139

The engulfment process per se is an astonishing event to behold under the microscope, the bacterium or other particle appearing to pass as if by magic through the cell membrane ... A clear space or vacuole may or may not be visible surrounding the engulfed object. Careful study of phagocytosis by electron microscopy has now established the mechanism by which it is accomplished ... The cell membrane is invagi-nated about the particle; as ingestion is completed, membranes meet and fuse. The engulfed particle is situated within a pouch or vacuole, the wall being inverted cell membrane.—James G. Hirsch, 1965140

During engulfment the phagocyte’s metabolism accelerates, and once engulfment is completed, digestion commences. The phagocyte has in suspension certain enzymes for digesting engulfed particles, contained in little sacs called “lysozomes” or “cytoplasmic granules.” At some point after engulfment they are released into the phagocytic pouch or vacuole (“degranulation”). Certain serum proteins (“opsonins,” about which more later) also have their role to play.

Most microorganisms and other particles are killed and dissolved rather rapidly, within ten or fifteen minutes. The resultant waste matter is partly excreted into the cellular environment and partly utilized by the phagocyte for its own metabolism. But some microbes resist engulfment, as was observed by Metchnikoff: “It is undeniable then that phagocytes possess digestive powers, and that in particular they are able to digest microbes. But it does not therefore necessarily follow that these cells kill and digest all the microbes they englobe. In certain diseases the phagocytes take in a number of bacteria ... a few of which may be digested while the others resist the digestive action of the phagocytes, multiply in the cells and finally invade the whole organism.”141

Why phagocytes take in large numbers of tuberculosis or sw ine erysipelas bacilli, but only digest some of them, remains a mystery.

Factors promoting or inhibiting phagocytosis are the physical nature of the microenvironment, salt concentration, acid-alkali balance (pH), temperature, and the like:

George Gabrichevsky [1860-1907] ... pointed out that whereas leukocytes are strongly attracted to sterilized or living cultures of most pathogenic and saprophytic bacteria ... they are repelled by the most virulent bacteria ... and by lactic acid ... alcohol, chloroform, glycerine, jequirity, bile, and quinine.—Elie Metchnikoff, 1893142

Its vitalist origins have made phagocytosis something of a stepchild of medical research; until the 1950s and 1960s it was largely neglected in favor of the humoral processes first suggested by Koch and Ehrlich, which were more readily amenable to biochemical explanations.143 The role of lymphocytes and mononuclear cells, as wrell as other aspects of cellular immunity, were discovered decades later than medicine’s scientific potential could have allowed.

The notion of cellular immunity was out of favor, and few investigators in that env ironment were stimulated to pose the questions that might have led to such studies. For a period of

almost fifty years few questions about cells in immunity were asked within a discipline comfortable with the dogma that circulating antibody would provide all essential answers to the problems of immunity and immunopathology.

Arthur M. Silverstein, 1979144

Metchnikoff, in a more general sense, called attention to the digestion as a technique of protection against morbific stimuli: “Immunity in infective diseases presents itself as a section of cellular physiology, and especially ... a phenomenon concerned in the absorption of microorganisms. This absorption being carried out by an act of intracellular digestion, the study of immunity comes into the chapter on digestion regarded from the general point of view.”145

Thus the digestion, always crucial to the Empirical medical Weltanschauung, came into its own with Metchnikoff and has retained its theoretical importance in late twentieth-century doctrines of infectious disease.0 F. Macfarlane Burnet (1960 Nobel Prize in immunology), for instance, equates infectious disease with a Darwinian struggle for existence between host organism and attacking microbe. At the bottom of the evolutionary scale, the amoeba engulfs a bacterium or other microorganism by enclosing it and creating a clear space (vacuole) around the food particle: “Within an hour or two the bacterium or alga begins to disintegrate, and when only debris is left, the amoeba flows on and leaves it behind.”146 But, if the bacterium possesses characteristics making it undigestible by the amoeba, it will be ejected. Or it can multiply inside the amoeba and thus cause its death—a primitive type of infectious disease: “At the lowest level ... we have an interaction between two organisms which, if it swings in favor of one, is an act of digestion, if in favor of the other, it is an attack of infectious disease.”147

The sponge, somewhat higher in the scale of evolution, possesses more differentiated cells, including “wandering cells resembling amoebae, which move about in the jelly-like struc-

tureless material at the base of the feeding cells ... they have the capacity to engulf and digest any food particles which may enter the deeper substance of the sponge ... This is the first indication in the animal kingdom of a mechanism to deal with invasion of the tissues by microorganisms.’’148

And the phagocytes observed in warm-blooded humans and animals at the top of the evolutionary scale have precisely the same function as those seen in sponges: “Eat or be eaten.”

Infectious disease is no more and no less than part of that eternal struggle in which every living organism strives to convert all the available foodstuff in its universe into living organisms of its own species.—F. Macfarlane Burnet, 1959149

NOTES

1.    Pasteur Vallery-Radot, 1954, 141.

2.    Ibid., 142.

3.    Emile Duclaux, 1920, 302-303.

4.    Ibid., 313.

5.    Louis Pasteur, 1940, II, 102-103; see also II, 214.

6.    Emile Duclaux, 1920, 256; John Farley, 1978, 149, 151.

7.    Quoted in Emile Duclaux, 1896, 256.

8.    Louis Pasteur, Oeuvres, VI, 127-128.

9.    Ibid., VI, 126; Karel Absolon et at., 1970, 254.

10.    Pasteur Vallery-Radot, 1954, 143.

11.    Ibid., 141.

12.    Emile Duclaux, 1920, 300.

13.    Rene Dubos, 1954, 97.

14.    Emile Duclaux, 1920, 315.

15.    Ibid., 317.

16.    Elie MetchnikofT, 1921, 116-117.

17.    Robert Koch, 1987, 46.

18.    James G. Hirsch, 1959, 52.

19.

Elie

MetchnikofT, 1921, 132.

20.

Emile Duclaux, 1920, 318.

21.

Elie

MetchnikofT, 1968, xxiii.

22.

Ibid.

, 539.

23.

Ibid.

, 566.

24.

Ibid.

, 206.

25.

H. fi

v. Lechevalier and M. Solotorovsky, 1974, 196

26.

Emile Duclaux, 1920, 317-318.

27.

Ibid.

, 320.

28.

Ibid.

29.

Elie

MetchnikofT, 1968, xxiii-xxiv, 551.

30.

Ibid.

,518-519.

31.

H. A. Lechevalier and M. Solotorovsky, 1974, 188

32.

Elie

MetchnikofT, 1968, xiv, xxiv.

33.

Ibid.

,519-521.

34.

Ibid.

, xviii.

35.

Ibid.

, 546.

36.

Ibid.

, 546-547.

37.

Ibid.

, 554.

38.

Ibid.

, xiii.

39.

Ibid.

40.

Ibid.

, 545.

41. William Bulloch, 1938, 202, 323; Serge Winogradsky, 1949, 127; F. Loehnis, 1922, 8, 21, 38, 40.

42.

F. Loehnis, 1922, 7fT.

43.

Elie MetchnikofT, 1968, 10.

44.

Emil Behring, 1915, 175fT.

45.

Ibid., 177.

46.

Ibid., 178

47.

Ibid., 179.

48.

Ibid., 183.

49.

Ibid., 185.

50.

Ibid., 6.

51.

Ibid., 188.

52.

Ibid., 158.

53.

Emil Behring, 1894, 8.

54.

Emil Behring, 1915, 159, 188.

55.

Ibid., 9, 159, 181-182.

56.

Ibid., 158.

57.

Ibid.

58.

Ibid.

59.

Carl Fraenkel, 1891, 135.

60.

Max Neuburger, 1926 (Cited in K. Koetschau, 1930,

975-976).

61.

Robert Koch, 1987, 143.

62.

Ibid., 148-149.

63.

Ibid., 95.

64.

Ibid., 37; Carl Fraenkel, 1891, 136.

65.

Robert Koch, 1987, 145.

66.

Ibid., 145.

67.

Ibid., 146.

68.

Ibid., 149.

69.

Ibid., 94.

70.

Ibid., 183; Carl Fraenkel, 1891, 151, 285; Emil Behring,

1894, 212.

71.

Emil Behring, 1915, 37.

72.

Robert Koch, 1987, 29.

73.

Ibid., 48.

74.

Ibid., 98.

75.

Ibid., 147.

76.

Carl Fraenkel, 1891, 338.

77.

Ibid., 151.

78.

Robert Koch, 1987, 183; Emil Behring, 1894, 212.

79.

Carl Fraenkel, 1891, 122.

80.

Paul Ehrlich, 1956-1960, II, 182.

81.

Alfred S. Evans, 1976, 178.

82.

Antonio Cadeddu, 1985, 88.

83.

Pasteur Vallery-Radot, 1954, 133; Rene Dubos, 1973, 177.

84.

Knud Faber, 1922, 56.

85.

Louis Pasteur, Oeuvres, VI, 337.

86.

Elie MetchnikofT, 1968, 7.

87.    James G. Hirsch, 1959, 54.

88.    Robert Koch, 1987, 27.

89.    Ibid., 98.

90.    Ibid., 117, 123.

91.    Ibid., 120.

92.    Ibid., 118.

93.    Ibid., 132.

94.    Ibid., 26.

95.    Emil Behring, 1915, 220.

96.    Rene Dubos, 1954, 93.

97.    Rene Dubos, 1973, 177.

98.    Robert Koch, 1987, 158.

99.    Alfred S. Evans, 1976, 178.

100.    Elie MetchnikofT, 1968, 538.

101.    Carl Fraenkel, 1891, 135, 146.

102.    Elie MetchnikofT, 1968, xxiii, 520.

103.    Robert Koch, 1987, 183.

104.    Carl Fraenkel, 1891, 135.

105.    Paul Ehrlich, 1956-1960, II, 179.

106.    Ibid., I, 495.

107.    Carl Fraenkel, 1891, 310, 327-328.

108.    Emile Duclaux, 1896, 319.

109.    Robert Koch, 1987, 109ff.; Emile Duclaux, 1896, 293; Carl Fraenkel, 1891, 140ff., 337ff.; Robert M. Frank and Denise Wrotnowska, 1968, 50; H. H. Mollaret, 1983, 58.

110.    H. H. Mollaret, 1983, 60.

111.    JosefM. Schmidt, 1991, 780.

112.    Carl Fraenkel, 1891, 143-144.

113.    Ibid., 142.

114.    Ibid., 145.

115.    Ibid.

116.    Paul Ehrlich, 1856-1960, III, 507.

117.    Carl Fraenkel, 1891, 147.

118.    A. M. Silverstein and A. A. Bialasiewicz, 1980, 164.

119.    Ibid., 163.

120.    Elie MetchnikofT, 1905,558.

121.    Ibid, 563.

122.    Ibid., 556-558, 561-562.

123.    Ibid., 560.

124.    Ibid., 557.

125.    Ibid., 562.

126.    Ibid., 295-296, 316.

127.    Ibid., 559.

128.    Ibid., 560.

129.    Ibid., 565.

130.    Ibid., 546.

131.    Ibid., 206.

132.    Ibid., 563.

133.    James G. Hirsch, 1959, 51, 56.

134.    Rene Dubos, 1973, 192.

135.    James G. Hirsch, 1965, 341.

136.    James G. Hirsch, 1959, 53.

137.    Ibid., 53.

138.    Ibid., 53.

139.    James G. Hirsch, 1965, 345.

140.    James G. Hirsch, 1965, 346.

141.    Ibid., 347.

142.    James G. Hirsch, 1959, 53.

143.    A. M. Silverstein, 1979, 219.

144.    Ibid., 219.

145.    Elie MetchnikofT, 1905, 566 567.

146.    F. M. Burnet, 1959, 30.

147.    Ibid.,?,?,.

148.    Ibid., 34.

149.    Ibid., 39.

CHAPTER V

DECLINE OF THE ENTITY: INFECTIOUS DISEASES

No perfect Rationalist therapeutic doctrine has ever been devised. Even Galen, who of all physicians in history worked hardest at theoretical consistency, left a few loose ends.3 But the formulation which emerged in the late nineteenth century—the specific bacterial disease treated by the “contrary” medicine—seemed to its devotees an almost unblemished depiction of reality.

The American Karl Menninger (1893-1991), who received his medical education just after World War I at the high tide of Rationalist confidence in the precision and reliability of its disease categories, described the mentality of the typical young physician of the day: “What I got out of medical school was the conviction that the world was full of healthy human beings, and that now and then a victim was struck down by a cruel blow from an unheeding Nature—an infestation, a lurking bacterium, a malignant cell. Now and then an inexplicable perversity seized the liver or the pancreas or the bone marrow. As a result, a ‘disease* developed and a patient appeared on the doorstep of the physician ... Disease, as I viewed it, and I think I fairly accurately caught the spirit of my preceptors, was an entirely unwanted, useless, purposeless misfortune, acquired inadvertently through an unfortunate concatenation of forces emanating from the best of all possible worlds or from the defective architecture of an hereditary constitution.”1

Two generations of physicians were raised to believe in these disease categories, but their confidence was misplaced. In the mid-1960s Rationalist physicians and philosophers began to revise and reinterpret the traditional disease descriptions and classifications, pointing out the many inconsistencies among the criteria used to define them:

The use of... particular diagnostic terms may lead us to believe that a real disease exists, whereas it really indicates our basic ignorance, masked by our ability to make superficial descriptions ... As the history of medicine has demonstrated, these shifting similarities which we call entities depend not so much on reality as on the things we are able to measure and choose to see.—Theodore Greiner, 19652

The current taxonomy of disease is a polyglot of diverse ideas and names. The available diagnostic terms for disease include different categories of topography, morphology, physiology, biochemistry, microbiology, genetics, “clinical states,” syndromes, signs, and habits.—Alvan Feinstein, 19773

Both the infectious disease, discussed in this chapter, and the non-infectious one, discussed in the next, have seen their boundaries disappear into the gloaming, like the Cheshire cat, leaving behind nothing but the smile.

The Koch-Henle Postulates

Menninger blamed an “infestation” or “lurking bacterium” for one class of diseases, and among his contemporaries it was an article of faith that many “diseases” are caused by specific and unchanging microbes.

The relationship between disease and microorganism was defined by the Koch-Henle Postulates, suggested in 1840 by Jacob Henle and restated several times by Koch in the 1880s:

• The microorganism occurs in every case of the disease and under circumstances which account for the disease’s

clinical course and the associated pathology;

•    I he microorganism does not occur in any other disease as a fortuitous and non-pathogenic parasite;

•    After being isolated from the host organism and cultivated outside it, this microorganism can induce the same disease in a healthy organism.—Alfred S. Evans, 19764

These postulates started to erode as soon as they were introduced and have today lost practical relevance. While lip-service is still paid to them, they are, in practice, all but abandoned. The first postulate was undermined by the continuing vitality of pleomorphism and the second by discovery of the disease “carrier,” while the third has not been capable of fulfillment in a number of diseases, especially those of supposed viral origin.

I he bacteriological paradigm has cracked at the faultline between its Rationalist and its Empirical components. The factors which engendered it at a particular moment in history have gone their separate ways, leaving the Koch-Henle postulates hollow and lifeless.

The First Postulate

Koch and his generation were confident of their monomorphist identification of microbes with “diseases,” but with time this relationship dissolved into ambiguity. Blind certainty about disease entities was possible only because allopathy ignored the factor of host resistance. As resistance came increasingly to the fore, the role and significance of the microbial cause has declined.

The first prominent threat to the germ theory was, of course, the pleomorphism of Carl Wilhelm von Naegeli, but the great Koch himself had made pleomorphist observations w'hich he later shunted aside. When Almquist, w'orking on typhus in Koch’s laboratory in 1881, observed not only the typical rods of Eberthella typhi, but also oval nonmotile bodies—the so-called Eberth-Koch forms—the latter were renounced by Koch, leading Almquist to comment: “Thus ... scientists have striven to make Nature less complicated than it is.”5

Ferdinand Cohn, too, was less monomorphist in his earlier writings than he became later, out of pressure from his disciples

and from circumstances generally. In 1872 he urged investigators to study the whole life history of a bacterium since otherw ise the different developmental forms could be mistaken for other microorganisms. And initially he regarded his bacterial genera as purely formal categories. Only with advancing age did he conclude that they were natural.6

These green shoots of pleomorphist thought were crushed by the juggernaut of monomorphism and went into hibernation for a decade or so. But then, in the early 1900s, bacteriologists started reporting mysterious form and phase changes in their cultures.

Albert Neisser and Rudolf Massini in 1906 and 1907 showed that B. coli-mutabile could be converted from non-lactose-fermenting to lactose-fermenting merely by adjusting the medium. At the same time Frederic William Tvvort in England described the acquisition of new fermentative powers by organisms of the colon-typhoid group. His colleague, E. G. Hort, in 1915 concluded that an organism detected in patients with cerebrospinal meningitis was a pleomorphic fungus belonging to the as-comycetes, a late non-virulent stage in the life-cycle of a microbe whose filterable phase is virulent.7

Hort also described a new mode of reproduction. Bacteria had been thought to reproduce exclusively by fission or sporula-tion, but in 1916 he observed reproduction through formation of gonidial bodies (buds) in colon-typhoid organisms.8 The same lateral and terminal buds w'ere observed on B. typhosus when grown on acid media; they were seen later to give rise again to normal rod forms, and he concluded that B. typhosus reproduces through sexual conjugation and endosporulation.9

The issue of how bacteria reproduce was at the center of the dispute. Allowing them too much sexual freedom, or even a sex life at all, clashed with Rationalism’s disposition to maintain control over the phenomena, and sexual reproduction by bacteria was denied vigorously for decades.

Felix Loehnis in 1916 observed a variety of cell forms in cultures of Azotobacter and concluded that the classic form of this organism is merely a stage in the life cycle of a spore-forming bacillus. In a lengthy monograph (1922) he demonstrated that these same structures had been observed by many previous bacteriologists who overlooked or underestimated their significance. Cohn, for example, had early on demonstrated the presence of gonidia in Crenothrix, suggesting a sexual mode of reproduction.10 Loehnis further extended the gamut of techniques by which bacteria could reproduce: “Contrary to the monomorphistic theory which only knows one constant type of vegetative cell for every species, and not more than one type of reproductive organ, the endospore, for merely one group of bacteria, it has been ascertained by numerous independent investigations that in reality all bacteria are not only distinctly pleomorphous in their vegetative growth, but are also able to produce various organs of reproduction. These are: gonidia, regenerative bodies, exo- and en-dospores, arthrospores, and microcysts.”11

The Socioeconomic Basis of Pleomorphism

A major socioeconomic factor contributed to the resurgence of pleomorphism in the early twentieth century. The causal organisms of the great scourges—diphtheria, anthrax, cholera, syphilis, tuberculosis and the like—had been identified or were on the way to discovery, and pharmaceutical substances or immunologic methods had been devised to combat them. With these pressing public health problems nearing solution, investigators could indulge their curiosity and transgress strict monomorphist guidelines.

fhe new observations were at first regarded merely as exceptions to the monomorphist rule.12 But in 1921 Joseph A. Arkwright made the fundamental discovery of “rough” (R), “smooth" (S), and mucoid (M) bacterial cultures, leading to general recognition of bacterial “dissociation”—the capacity to separate into different strains with quite different characteristics, of shape, presence or absence of capsule, colony type, biochemical characteristics, or virulence.13

“Dissociation” could be, and was, demonstrated with pure cultures and even single-cell cultures, proving that it was not due to contamination of the medium by other species or strains.14

This was a blow to the doctrine of “normality,” and pleomorphism now sensed its own legitimacy.

So firmly has the monomorphistic viewpoint been established that research on [morphologic variation in bacteria] has been almost completely discouraged; bacteriologists have frequently noted that their organisms appeared different from day to day, but have blindly considered all variations from the textbook picture as pathological, as evidence of injury or death of the cells, or else have considered the variations noted to be of such a haphazard character as to be of no significance.—Arthur T. Henrici, 192815

Little by little, bacteriologists appreciated that “pure culture” is a misnomer and that any culture medium has an effect on the microbes living in it:

The isolation of a pure culture does not merely consist in the elimination of unrelated microbial species. It involves a process of domestication, an adaptation of the culture to life on a certain medium and under certain conditions. Pure cultures of microorganisms, even issued from single cells, do not consist of identical individuals, and bacteria are more striking in their variability and plasticity than in the fixity of their morphological, biochemical, and physiological characteristics. The pure culture technique results in the selection of a population made up to a large extent of the type of cells best adapted to a given environment, and any change in the latter is likely to be reflected in some modification of the appearance and of the very constitution of the cells. Moreover, the characters of a pure culture do not always remain unchanged even when the conditions of growth appear well defined and stable. Transformations—permanent or transient—not only of a quantitative, but often of a qualitative nature—appear in an unpredictable manner under conditions w’here the “purity” of the culture cannot be doubted.—Rene Dubos, 194616

Almquist was one of the leaders of the new trend. In 1911 he worked with members of the colon-typhoid-dysentery group of organisms in old cultures kept at low temperatures on drying media, observing the formation of exogenous globular forms (conidia) out of normal rod forms by lateral or terminal budding. Sometimes the conidia, in turn, generated rod forms, sometimes new conidia. When the conidia were filtered, the filtrate yielded new conidia, suggesting that the bacterium could assume a filter-passing form. In later papers (1924) Almquist claimed to have crossed typhoid and dysentery organisms, forming a hybrid.17 After twenty-one years investigating pleomorphic forms, he commented: “Nobody can pretend to know the complete life cycle and all the varieties of even a single bacterial species. It would be presumptuous to think so, at least in our day.”18

Five years later, Philip Hadley concurred with Almquist: “When confronted on every side with such pictures of bacterial instability, certainly of a pattern too extensive and intricate to admit of clear exposition, but the general nature of which most bacteriologists realize, it is logical, first, to inquire whether the confusion we observe is pure chaos, or whether there exists any trace of orderliness amidst the general disorder, the extreme possibilities of which were first pointed out by Naegeli ... Bacillus an-thracis, as a ‘bamboo rod' of certain shape, size, colony form, and pathogenicity, has occupied the attention of countless bacteriologists for fifty years: but who at present would dare affirm that we know the anthrax species? Our ignorance of some of its most intrinsic characteristics is nearly as great today as it was half a century ago.”19

Ralph R. Mellon, in 1926 and 1927, described morphologic, serologic, and cultural variations in diphtheria, typhoid, and colon bacilli. He suggested that bacteria pass through a life cycle in which rods, spheres, branching forms, etc., appear in sequence. Further, that any one of these types may be “stabilized,” meaning that each stage in the cycle can reproduce itself without continuing through the cycle. He also described the separation of variant forms from cultures through filtration: they differ markedly from the parent forms, especially in virulence. Mellon stressed, as had other pleomorphist pioneers, that the filtered variants are derived from minute, perhaps ultramicroscopic, conidia.20

While life-cycle variations could still be contained within a modestly expanded monomorphism, these more radical tendencies led automatically to consideration of inter-species, intergeneric, and even inter-family transmutation:

It does not necessarily follow that because Koch was wrong Naegeli was right; and yet in the writings of at least some of these new pleomorphists, their protests to the contrary notwithstanding, there is clearly evident a tendency to return to the old idea that any bacterium may transmute to the form of any other ... Naegeli redivivus ... What does the dominant school of Koch say to that?

—Arthur T. Henrici, 192821

The process was different in each country. The German/Austrian school went from dogmatic monomorphism to moderate pleomorphism. The French from the outset had a penchant for pleomorphism. The British were somewhere in between. The Americans, newcomers to the scene and perhaps feeling insecure in the Big Leagues of bacteriology, were usually more Catholic than the Pope:

There are ... only comparatively few American textbooks which do not adhere to the rigid monomorphism which had been taught in Germany.—Felix Loehnis, 192222

Guenther Enderlein

The 1924 masterpiece, Bacterien Cyclogenie, by Guenther Enderlein (1872-1968) gave a somewhat different slant to pleomorphism. While rejecting the views of von Naegeli: “It is truly no wonder that this type of judgment of the facts, which shot well beyond the mark, completely discredited the entire concept of pleomorphism, ” Enderlein proposed a similarly complex and far-reach-ing theory of bacterial transformation, backed by a decade of laborious and systematic microscopic observations.23

He followed medical tradition in distinguishing between acute and chronic disease. The former, caused largely by microorganisms from outside the body, were also outside the frame-w'ork of his analysis, wrhich dealt exclusively with the allegedly endogenous microbial causes of chronic illness.24

The healthy host, in Enderlein’s view, is filled with primitive life forms—“protits” or “centrosomes”—which reside in the red cells, white cells, plasma, and other fluids, are 0.01 micron in radius (about the size of a virus), and can be seen by dark-field microscope as tiny shining points. When the host is in health, protits live in symbiotic relationship with the tissue cells. But when the host balance is destroyed, they lose their symbiotic qualities and evolve upward through a virus-bacillus-fungus cycle which is progressively more hostile to surrounding tissue cells. This “endobiosis complex” or “endobiont” (Enderlein’s term for all developmental forms of protits) generates much chronic illness. Factors which lead to such disturbance in the body’s balance include a diet with too much animal protein and fats, exposure to mutagenic substances, excessive intake of tobacco or alcohol, and various deleterious environmental influences.25

He saw the “endobiont” as a hydra-headed monster causing a variety of chronic conditions: cancer, leukemia, arteriosclerosis, rheumatism, arthritis, diabetes, ulcers, multiple sclerosis, glaucoma, stroke, and others. In their ultimate pathogenetic development the protits transmute into Alucor racemosus Fresen (in blood-related diseases, hemorrhoids, varicose veins), Aspergillus niger (in tuberculosis-related diseases, prostate cancer, AIDS), Mucor mucedo (in chronic sinus conditions, bronchial infections, rhinitis), Penicillium notatum (in streptococcal and staphylococcal infections, scarlet fever, rheumatic fever, yeast and fungal infections), Penicillium frequentans (in multiple sclerosis, influenza, herpes, varicella-zoster), Candida parapsilosis (in herpes simplex, Candida, and chlamydia infections), and others.26

Enderlein’s therapeutics was simple isopathy, using a homoeopathic dynamization of the microbe assumed to lie at the root of the given chronic condition.2713

Universal acceptance of his novel formulations was inhibited by the fact that he was theorizing beyond the limits of resolution of existing microscopes. Henrici commented in 1928 that Ender-

bIf Penicillium notatum is indeed, as Enderlein maintained, at the root of streptococcal, staphylococcal, and other infections, medicinal penicillin may act as an isopathic idem in these conditions! See below, p. 543.

lein’s “description of the centrosome with dimensions of 0.01 micron ... seriously impairs one’s faith in the accuracy of his other observations.”28 But his theories, nonetheless, have retained credibility to this day.

Enderlein died at ninety-six, having developed his pleomorphism for sixty years or longer. Hence not every detail can be given. Indeed, the theory changed over time, as did his idiosyncratic vocabulary of two hundred neologisms. But the essential thrust remained the same, constituting an amalgamation of homoeopathy and the “microzyme” theory of Pasteur’s nineteenth-century opponent, Antoine Bechamp.

Bechamp had described the microzymes as tiny granules contained within animal and plant cells which, under appropriate circumstances, develop into pathogenic bacteria.29

While Enderlein and other investigators popularized the concept of bacterial growth cycles, most bacteriologists were still unwilling to accept sexual forms of reproduction.30 Another objection was that experimenters were rarely able to show the complete cycle from start to finish:

It is often stated that although a sequence of developmental forms may be observed microscopically, they do not reveal a cyclical trend that brings them back to the starting point ... such culture developments should include a reversion to the original culture stage rather than manifest merely indefinite transitions—leaving the new form hanging in the air, as it were.—W. H. Park and A. W. Williams, 193931

But Enderlein’s ideas fascinated many who (like Arthur Henrici) noted that, “While the whole thing sounds like a strangely complex product of the imagination, the hypothesis is a very orderly and systematic one compared with the rather vague and confused ideas of Almquist, Loehnis, Mellon, and Hort.”32 In 1927 Philip Hadley’s 312-page article in the Journal of Infectious Diseases recapitulated and put on a solid basis existing knowledge about microbic dissociation, this being seen as part of a pleomorphic process: “For the past three decades there has been accumulating an ever-increasing mass of evidence pointing to the instability of bacterial species. Cocci become rods and rods cocci or spirals; forms of growth change overnight; motility is lost and regained; fermentation reactions are modified by time and opportunity; spore formers become sporeless; hemolytic activity comes and goes; capsulated bacteria lose their capsules, and capsules are gained by noncapsulated forms; antigenic power vanishes and reappears; cultures become spontaneously agglutinative or fail of agglutination; virulent cultures become harmless and harmless cultures virulent.”33

Hadley hypothesized that “many aspects of observed bacterial instability, far from being a sign of chaos, are in reality indicative of the action of certain biologic laws which are orderly in their operation” and these laws looked very much like the bacterial cyclogeny of Guenther Enderlein.34

Viruses and Filtrable Forms of Bacteria

In the United States, the last upsurge of the pleomorphism controversy was the struggle in the early 1930s over the relationship between viruses and the so-called “filtrable forms” of bacteria.

The era of virology commenced in 1892 with the discovery that the tobacco mosaic disease is caused by an agent—later called “virus”—capable of passing through earthenware filters impervious to bacteria. Smallpox, influenza, hoof-and-mouth disease, and others were found to be caused by viruses, and virology soon became an independent discipline, very much identified in the United States with the name of Thomas Milton Rivers.

A major distinguishing feature of the virus was said to be its inability to grow and develop in a lifeless medium, necessitating cultivation in one containing live cells.

From the beginning virology was threatened by the pleomor-phist currents in bacteriology. According to Enderlein, for example, all microorganisms developed from virus to bacillus to fungus, and if this were true, the whole status of virology as an autonomous discipline was undermined.35 The issue became acute in the late 1920s when several investigators announced the

discovery of an invisible and filtrable stage in the life cycles of many bacteria. Since the work of Almquist in 1911 011 typhoid, it had been suspected that this bacillus, as well as the meningococcus, Azotobacter, tubercle bacillus, Shiga bacillus, cholera vibrio, streptococci, staphylococci, and other microbial life forms manifested a smaller, filtrable stage in addition to the familiar larger, non-filtrable one by which they were usually identified.36

This raised the issue of a relationship between the “filtrable stages” of bacteria and the viruses.

Philip Hadley, an admirer of Enderlein, held the two to be identical. In 1927 he outlined a new' theory involving a mechanism of sexual reproduction in bacteria, recognition of the En-derleinian theory of cycles, and acceptance of viruses as part of the cycle.37

Hadley’s thesis was actively resisted by Rivers and other leaders of bacteriology and virology.

The issue became exacerbated in 1931 when Arthur Isaac Kendall, a prominent and respected bacteriologist, announced development of a non-living, cell-free medium (the “K-medium”) upon which he professed to be able to grow viruses. The institutional autonomy of virology was thereby seriously threatened, since the one clearcut distinction between viruses and bacteria was about to disappears

Kendall’s position was buttressed by his access to a new, and far more powerful, light microscope developed by an otherwise unknown inventor, Royal Raymond Rife.

The Rife microscope had a magnification of up to 50,000 diameters, at a time when the best existing light microscopes could magnify only 1000-2000 diameters (the electron microscope, capable of 100,000 diameters’ magnification, was still in the future).38 It illuminated the specimen by a narrow polarized beam, sometimes a single frequency, causing it to “glow" with its own specific color.39 Kendall used it to observe filtrable forms of B. typhosus, the poliomyelitis and scarlet fever microor-

cSixty years later, in 1991, researchers again announced that virus had been raised in a cell-free medium (A. Molla et at., “Cell-Free, De Novo Synthesis of Polio virus”).

ganisms, B. paratyphosus alpha, Leptospira icteroides, and Staphylococcus aureus.40

In an article coauthored with Rife, Kendall described growing B. typhosus on the cell-free medium, filtering it and examining it under the Rife microscope: “In this polarized light the thrice-filtered culture of B. typhosus cultivated in K (protein) medium showed small oval granules, many of them quite actively motile. These motile granules when in true focus appeared as bright turquoise-blue bodies which contrasted strikingly, both in color and in their active motion, with the noncolored, nonmobile debris of the medium.”41

This and other articles on the Rife microscope in 1931 aroused great professional interest.42 Science called it a “sensational new instrument.”43 California and Western Medicine published an editorial: “Is a New Field About to be Opened in the Science of Bacteriology?”44

But the field was never opened, as further discussion of this potentially revolutionary development in pleomorphism wras foreclosed by fiat of the current leaders of virology and bacteriology. At the May, 1932, meeting of the Association of American Physicians both Rivers and Hans Zinsser, professor of bacteriology at the Harvard Medical School, attacked Kendall personally and violently, accusing him of introducing spontaneous generation into bacteriology, charging that his experiments were impossible, that virus could not be induced to grow on a cell-free medium, and suggesting that he had simply made up the data.45 Rivers later told his biographer, “I got up and in a very temperate manner, called the fellow a liar. Not in so many words. Actually, all I said was that I couldn’t repeat the experiments, and I therefore didn't believe his findings were true.”46

There was little further discussion of filtrable forms after that, and the Rife microscope was relegated to oblivion, to be rediscovered some decades later in pieces in a San Diego garage.47 Amazingly, the research community turned its collective back on a microscope that was an order of magnitude more powerful than those in current use.48

American bacteriology thereafter settled into the uneasy monomorphist mode where it has remained.

Bacterial Classification

But pleomorphism, while largely expunged from bacteriological therapeutics, made its presence felt in bacterial classification.

Implicit in the doctrine of the fixity of bacterial strains was the assumption that they can be ranged hierarchically into families, orders, genera, species, and the like. This, however, has proved impossible.

It was not from lack of trying, as the categorization of phenomena is always high on the Rationalist agenda. But such efforts have all collapsed.

In the eyes of pleomorphist critics, monomorphist failure to include information about life-cycles meant incorporation of “many badly studied unstable varieties as constant species'” and led to “chaos in systematic bacteriology.”49

Among the bacteria the species-concept has always offered peculiar difficulties ... And the manner in which solutions have been attempted, probably under the misapprehension that the private life of bacteria is really as simple as it seems, has done small credit to taxonomists or to bacteriologists in general. One result of this failure to obtain a firm basis for taxonomy has been that numerous so-called “species” have been described and catalogued long before there was at hand any fundamental know ledge concerning the nature and organization of bacteria; or any valid conception of the nature of the bacterial individual.—Philip Hadley, 193950

In the 1940s the emerging science of genetics promised a solution, but geneticists, while displaying much wishful thinking, wrere no more successful than their predecessors:

The characteristics which determine species barriers ... must [??] have reached stabilities which cannot be affected by ordinary mutations and lead to viable progeny, [emphasis added]—Werner Braun, 194751

It must be recognized that mutational ranges of [bacterial] species may overlap, resulting in the often confusing observations that the progeny of one species may display characteris-

tics typical of another species, or even species belonging to different genera [emphasis added]—Werner Braun, 194752

Werner Braun’s 1953 Bacterial Genetics admitted failure in establishing bacterial genera and species: “Such overlapping of the mutational ranges of diverse species does not mean that there is a continuous genotypic spectrum connecting all bacteria. [??] In other words, the potential genotypic and phenotypic range of each species, i.e., the potential mutations of a given biotype, are normally limited ... changes within initially homogeneous bacterial populations apparently do not progress beyond certain boundaries under experimental conditions ... However, in nature, countless generations of bacteria have been subjected to a great variety of environmental conditions throughout the ages, which greatly increased the opportunity for the rare occurrence of a particular genotype (chance association of certain genes) that would yield viable progeny with selective value when an additional mutation occurred. Such rare mutants, overstepping the normal boundaries of a species’ mutational range, then could attain evolutionary significance” [emphasis added].53

No official genetics-based or other classification of bacteria has yet been achieved.54

The lack of definitive unifying criteria for species designation in bacteria has understandably resulted in variation in levels at which groups are divided, depending upon whether the describing investigator is a splitter or a lumper. In the splitter category are those who have designated each Salmonella serotype (serovar) as a species with its own name. The lumpers, on the other hand, have designated individual serotypes as numbered types within a single species of, for example, Klebsiella or Streptococcus.—Wr. K. Joklik et al., 198855

Bacterial species collections contain strains of interrelated but differing organisms, sometimes known as a cluster. The species description includes the main features of the collection. Within each species collection or cluster, a strain is chosen arbitrarily to best represent that species, [emphasis added]—W. K. Joklik et al., 198856

A true classification of bacteria, thus a true delineation of families, orders, genera and species, would have to be based upon evolutionary, i.e., phylogenetic, lines of descent and checked by evidence of genetic relations between species and genera. But, for lack of fossil records, no phylogenetic classification is possible, and the evidence of genetic relationships is too confused to be a guide.57

Despite inability of a century of bacteriological research to define the boundaries of these supposed genera and species, the suggestion is never heard that the search for them should be abandoned another example of the power of unexamined Rationalist assumptions. Definitional criteria are advanced at regular intervals, and as regularly rejected. But the monomorphist conviction that genera and species do exist somewhere still retains a “peculiarly tenacious hold.”d

Against this background of confusion, pleomorphism has made a comeback, as seen in such works as Lida Mattman’s Cell Wall Deficient Forms: Stealth Pathogens (1974, 1992) or A New Bacteriology by the French scientists Sorin Sonea and Maurice Panisset (1983).

Mattman demonstrates that all bacterial species have variant forms (L-forms) which may play important roles in medicine and agriculture and have been largely ignored by Rationalist medicine.58

Sonea and Panisset (embodying the French penchant for pleomorphism) are more radical, and also more theoretical, totally rejecting all bacterial classification. They maintain that the whole of the earth’s microbial life constitutes a single collection of genetic material (“genome”) adequate to supply every microbial genus and species. Each microorganism, in their view, has access to this genome and borrows from it genes as needed—employing conjugation, transformation, transduction, and other mechanisms of gene transfer which are still incompletely known. Genes are relinquished when environmental circumstances no longer require their use for survival.59

The French microscopist and bacteriologist Gaston Naessens follows Bechamp and Enderlein in holding that bacteria and other microorganisms arise from degenerated subcellular components of higher organisms.60 What were earlier called “mi-crozymes” or “protits” Naessens calls “somatids”—immortal particles of life which survive the death of the individual. When the individual is unhealthy, the somatid passes through a multistage cycle of degeneration and regeneration, each stage, in turn, being capable of independent life and reproduction. The degenerated stages of somatids give rise to bacteria and other microorganisms.

Naessens demonstrates and describes each such stage, with return to the starting point, thus meeting an earlier objection to the idea of a bacterial life cycle.

Like Royal Raymond Rife, Naessens employs a light microscope of his ow'n design (the “somatoscope”) which permits enlargements of 30,000 diameters with a high degree of resolution (150 angstroms).61 Through it he can observe the somatids— which appear as tiny points of light moving around in blood samples. With this information he diagnoses and prognoses disease states.

The somatids, in fact, greatly resemble the description given by Kendall and Rife to their “filtrable forms” of bacteria, showing up in a dark-field microscope as rapidly moving brightly colored dots of turquoise, yellow, red, and blue.

Although the doctrines of Enderlein and Naessens have yet to be acknowledged by Rationalist school medicine, late twentieth-century bacteriology has nonetheless lost confidence in the fixity of microbial species. This, in turn, renders unstable the first Koch-Henle postulate.

Host Resistance: Exogenous and Endogenous Disease

Ignored by the Koch-Henle doctrine was the factor of host resistance to exogenous microbial causes. To societies confronted with the virulently infectious diphtheria, typhoid, and Asiatic cholera, host resistance seemed a negligible consideration. But with the progress of nutrition and public health, with the introduction of

clean water and the improvement of urban and rural sanitation all of which supported the resistive capacities of the host organism—infectious epidemic diseases declined in significance.

Sickness was seen to involve interaction between the causal microbe and the defensive and reactive capacities of the host organism:

The period in which all zymotic diseases were attributed solely to the introduction of bacteria, or protozoa, into the otherwise healthy subject is, happily, passing away, and pathologists and others are increasingly recognizing as a fact the necessity for the bodily conditions being suitable before the disease germs can multiply extensively in it.

—Alfred B. Searle, 192062

Infection is nothing more nor less than the reaction of an individual to a particular kind of insult ... with two people equally exposed to infection one may acquire it and one may not.—Hugh Cabot, 192163

It was very soon discovered that the germ was not enough to explain the whole pathologic process. The factors of environment were understood better, and it was easy to see that the organism was not passive before the “attack" of the microbe. Predisposition, immunity, resistance, etc., had to be taken into consideration ... the microbe produces disease only because there exists in the organism the potentiality to answer in a determined sense.—Alberto Seguin, 194664

The notion of socially induced stress as a precipitating factor in chronic diseases is gaining acceptance among a wide spectrum of scientists ... Even susceptibility to microbial infectious diseases is thought to be a function of environmental conditions culminating in physiological stress on the individual, rather than simply of exposure to an external source of infection.—Judith Rabkin and Elmer Struening, 197665

As the microbe’s importance declines, and that of the host is enhanced, the interaction between them becomes unstable, further undermining Koch’s first postulate:

The same pathologic or clinical state can be produced by different etiological agents ... These causative agents may vary in different geographic areas, in different age groups, or with different patterns of host susceptibility ... Some diseases require the presence of two or more agents or cofactors acting together to produce the disease ... A single agent may produce different clinical and pathological responses in different settings.—Alfred S. Evans, 197666

Resistance resembles immunity and shades over into immunity. Persons immune to poliomyelitis can become infected with polio virus without falling ill; the virus multiplies for a while in the intestinal tract, but illness does not develop.67 The same is true for herpes virus and many others.68

Causation is rarely ... simple or direct ... while the tubercle bacillus can be demonstrated in all people with tuberculosis, the opposite does not hold true. All people exposed to, or harboring, mycobacteria do not develop tuberculosis. This concept of cause essentially excludes factors within the patient as host to the disease^ or aspects of the environment which may promote the disease ... Because disease theory so effectively concentrates medical attention on the disease and the classical understanding of its cause, such other factors may be dismissed as non-medical—in the province of, say, social workers.—EricJ. Cassell, 198669

The expression “attenuated infection” was introduced in 1960 to designate the ability of a microbe to cause infection which, because of host resistance, does not eventuate in full-scale disease.70

The peaceful coexistence of microbes with the host organism has been called “commensalism” by Rene Dubos—i.e., “eating at the same table.” It is, of course, related to the carrier state and to “premunition.”e

Adaptation plays an even greater role in endogenous than in exogenous disease. As the strikingly noxious diseases caused by

' Rene Dubos, Alan Adapting, 183 185 (see above, pp. 161 165).

exogenous bacteria were brought under control, attention was increasingly directed to diseases of endogenous origin.71 Where loss of resistance in the past had often led to death from one of the great epidemics, in late twentieth-century industrial societies it more commonly means illness from one of the usually harmless microorganisms which each harbors in his body or on it:

Awareness of the fact that most pathogens are widely distributed and yet do not cause clinical disease except in a very small percentage of persons and animals harboring them has come chiefly from the study of latent viral and rickettsial infections. Laboratory animals carry a large variety of viruses, which can be evoked into activity ... by all sorts of non-specific stresses ... The isolation of adeno viruses from the tonsils and the adenoids of healthy persons constitutes evidence that latent viral infections occur also in man ... some 150 different viruses have been recovered from man, and for many of them there is no evidence that they are associated with disease states ... Latent infections of man with virulent bacteria, fungi, and higher parasites are at least as common as are those with viruses and rickettsia ... Until a few years ago, practically all human beings in the Western world became infected with tubercle bacilli early in life, and this situation still exists today in most underprivileged countries; yet only a small percentage of tuberculin-positive persons develop clinical tuberculosis.

In the United States, Amoeba histolytica can be isolated from the stools of a surprisingly large number of persons who have never suffered from amebiasis. Similarly, some thirty percent of the population give a positive skin test for toxoplasmosis, and encysted trichina are often found in the muscles in the absence of any clinical sign of trichinosis ... the causative agents of syphilis and gonorrhea can also persist in apparently healthy persons. Indeed, the list of latent infections with all classes of pathogens continues to grow as the search for them is expanded.—Rene Dubos, 196572

Just as exogenous microbial causes can yield infection, but not “disease,” if host resistance is sufficiently high, so endogenous

microbial causes can coexist undisturbed for decades with the host organism and flare into “disease” when resistance is undermined.

Coliform and other gram-negative bacteria, the non-he-molytic streptococci, various yeasts and fungi, and other usually innocuous microorganisms can generate serious pathological states when host resistance is depressed.73

The human skin harbors all the gram-negative bacteria found in infected wounds, but they do not infect ordinary cuts and scratches.74 Pharyngitis, sinusitis, and pneumonia are associated with microorganisms commonly found in the mouths of healthy persons.75 In an epidemic one member of the family falls

ill, while the others remain healthy.76

The discovery of endogenous disease is a belated justification of Bechamp’s assertion that most diseases originate within the body, merely awaiting the right moment to display full toxicity, an assertion which provoked both Pasteur and Koch to claim that the body’s internal environment is sterile.77

Adaptation and Pleomorphism

Pleomorphic change, in both exogenous and endogenous diseases, is the microbe’s adaptive response to the resisting host organism:

I he truth we shall eventually come to is that the free-living microorganism is potentially a kaleidoscopic thing, in which the power of responding successfully to a changing environment by alterations in body state, both morphologic and biochemical and even by self-destruction, if need be, in order to generate another and more stable type—stands as its one most important attribute.—Philip Hadley, 192778

I he microbe adapts to the host, or the host to the microbe, depending on the relative strength of the two sides. Clinical illness develops when resistance is low—because of stress, malnutrition, concomitant disease, the individual’s immunologic history, constitution, or some morbific force in the environment.'9 These factors cannot always be measured, or even estimated, with precision:

The ability of microorganisms to produce pathologic changes is under the influence of large biologic forces as yet poorly understood which do not necessarily manifest themselves in the form of recognized immunochemical reactions.—Rene Dubos, 195880

The struggle with the host organism makes microbial species labile and capricious; it is responsible for the non-fit between bacterial species and “disease.”

Respiratory diseases, diarrheas, infections, skin diseases, and central nervous system infections fall in the class where a given clinical state is associated with a variety of microorganisms, or with no identifiable microbial cause:

Despite intensive investigation no causative agent [can] be identified in twenty-five to fifty percent of common acute respiratory syndromes, in seventy-five percent or so of acute febrile clinical syndromes involving the central nervous system, or in most cases of common acute gastroenteritis.

Alfred S. Evans, 197681

Bacterial endocarditis used to be associated exclusively with streptococci, but after antibiotic treatment was introduced, other microbial species were seen to be replacing streptococci in the cardiac lesions.82 Nephritis is usually associated with some bacterial infection but can occur as well in the absence of infection.83

The reverse situation—where the same microbe causes a multiplicity of different clinical states—is true preeminently of viral diseases. Baruch Blumberg (1976 Nobel Laureate in Physiology and Medicine) found that hepatitis B virus can yield such different clinical processes as acute hepatitis, chronic hepatitis, chronic infection of the liver without hepatitis, end-stage liver disease, and cancer of the liver, or, in the alternative, have no effect at all on the host.84 Respiratory syncitial virus is a major cause of severe respiratory disease in infants but yields mild or asymptomatic infections in older children; some strains of adenovirus cause acute respiratory diseases in soldiers but have no effect on young adults in a civilian setting; and the same viruses provoke quite different central nervous system inflammations, depending upon the host characteristics.85

The Second Postulate

The second Koch-Henle postulate—that the microorganism does not occur as a fortuitous and non-pathogenic parasite—has been undermined by the disease carrier.

The diphtheria “carrier state” was a major source of anxiety for health departments in the early 1900s, since carriers were responsible for many outbreaks.86 But the carrier state exists in many other infectious diseases: Asiatic cholera, bubonic plague, typhoid and paratyphoid, epidemic cerebrospinal meningitis, bacillary dysentery, poliomyelitis, pneumococcal pneumonia, streptococcal infections, influenza, etc.87

The existence of infection without disease was recognized early, long before the designation “carrier state” was coined for the concept and long before Typhoid Mary became its personification. But it is only during the past two decades that the generality of the phenomenon has been appreciated.—Rene Dubos, 196588

The Third Postulate

Koch’s third postulate—that the causal microorganism must be isolated and shown capable of generating the disease in an animal host—was the first to topple. In 1883 Koch discovered the cholera vibrio and was able to cultivate it in the laboratory, but he could never reproduce cholera in test animals.89

His great contemporary, the hygienist Max Pettenkoffer, was so unconvinced that a microbe can at all times cause its specific “disease” in any host organism that in 1880 he drank a cubic centimeter of fresh Asiatic cholera culture with no ill effect, other than excreting a large amount of vibrio in his stool (some of his students who repeated the experiment suffered mild diarrhea).90 Koch himself would go only so far as to admit that those who have “previously suffered from some disruption of the digestive

tract or overloaded their stomachs with indigestible food” might be vulnerable: “everyone is certainly aware that most cases of cholera occur on Mondays or Tuesdays, thus on days preceded by excessive eating and drinking.”91

Later research has revealed that cholera is caused by several endogenous bacilli which become dangerous to life when the individual is already weak; more than most diseases, cholera morbidity and mortality reflect the level of host resistance.92 The vibrio and its congeners are endemic to the water supply of many countries where they are ingested without harm by thousands who remain in good health.93

About tuberculosis Koch was more forthcoming, ultimately accepting a general congenital predisposition: “First, there are striking differences in the course of the disease between children and adults, there is also the unmistakable predisposition of many families for tuberculosis.”94

Further investigation showed that the supposed causal microorganisms of typhoid, diphtheria, leprosy, and relapsing fever could not be induced to meet the criterion of the third Koch-Henle postulate; the diseases could not be produced anew in an experimental host.95 “Predisposition,” i.e., a factor intrinsic to the host, entered the picture at an early stage and to this day undermines the Koch-Henle postulates, so that the third postulate is sometimes interpreted to read that the isolated organism should reproduce the disease in other “susceptible” animals:

What is meant here by “susceptible,” other than not immune, is an interesting but difficult question.

—J. H. Woodger, 195696

Empiricism and Rationalism in the Pleomorphism Controversy

A therapeutic doctrine should not be so complex or cumbersome that physicians are unable to apply it; hence the subconscious impulse to restrict the heterogeneity of nature. The phenomena are forced into categories which can be manipulated to make a living from the practice of medicine.

A doctrine which limits the variety of diseases or bacterial species will always be more popular with physicians than one which extends this variety. Monomorphism simplified reality at the expense of scientific precision, but it also simplified medical practice—which did not detract from its popularity.

This clarifies Hadley’s peculiar comment in 1931 that the discovery of R, S, and M bacterial cultures was not welcomed everywhere: “Even today these are a source of anxiety to many workers, especially those engaged in the field of systematic bacteriology.”97 He continues, “Although [monomorphism] has now become hardly more than a matter of historical interest among many laboratory bacteriologists, [it] still retains a peculiarly tenacious hold on many of the principles of systematic bacteriology and taxonomy. Bacteria, as described in the latest systematic works, are still portrayed as essentially monomorphic; and this is because, in taxonomy at least, the bacterial individual is still regarded as monomorphic. This viewpoint has, through the years, taken on such an aspect of truth that to question it now seems a scientific sacrilege.”98

Because a conflict between the Empirical and Rationalist paradigms must necessarily extend to other areas of medicine and therapeutics, the parties instinctively feel that much is at stake. The rigid monomorphists adhered equally rigidly to other tenets of Rationalism, while pleomorphists were attached with equal tenacity to Empiricism.1 Hence the emotional heat which infused the controversy from its inception. Observers and participants alike remarked on its peculiar bitterness.

The followers of Koch proclaimed monomorphism w ith “religious fanaticism,” stated Max Gruber in 1885.99 Sonea and Panisset write: “The intransigence and verbal violence displayed by the various factions in this conflict resembled certain historic theological quarrels.”100

The monomorphists went so far as to equate an attack on their doctrine with an assault on “science” itself. Carl Fraenkel responded to the von Naegeli position: “If the above were cor-

fVon Naegeli’s research brought him very close to homoeopathy late in life (Carl von Naegeli, Ueber oligodynamische Erscheinungen). See below, p. 293.

rect, scientific investigation of bacteria would be an impossibility ” [emphasis added].101 A German bacteriologist in 1910 exclaimed: “Hearing [pleomorphist] views one grasps one’s head to make sure it is still on the shoulders. The whole structure of our science threatens to collapse.”102

Winogradsky called pleomorphism “chaotic ... truly, the whole of a researcher’s lifetime would hardly be sufficient to follow directly all of the transformations indicated by [Felix Loehnis].”103

Hans Zinsser in 1932, attacking Kendall and Rife, stated that acceptance of pleomorphism would be “intellectual recklessness” leading bacteriology to “flounder in a bewildering confusion.”104

If [Kendall's] surmise is a correct one, the entire structure of our attitude toward the biology of disease must be changed ... If his conclusions are correct, he has brought about a revolution in biology ... At the present time it is dangerous for the progress of bacteriology to accept this work until it has been satisfactorily demonstrated ... Nothing short of absolute proof should be accepted or we may risk making research more difficult than it already is [emphasis added].

Hans Zinsser, 1932105

This high level of tension and emotion reflected the fact that the adoption of pleomorphism would revolutionize bacteriology, restructuring the whole discipline and making both research and the practice of medicine immeasurably more complex—thus impinging greatly on the economic interests of physicians and the taxonomists w ho serve their needs.

The existence of a body of physicians implementing doctrine affects the doctrine’s formulation, not only with respect to pleomorphism but in all other areas.

The assault on Kendall by Rivers and Zinsser exemplified how medical bureaucrats deal with a scientific issue. Kendall’s data were revolutionary and thus very unwelcome. They had to be dismissed summarily, and were—by a statement from Rivers (who had the most to lose) that he could not repeat the experiments.

Such techniques are not unknown even today.® A genuinely scientific approach would have dictated repeating the experiments as many times as need be to satisfy all parties and ensure resolution of the issues.

The Koch-Henle Postulates are no longer valid. In Dubos’ view they have “hardly ever been satisfied in man.”106 Rivers denied their applicability to viral diseases as early as 1937: “Koch’s postulates as proposed by him do not have to be fulfilled in order to prove that a virus is the cause of a disease.”107 And they are quietly being laid to rest in other areas of bacteriology today.

One suspects that they are held in reserve mainly for political purposes—to undermine therapeutic claims to which medical authorities are opposed:

While the f ulfillment of all [Koch’s] criteria is not considered essential at the present time for establishing the relationship of an organism to a particular disease, their value in checking preposterous claims by inexperienced workers has been considerable.—R. W. Fairbrother, 1953108

J. H. Woodger’s response was: “[This indicates] that laxer criteria are applied to orthodox than to unorthodox hypotheses and that bacteriologists are usually satisfied with something short of strict causal laws.”109

Medicine is still far from understanding the dynamics of infectious diseases. Why microorganisms have particular affinities for particular parts of the body, such as mumps virus for the testes and the parotids, or the pneumococcus pneumoniae for the lungs, remains a mystery.112 Why does the toxin released by the diphtheria bacillus, for instance, act on the heart, while that of the tetanus bacillus attacks the spinal cord? And how is the body harmed by influenza virus?

Influenza virus ... produces marked systemic eruptions, but only rarely and under unusual circumstances is it recoverable from deep tissues.—John B. Utz, 1967113

Science does not know why microorganisms such as the actinomyces fungus, the syphilis treponema, or the tuberculosis bacillus move from surface cells to the underlying tissues, while the diphtheria microbe remains in the upper respiratory tract, and the tetanus clostridium remains at the point of its penetration.114

Physicians have known, for almost a century, that Koch’s bacillus “causes” tuberculosis, but our knowledge of how or why remains incomplete. We still do not know why or even how the bacillus does its w'ork, why it is sensitive to certain drugs but resistant to others, and why only certain human hosts are clinically susceptible to the disease [emphasis added].

—Alvan Feinstein, 1967110

Disease is still largely a mystery. We don’t know how a bacterium causes disease. We know, for instance, that epidemic meningitis is caused by a microorganism called a meningococcus, but we have no clear idea as to how it works, nor do we know why some people develop meningitis while others have nothing more than a mild respiratory infection.

—Lewis Thomas, 1976111

The possibility that the behavior of microbes is a function of the disease dynamics, i.e., of the host resistance, has not been systematically developed.

Dubos has noted that George Bernard Shaw, in The Doctor’s Dilemma, “was not entirely wrong when he wrote ... ‘The characteristic microbe of a disease might be a symptom instead of a cause.’”115

Rationalist thinking about bacterial diseases over the past century has moved from complete neglect of host resistance to its belated recognition. Even though never “scientifically" defined, its significance for preventing disease and maintaining health has come to the fore in the late twentieth century.

NOTES

1.    Karl Menninger, 1948,318-319.

2.    A. D. Herrick and McKeen Cattell, 1965, 132.

3.    Alvan Feinstein, 1977, 363.

4.    Alfred S. Evans, 1976, 177; 1977. Rene Dubos, ed., 1958, 3; Thomas M. Rivers, 1937; Alfred S. Evans, 1977, 1277.

5.    Ernst Almquist, 1922, 483.

6.    F. Ixtehnis, 1922, 11.

7.    C. E. A. Winslow, 1932, 121; Arthur T. Henrici, 1928, 3.

8.    C. E. A. Winslow, 1932, 122; Philip Hadley, 1927, 279; G. Enderlein, 1925, 19.

9.    Philip Hadley, 1927, 279.

10.    G. Enderlein, 1925, 18.

11.    F. Loehnis, 1922, 162, 195.

12.    C. E. A. Winslow, 1932, 121.

13.    Ibid.

14.    C. E. A. Winslow, 1932, 121; Philip Hadley, 1927, 10.

15.    Arthur T. Henrici, 1928, ix.

16.    Rene Dubos, 1946, 136.

17.    Arthur T. Henrici, 1928, 2.

18.    Ernst Almquist, 1922, 484.

19.    Philip Hadley, 1927, 5, 291.

20.    Arthur T. Henrici, 1928, 5.

21.    Ibid., 1.

22.    F. loehnis, 1922, 15.

23.    Erik Enby etal., [1990], 12.

24.    Ibid., 33.

25.    Ibid., 40-47.

26.    Ibid.

27.    Ibid., 103.

28.    Arthur T. Henrici, 1928, 5, 7.

29.    Erik Enby et at., [1990], 15.

30.    Philip Hadley, 1927, 280.

31.    W. H. Park and A. W. Williams, 1939, 83.

32.    Arthur T. Henrici, 1928, 5, 7.

33.    Philip Hadley, 1927, 5.

34.    Ibid., 269-270.

35.    W. Devrient, 1951, 9.

36.    Ibid., 5.

37.    Philip Hadley, 1931, 4, 151-153; 1927, 284, 296.

38.    “Filterable Viruses Seen with the Rife Microscope,” 1931; R. Seidel and E. Winter, 1944; C. Bird, 1991, 270-293.

39.    C. Bird, 1991, 274.

40.    A. I. Kendall, 1931, 134-135.

41.    A. I. Kendall and R. R. Rile, 1931, 410.

42.    Edward C. Rosenow, 1932a, 1932b; Arthur W. Yale, 1940.

43.    “Filterable Viruses Seen with the Rife Microscope,” Science, 1931.

44.    “Is a New Field About to be Opened in the Science of Bacteriology?” California and Western Medicine, 1931.

45.    A. I. Kendall, 1932a, 104-107.

46.    Saul Benison, 1967, 14; Rivers’ data were published in T. M. Rivers and

S. M. Ward, 1933, 60-61.

47.    C. Bird, 1991, 291.

48.    R. Seidel and M. E. Winter, 1944.

49.    F. Loehnis, 1922, 30; Ernst Almquist, 1922, 492.

50.    Philip Hadley, 1939, 267.

51.    Werner Braun, 1947,98.

52.    Ibid., 97.

53.    Werner Braun, 1953, 225.

54.    W. Joklik, 1988, 7.

55.    Ibid., 1.

56.    Ibid., 6.

57.    Ibid., 7.

58.    L. Mattman, 1974, 1992.

59.    Sorin Sonea and Maurice Panisset, 1983, 40, 98.

60.    C. Bird, 1991.

61.    Ibid., 300-301.

62.    Alfred B. Searle, 1920, 37.

63.    Hugh Cabot, 1921,610.

64.    Alberto Seguin, 1946, 253.

65.    J. Rabkin and E. Struening, 1976, 1014.

66.    Alfred S. Evans, 1976, 193.

67.    Rene Dubos, ed., 1958, 15.

68.    Ibid.\ W. A. Sodeman et al., 1967, 196.

69.    EricJ. Cassell, 1986, 24.

70.    Harold J. Simon, 1960.

71.    Rene Dubos, 1973, 177.

72.    Ibid., 178.

73.    Ibid., 176.

74.    W. A. Sodeman et al., 1967, 198.

75.    Ibid.

76.    Ibid., 202.

77.    Erik Enby, [1990], 15; Robert Koch, 1987, 27; Rene Dubos, 1973, 181.

78.    Philip Hadley, 1927, 289.

79.    Rene Dubos, 1958, 15.

80.    Ibid., v.

81.    Alfred S. Evans, 1976, 181.

82.    Rene Dubos, 1973, 327.

83.    Marcia Angell, 1968.

84.    Carol Kahn, 1979.

85.    AlfredS. Evans, 1976, 181.

86.    “Preliminary Report of the Committee on Diphtheria Bacilli,’ 1901.

87.    Charles E. Simon, 1919.

88.    Rene Dubos, 1973, 177.

89.    H. A. Lechevalier and M. Solotorovsky, 1974, 109.

90.    Alfred S. Evans, 1976, 177.

91.    Robert Koch, 1987, 162.

92.    F. P. Gay, 1935, 590; Rene Dubos, ed., 1958, 468.

93.    Lancet, November 8, 1947, 695.

94.    Robert Koch, 1987, 149.

95.    Alfred S. Evans, 1976, 177.

96.    J. H. Woodger, 1956, 91.

97.    Philip Hadley et al., 1931, 108.

98.    Philip Hadley, 1939, 268.

99.    F. Loehnis, 1922, 39.

100.    S. Sonea and M. Panisset, 1983, 17.

101.    Carl Fraenkel, 1891, 2.

102.    F. Loehnis, 1922, 14.

103.    S. Winogradsky, 1949, 141.

104.    Hans Zinsser, 1932, 256, 257.

105.    A. I. Kendall, 1932a, 104-105.

106.    Rene Dubos, 1954, 97.

107.    T. M. Rivers, 1937, 104.

108.    R. W. Fairbrother, 1953, 8.

109.    J. H. Woodger, 1956, 91.

110.    W. A. Sodeman et al., 1967, 197.

111.    Lewis Thomas, 1976, 196.

112.    Ibid., 194-196.

113.    Alvan Feinstein, 1967, 56.

114.    Lewis Thomas, 1976, 109.

1 15. Rene Dubos, 1953, 95.

DECLINE OF THE ENTITY: NON-INFECTIOUS DISEASES

Karl Menninger’s second class of diseases is the non-infectious ones generated by an “inexplicable perversity.” Since they are not associated with a specific microbe, some other criterion of identity must be sought—either an internal “cause” or, when that is unavailable, other pathophysiological data and symptoms which are cobbled together to form an “entity.”

But non-infectious diseases have suffered the same definitional vicissitudes as infectious ones. Where their diagnostic criteria once seemed secure, closer inspection reveals fuzzy indeterminacy, whether the condition is analyzed as an “entity” or in terms of its supposed internal “cause.”

Human Variety in Disease

The definition of disease categories has always been plagued by the demon of human variety, as witness the lament of an Empirical physician from the second century A.D.:

The number of diseases and their accompanying symptoms are endless, owing to the isolation of each case ... We understand by endlessness the variations in their degrees and arrangement which complicate the diseases and their symptoms through some of them preceding and some following others.

In the almost endless variety of their diseases and the symptoms of them, the sick themselves differ from one another ... What is more manifold, more complicated, and more varied than disease? How does one discover that a disease is the same as another disease in all its characteristics? Is it by the number of symptoms or by their strength and power? For if a thing be itself, then in my opinion, it must be itself in all these characteristics, for if even one of them is lacking, it is perverted, and it ceases to be itself/*

Almost two thousand years later the American Ian Stevenson stated the same: “Wre have forgotten that the actual number of differential diagnoses is no less than the number of people upon this planet.”1

As already noted, the Empirical and Rationalist outlooks are distinguished from one another primarily by how they react to this heterogeneity.

In a group of people suffering from a similar complaint everyone will manifest a core set of symptoms and pathology, while in other respects each patient will be somewhat different.

Rationalism looks to the phenomena which sick people have in common and hypostatizes or materializes them into the “entity.” Thereafter the phenomena defining the “entity”—the “common” symptoms of the patients—are more significant for diagnosis and treatment than those falling outside this definition:

The methodology' of... clinical science is the planned observation of the sequence of phenomena in that number of sick people which allows us to know the common course of the disease under study ... and to estimate and know' the variations from that course [emphasis added].—James Spence, 19532

Even when the “disease” is not hypostatized or reified into an “entity,” the physician views the “common” features as significant:

The term “disease” refers to nothing concrete, but to a concept by which we generalize the manifestations of closely similar illnesses ... in nature there are not diseases but sick persons [emphasis added].—Francis Wralshe, 19563

The concept of “normality,'’ and departure from the “normal'’ or “natural,” has a central role here:

For all practical purposes the physician assumes that illness is a deviation from a biologically given norm.

—Geoffrey Vickers, 19654

Pathological physiology ... is concerned with disturbances in normal physiology.—William A. Sodeman and William A. Sodeman, Jr., 19675

I believe that disease is fundamentally unnatural ... I believe that disease results generally from biological mistakes. —Lewis Thomas, 19726

The physicians of the Empirical tradition have always taken a different position, ignoring “normality” as defined by the “common” symptoms and attributing greater diagnostic significance to the “peculiar” ones. Thus, an Empirical physician of the second century AD stated that the symptoms found in a single patient are the most important for treatment, those common to two patients rank next in importance, those common to many are next, while those found in all patients are the least important.6

Hahnemann and homoeopathy followed the same course, stressing the “strange, rare, and peculiar” symptom as the key to treatment.0

“Disease” definitions or “entities” play a central role in the development of Rationalist medicine.

The description of a new disease is of extremely great importance in practical medicine. To the physiologist and the worker in the laboratory, morbid categories are subordinate concepts, but to the physician, to the clinician, the reverse is the case; he cannot live, cannot speak, cannot act without them.—Knud Faber, 19227

Not long ago, during the pathology era of medicine, we were concerned mainly with structural changes. With the rise of

microbiology the clinical entity shifted to changes based on common etiological factors. More recently we have been concerned with underlying metabolic disturbances. But all of these have simply been devices for tying independent characteristics into a unit of identification ... It is a way of recognizing uniformity among patients and using it as a basis for therapeutic decision.—Theodore Greiner, 19658

The Rationalist physician perceives the “disease” and not the patient. He treats the “disease” of which the patient is merely the embodiment and usually becomes impatient when reminded of human heterogeneity:

Although the primary object of medical science is to improve the health or cure the sickness of the individual, the relevant knowledge usually has to be accumulated slowly by the observation of groups of individuals ... it is a reversion to primitive ways of thinking to say there are no diseases, there are only sick people.—L. J. Witts, 19649

We are, to be sure, all different from one another, and it is probably true that one could listen to hundreds of lungs during the pneumonia season and not find two that sounded exactly alike. But that is not the same as saying that there are no common features in such patients or that therapeutically one starts from scratch every time one faces a patient with pneumonia. If this were so, medical teaching would be impossible, and the practice of medicine chaos, or at least anarchy. 'I he problem of individual differences is a challenging one ... but it is no reason for paralytic despair.

—Louis Lasagna, 1964 10d

i he uncomfortable fact remained that doctors could not get at diseases without dealing with patients—doctors do not treat diseases, they treat patients.—Eric J. Cassell, 1986”

dCf. the monomorphist criticism of pleomorphism as destructive of medical science (p. 205-206 above).

Human Variety in Health

Disease heterogeneity is a function of the biological heterogeneity found in the healthy.

The physiologist Roger Williams devoted particular attention to the dimensions of biological variation in health, showing in several writings that supposedly “normal” young men manifest very different metabolic patterns. These differences, he states, “may be quite large and of more than academic interest.”

While healthy young men of the same height and weight may resemble one another in their overall oxygen consumption, specific chemical reactions may take place, under basal conditions, five or ten times as fast in one individual as in another. Perhaps the most direct extensive evidence on this point is based upon differences in enzyme levels and enzyme efficiencies. Perhaps next to this in importance is the fact that there are wide individual differences among “normals” with respect to several endocrine activities, and there is also anatomical evidence of substantial differences in endocrine patterns ... I he overall conclusion seems clear that, while the body chemistry of each individual is subject to some change with environmental conditions, each individual would, if subjected to the same stress and given the same food, exhibit a highly distinctive metabolic pattern. This pattern is genetically determined and undoubtedly correlated with his distinctive set of organ weights and activities ... “Normal” indiv iduals yield not only average, or nearly average, values, but also values which may be distinctly high or low, or slightly variable. In our experience with control young men we have never found one who exhibited a pattern which was free from distinctive variations from the average.—Roger J. Williams, 195712

The metabolism alters with age. The liver of the fetus, for instance, contains large quantities of iron and copper, while both levels decline after birth; then, after the first year of life, the iron content starts to rise, while that of copper remains low.11

The proportions of different cell types and rates of cell division continually change during growth and development, suggesting equally substantial changes in metabolic activity. After age thirty, for instance, there is a decline in the number of fibers in the nervous system, in nerve conduction, basal metabolism, cardiac output, and pulmonary function, while the rate of cell turnover in the skin and gums increases.

Sexual differences are significant for metabolism. Men and women have different blood composition, women’s blood being characterized by less hemoglobin and plasma protein and fewer red cells. In most animal species the organs reveal sex-related differences in metabolic capacity and response.14

Diet has a profound effect on metabolism; this holds true especially for protein intake, since it affects albumin production by the liver. In the adult, albumin comprises sixty percent of the protein in the plasma and extracellular fluid; in the infant this can be as high as seventy-five percent. About fourteen grams of albumin are manufactured every day by the liver of the “average 70-kilogram man'1 who is the chief object of research in physiology. An equivalent amount is destroyed every day as well. Hence the protein content of the diet affects all the body’s physiological processes.15

The human body contains more than 200,000 different types of protein, each varying in function of the individual’s genetic makeup.

The metabolism undergoes variation from season to season and from day to night. Body temperature is lowest upon awakening, while plasma steroid and iron levels in the blood are highest at that time. Thereafter the temperature rises, while plasma steroid and iron levels decline. Body temperature is different in the tropics and also in arctic zones; in women it varies with the menstrual cycle.16

Metabolism is greatly affected by emotional stress, which acts through the pituitary gland on the production of adrenal steroids. And these steroids, in turn, affect the body’s enzyme activity, immunologic defenses, and other major processes.

These factors stamp a degree of uniqueness on every individual!

But the ultimate dimension of uniqueness is conferred by variations in the “immune globulins,” a group of proteins found in the bloodstream.

They come in five classes, the largest being gamma-globulin (IgG). Each globulin class is composed of four peptide chains, two “light” and two “heavy,” which constitute the basic structure of the molecule. In the human population a total of twenty-three inheritable variations in portions of basic chains of IgG have been identified—twenty in the heavy chains and three in the light chains. In just this one subcategory of protein, gamma globulin, overall variety is determined by the permutations and combinations of twenty -three inheritable features.

Specific changes in immune globulins represent reactions to antigens; when introduced into the body, antigens alter the makeup of the immune globulin by stimulating their transformation into antibodies.

The possible number of antibodies which an individual can generate is enormously large: “Estimates (perhaps better described as guesses) of this number have ranged from a lower limit of 100,000 to ‘effectively infinite.’”17 Thus each individual possesses a unique set of antibodies, representing the history of his or her lifetime exposure to the environment:

It is certain that the phrase “human constitution” implies much more than the genetic endowment. I he characteristics of a person and the responses (healthy or pathological) he makes to the environment are profoundly conditioned by the past experience he has embodied in his biological and moral being.—Rene Dubos, 197018

In this sense the latest findings of immunology only confirm the two-thousand-year-old intuition of the Empirical physicians—that each individual is, by virtue of his or her history and experience, different from all others.

When the indiv idual’s life history is factored into the equation, “normality’” loses all meaning.

Patients have been falsely diagnosed as having infectious hepatitis, coronary artery disease, diabetes mellitus, rheumatic carditis, or prostatic carcinoma because of “abnormalities,” respectively, in cephalin flocculation, electrocardiographic T-waves, blood sugar, P-R interval, or serum acid phosphatase tests that might have been called “normal” if a better epidemic sampling had been used for establishing the basic range of normal ... Because of these deficiencies, there now exist almost no satisfactory absolute criteria for designating a clinical phenomenon as normal or abnormal.

Alvan Feinstein, 196719

Extreme values of “normality” gradually become “pathology,” and the pathological state, in turn, is also stamped by the patient’s particular “normality.”

Many failures in diagnosis and treatment occur because physicians are not sufficiently individual in their diagnosis and treatment. Every invalid is a special case—a unique example. Every illness is a factor which is complicated by another complex factor—the individual who is sick. —J. W. Murray, 193620

Hence the entity in non-infectious diseases is always under attack, not less so today than at other times in history, always dogged by the patient’s suspicion that he or she is unique and not part of a conglomerate. And while a majority of physicians may accept the “entity” (“the semantic and philosophic problems in defining diseases have been exaggerated, for it is no more difficult than defining other biological reactions”), a respectable minority has discovered that defining the “entity” is more difficult than was assumed by Pavlov and others in the optimistic “heroic age” of early twentieth-century medicine.21 Disease, in this minority' view, is a continuum, a seamless web of suffering, while individual “diseases” represent clusters of pathological data which are selected as significant for reasons only marginally related to any ultimate medical reality.

Defining the Entity

Attempts to define one or another disease “entity” invariably run up against this factor of heterogeneity. Patients differ in their symptoms, pathology, and biochemistry, and in the course of the disease.22

Symptoms may not correspond to pathological lesions. The patient with duodenal ulcer has no stomach pains. The one with severe pain of arthritis has no calcium buildup in the joints (and vice-versa). The woman with endometriosis (overgrowth of the mucous lining of the uterus) has no bleeding and cramps. The man with emphysema has no difficulty breathing. The diabetic does not urinate to excess.

The patient with myocardial infarction has no chest pain, as noted in 1906 by William Osier: “Extreme sclerosis of the coronary arteries is common, and a large majority of the cases present no symptoms of angina. Even in the case of sudden death due to blocking of an artery, particularly the anterior branch of the coronary artery, there is usually no pain either before or during an attack.”23

And the patient with normal coronary arteries, whose reading on an exercise test is normal or who only has shortness of breath when walking upstairs, may nonetheless have angina pectoris—described by O. B. Ross in 1967 as “a disease of unknown evolution, confusing symptomatology, and objective manifestations—such as electrocardiographic abnormalities—which do not correlate well with those symptoms.”24

X-ray findings may not correspond to the patient’s clinical state: he has a shadow on the lung but no symptoms of tuberculosis.

The same is true for biochemical findings—which may not correlate with either symptoms or pathology. The patient has gallstones, but her symptoms are not related to gall-bladder disease. Her blood has a high uric-acid level, but she has no gout. Nitrogen compounds in the blood of patients with nephritis may be unrelated to tissue changes in the kidneys.

Confusion stems in part from the fact that different “diseases” have emerged at different periods of history, and physicians define them by the data in vogue at the time when the disease entity came into being. But the outcome may be chaos.

There is no unified concept of disease ... in diagnosing different diseases, we often use entirely different types of fundamental criteria. We may have a concept of disease ... based upon gross anatomical defects, microscopic anatomical changes, so-called specific etiologic agents, specific deficiencies, genetic aberrations, physiological or biochemical abnormalities, constellations of clinical symptoms and signs, organ and system involvements, and even just description of abnormalities.—J. G. Scadding, 196325

Textbooks avoid precise symptomatic or pathological definitions of individual “diseases,” and physicians must develop their personal rules of thumb:

No other branch of natural science is so imprecise in defining the material exposed to experiment. Although all the diagnoses are made differently, although no uniform standards have been ratified and disseminated, it is commonly believed that rigorous criteria are invariably present. The clinician’s capacity for intellectual self-deception is illustrated by the widespread acceptance of this illusion. For most of the “established” diagnoses of modern “disease” standardized criteria do not exist, but are necessary, and must be established for true scientific progress in clinical medicine.

Alvan Feinstein, 196726

Every clinician has his own criteria for clinical diagnosis of congestive heart failure, nephrotic syndrome, and hepatic decompensation, but no criteria have been standardized, and none are used uniformly. Every' clinician has his own criteria for such clinical entities as hypertension, or coronary artery disease, but no definitive criteria have been established. Every clinical textbook contains many remarks about diagnosis of disease, but none present the rigorous delineation required of scientific criteria ... Lacking any formal means of classifying clinical observations, the clinician has 110 place to put the information when he communicates with himself or with his colleagues ... He cannot speak his clinical distinctions well, or think about them clearly, or read about them specifically, or write about them formally, because he cannot stipulate them—he has no ordered taxonomic vocabulary for them.—Alvan Feinstein, 196 727

Mental Illness

The categories of “mental illness” are especially confused, since they can rarely be correlated with anatomical or biochemical changes and are established by signs and symptoms alone.

[Mental illnesses] resemble many other illnesses also in not being understood. Most of them are at present classified only by their symptoms. What appears as the name of an illness schizophrenia, hysteria, and so forth—stands for an unknown common factor which is assumed to underlie particular syndromes. Any of these names might disappear overnight if deeper knowledge were to provide a better classification or even to prove that the existing one is without practical value.—Geoffrey Vickers, 196528

The current psychiatric debates about systems of classification, the many hypothetical and unconfirmed schemes of “psychodynamic mechanisms,” and the concern with etiological inference rather than observational evidence are nosologic activities sometimes reminiscent of those conducted by the medieval taxonomists.—Alvan Feinstein, 196729

Though large sums have been poured into psychiatric research, very little is clearly established. Body fluids have been minutely studied for changes in mental illness, but with as little result as if we studied the sewage effluent of a recording studio to establish correlations with the music played ... In psychiatry there are innumerable observations, but virtually no agreed-upon theoretical basis. Systems of classification are changed every few years and vary from country to country. Explanatory theories have no general acceptance and resemble religious systems in that they comfort the believer without being susceptible to proof or disproof. They are subject to fashion and imposed by intrigue ... Credo quia absurdum est seems to pertain here as in theology.

—Elliott Emmanuel, 197830

“Schizophrenia” is the most common mental illness, affecting up to forty percent of all mental patients. Its official definition, the “core schizophrenia syndrome,” consists of the most commonly encountered symptoms of patients diagnosed as “schizophrenic” in several countries during an “International Pilot Study of Schizophrenia.”31

But few psychiatrists adhere to this definition. “Schizophrenia and essential hypertension are excellent examples of descriptive terms which seem to carry the illusion that concrete disease exists.” In one hospital the physicians will call “schizophrenic” only those patients who have been confined two years or more, while others will call these same patients “depressed” or perhaps “brain-damaged,” or even “epileptic.”32

Schizophrenia has been a vast wastebasket. All kinds of psychiatric disorders have been labelled schizophrenic, but I hope that will change.—Director of the New York State Psychiatric Institute, 197933

And while the literature is full of studies of “depression,” no precise definition of this condition exists either. A group of patients diagnosed by one physician as “depressed” will contain many whom other diagnosticians would call “schizophrenic,” “psychopathic personalities,” or even brain damaged.34

Prevalence of Undiagnosable Disease

In twentieth-century practice in industrialized societies one-half to three-quarters of patients have no defined “disease” or syndrome:

Mrs. Ruth LaMotta is a 53-year-old patient of mine with one husband, one job, three children, and countless pains. One week her throat hurts, another her back. She is plagued by colds which prevent her from working. She thinks her sinuses might be infected. She feels tired and is sure she has the kflu. Her eyes get “weak all over” at work, and she is afraid she has glaucoma. Mrs. LaMotta is sure her body is gravely ill. I am sure it isn’t.—Michael Halberstam, 196735

In one physician survey twenty-three percent stated that such “problem patients” were their chief annoyance.36 The reaction all too often is to deny the reality of their illnesses—because the physician cannot put a label on them:

Every doctor has had patients who are not found to be physically ill, but refuse to be well. In other words, no organic basis can be found for their complaints. A common reaction is to write off such patients as “crocks.” The label may be both derogatory and unfortunate, and patients so labelled rarely receive effective care. Nevertheless, “crock” and many other patient labels flourish in medical practice. Undoubtedly, this is because physicians have found them useful—as a comforting explanation or excuse for their feelings of uncertainty and and inadequacy when confronted by such a clinical problem. In effect, the label represents a pseudodiagnosis. It tells us that the physician has decided there is no organic illness—that the patient’s complaints are rooted in some complex emotional problem.—David Barton, 197237

The phenomenon is not new. Hugh Cabot noted in 1925: “A large number, and a considerable proportion of the people with whom [the physician] will have to deal as patients will have no disease upon which he can put a label.”38 But the incidence of such patients is rising and has even provoked calls for new sets of “non-disease entities” to assist the physician in dealing with them.39

The “Controlled Clinical Trial”

Inability to define the “disease entity” means that the so-called “controlled clinical trial” lacks scientific value.

Such trials are premised upon the presumed existence of “homogeneous groups” of patients—meaning smaller samples of one or another disease “entity.” But if the “entity” itself cannot be defined, neither can the sample, and decades of experience have demonstrated that clinical trials suffer seriously from inability' to assemble patients into “homogeneous groups”:

In discussions of the ethics of clinical trials there is usually a tacit assumption that the trial is scientifically sound. This is

far from being the case in many instances, if only because clinical scientists often naively seem to believe that the material of the trial, which is human material, is reasonably homogeneous, and that treated and untreated cases can be “matched,” to use the jargon of modern clinical science. In actual fact, it usually turns out to be impossible to control all the variables ... We are inclined to underestimate the extent of biological variation, which is such that a controlled trial is not always possible.—Robert Platt, 196340

In psychiatry, where diagnosis is highly subjective, and therefore imprecise, it is impossible to have homogeneous groups. Double-blind studies have been reported using anti-depressants for treating depression. The matched groups contained endogenous depressives, schizophrenics who were depressed, and neurotic depressives.- Abram Hoffer, 196741

Research into the nature of depression and its treatment by drugs is hobbled by the fact that depressions do not constitute a single homogeneous entity. Furthermore, interpretation of reported research data in this area has been confused by a general disregard for this heterogeneity and by a lack of precision and uniformity with respect to terminology.

—Charles A. Walton, 196842

Statisticians know that the source of the largest uncontrolled variation in clinical experiments is not measurement variation, but the variation from patient to patient.

Byron Wr. Brown, Jr., 198043

Austin Bradford Hill, who provided statistical support for the clinical trial concept, criticized it severely in the end of his life. He described clinical trials as insensitive and incapable of revealing the all-important small differences among patients because of the “biological variation of the human material with which we have to deal ... Clearly our predecessors would not have got a very useful answer by applying one and the same treatment to a mixture of patients suffering from typhoid and typhus fevers before these two conditions were accurately differentiated from one another.”44 But making the needed distinctions among patients

risks .. loading the trial with irrelevancies ... It is no trouble for the modern computer to look after them, but someone has to make and record all these observations, someone has to program them for the computer, and someone has to study the answers it gives ... The trouble is that with many diseases and many treatments we are too ignorant to know where even to begin to look.”45

From the Empirical point of view, the “homogeneous group” is “homogeneous” only in respect of the common symptoms which do not determine the uniqueness which is the key to successful treatment.

Before proceeding with trials premised upon the assumption that homogeneous groups can be assembled, allopathic Rationalism should first have proved this to be possible. In fact, the “controlled clinical trial” is an example of utopian thinking, an ideal which cannot be realized in practice, a “dream of reason” leading its ghostly existence on the pages of medical journals and largely disregarded in practice. No controlled clinical trial matching the book definition has ever been performed:

Having been associated with numerous trials, we cannot recall any that have been entirely satisfactory. /Ml have entailed some compromise short of the ideal.—T. B. Binns, 196446

The perfect trial has never been achieved. Most trials suffer from defects of one sort or another, such as the need to administer agents other than the one in question (because of ethically required fail-safe clauses), the breaking of the double-blind because of the production of side-effects by the active agent, differences in baseline variables in treatment groups in the study, and the occurrence of drop-outs ... I he more practical-minded individual settles for a good deal less than the ideal, realizing that the latter is not attainable. —Louis Lasagna, 197147

The design and administration of clinical trials are important interrelated aspects that require many compromises between the art of the possible and the theoretical ideal.

—James E. Grizzle, 198248

Donald Fredrickson, director of the US federal medical research establishment in Bethesda, Maryland (the “National Institutes of Health”), stated in 1977 that of 31,000 clinical trials conducted during the previous decade in the field of gastroenterology, only one percent had been randomized; closer scrutiny of a sample of 100 led to the conclusion that none satisfied the requirements for a convincing trial.49 e

Allopathy came to understand this in due course, and the “nonhomogeneity” of the “homogeneous group” is recognized as a fatal weakness. A 1987 “consensus conference” representing several hundred specialists in clinical trial methodology, when asked why clinical trials were in a state of “crisis,” concluded that trial protocols are often inadequate, that results are ambiguous and uninterpretable, that they are corrupted by too many commercial considerations, and that the gap between the trial and clinical realities cannot be bridged.50 But for economic, legal, and institutional reasons “controlled clinical trials” continue to be organized and implemented.1

Need for Disease Entities

On a few occasions the allopathic profession has attempted to reach agreed definitions of diseases. In 1956 a committee of the American Rheumatism Association established eleven criteria for the diagnosis of rheumatoid arthritis: it was said to be “definite” if the patient manifested five of these criteria, “probable” if three.51 A committee of the American Heart Association did the same for rheumatic fever in 1963, coming up with five “major” manifestations, three “minor” clinical manifestations, and two “minor” laboratory manifestations.52 Evidence of preceding streptococcal infection was also required “except in situations in which the rheumatic fever is first discovered after a long latent period from the antecedent infection.” The committee conclud-

c“Randomization” signifies random allocation of patients to “test” and “control” groups.

Tor more on clinical trial methodology see Harris L. Coulter, The Controlled Clinical Trial: an Analysis (1991).

ed that two “major,” or one “major” and two “minor” criteria indicated a high probability of the presence of rheumatic fever.

The American Psychiatric Association in 1987 advocated a similar approach to the diagnosis of “depression” (“Major Depressive Episode”), listing nine symptoms (“loss of interest in pleasure,” “lack of reactivity,” “depression regularly worse in the morning,” “psychomotor retardation,” “significant anorexia or weight loss,” etc.) and requiring the patient to manifest at least five of them.53

But with these definitions patients may have very differing sets of symptoms and laboratory findings and be diagnosed with the “same disease.” One maleficent effect of this definition is inability of “depression” trials to yield scientifically meaningful answers. In rheumatoid arthritis two patients could each have five quite different manifestations, and there would still be one left over. In rheumatic fever two patients could each have two different “major” manifestations (with one left over) or a variety of combinations of “major” and “minor,” and still receive the same diagnosis.

Despite these methodological problems, no reasonable alternative has come forward:

All these examples of “clinical” diagnoses persist today because the names are necessary. No alternative morphologic, physiologic, or biochemical designations have been adequate to include the wide spectrum of clinical manifestations covered by the “clusters” or to provide a consistent specificity in identifying the affected patients. Alvan Feinstein, 196704

However grotesque these definitions may be, entities are needed to classify patients into treatment categories:

The doctor may ask twenty or more questions of the patient. How does he manage to remember all the patient’s answers? Of course he does not. Experiments have shown that he is less able to remember answers or points in the examination that fail to substantiate particular differential diagnostic hypotheses. In other words, the differential diagnosis forms the system the doctor uses in order to remember clinical facts,

_


and he is especially likely to forget data that are irrelevant to his system.—A. J. Scott, 197755

The entities are socio-economic categories, not scientific ones. They correspond to nothing in nature other than vague and shifting similarities among patients.

No disease entity can withstand rigorous scientific criticism. Defining “schizophrenia” by consensus among the health ministries of several countries—or even by majority vote—is hardly scientific. However long this and other disease names may have been in use, and however widespread they may be, they are merely conveniences for the physician.

But while convenient for the physician, they are less so for the patient—whose particular condition will not quite correspond to the name on his diagnostic chart and whose treatment may not be quite adapted to his true illness.

The Internal Cause

An alternative approach to establishing uniformity among patients is by identifying in each the same “internal cause.”

Rationalist medical philosophy vaunts its “causal” knowledge of physiology and pathology. The living organism is viewed as a mechanism, with “disease” (Menninger’s “inexplicable perversity”) representing a malfunctioning of that mechanism.

Many medical men have graduated with two vaguely defined impressions. The first is that in every patient there must be a localized fault or disease which is the “cause” of the illness.

—James L. Halliday, 194156

Philosophy is the attempt to understand things by their causes ... To probe behind phenomena and seek the first principles they exemplify is the first step in a philosophy of medicine.—Francis Walshe, 195057

A disease is regarded as a sequence of phenomena in a sick person arising from and following on a noxious injury, and this is in accordance with the Aristotelian idea of the nature of things ... to know disease in this way is the basis of exact therapy in professional practice.—James Spence, 195358

This way of thinking assumes that the elements and components of the body interact with one another following the laws of physics, chemistry, mechanics, and the like.

The aim of all physiological explanation is to express vital processes in terms of physical and chemical laws. We call this “explaining” them. J. H. Woodger, 195659

Mechanistic interpretations simplify, since the number of possible mechanisms is necessarily limited:

Nature is inventive, I grant, but not so inventive as to continue elaborating endless successions of brand-new impenetrable disease mechanisms. After we have learned enough to be able to penetrate and control the mechanisms of today’s diseases, I believe we will automaticaly be well-equipped to deal with whatever new ones turn up. I do not say this in any arrogance____—Lewis Thomas, 197260

The record of the past half-century' has established, I think,

... [that] for every disease there is a single key mechanism that dominates all others. If one can find it, and then think one’s way around it, one can control the disorder.

—Lewis Thomas, 197761

When the news is in, I think you’ll find that cancer is the result of a single mechanism ... there is in any case a high probability that a centrally placed regulatory mechanism whose nature remains to be elucidated has gone wrong, and that it is the same mechanism for all forms of cancer.

—Lewis Thomas, 198062

The internal cause, often defined in structural terms, is thought to generate disturbed function and the ensuing symptoms; it is the criterion by which their weight and significance are judged:

If a human organism ... failed to function properly, the “cause” of the breakdown was similar to that of a machine, viz., a fault in one or more of the component bits and pieces.

In this way the idea arose that the main and primary concern of medicine was to identify the faulty parts and to relate these to the symptoms of the patient.

—James L. Halliday, 194163

That the basic disease process causes the symptom ... is self-evident.—Walter Modell, 196164

Every significant clinical finding ... can be regarded as the toponymic consequence of a particular lesion, complication, or other effect of the disease.—Alvan Feinstein, 196765

The study of anatomical changes must be the basis of inquiry into their cause, their development, and their future course, and the functional effects they produce.

D. B. Brewer, 196866

Symptoms stemming directly from the “cause” are more important than those merely reflecting the patient’s idiosyncrasy.® Symptoms can also be interpreted in Rationalist thought as a too-violent reaction which must be tamed by the physician:

The symptom might perhaps usefully be considered as a disturbance in the normal balance between stimulus and response: a normal response to an abnormal stimulus, or an abnormal response to a normal stimulus.

-Walter Modell, 196167

Inflammation, in particular (today as in the mid-nineteenth century), is seen as pathological, and drugs are devised to “combat” it:

Inflammation is part of the body’s defense mechanism against disease, but in excess it can become a pathological condition ... prostaglandin antagonists are expected to open a new approach to treating inflammatory conditions.

—Gene Bylinsky, 197268

*Cf. Mitscherlich’s distinction between “signs” and “symptoms,” above, p. 107.

Confusion Among Disease, Cause, and Symptom

Inevitably, the “cause,” the “disease,” and the dominant symptom are confounded with one another:

The symptom should be regarded and treated as a phenomenon of, and an entity in, disease.—Walter Modell, 196169

Research into the nature of depression and its treatment by drugs is hobbled by the fact that depressions do not constitute a single homogeneous entity. The term, “depression,” is employed to refer to a symptom, a syndrome, or a diagnostic entity. It has been unclear whether so-called antidepressant drugs are to be regarded as specifically effective for treatment of the symptoms, syndrome, or diagnostic entity.

—Leo E. Hollister, 196770

In gout the supposed “cause” (sodium urate crystal deposition) is identified with the “disease” and with the most prominent symptom or symptoms (acute synovitis).71

Thus “cause,” to all intents and purposes, means “disease" and is identical with the principal mechanisms, symptoms, and pathology of the disease. Rationalism hopes to extricate itself from this impasse by pursuing research deeper and deeper into the “ultimate mechanisms” of disease and of the organism. Unsatisfactory clinical outcomes can always be blamed on the supposed dearth of “basic causal knowledge”:

A fully effective attack on the major health problems facing the public requires ... new basic information concerning such diseases as atherosclerosis, cancer, arthritis, and schizophrenia.— Louis Lasagna, 196972

The real high technology of medicine ... comes as the result of a genuine understanding of disease mechanisms ... I would regard it as an act of prudence to give high priority to a lot more basic research in biological science.

—Lewis Thomas, 197273

The great need now, for the medicine of the future, is for more information at the most fundamental levels of the living process.—Lewis Thomas, 197774

We can’t understand the operation of a machine unless we know its working parts. We can’t repair a car if we don’t know what goes on under the hood. This is the basic approach to understanding the working parts of the cellular machinery that is responsible for duplicating the chromosomes and making division and growth possible ... If there are aberrations in the control of this—when the car is running instead of being idle, as is the case with cancer, or is not running when it should be active, as in other diseases—basic questions need to be answered before we can understand what has gone wrong. Arthur Kornberg (Nobel Laureate), 198275

Expressions such as “basic mechanisms,” “underlying causes,” “fundamental levels,” and the like are irresistible to the Rationalist mind, evoking the world of physics and engineering where the twentieth century has demonstrated its mastery over nature, and suggesting that the physician possesses the same powers.

Hut this supposedly “causal” knowledge is merely the description of intermediate pathological processes or “mechanisms”:

Ask any medical student what is the cause of diabetes, and he will reply, “A disturbance of the pancreas.” Ask any psychiatrist the cause of an anxiety state, and he probably will reply, “conflicts, repressions, and regressions.” The Lancet gave the title, “The Aetiology of Peptic Ulcer,” to a survey dealing solely with the bodily mechanisms concerned in its production ... We may read that “the cause of rheumatism is imbalance of the endocrine and autonomic systems which brings about changes in the vascularity of the tissues which in turn causes errors in the metabolism of the joints.” To make such inferences is, of course, legitimate provided the writer recognizes that they represent only a partial aspect of cause, viz., that of mechanism.—James L. Halliday, 194176

Experiments have helped physicians to glimpse the intermediate pathways of disease but have thrown little light upon the true nature of disease. The pancreas of a dog is removed. The dog thereupon shows symptoms much like those of diabetes mellitus, and that fact leads to the isolation of the pancreatic hormone, insulin ... a great discovery, yet few diabetics develop diabetes as a result of having their pancreas removed, and though we are now able to control the disease with considerable effectiveness, we cannot claim to be much closer to understanding the cause of it than we were fifty years ago.—Ian Stevenson, 194777

It has been said that epilepsy may be defined as cortical dysrhythmia, in virtue of the fact that the electronic recording system reveals deviations from the normal electrical activity of the cortex in the epileptic subject. Yet to say that there is cortical dysrhythmia is a statement of the same order as to say that the subject has fits and has no defining or generalizing quality. The observer’s eye picks up the convulsive movements or the disorder of consciousness that we call a fit, and the electroencephalograph records an associated electrical disturbance in the cortex. Here we have two items of information, both to be built into the complete description of the disease state. But neither tells us how or why the sufferer suffers as he does. They are details of description and no more [emphasis added] .—Francis Walshe, 195678

In many cases the primary causative agents or factors are unknown ... The study of the precipitating and perpetuating factors, the mechanisms of their action, and the pathologic physiologic responses they bring about give us an understanding of the development of symptoms and signs, and lead to procedures in therapy effective in blocking these mechanisms and bringing about control of the disease process despite the fact that basic causation is not understood.—William A. Sodeman and William A. Sodeman, Jr., 196779

Disease is still largely a mystery ... As for the noninfectious diseases, we’re equally at a loss to understand the mecha-

nism. Of course, in earlier eras there was no shortage of theories, but we can’t go back to the ancient Greek idea that disease was an imbalance of humors in the body.

Lewis Thomas, 197680

So-called “causal” knowledge in Rationalist medicine is the same as describing epileptic fits as “cortical dysrhythmias” adding nothing of practical value, providing no insight into the etiology of epilepsy, mystifying the patient, and even confusing the physician by giving him counterfeit coin to trade with. Is the diabetic sick because his pancreas produces too little insulin, or does his pancreas undersecrete insulin because the patient is diabetic? The answer is very important, since it will determine the type of therapy. I he Rationalist physician usually opts for the first alternative and gives the patient insulin (or an “oral hypoglycemic”)—which enhances his dependence on an outside source of this important substance and depresses his own ability to synthesize it.h Opting for the second alternative would indicate dietary adjustment (which is still the best treatment for diabetes today) in order to limit insulin demand or, alternatively, a treatment which enables the patient’s pancreas to secrete more insulin.

Empirical Criticism of Rationalist Disease Theory

The mechanistic-reductionist interpretation of health and disease makes little sense from the vitalist Empirical viewpoint or even in the light of much contemporary biology:

The refusal to draw a sharp distinction between animate and inanimate matter is the ultimate in reducing life to physics, a viewpoint that has been forcefully advocated within the scientific community since the mid-1800s. However ... I have the feeling that this simple reductionism is losing support ... In 1946 Erwin Schroedinger pointed out ... that biological material has a totally different character from all other states

of matter that are dealt with in physics and chemistry ... There is a vast gap between the information density of life— that is, the information stored per unit of volume—and that of any inorganic system that has not been produced by living forms ... The silicon chip must use many orders of magnitude more atoms to store the same amount of information as a gene.—Harold J. Morowitz, 198081

Albert St. Gyoergyi, Nobel Prize Laureate for the discovery of vitamin C, once observed that if the living organism obeyed the laws of thermodynamics it would rapidly burn itself out: “Biology is the science of the improbable, and I think it is on principle that the body works only with directions which are statistically improbable. If metabolism were built on a series of probable reactions and thermodynamically spontaneous reactions, then we should burn up, and the machine would run down, as a watch does if deprived of its regulators. The reactions are kept in place by being statistically improbable, and made possible by specific tricks which may then be used for regulation, so that in living organisms reactions are possible which seem impossible, or at least improbable, to the physicist.”82

At the cellular level, of course, mechanistically inexplicable processes occur continually—such as the transport of food and waste matter through the same cellular ducts at the same time and in opposite directions, a proposition which would have seemed preposterous to Virchow or Claude Bernard.

Hence the more perspicacious thinker realizes that mechanistic reductionism is a false hope. St. Gyoergyi turns away from the laws of thermodynamics and appeals to “statistically improbable reactions.” Roger Williams abjures “normalities” and seeks to base medical treatment on “abnormalities,” i.e., what has historically been called “idiosyncrasy”: “The character of these distinctive metabolic patterns is directly related to the susceptibility of individuals to many diseases of obscure etiology, as well as to others belonging in the infectious, nutritional, metabolic, malignant, degenerative, geriatric, mental, or other categories ... the ‘seeds’ of many of these causes of death and disability probably reside in the ‘normal’ young men at age twenty and may be discoverable at that time if we take the pains to find them. Even those individuals who die in their later years of infective diseases may exhibit, at age twenty, distinctive signs of susceptibility ... the purpose of such an investigation would be to ferret out the ‘abnormalities, rather than the ‘normalities, ’ existing in these ‘normal’young men” [emphasis added] ,83

St. Gyoergyi’s “statistically improbable” and Williams’ “abnormalities” have the same function as the “peculiar symptom" in homoeopathy.

This idea, however, is unacceptable to the Rationalist majority, which doggedly pursues research into thermodynamic causal chains well beyond the cellular level—to molecular elements and groupings, individual molecules, and even to ultra-tiny submolec-ular particles which combine aspects of both mass and energy.84 Much research is premised upon the hope that at some future point the behavior of these ultimate units can be measured with the techniques and methods of quantum mechanics.

It is quixotic, however, to believe that the behavior of the whole organism could ever be determined merely by summing a quasi-infinite series of differential equations. The human body contains sixty trillion cells, each with up to several million molecules; mathematical analysis of the functions of these molecules, in the hope of reaching an understanding of the whole body, is a theoretical impossibility and an absurdity in practice. The very largest computers could not integrate the equations for even a microscopically tiny piece of isolated tissue. As one researcher expressed it: “Biology is awfully big. I’d hate to try to calculate the wave functions even on a frog.”85

And such a procedure would be theoretically wrongheaded, since whole-body functions are not determined by adding up the functions of the parts:

No ... organism ... is a mere accumulation of its component parts, but rather by virtue of complex interactions new potentialities occur, the nature of which can never be understood by analysis of the parts.—Harold C. Wolff, 194786

The person as a whole is something different from a collection of viscera; the wholeness gives some extra, if undefin-able, quality to the individual organs. Today we pay for our knowledge of the parts in ignorance of the whole.

—Ian Stevenson, 194987

One of the basic features of life is “organization,” by which we mean that if two things are put together, something new is born, the qualities of which are not additive and cannot be expressed in terms of the qualities of the constituents. This is true for the whole gamut of organization, for putting electrons and nuclei together to form atoms, atoms to molecules, amino acids to peptides, peptides to proteins, etc.

—Albert St. Gyoergyi, 196088

The research scientist has often become so fascinated with his studies of such progressively disintegrated systems that he may forget the complex organism, man, that started him on his way. This is understandable because the scientist tends to continue to explore the research system in which he has been successful.—David Rutstein, 196789

The more one analyzes the parts and processes of an organism, the more one finds oneself at a remove from the life of the animal. Only by experiencing the animal as a living, sentient, responding creature can one begin to awaken the faculty of comprehension needed to understand life.

—George K. Russell, 197290

Investigating “mechanisms” never reveals the meaning of phenomena:

As to the living machinery itself, the biochemist will tell you that its central parts are proteins, nucleic acids, and nucleo-proteins. He will point out the great progress made in the structural analysis of these substances, show their building blocks, amino acids and nucleotides, their links and relative position, will speak about bond angles and distances and the various helices formed. But if we ask why Nature has put together that very great number of atoms in that very specific way, what property did she want to achieve, our biochemist will become silent ... What Nature had in mind when doing

this we cannot even guess at present. So here too we find the door to the central problem locked ... We find that the problems with which biochemistry was successful were problems of structure, or changes of structure taking place in simpler reactions which could be duplicated mostly in homogeneous solutions and could be expressed and answered in terms of letters and dashes, while the problems which remained unanswered were problems of function of complex systems which cannot be expressed in this language.

Albert St. Gyoergyi, I96091

Good applied science in medicine, as in physics, requires a high degree of certainty about the basic facts at hand, and especially about their meaning, and we have not yet reached this point for most of medicine. Nor can we predict at this stage, with much confidence, which particular items of new information, from which fields, are the likeliest to be relevant to particular disease problems [emphasis added].

Lewis Thomas, 197792

Physicians (who know little about physics) sometimes hope that physicists (who know little about medicine) will rescue them from their frustrations and disappointments in the search for ultimate causes. But a real physicist, such as Niels Bohr, views this as vapid and silly: “The closed processes studied in quantum physics are not directly analogous to biological functions ... Moreover, any experimental arrangement which would permit control of such functions to the extent demanded for their well-defined description in physical terms would be prohibitive to the free display of life. This very circumstance, however, suggests an attitude to the problem of organic life providing a more appropriate balance between a mechanistic and a finalistic approach. In fact, just as the quantum of action appears in the account of atomic phenomena as an element for which an explanation is neither possible nor required, the notion of life is elementary in biological science ... The main point is that only by renouncing an explanation of life in the ordinary sense do we gain a possibility of taking into account its characteristics [emphasis added].”93

Bohr’s prescription has always been the basis for medical Empiricism. No attempt is made to “explain” life “in the ordinary sense,” i.e., mechanistically. “Life” is accepted as a given, and the physician seeks its laws and regularities.

NOTES

1.    Ian Stevenson, 1949, 38.

2.    James Spence, 1953, 629.

3.    F. M. R. Walshe, 1956, 1060.

4.    Geoffrey Vickers, 1965, 1026.

5.    William A. Sodeman et al., 1967, 3.

6.    Lewis Thomas, 1972b, 52.

7.    Knud Faber, 1922,63.

8.    A. I). Herrick and McKeen Cattell, 1965, 132.

9.    L.J. Witts, 1964, 7, 13.

10.    Paul Talalay, ed., 1964, 93-94.

11.    EricJ. Cassell, 1986, 189.

12.    Roger J. Williams, 1957-1958, 98-99, 100.

13.    Maria Linder, 1979, 1 14—115.

14.    Ibid., 120-123.

15.    Ibid., 124-126.

16.    W. A. Sodeman et al., 1967, 203.

17.    H. H. Fudenberg et al., 1972, 3.

18.    Rene Dubos, 1970, 183.

19.    Alvan Feinstein, 1976, 331, 333.

20.    J. W. Murray, 1936, 21.

21.    L.J. Witts, 1964, 7.

22.    Alvan Feinstein, 1976, 69, 212.

23.    W'illiam Osier, 1906,841.

24.    O. B. Ross, 1967, 35.

25.    J. G. Scadding, 1967, 882.

26.    Alvan Feinstein, 1976, 101-102.

27.    Ibid., 83-84, 126.

28.    Geoffrey Vickers, 1965, 1024.

29.    Alvan Feinstein, 1976, 100-101.

30.    Elliott Emmanuel, 1978, 1234.

31.    Richard M. Kapit, 1977, 207; J. Wing andj. Nixon, 1975.

32.    A. Hoffer and H. Osmond, 1961, 221-222.

33.    The New York Times, November 13, 1979, C-2.

34.    L. E. Hollister, 1967, 486; A. Hoffer and H. Osmond, 1961, 221-222.

35.    Michael Halberstam, 1967, 18.

36.    Ibid., 19.

37.    David Barton, 1972, 362.

38.    Hugh Cabot, 1925, 13.

39.    A. J. Scott, 1977.

40.    Robert Platt, 1963, 1158; Robert Platt, in Lancet, October 31, 1964, 949.

41.    Abram Hoffer, 1967, 124.

42.    American Society of Hospital Pharmacists, 1969, 74.

43.    Byron W. Brown, Jr., 1980, 19.

44.    Austin B. Hill, 1966, 108.

45.    Ibid., 110.

46.    T. B. Binns, 1964, 1150.

47.    Joseph D. Cooper, ed., 1971b, 16.

48.    James E. Grizzle, 1982, 365.

49.    Donald S. Fredrickson, 1979, 631.

50.    A. L. Blum et al., 1987, 8.

51.    American Rheumatism Association, 1956.

52.    “Committee Report—Jones Criteria (Revised),” 1963.

53.    American Psychiatric Association, 1987, 224.

54.    Alvan Feinstein, 1976, 100.

55.    A. J. Scott, 1977, 135.

56.    James L. Halliday, 1941, 368.

57.    F. M. R. Walshe, 1950, 782.

58.    James Spence, 1953, 629.

59.    J. H. Woodger, 1956, 1.

60.    Lewis Thomas, 1972b, 52.

61.    Lewis Thomas, 1977, 167.

62.    Lewis T homas, 1980, 96.

63.    James L. Halliday, 1941, 368.

64.    Walter Modell, 1961, 30.

65.    Alvan Feinstein, 1976, 137.

66.    D. B. Brewer, 1968, 1.

67.    Walter Modell, 1961, 21.

68.    Gene Bylinsky, 1972, 99.

69.    Walter Modell, 1961, 21.

70.    Leo E. Hollister, 1967, 486.

71.    W. A. Sodeman et al., 1967, 955.

72.    Louis Lasagna, 1969, 1227.

73.    Lewis Thomas, 1972b, 54, 57.

74.    Lewis Thomas, 1977, 169.

75.    The Washington Post, January 5, 1982.

76.    James L. Halliday, 1941, 373, 377.

77.    Ian Stevenson, 1947, 37.

78.    F. M. R. Walshe, 1956, 1061.

79.    W. M. Sodeman et al., 1967, 4.

80.    Lewis Thomas, 1976, 109.

81.    The New York Times, June 23, 1980: Op-Ed page.

82.    Albert Szent-Gyoergyi, 1960, 3-4.

83.    Roger Williams, 1957-1958, 100.

84.    David Rutstein, 1967, 109.

85.    The New York Times, September 18, 1979.

86.    Harold C. Wolff, 1947, 945.

87.    Ian Stevenson, 1949, 38.

88.    Albert Szent-Gyoergyi, 1960, 10.

89.    David Rutstein, 1967, 109.

90.    George K. Russell, 1972.

91.    Albert Szent-Gyoergyi, 1960, 10-11.

92.    Lewis Thomas, 1977, 169.

93.    Niels Bohr, 1958, 76; See EricJ. CasseU, 1986, 32.

PART TWO

EMPIRICISM AND VITALISM IN TWENTIETH-CENTURY MEDICINE

While the disease-entity doctrine was passing through its various reformulations and crises, physicians continued to treat patients.

The two major traditions in therapeutics inherited from earlier centuries—treatment with “similars” and with “contraries” remain vigorous today.

In the following pages we discuss the therapeutics of similars- both within the Empirical tradition and in allopathy. In Part III we examine the twentieth-century doctrine of contraries and its consequences.

The principal focus of the modern use of similars has been the homoeopathic school, founded at the turn of the nineteenth century by Samuel Hahnemann and, in the late twentieth century, the most popular system of practice in Western medicine after allopathy itself. Since its operating assumptions conflict on all points with those of Rationalism/allopathy, the resulting doctrinal structure is the mirror-image of allopathy, and the systems have remained in a state of tension.

Two other significant systems of vitalist medicine emerged in the late nineteenth century—osteopathy and chiropractic. They both secured powerful positions in American medicine and became established in England, France, Germany, Scandinavia, and elsewhere. “Naturopathic” medicine, combining elements of homoeopathy, osteopathy, chiropractic, hydropathy, herbal medicine, nutrition, and acupuncture, has also become accepted, especially in the United States.

Rationalist practice has been steadily fertilized by Empirical/homoeopathic ideas, despite its antagonistic attitude. Such concepts as treatment with “similars,” isopathy, recognition of the “physiological action” of medicines on the host organism, and “attenuation” have all entered allopathic therapeutics.

Vitalist elements can also emerge within allopathy, for the Empirical impulse in medicine is perennial and ubiquitous. I he doctrines of immunology and allergy, even though in a theoretical limbo, are a powerful Empirical presence within Rationalism.

HOMOEOPATHY

The isopathic techniques discussed above, which inspired Pasteur and Koch, were a minor addendum to Samuel Hahnemann’s homoeopathy.

From its earliest years to the present, this architectonic structure of thought has been an ever-ready source of inspiration and renewal, for, as a true science of therapeutics, Empiricism must redress the balance whenever Rationalism becomes hypertrophied beyond the patient’s (or the physician’s!) point of endurance.

While homoeopathy’s contributions to allopathy are not common knowledge, their impact has been substantial, in both the nineteenth and twentieth centuries.

The Proving

As described in the Introduction, homoeopathy represents the continuation and development of traditional Empirical therapeutic ideas filtered through Hahnemann’s proving.3

Empirical thinkers since ancient times had been concerned, above all, with discovering or developing a systematic basis for

“See Introduction, above. A more comprehensive account of homoeopathic doctrine is found in Divided Legacy, Volumes II and III, and in Harris L. Coulter, Homoeopathic Medicine (1975).

selecting and prescribing remedies. More generally, how does the physician know the therapeutic application of a new medicinal substance? How are the curative properties of drugs ascertained?

Hahnemann's answer was: by administering such substances to healthy individuals in small quantities for days or weeks until they manifest the set of symptoms peculiar (or “specific”) to that substance. The procedure was called by him the “proving” (from German: Pruefung, meaning “test” or “trial”), and the homoeopathic medical literature consists, in its essence, of lengthy lists of symptoms from proving remedies on healthy persons (the lists themselves are also called “provings”).

The homoeopaths found that their proving symptoms were milder versions of the well-known poisonous symptoms of these same drugs, leading to the realization that “poisons,” when suitably prepared and administered in sufficiently small doses, possess powerful medicinal properties.

By the late twentieth century homoeopathy had generated full or partial provings of about 1500 remedies, while about 1000 were in common use and remain so to this day.b

The homoeopathic physician seeks to match the symptom-pattern of the patient before him with that of a medicine. This necessitates a full symptomatic description of the patient’s ailment, including every thing that can be seen with the eyes or perceived by the other senses. The patient is questioned about his perceptions and sensations, since he can know information which is not accessible to the physician’s own observational powers.

Having assembled a complete and exhaustive listing of symptoms, the physician compares it with the lists in the books of provings. The medicine whose symptom-pattern is “most similar” to that of the patient is the one to be prescribed.

It is efficacious because it supports and strengthens the healing effort of the patient’s own body:

bThe homoeopathic materia medica is thus static and unchanging, lacking the peculiar allopathic impulse to fabricate a new medicine for each new concatenation of symptoms (on the allopathic “Doctrine of the indispensability of new drugs” see below, pp. 677-678).

Since the natural healing process is based upon the reactive power of the organism, the simile therapy can be designated perhaps as a therapy with the same aims as the healing processes or as a specific (almost causal) therapy.

Karl Koetschau, 19301

The discovery of the proving was a crucial event in the history of world medicine. Although the idea itself is simple enough, and could have been revealed to millions of others, that honor fell to Samuel Hahnemann.

Reinterpreting Empiricism: Primacy of the Visible

The proving was not only a practical technique for ascertaining the curative powers of remedies. It was also of great theoretical significance, providing a new point of departure for reinterpreting the elements of traditional Empirical doctrine.c

Ideas and procedures which had earlier been found valuable by experience were now seen to fit together doctrinally like a Japanese puzzle, with no seams showing or butt ends protruding, to such a degree that this culmination of medical Empiricism has for two centuries constituted a viable and radical challenge to the dominant Rationalist medical orthodoxy

The proving infused the concept of “similarity” with new content. This ancient idea is found in the Hippocratic Corpus, as well as in all systems of folk medicine, and has had varying interpretations over the years and centuries. In particular, it has often

'The connection with Greek Empiricism was known to physicians of an older generation, still acquainted with the classics. An early American adherent of homoeopathy, John F. Gray, wrote in 1845: “This practice in our school is a return to the long extinct mode of the Empirical Sect. That very clearsighted school of physicians maintained that human knowledge could not be carried deep enough into the science of life to enable the wisest of men to develop a synthetic science of medicine, a rational art of healing; and that the only possible basis of medicine as an art of cure was a simple and most humbly conducted series of observations. Pity, a thousand pities, that so wise a sect of real observers should have been driven off the stage by a terrible rabble of‘Rationalists’ in medicine who, knowing nothing of anatomy, physiology, or chemistry, held undisputed possession of the suffering sick for more than a thousand years” (Homoeopathic Examiner I, 1845-1846, 4).

been confused with the “doctrine of signatures”—that the external form or color of the substance reveals its medicinal use (red coral for hemorrhages, walnuts for brain diseases, and the like). But after Hahnemann’s proving, “similarity” lay between the symptoms of the patient and those developed in the provings-similarity of symptom, not of substance.

Another traditional Empirical concept clarified by the proving was the unknowability of internal pathological processes, or to put it less starkly, that such knowledge is unreliable for therapeutic purposes.

Empirics had always maintained that the physician could not have reliable information about invisible internal processes or mechanisms and should not attempt to base therapeutic procedures on mere assumptions. For if the patient’s vitality is always reacting dynamically to specific morbific impulses impinging on it from the outside, these internal processes are continually in flux, and stable or reliable knowledge of them cannot be had. Knowledge of physiological and pathological “processes” and “mechanisms” is necessarily “average,” while the vital force of each patient operates in its own specific way. Hence “average” knowledge of internal processes is never sufficiently reliable to guide the physician in a given concrete case.d

This is why homoeopathic physicians have been reluctant to describe with too much assurance the precise nature of the pathophysiological mechanism underlying the patient’s symptom picture, or, in other words, to give the patient’s “disease” a name.

For the same reason they have disclaimed intimate knowledge of the actions of medicines. No attempt was ever made in classical homoeopathy to hypothesize or speculate about the dy-

llIn 1855 an American writer sympathetic to homoeopathy rebutted the allopathic equation of the human body with a pocket watch, and the supposed need to base diagnosis and treatment on an intimate knowledge of anatomy, as follows: “The watch is a mere mechanism ... Man is a mechanism, it is true, but one of utterly infinite complexity ... when the watch ceases to move ... the watchmaker examines the very watch to be mended, not watches in general. The anatomist proceeds in the opposite way. If the ‘anatomical’ theorists [i.e., allopathic physicians] are prepared to cut open and examine every patient who applies to them for cure, we admit that there will then be (but not until then) a practical analogy between the cases upon which they build their argument” (Anonymous, “The Medical Controversy,” 267).

namics within the prover’s body giving rise to the medicine’s symptoms. Only the visible symptoms can be objects of knowledge. No classical homoeopathic physician has ever claimed to understand how a medicine produces symptoms or how it cures the conditions characterized by these symptoms.e

The doctrine of the “visible” is linked to the concept of treating the “whole organism.” For the whole body is prior to all particular manifestations. The state of the whole body determines morbid processes in the interior, and the state of the whole body can be read only from the symptoms manifested by the whole body.

The homoeopathic physician seeks the laws and regularities of life, not in the intimate recesses of the patient’s organism, not at the submolecular level of the tissues, but right on the surface.

Any investigation of causality in medicine, when pursued to its logical conclusion, leads back to the “whole organism” as the ultimate cause and to the symptoms it makes visible as the ultimate guides to treatment.

Die 14 ahrheit die wir alle noethig haben,

Die uns als Alenschen gluecklich macht,

Wird von der weisen Hand die sie ms zugedacht,

JVur leicht verdeckt, nicht tief vergrabenJ

The proving, furthermore, demonstrated the correctness of the Empirical assumption that symptoms are beneficial phenomena, representing the body’s own healing effort. If the patient’s disease is cured by a substance giving rise to precisely his or her set of symptoms in a healthy person, symptoms must ipso facto be curative manifestations.

The very fact that the organism reacts to administration of a medicinal substance during the proving process demonstrates—if

cFor the quarrel within homoeopathy over this point see Divided Legacy, III, 346, 352.

f“The truth we hold so needful/That makes us mortals happy/Is by the wise hand that intends it for us/Only lightly concealed, not deeply buried.” See Divided Legacy, II, 654. This verse by Christian Gellert (1715-1769) was the motto on the tide page of the first edition of Hahnemann’s Organon.

that were needed—that the organism is, as maintained by Empiricism, a reactive entity.

The doctrinal or theoretical value of the proving was also seen, for instance, in the evaluation of “mental” symptoms and “mental” diseases. The provers manifested mental and emotional symptoms as well as physical ones, and it became apparent that there was (and is) no qualitative difference between the two classes of disease; hence homoeopaths from the outset treated the “insane” with the medicines they used for somatic complaints.

The data from provings strongly reinforced the traditional Empirical doctrine of “Common” and “Peculiar” symptoms.«

Since ancient times these physicians had called the Peculiar symptoms the key to treatment. But it was never possible to adduce a rule determining which symptoms fell in which category. While many attempts along these lines were made, the argument was always circular; the author, usually on traditional grounds, selected some particular disease syndrome or category as significant and then in the context of that syndrome defined some symptoms as Peculiar, others as Common.11

This was an elementary logical fallacy, but, in the absence of an external criterion for classifying symptoms into Common and Peculiar, it could not be avoided. The proving for the first time provided such an external criterion. Common symptoms were the ones found in the provings of most medicines and experienced by most participants, while Peculiar ones were those associated with only one medicine.

The homoeopathic experience with provings has generated such Peculiar symptoms as:

•    “Earnest and unceasing talking” (Stramonium)

   “Fear of sharp and pointed things” (Spigelia)

   “Chilliness from the slightest draft” (Hepar sulphuris)

•    “Indifference to family and loved ones” (Sepia)

*On the commuma and propria see Divided Legacy, I, 250. hSee Divided Legacy, II, 503fT.

•    “Sensation as if soul and body were separated” (Thuja occi-dentalis)

   “Feels as if she had on cold damp stockings” (Calcarea carbonica)

   “Everything worse on the left side” (Lachesis trigonocephalus).

Hahnemann spoke of “similarity” between the totality of the symptoms of the patient and those of the remedy. Symptoms such as loss of sleep, headache, weakness, nausea, dizziness, and the like—even though causing discomfort to the patient and often what brings him to the physician in the first place—are of secondary importance because found in many patients and many diseased states. Hence, they are not “specific.” As Hahnemann stated: “The most singular, most uncommon signs furnish the characteristic, distinctive, and peculiar features.” “The more striking, singular, uncommon, and peculiar (characteristic) signs and symptoms of the case of disease are chiefly and most solely to be kept in view.”'

The homoeopathic distinction between Common and Peculiar symptoms parallels the allopathic one between “signs” and “symptoms,” since Common symptoms often become identified with the so-called “objective” pathophysiological “signs.” But homoeopathy does not recognize a distinction between “signs” and “symptoms”; it views all the patient’s manifestations as symptoms and attributes greater weight to the Peculiar ones.2 This is a fundamental contrast with allopathy, which views “signs” as more significant than “symptoms.”

I he medicine which resembles the patient’s syndrome in only the more Common features will have little or no curative effect. The highly similar remedy, the simillimum, derives curative power from close resemblance to the Peculiar, thus strongly characteristic, symptoms of the patient.

fhe Peculiar symptoms, reflecting the patient’s idiosyncrasy, are thereby the symptoms of his or her “holism”—that otherwise

undefinable dimension of “wholeness” at which all therapeutic procedures should be directed.

Diseases and Disease Causes

Homoeopathy differed, and differs today, from Rationalism in its interpretation of “disease,” “disease cause,” and “disease class.”

The “disease” or “disease class” is given by the symptom-patterns developed in the provings. Each proving yields a set of symptoms, a syndrome suitable for describing a series of differing diseased states, i.e., different patients.

The contrast between these homoeopathic disease classes and the entities of Rationalism is dramatic. In the first place, they are based upon symptoms, not upon internal pathophysiological mechanisms which are, by definition, mere suppositions beyond the physician’s ability to perceive.

Secondly, they are based upon Peculiar symptoms, not upon Common ones. “Specificity” is carried to its logical extreme. The specificity of each syndrome is given by the Peculiar symptoms associated with it, not by the Common ones. Every single patient has his or her own “specific” complaint; no patient is identical with any other patient.

In the third place, disease “classes” are as numerous as the medicines subjected to proving. And such “classes” are not really classes at all, but a technique of individualization. When Peculiar symptoms become the criteria of classification, classes or entities dissolve, and what is left is the individual patient with his or her Peculiar symptoms.

The disease “class” is not the precondition and basis of therapy, as in Rationalism, but the consequence and outcome of therapy. In Rationalism the disease category is put together from the Common symptoms and used as the criterion of diagnosis. Diagnosis is primary, and treatment follows therefrom. In homoeopathy therapeutics is primary, while diagnosis in its allopathic sense is an unnecessary step, since the Peculiar symptoms yield the remedy directly, without the intervention of a disease name, category, or entity. If the remedy is effective, the physician

knows that the prescription was correct, and thus he knows what the patient was suffering from j

Disease “causes” play almost no role in homoeopathy. The internal (pathophysiological) cause is, by definition, unknowable. And most external (exciting) causes, whether changes in the weather, microbes, or some sort of emotional distress, are incorporated in the patient’s reaction (Hahnemann urged removal of obvious exciting causes such as strong-smelling flowers, a foreign body in the eye, an overtight bandage causing gangrene, etc.).

Such external (exciting) causes included psychosomatic factors: “With only slight physical illness, they arise and proceed from the psyche, from persistent grief, resentment, anger, humiliation, and repeated exposure to fear and fright. In time, such psychic diseases often greatly harm the physical health.”k

Treatment is oriented toward the reaction, rather than toward the environmental factor provoking the reaction.

The Three Rules of Practice

In his Organon, first published in 1810, Hahnemann presented the homoeopathic therapeutic system as three rules of practice:

•    Prescription of the drug according to the Law of Similars,

•    In the minimum dose, and

•    Unmixed with any other medicine.

I he meaning of prescribing according to the Law of Similars has already been discussed.

JThe great Paracelsus wrote four centuries ago: “The physician shall divide all illness according to the names of his medicines ... and say thus: he shall not say, ‘This is icteritia.'' That is unmasterly, for any peasant’s hand knows that much. But thus he shall speak, ‘That is morbus leseoli," and for that reason—you thereby comprehend cura, property, name, quality, disposition, and art in science in one name. For leseolus cures icteritia and nothing else” (.Divided Legacy, I, 451). A homoeopathic parallel was described by James Tyler Kent in 1900: “An old Irishman walked into the clinic one day and, after giving his symptoms, said, ‘Doctor, what is the matter with me?’ The physician answered, ‘Why you have Nux vomica,'' that being his remedy. Whereupon the old man said, ‘Well, I did think I had some wonderful disease or other!’” (James Tyler Kent, Lectures on Homoeopathic Philosophy, 23).

kHahnemann, Organon, Par. 225. On the “exciting cause” and “psychosomatic disease” in Hahnemann’s philosophy, see Divided Legacy, II, 344, 392.

Hahnemann’s second rule, that the medicine should be prescribed in the “minimum dose,” reflected his experience with “aggravation.” Patients were ultrasensitive to the “similar” remedy, and it often caused an initial aggravation of the symptoms, followed by their disappearance. When some patients’ symptoms were intensified to dangerous levels, Hahnemann decided to reduce the size of his doses.

Trial and error revealed that the dilution of remedies apparently has no lower limit. As early as 1800 Hahneman prescribed a dose of arsenic “one ten-millionth the usual size,” and thereafter he made general use of the so-called “high dilutions.”

Three scales of dilution have been adopted—1:9 (designated the “X” series), 1:99 (designated the “C” series), and 1:50,000 (designated the “Q” series). Thus, a medicine in the “24X dilution” has been diluted 24 times at the ratio of 1:9; one in the “12C dilution” 12 times at the ratio of 1:99. The medium used is 87 percent hydroalcohol (87 percent alcohol, 13 percent distilled water). The medicine must be shaken (“succussed”) at each stage in the dilution. Preparation of the “Q” series, proposed by Hahnemann in the Sixth edition of the Organon, requires a more complex procedure.

But Hahnemann was a contemporary of Amadeo Avogadro (1776-1856), who discovered that the number of molecules in one gram/mole of any substance is 6.0253 x 1023. Therefore, in a medicine diluted beyond that limit (i.e., the 12C or 24X levels) it is statistically improbable that a single molecule of the original medicinal substance remains present. Moreover, the homoeopaths held that diluting medicines beyond the “Avogadro Limit” enhanced their effect on the intellectual and emotional spheres, as well as the physical. Thus they rejected the “law of mass action” and the concept that the medicine’s effect on the body is intensified by increasing the dose (the “monotonicity” rule).1

The “ultramolecular dose” was an empirical discovery, and no rule obliged homoeopathic physicians to prescribe in this dose

range. Historically they have prescribed doses from the “lowest” potencies (tinctures and the like) to the most extreme level of dilution."1 Hahnemann’s rule, which is deliberately ambiguous, only calls for the “minimal dose” which will accomplish the desired effect.

The “minimum dose” rule is also interpreted to mean that medicines should not be administered at too-frequent intervals.

A corollary of the dynamization of remedies was the discovery that substances which have little or no effect on the body in their unpotentized state—gold, silver, platinum, silica, charcoal, and many others—take on medicinal powers when prepared according to the homoeopathic procedures.

Hahnemann’s third rule, the “single remedy,” requires the physician to administer one medicine at a time. This is because “provings” are always of one single medicine, never of mixtures, and no reliable guide exists to the action of a medicinal mixture on the body.

In both the nineteenth and twentieth centuries the homoeopathic reliance on “ultramolecular” dilutions was a major accusation directed against them in the political warfare waged by allopathy.3

Chronic Disease

When Hahnemann was seventy-three, he added to his system a doctrine of chronic diseases. Die chronischen Krankheiten, ihre eigen-thuemliche Natur und homoeopathische Heilung (1828, 1830) concluded that the acute conditions noted in day-to-day practice were often generated by one of three preexisting hereditary “chronic diseases”: “psora,” syphilis, and “sycosis” (gonorrhea).4

He came to this doctrine after finding that his apparently cured patients sometimes suffered relapses. He hypothesized that this was due to an underlying morbid process blocking a complete cure of the superimposed acute illness.

mThere is no “law of infinitesimals,” as alleged by at least one critic of homoeopathy (Norman Gevitz, ed., Other Healers, 99).

“Psora” he characterized as largely the equivalent of scabies, representing an attenuated form of leprosy, while syphilis and “sycosis” (gonorrhea) were related to the acute conditions of the same name. But many other chronic diseases also exist, especially the nameless ones generated by the abuse of medicinal drugs.

The doctrine of chronic disease at first aroused fierce opposition within homoeopathy because it seemed to resurrect the specific disease entity, now in chronic form. If a chronic disease could coexist with an acute condition in the same patient, it seemed to suggest that “disease” is an entity with a life and existence of its own, not merely a disturbance of the vital force. Accepting the three chronic diseases seemed to conflict with the homoeopathic emphasis on strict individualization of treatment .

But this doctrine was in due course accepted by all homoeopathic physicians, even though its precise meaning for practice, and the relationship between the chronic “miasm” and the associated acute disease remained subjects of controversy.”

Symptoms: Primary and Secondary

Homoeopathy recognizes and distinguishes between “primary" and “secondary” symptoms.

In 1796 Hahnemann first realized that the action of medicines on the body is biphasic: “Most medicines have more than one action: the first a direct action which gradually changes into the second (which I call the indirect secondary action). The latter is generally a state exactly the opposite of the former ... It may almost be considered an axiom that the symptoms of the secondary action are the exact opposite of those of the direct action.”1 Both the primary and secondary symptoms of a drug can be detected in each part of the body, every organ and system; additionally, every medicine is associated with “mental” and “emotional” symptoms as well as physical symptoms of the “whole body.”

"The major twentieth-century exponent of Hahnemann’s “chronic-disease” or “miasmatic” doctrine has been Proceso Sanchez Ortega (see his Apuntes Sobre los Miasmas o Enfermedades Cronicas de Hahnemann, 1977, and Introduction a la Medicina Homeopalica: Teoriay Tecnica, 1992).

“Large” doses of medicines were found to have a powerful primary action, followed by an equally strong secondary action. With small or “infinitesimal” doses the primary action is “perceptible to a sufficiently attentive observer,” while “the living organism employs against it only so much reaction (secondary action) as is necessary for restoration of the normal condition.”6 The violent reactions to Tuberculin were graphic reminders of what occurred when a medicine’s primary action was too strong.

In the proving as well, experiments with moderate doses on healthy persons gave rise mainly to primary symptoms. “There is seldom or hardly ever the least trace [of secondary action] from experiments with moderate doses on healthy bodies, and from small doses none whatever.”7

The “similarity” contemplated by the Law of Similars is thus between the primary symptoms of the remedy and the symptoms of the patient.80 The patient’s symptoms are thereupon extinguished by the secondary action of the remedy or, in other words, by his reaction to the remedy

Awareness of the relationship between dose size and the type of symptom produced led Hahnemann to the further conclusion that substances classified as “poisons” do not differ essentially from those classified as “medicines.” His 1806 essay, “What are Poisons? What are Medicines?” observes that “poisons” differ from “medicines” only in quantity.9 A substance such as table salt, innocuous and even healthy in small amounts, can become poisonous if consumed in larger quantities. And a substance such as arsenic, toxic in even small doses, loses this toxicity and reveals medicinal qualities if taken in an infinitesimal dose. The strongest poisons, in Hahnemann’s view, make the best remedies precisely for their inherent ability to exert an effect on the organism:

Where the public sees only objects of abhorrence, the wise man beholds objects worthy of the deepest veneration and

°An exception was Hahnemann’s prescription of camphor preventively and cura-tively in Asiatic Cholera, for its primary action (Harris L. Coulter, Homoeopathic Influences, 48).

avails himself of them whilst adoring the eternal fountain of love.—Samuel Hahnemann, 180610

The Constitutional Type

Homoeopathic experience has disclosed the existence of a series of “constitutional types,” each identified with the medicine to which the given type is most sensitive and responds best: Bel-ladona type, Sulphur type, Nux vomica type, and so forth.11 The individual will be found to require his “constitutional remedy” as part of the treatment, regardless of the particular illness from which he or she is suffering.

When you have once discovered the constitutional remedy of a patient, you know a great deal about him. After that he should be an open book to you. His remedy will be a suitable one for nearly everything he may have in the future ... A married woman came to me for dysmennorrhea. It did not take me long to make her prescription. I gave her Pulsatilla, and she got rid of her dysmenorrhea. The next time she came to me, it was for diarrhea. Pulsatilla was again indicated. I did not carefully note the symptoms of her diarrhea. I had her constitutional remedy, and that was all I cared for and all that was necessary.—D. C. McLaren, 190112

Catherine Coulter’s Portraits of Homoeopathic Medicines, Volumes I and II (1986, 1988), and her Portrait of Indifference (1989) are classic descriptions of several major constitutional types and subtypes. They build and expand upon James Tyler Kent’s lectures on Homoeopathic Materia Medica (1904) and Margaret Tyler’s Homoeopathic Drug Pictures (1942). The Materia Medica Viva of George Vithoulkas is another very important work in this category.

The “constitutional type” is obviously linked to such concepts as “idiosyncrasy,” “resistance,” and “predisposition.”13 Modern Rationalist medicine has (in the work of

E. Kretschmer and W. Sheldon) also sought a system of biological types, but it is structure-based, while the pure homoeopathic ty-

pology is functional.14 The French school of homoeopathy, under its leader Leon Vannier (1880-1963), developed a “mixed” typology involving both structural and functional elements.15

Allopathic physicians and writers have taken note of the constitutional type and expressed the desire for a functional typology:

However obscure in character and origin ... constitutional factors must be recognized and considered. The same individual differences that make men more or less resistant to the disturbing influence of bacteria, toxins, physical forces, emotion, and other excitants of disease also make them more or less resistant to the influence of disease. Undoubtedly genetic factors are involved here.—Samuel Irwin, 196416

But a system of constitutional types has purpose and function mainly for therapeutics. Where there is no therapeutic theory, as in allopathy, no criterion exists for distinguishing one constitutional type from another.P

Mental Illness

The proving elicits “mental” and “emotional” symptoms as well as physical ones, and homoeopaths from Hahnemann’s time onward have treated mental illness with their remedies.17 Indeed, homoeopathy does not make a distinction between “mental” and “physical” illness, since patients with “somatic” conditions manifest “mental” symptoms, while those with “mental” conditions display “somatic” symptoms:

A woman about fifty years of age being in poor health developed an insane fear of poverty and ruin; was sure her son and daughter were wasteful with the family’s small means, and insisted on economy to the extent of stinginess, while she wept freely over her miserable condition. A dose of Pulsatilla made apparently a good cure at the time, but six months later the patient broke out again with quite a different train

of symptoms. She was wildly insane, and much of the time had to be held in bed for her own and the family’s safety; was talkative, suspicious, and jealous, and showed other physical symptoms which plainly indicated iMchesis, a dose of which cured her so entirely that there has been no reappearance of the trouble for two years.

D. C. McLaren, 190118

Homoeopathic physicians have treated the whole range of mental conditions: visual and auditory hallucinations, violent outbursts of aggression, postencephalitic syndrome following influenza, depression with anorexia, excessive libido, catatonic and other types of schizophrenia, paranoia, senile sclerosis, depressions, manic states, and the like.19 An early treatise on the subject was Mental Diseases and Their Modern Treatment (1901) by Selden Talcott, for decades superintendent of the Middletown (New York) State Homoeopathic Hospital (for mental diseases), which discusses the homoeopathic treatment of melancholia, hallucinatory states, hysterical mania, dementia, acute and chronic mania, cataleptic states, senile dementia, idiocy, and other states.20

The homoeopath Oswald H. Boltz, who was from 1934 to 1959 Director of Clinical Psychiatry at the Binghamton State Hospital (New York), wrote in 1968: “Most of my patients were treated prior to the advent of modern therapies (electro- and insulin-shock, tranquilizers, etc.). A good many of the tranquilizer-treated patients required maintenance therapy after they were released from the hospital. Most of mine, who were properly treated with the organ and constitutional remedies indicated, remained recovered anywhere from seventeen to thirty years without any maintenance therapy or relapse.”21

Symptoms: Classification

The most remarkable contribution to homoeopathic practice since the death of Constantine Hering in 1880 was the Repertory of the Homoeopathic Materia Medica by James Tyler Kent (1849-1916), issued during the first two decades of the new century.

Kent is the only American-born physician who can be ranked with the Empirical Hippocrates, Paracelsus, Van Hel-mont, Sydenham, Hahnemann, Laennec, Hering, and a few others, for his insight into the processes of disease and health and for the restatement of homoeopathic therapeutics embodied in his Repertory.

He was born in upstate New York to a family of farmers and received the BA degree from Madison College (later Colgate University) at the age of nineteen.^ Two years later he had an MA degree from the Bellevue Medical College and thereafter studied for two years at the Eclectic Medical Institute in Cincinnati. At age twenty-six he set up practice as an Eclectic physician in St. I,ouis and soon afterwards converted to homoeopathy when his wife was cured of a severe illness by a physician of that school.22

During his lifetime he taught materia medica at homoeopathic colleges in St. Louis, Philadelphia, and Chicago, and was the leader of the classical Hahnemannian (“high potency”) wing of American and world homoeopathy until his death.

Kent’s Repertory was a new arrangement of the mass of pharmacologic and therapeutic information which had emerged since Hahnemann performed the first provings.

By the end of the nineteenth century about a thousand medicines had been proven, many of them—Sulphur, Natrum muri-aticurn (sodium chloride), Arsenicum album, and others—yielding seventy or eighty pages of symptoms apiece. This information had been accumulated in such compendia as Hering’s Guiding Symptoms of Our Materia Medica or T. F. Allen’s Encyclopedia of Pure Materia Medica, each comprising ten volumes.

In these works the proving-symptoms of a given remedy were all listed under that remedy’s name, with subdivision according to parts of the body, time of appearance, modalities, and the like/ Hence there was no convenient way to compare the symptoms of

'iHela Michot-Dietrich has unearthed evidence strongly indicating that Kent was actually the incestuous child of his fifteen-year-old brother and thirteen-year-old sister; this genetic reinforcement may account for his genius (Hela Michot-Dietrich, “In Search of James Tyler Kent’s Ancestors,” 1990).

several different remedies relating to a particular part of the body. If the patient manifested a symptom such as “coldness of hands in warm weather,” the physician had to search under many different medicines for this particular subentry. As more and more medicines came to be proven, the process became excessively laborious.

What practitioners needed was an arrangement which proceeded from symptom and part of body to remedy, the parts of the body being the principal entries with the symptoms and remedies as subentries. Then, noting “coldness of hands in warm weather” in his patient, the physician would at once have a list of all the remedies whose provings contained this symptom.

Several repertories of the materia medica designed to meet this need had been compiled in the nineteenth century and are associated with the names of practitioners such as Hering, Calvin B. Knerr (1847-1940), Adolphus Lippe (1812-1888), and Clemens von Boenninghausen (1785-1864), but they were increasingly recognized as inadequate.23,8

The task confronting Kent was to combine in a single volume all the symptoms of some seven hundred remedies, together with their “modalities”; to provide a method for distinguishing among them according to the degree of their reliability; to allocate them to the various parts, organs, and systems of the body, as revealed by the provings; and to structure all this information in an accessible form.

The Kent Repertory marked a new dimension in the organization of symptomatic information and a new' starting-point for therapy. While further data have been added in recent decades, Kent’s original version remains in use by hundreds of thousands of homoeopathic practitioners worldwide. Its compilation required an effort of intellect and will ranking Kent among the very greatest of medical thinkers.1

' Boenmnghausen’s Characteristics and Repertory (1937) by Cyrus M. Boger (1861-1935), as well as the latter’s Synoptic Key of the Materia Medica (1915), were also fundamental contributions (Harald Gaier, Encyclopedic Dictionary, 64).

'This stupendous achievement, amounting to nearly 1500 pages—the twentieth century’s response to the challenge of Hippocratic medicine—has probably never been mentioned, let alone praised or reviewed, in an allopathic medical journal.

In his classification of symptoms Kent placed at the forefront those predicated of the patient as a whole, calling them Generals. The Generals, in turn, were subdivided into “mental” and “physical.”

Since all “mental” symptoms are by definition “general,” i.e., predicated of the patient as a whole, Kent used the term Mental symptoms or “Mentals” (rather than “Mental Generals”). Physical symptoms predicated of the patient as a whole were called Generals (not “Physical Generals”). All other physical symptoms were called Particulars.

So Kent’s three classes of symptoms were Mentals, Generals, and Particulars.

The symptoms “of supreme importance to the case, as expressing most absolutely the patient” are the Mentals. Margaret Tyler’s introductory essay, “A Study of the Kent Repertory" (1914), states: “You may find that a patient is intensely jealous, or suspicious, or tearful, or indifferent to loved ones, or reserved and intolerant of sympathy and consolation. In sickness these things come out. Often in sickness the very nature seems to change; the rash and reckless become timid for themselves and others; the good-tempered snappy; the irritable and restless, patient. If a mental trait is marked, and especially if it denotes change from the patient’s normal, it is of the utmost importance to the case.”24 Kent graded Mentals into symptoms affecting:

... the WILL, with loves and hates, suspicions and fears. She hates her child—is jealous—fear of disease—of solitude— these are among the highest mentals.

... the UNDERSTANDING, with delusions, delirium, loss of the sense of proportion, with exaltation of trifles, delusions of grandeur, or persecution.

Of third and lowest mental grade are those [symptoms] that relate to MEMORY.25

The Generals include pains of the whole body or a substantial part of the body (right side, left side, several organs), convulsions, character of discharges, sexual behavior, appetites, thirst, food desires and aversions, menstruation, reaction to heat or cold, dampness and dryness, etc.

Particulars are symptoms of the parts, organs, and systems of the body, and Kent used the following categories: abdomen, back, bladder, chest, ear, throat, external throat, extremities, eye, face, male and female genitalia, head, kidneys, larynx and trachea, mouth, nose, prostate, rectum, anus, perineum, skin, stomach, teeth, and urethra.

All symptoms—Mentals, Generals, and Particulars—can be Peculiar or Common. The former take precedence over the latter because the more Peculiar the symptom is, the more closely it approximates the specific nature, the idiosyncrasy, of the patient. In other words, the more Peculiar the symptom, the more General.

Common symptoms are converted into Peculiar ones through greater refinement of the category, i.e., through the application of “modalities.” This idea, always at the heart of homoeopathic doctrine, was systematized and perfected in the Kent Repertory. All Common symptoms are qualified and specified as to: (1) time, (2) conditions which affect them, and (3) locality, character, and extension (the point from which the symptom extends).

Common symptoms are of two kinds, symptoms common to the disease, which ... do not show how the patient reacts to this particular “morbific agent,” as Hahnemann puts it; and symptoms common to an enormous number of drugs, and therefore useless for the selection of one remedy—such as diarrhea, vomiting, excessive sweating, headache. Common symptoms do not serve to distinguish, and you need to distinguish, if you are to pick out THE drug.—Margaret Tyler, 191426

Tyler gives examples of how this is done for Mentals, Generals, and Particulars:

Take a MENTAL symptom ... take anxiety.

First, always, TIME ... ANXIETY: morning, afternoons, at night; at some special hour.

Then, conditions under which anxiety has been observed, in alphabetical order ... ANXIETY: in open air, in bed, as of a guilty conscience, during fever, for others, before menses, about salvation, on waking, and so on.

Now turn to the ... Generalities, or GENERALS. Here

we have the aggravations, ameliorations, and reactions of the patient as a whole to physical environment; and here again precisely the same arrangement is found.

First, in regard to TIME. The patient is generally worse in the morning, at noon, at night, at such an hour ... Then, after time, comes the general conditions of the patient, as a whole, in alphabetical order. These always apply to the patient generally ... Among these Generalities at the end of the book we find worse and better from bath and washing; from cold, from wet and dry; from position, motion, pressure, eating, sleep, and so on. Here, also ... certain conditions, in their alphabetical place, such as faintness, convulsions, fullness, pain in general—its onset, gradual or sudden, and its disappearance in the same way, and their combinations; its character, burning, pressing, shooting, etc., and its direction, pains that shoot up, down, inward, outwards, across ...

But under these broader headings, such as faintness, convulsions, you will again find qualifications, aggravations and ameliorations; and in all of these, down to the smallest subsections, the same order reigns. TIME first, then CONDITIONS, alphabetically. As FAINTNESS morning, after midnight, at such an hour, during fever, before or after eating, on exertion, after menstrual period, while standing, and a host of others.—Margaret Tyler, 191427

A General symptom can also be made increasingly Peculiar:

fake the question of thirst your patient has a fever, and is extremely thirsty. This is a Common symptom: doubly Common as a matter of fact, for thirst is common to very many remedies, and to most fevers. You must have something more, something that distinguishes and qualifies to make the symptom of the slightest use to you—and yet the symptom is a General symptom, and, as concerns the patient, urgent. Enquire further and see if you cannot make it useful. Suppose you find that the thirst is at one particular hour; or only during the cold stage, or before it; or that it is for large quantities, or small; or that there is thirstlessness during the period of high temperature only; or a raging thirst with no desire to

drink; why these things are peculiar to individual patients and to fewer drugs and are therefore of importance ... You see how a Common and useless symptom may be transformed into one of Kent’s “strange, rare, and Peculiar, therefore General symptoms.”—Margaret Tyler, 191428

In the Particulars, Kent’s system of refining and qualifying symptoms at each stage in the movement from greater to lesser generality becomes most elaborate.

Let us now take pain in the extremities, the most alarming and bewildering of all to the neophyte; for it occupies more than 120 pages of the book ...

It starts, as usual, with what is more general ... PAIN GENERALLY IN THE EXTREMITIES. First, as to TIME, then the usual modifying conditions in alphabetical order during chill; when lying; during menstrual period; rheumatic; alternating with different ailments; wandering and shifting; in wet weather, and so on.

Next, PAIN, as LOCALIZED GENERALLY; in bones, flexor muscles; joints, nails, tendons; always qualified as to various conditions, first as regards time, and the rest in alphabetical order.

Then PAIN as localized in the UPPER LIMBS GENERALLY, right; left; with the same conditions; following, first as to time, then the rest alphabetically, then EXTENSION. After finishing with the upper limb as a whole, Kent now takes its parts, SHOULDER, UPPER ARM, ELBOW, WRIST, HAND, FINGERS, with all their details, to individual fingers, with joints, nails, tip; each time with conditions in the same order—time, other conditions alphabetically, then extension.

The upper limbs so far disposed of, the LOWER LIMBS are now taken in precisely the same way, with the same detail, and the same arrangement; and that ends localities generally; and Kent next proceeds to consider the CHARACTER OF THE PAIN, and under the various headings, ACHING, BURNING, CUTTING, DRAWING, ETC., the whole thing is gone into again! As for instance —

• ACHING, generally, with its TIME and other conditions.

•    ACHING IN BONES, JOINTS, EXTENSORS, FLEXORS.

•    ACHING IN UPPER LIMBS, with time, other conditions, extension.

Then ACHING in all the LOCALITIES in order, first of upper limb, then of lower, with in each case, the usual conditions, first as to time, then the rest in alphabetical order, then extension.

So through all the various kinds of pain, burning, pressing, shooting, tearing; each being carried down through all the localities, from the larger and more general, to the smaller and more particular, with always, time aggravations, other conditional aggravations, and extension. Truly an amazing work.—Margaret Tyler, 191429

This refining process, providing insight into the patient’s idiosyncrasy, converts the relatively useless Common and Particular symptoms into the invaluable Peculiar and General ones. “Those symptoms,” as Kent puts it, “strange, rare, and Peculiar, are therefore among the highest Generals, because strange, rare, and Peculiar must apply to the patient himself.”30

Kent introduced one further refinement: the grading of symptoms in function of their reliability.

Earlier volumes of Divided Legacy have stressed the importance of reliability of medical information for the Empirical tradition.0 This was also true for Kent, and the Repertory distinguished three “grades” of reliability of symptoms by three different typefaces.

The highest grade, in heavy type, were symptoms expressed by most or all provers, substantiated by reprovings of the medicine, and whose reliability was further confirmed by their disappearance in patients treated with that remedy.

The second grade, in italic type, were symptoms expressed by several provers, confirmed by reprovings, and verified clinically by definite cures.

The third grade, in ordinary type, were symptoms “consistent with the nature of the remedy” but which had never appeared in a proving and had been mainly verified by clinical cures. Roger Schmidt, a leading American homoeopath, wrote that these symptoms “should be overlooked by the beginner, but judiciously used by seasoned homoeopaths.”31

Reliance on symptoms of the lowest grade is dangerous because of the inherent difficulty of ascribing a symptom to a drug (even on the authority of Kent!) merely because it has been cured by that drug. Again to quote Margaret Tyler: “A drug in its provings can only evoke in each case what was there already, latent in the prover—even as disease brings out weak points, and therefore does not affect two patients exactly alike. It requires many provers of different types, and different defective resistances, to bring out the whole picture of a drug pathogenesis. Had more drugs been more extensively proved, many more ‘rare, peculiar, and distinctive’ symptoms would probably have seen the light. A patient’s own individual remedy, prescribed on mental and general symptoms, will often wipe out peculiar symptoms that it has never been recorded as having invoked, and which are the striking keynotes of some other remedy ... [ButJ where there is nothing in the Generals to contradict, [symptoms from cures] afford a strong reason for the exhibition of a remedy that has been known to produce and cure them. They are invaluable often to give the casting vote.”32

Prescribing homoeopathically, following the Kent Repertory, means individualizing treatment by refining the Generals and Mentals, to bring out their Peculiar features, then doing the same for the Particulars: “... individualize still further, using the symptoms predicated of the organs, functions and sensations, always giving an important place to the time of occurrence of every symptom until every detail has been examined.”33 Kent’s own advice on using his Repertory was:

After taking the case according to the lines laid down in the Organon ... write out all the mental symptoms and all symptoms and conditions predicated of the patient himself and search the Repertory for symptoms that correspond to these. Then search for such physical symptoms as are predicated of the blood, color of discharge, and bodily aggravation and amelioration that include the whole being, as well as desire for open air, desire for heat, for cold air, for rest, for motion ... It should be understood that a circumstance that makes the whole being feel better or worse is of much greater importance than when the same circumstance only affects the painful part, and these are often quite opposite. Then individualize still further, using the symptoms predicated of the organs, functions, and sensations, always giving an important place to the time of occurrence of every symptom until every detail has been examined.34

In sum,

Get the strong, strange, Peculiar symptoms, and then SEE TO IT THAT THERE ARE NO GENERALS IN THE CASE THAT OPPOSE OR CONTRADICT.35

By refining the traditional Empirical distinction between “common” and “peculiar” symptoms, homoeopathy provided an answer to the vexed question of the meaning of “specificity.” “Specificity” in pharmacology is the counterpart of “idiosyncrasy” in pathophysiology and is ascertained by “individualizing” the diagnosis/

Where allopathy diagnoses the patient to assimilate him to some preexisting disease category, homoeopathy distinguishes the given patient from all others with similar diseases, administering to each patient the “specific” for his or her case.

Homoeopathic Opposition to Kent

I he Repertory promptly became the central issue in a rancorous controversy within American (and British) homoeopathy—pitting a group represented by the International Hahnemannian Association, holding that Kent represented the true continuation of classi-

cal homoeopathy, against the American Institute of Homeopathy which deliberately or unconsciously sought to bring homoeopathy into line with the doctrinal structure and procedures of allopathy.

Since this internecine conflict (usually known as the dispute between the “high-potency” and the “low-potency” wings of the homoeopathic profession), which did so much to weaken this school in the face of its enemies, has been analyzed in detail elsewhere, there is no need to repeat the history of its origins."

In the twentieth century the spirit of strict Hahnemannian homoeopathy has been represented by this Repertory, and the degree to which practitioners in any country abide by Hahnemann’s Empirical legacy is defined by how closely they follow the Kentian method.

In the century’s early years the low-potency trend dominated homoeopathy everywhere, and the unfolding of Kentian influence came over the vociferous and tenacious resistance of these physicians. Their world leader in the latter decades of the nineteenth century was the Englishman Richard Hughes (1836-1902), whose Cyclopedia of Drug Pathogenesy (written in collaboration with several American homoeopaths) and Manual of Pharmacodynamics strove to place the homoeopathic provings, and homoeopathic practice, on a pathophysiological basis, to limit or end the use of the “high dilutions” (meaning, usually, remedies diluted beyond the 30C limit set by Hahnemann in 1829), to introduce standard disease nomenclature, to interpret the pharmacopoeia in chemical terms, and to “cleanse” the materia medica of what Hughes regarded as “doubtful” remedies and “doubtful" proving symptoms. Veering ever closer to allopathy, it ended by authorizing polypharmacy and multiple prescribing. 16,x

The central argument was over the role and definition of the proving symptoms. Which symptoms of provers were to be accepted as legitimate? Which were to be excluded?

The only possible answer to this question had been given decades earlier (1873) by Constantine Hering: “We certainly

“See Divided Legacy, III, Chapter VI

'For an American text representing this trend see A. W. Woodward, Constitutional Therapeutics (1903).

cannot do anything except to find some observations more, and others less, probable, and, of course, confirmation increases the probability until a higher law decides ... It is fifty years now since I joined the homoeopathic school, and I have never met a single prover who did ‘believe’ the symptoms he obtained and who did not seek confirmations. We not only repeated experiments again and again, but we were anxious to have other provers, and if the results were published, we always compared anxiously those of others with our own ... W^hat we repeatedly found confirmed by cures, day after day, week after week, and year after year, is what we took as our basis, as a true gain in the new science; these were what we called the characteristics of the drug.”37 But where Hering wanted to work within homoeopathy, “anxiously” discussing and comparing the symptoms of provings and in this way separating the genuine ones from contaminants due to provers’ inexperience, carelessness, or inability to observe, Hughes and his fellow-travelers invoked the typically Rationalist device of a criterion from the outside, namely, the association of symptoms with presumed “underlying” anatomico-pathological disorders (taken, of course, from contemporary allopathy!).

The low-potency wing was very attracted by the “germ theory” and prepared to accept the bacterial cause as the criterion of reliability of symptoms. Homoeopaths had had experience with disease conditions associated with small insects, most especially the Acarus scabiei often found in the skin of persons with scabies (and blamed by allopathic medicine for this condition!). And Hahnemann in 1832 had ascribed cholera to microbes.38 But he had not urged combating this disease by antiseptic remedies directed at said “miasmatic animated beings.” Instead, he advocated remedies to reinforce the host response. His classical followers steadily maintained that germs cause disease only in the predisposed or weakened host.39 They referred often to Pettenkoffer’s experiment of drinking a cholera culture without falling ill and noted that cholera cannot be generated by feeding the vibrios to healthy animals.40

There must be a disposition in the organism to be affected by the contagium vivum, or else it will not be taken with it. This

disposition, if analyzed, turns out to be entirely of a spiritlike nature; it repels the aggression or it succumbs to it, and then it takes a certain time of incubation, after which the strange symptoms appear, as the reaction of the organism against the infection, and this is the disease. Taken in this way the contagium vivum is only the accidental cause, but not the essential one, and this is exactly Hahnemann’s teaching.—Bernhardt Fincke, 190141

Hereditary disposition is also crucial for susceptibility to infection.42

The “classical” wing drew an analogy with the treatment of worms: rather than expelling them directly with a vermifuge, the patient’s health must be improved, whereupon the worms disappear by themselves.43 Hence the correct treatment was to strengthen the resistance of the host by employing the similar remedy and not to assault the supposed microbial cause directly:

[Homoeopathists] seem to fear their medicines cannot cure diseases which are said to be produced by microorganisms. “We must do something more than simply prescribe the specific remedy,” cry some. “The remedy cannot act while the cause of the disease is present,” say others. It is well known that these germs do not exist in a healthy man. The sickness of the individual produces the habitat, the proper soil, for their growth; hence they cannot be the cause of the disease. Therefore, destroying these germs is really destroying an effect and not the cause of the disease ... It is a much-debated question whether any varieties of bacteria may exist in the blood or tissues of a healthy animal ... The familiar fact that a dead fetus may remain in the mother’s body for months or years without putrefaction, as in extra-uterine pregnancy, supports the same conclusion ... For seventy years a man may eat, drink, and breathe the ordinary bacteria, and carry' a vast and varied assortment of them in his alimentary canal, without suffering putrefaction; yet so soon as his component cells are destroyed generally as in the death of the animal, or locally, as in the gangrene of a toe, the tissues swarm with these minute organisms. Bacteria cannot maintain the struggle for existence against the animal cells indigenous to the soil.—Homoeopathic. Physician, 188344

Even anti-bacterial agents cannot act on bacteria directly but only by stimulating the host, i.e., homoeopathically. And whenever they are not selected for their symptom-similarity, they are wrongly directed:

Thus the supercilious neglect of Hahnemann’s groundlaw, that diseases are spirit-like perturbations of health ... prevents the advance of the healing art, leading on the contrary to a new pathology, poisoning the present generation instead of healing it.—Bernhardt Fincke, 190145

To the Hahnemannians the bacterium was just the Rationalist “proximate cause” redivivus:

The plausibility of the germ theory has made many members of the Old School [allopathy] more arrogant and defiant than they ever were before, and has raised in their minds high hopes that at last allopathy has a firm pathological basis upon which to build a new and improved therapy ... [They say] the progressive advancement of our knowledge of the causes of infectious diseases will revolutionize not only etiology and pathology, but also therapeutics ... It is because of the unsatisfactory state of its therapeutics that the Old School looks forward with such hope to the germ theory. I do not think the germ theory has much to offer for [homoeopathic] therapeutics, but may be very useful for prevention.—Medical Era, 1885-188G46

They scoffed at Koch’s discovery of the cholera vibrio and the tuberculosis bacillus. No perceptible advance in treatment had ensued: “All that’s needed is a ‘germicide,’ and then the problem is solved. So it would seem. But the sad fact is, after great and earnest ‘stamping out’ of these causal ‘microbes,’ cholera continues and kills just as before.”47 “All Koch has discovered is the presence of these organisms in the excreta of cholera patients. His ascription to them of the office of causation is wholly gratuitous.”48 “Cholera continues to seize its victims

and quench their lives even before the eyes of the ‘cholera experts,’ including Koch, just the same since he proclaimed his discovery ... as before his discovery ... self-styled ‘scientific medicine’ stands as to the cure precisely in the attitude of Faust:

Da steh ich nun, ich armer Tor,

Und bin so klug als wie zuvor. ” 49,y

In the classical view, the more the low-potency practitioners deviated from Hahnemann’s three rules, the less effective was their prescribing. Unable to cure proficiently, they lost interest in therapeutics and sought professional satisfaction in pathology, diagnosis, and the like. A high-potency journal commented:

Having made of disease an entity, and having built up elaborate theories of pathological action of the tissues, and having withal based prescriptions upon these theories, they have met with so many failures in their efforts to cure that they have despaired of ever bringing therapeutic measures to a condition of efficiency and reliability. Scepticism of the value of any curative measures has slowly and surely taken possession of the best minds in the profession, and they have, in consequence, turned their attention to an investigation of the causes of disease and of the nature of the pathological processes involved.—Homoeopathic Physician, 189250

Some went so far as to mistrust Lister’s antiseptic surgery: infected surgical operations and wounds are best cured with the similar medicine.51

The Triumph of the Kent Repertory

The gradual expansion of Kentian influence in twentieth-century homoeopathy has proven the viability of the classical doctrine which at one point seemed close to extinction.

The Repertory itself had a dramatic history. In 1908 Kent issued a second edition and immediately commenced work on a

v“I stand there, poor fool/No wiser than before” (from Goethe’s Faust).

third, which had been completed in three copies at the time of his death in 1916. It was published in 1924 under the direction of his seventy-two-year-old widow, Clara Louise Kent, and contained numerous mistakes and omissions. The fourth edition appeared in 1935, again edited by Clara Louise Kent but with the collaboration of Frederica Gladwin and the French-Swiss homoeopath Pierre Schmidt, who would later attain even greater eminence. The fifth American edition appeared in 1945 and a sixth American edition in 1957.

Thereafter responsibility for the Repertory passed into the hands of Indian publishers. In that country three editions were published simultaneously in 1961, with numerous reprints in following years. Since the pages of new editions were reset by hand, numerous errors crept in, and the need was felt to check against Kent’s own draft of his third edition. Fortunately, one of his three original copies was still extant, having passed from Frederica Gladwin and Alonzo Eugene Austin into the possession of Pierre Schmidt in Geneva.

But then a most improbable event occurred: an Indian physician working under Schmidt’s tutelage absconded with the Kent manuscript, cut it into small pieces, and buried it in the ground in a small village of northern India.

Only thanks to persistent efforts by Diwan Harish Chand of New Delhi and Ahmed Currim, an American homoeopath of Indian origin, were the pieces at length recovered and returned to Geneva, where they could be used as the basis for a new edition in 1980.52

The conflict between the two wings of homoeopathy was played out first in the United States and England. The overwhelming majority of the 15,000 American homoeopaths in practice at the turn of the new century were of the low-potency Rationalizing persuasion. Their attitude toward Kent and all his works may be seen from the comments of their spokesman Linn J. Boyd. By 1865, he observes, there was agreement that Hahnemann’s “hy-persubjective materia medica” needed “retesting and modification and the important supplement of organotropic effects added from animal experimentation.”53 One of the sources of the con-

taminated materia medica of the times was “the dangerous procedure of using clinical symptoms as a source of provings ... when drugs relieved symptoms, it was presumed that they are also capable of producing these symptoms in the healthy It seems hardly necessary to point out that this reasoning is based on very fragile evidence.”54

Here one may perceive another trend of difference in the two groups of homoeopathic physicians. Whereas the natural scientific [i.e., “low-potency”] group became more wary of all unusual subjective symptoms and tended to emphasize the common or major phenomena, the purists attempted to “preserve” the status of the materia medica and not rarely to prescribe on the basis of the rare symptom, basing the process on the speculation that if the symptoms corresponded in respect to the rare, they would also correspond in respect to the common ... As time went on one group paid more attention to the “important,” common, usual, symptoms with increasing attention to objective phenomena. "I he other group tended to preserve each fragment and maintain emphasis on the subjective symptoms.—LinnJ. Boyd, 193655

I he Kentian materia medica, in Boyd’s opinion, consisted of many “entirely inadequately proven substances,” “a wide variety ... introduced on evidence which at best is little more than meager.”56

There is ... no evidence to support the contention that some rare, unusual subjective symptoms equal in value objective common phenomena. A red, swollen, smoothly glazed tonsil without exudation on the surface, associated with streptococci and with involvement of the eustachian tube, is relatively more important than whether the patient complains of a splinter-like or a burning pain. On the other hand, when burning pain has been repeatedly recorded in the provings and is found to be a useful symptom clinically, it attains importance. In the final analysis the problem is not one of objective versus subjective, but the inclusion of both when they have attained certainty, through quantitatively

sufficient experimental and clinical experience.

LinnJ. Boyd, 193657

Boyd regarded the low-potency trend as “scientific” and expressed the hope and desire that some day homoeopathy would be duly incorporated into a “unified medicine.”58 In the meantime, homoeopathic practice should be based on “objective” symptoms, meaning ones which could be readily associated with pathological changes:

The anatomico-physiologic trend usually provides the most important indications in practical therapeutics. Considerable confusion arises in the mind of the student when first confronted by the innumerable symptoms in the textbooks of materia medica, but separation of these pictures into anatomico-pathologic trends greatly simplifies the procedure.—Linn J. Boyd, 193659

The remainder of the low potency doctrine flowed ineluctably from the initial decision to favor the Common symptoms, and to ignore what these physicians called “subjective” symptoms, meaning the “strange, rare and peculiar” ones which, in the pure Empirical formulation of homoeopathy are the very keys to the patient’s uniqueness.

Opting for Common over Peculiar symptoms as the guide to treatment is a watershed decision. It means choosing the barren logic of Rationalism over Empiricism’s rich legacy of observation and experience.

The imprint of Hughes on British homoeopathy was profound, and could still be discerned in the late twentieth century A residual animus against Kent was evident for decades in the writings of many British homoeopaths, who accused him of “spiritualism” and Swedenborgianism, of mixing homoeopathy with psychotherapy, and the like. This heavy dough, however, was leavened by the contributions of a small group of outstanding practitioners and personalities who upheld the true Empirical doctrine and expanded use of the Kent Repertory in England.

Hughes’ foremost opponent was John Henry Clarke (1853-1931), author of the four-volume Dictionary of Practical

Materia Medica (1900) and formerly Hughes’ intimate friend and colleague. He accused the latter of pandering to the allopaths and propagating an imprecise, hence therapeutically ineffective type of homoeopathy.60 Indeed, toward the end of his life Hughes decided that certain diseases did not fall within the scope of homoeopathy at all:

The intrinsic value of each individual symptom was of no concern to him; what was important was the way the allopath would regard it ... Many of those converted by him have slid back into allopathy ... Diseases are regarded as things to be cured, in place of the much more difficult and much more successful business of individualization ... Failures to spot the remedy by the help of Hughes were sufficiently frequent to produce in me a chastened spirit and to send me elsewhere for help. John Henry Clarke, 191 l61

But Clarke was a Hahnemannian rather than a Kentian. The British first learned about Kent through a scholarship fund established by Sir Henry James Tyler, which enabled three young physicians, John (later Sir John) Weir (1879-1971), Douglas Borland, and Fergie W'oods to travel to the United States in 1908 and study with him. The Scotsman, Robert Gibson Miller, had already studied under Kent in St. Louis in 1884.

John Weir later became physician to the British Royal Family.

These four, with their associates and disciples—including, in particular, Margaret Tyler (1875-1943), the daughter of Sir Henry James Tyler, and Margery Blackie (1898-1981), great-niece ofjames Compton-Burnett (as Lady Margery Blackie she later succeeded to Sir John Weir’s royal appointment)—became a fertile nucleus of Kentian homoeopathy in Great Britain/ At Weir’s initiative, Parliament in 1950 passed the Faculty of Homoeopathy Act which established homoeopathy as a separately licensed medical specialty.

z“There were two books always at her bedside, her homoeopathic Bible, Kent’s Materia Medica, and the Bible itself” (C. Babington-Smith, Champion of Homoeopathy, 166).

By the latter decades of the twentieth century Kentianism had established a major position in British homoeopathy.62

In the French-speaking world the chief propagator of Kentian homoeopathy was Pierre Schmidt (1894-1987). Impressed by a homoeopathic cure of his father’s lifelong enteritis, and also by the benefits of the nosode Injluenzinum during the 1918 influenza pandemic, he worked for a while at the London Homoeopathic Hospital under John Weir and subsequently studied in Philadelphia with Kent’s students and associates, Frederica Gladwin and Alonzo Eugene Austin.63

As already noted, Schmidt was for decades intimately involved in the fate of the Kent Repertory.

In 1925 he, Jean-Paul Tessier, and J. Thuinzing of the Netherlands founded the Liga Medicorum Homoeopathica In-ternationalis; its purpose was to renovate world homoeopathy, which had veered far into allopathic territory, by restoring the ideas of Hahnemann and Kent to their rightful place.64 In so doing he was met with “ferocious hostility from those whose partisan ideas and practices he had to refute,” but the Liga remained an active focus of worldwide homoeopathic cooperation throughout the twentieth century.65

In 1946 Schmidt started teaching Kentian doctrine within the framework of “Le Groupement Hahnemannien du Docteur P. Schmidt,” an ongoing seminar, first in Lyons and later in Geneva, which trained several hundred physicians from every country where homoeopathy is practiced.

In France itself the most prominent Kentian has been Jacques Baur ol Lyons, editor of the Cahiers du Groupement Hahnemannien du Docteur P. Schmidt. The Kent Repertory was translated into French and published in 1966 by Georges Broussalian; another translation, by Alain Horvilleur, appeared in 1992.66

In the Spanish world the major schools of Kentian homoeopathy have been those of Proceso Sanchez Ortega, in Mexico, who creatively developed the Hahnemannian theory of the chronic miasms, and of Tomas Pablo Paschero (1904-1986) in Argentina, who also elaborated the miasmatic theory, emphasizing environmental rather than congenital factors. The Kent

Repertory was translated into Spanish by Francisco Eizayaga in 1979.

It was translated into Italian in 1991 by Claudio Mazza.

In the German culture area the leader of Kentian thinking was the Swiss Jost Kuenzli von Fimmelsberg (1915 1992), who, together with Georg von Keller, in 1960 published the second German edition of the Repertory.aa The year 1973 saw the appearance of the three-volume Synthetic Repertory by H. Barthel and W. Klunker, in English, French, and German; while based upon the Kent Repertory, it is limited to the Mentals and Generals.67 In 1987 Kuenzli published Kent’s Repertorium Generate, an enlarged and expanded English-language version.

The Kentian doctrine has been vigorously propagated in most countries of Europe and in the United States by Ho-moeopatia Europaea, an offshoot of Schmidt’s Groupement Hahnemannien, which from its founding has been animated and led by the Belgian homoeopath Jacques Imberechts.68

In India, which today has as many homoeopathic physicians and practitioners as the rest of the world together, the leading Kentian spokesman has been Diwan Harish Chand, himself a student and close associate of Pierre Schmidt.69 In 1980 he and Schmidt issued the Final General Repertory of the Homoeopathic Materia Medica (Revised Edition), which incorporated the lost fragments of Kent’s revisions after their years of fecundation in Indian soil. Two years later a 456-page Corrections and Additions to Kent’s Repertory was published by P. Sivaraman.70

In American homoeopathy the quarrel was resolved by time and the Grim Reaper. As the medical schools—the seed-beds of “low potency” practice—became allopathic, no one was left to imbue the younger generation with these concepts. In fact, by the 1950s

“The first German translation, by Willy Erbe, appeared in 1937, a time when, in the words of Jacques Baur, “... the teachings of Dr. Kent had hardly made an impression on Europe. Whether German, French, or British, practitioners were, for the most part, attached to a low-potency practice with strong tendencies to polypharmacy and even multiple prescriptions” (“Le Repertoire de Kent”). The Erbe edition was reprinted in 1981.

only a few dozen homoeopaths remained active in the United States, but there was benefit in that this group, including Elizabeth Wright Hubbard (who had studied with Pierre Schmidt), James Stephenson, Maesimond B. Panos, and William Gutman, were all Hahnemannian and Kentian purists.bb

When American homoeopathy resumed its upward course in the 1960s, Kentian philosophy dominated.

The preeminent exponent of Kentian philosophy and practice, and the most influential homoeopath of the late twentieth century, has been George Vithoulkas who, after graduating as a civil engineer in Greece and working in that capacity, studied homoeopathy at several colleges in India. Together with Irini Bachas, he established a school and a center of homoeopathy in Greece and organized training programs there, in Europe, and the United States:

Vithoulkas spent the two decades from 1970 traveling as homoeopathy’s impassioned articulate crusader to many major cities of the world lecturing, conducting seminars, addressing conferences, and indefatigably bringing homoeopathy to the attention of the general public and creating an awareness of this scientific medical system in the entrenched, institutionalized, orthodox medical establishment. He follows in the tradition of James Tyler Kent whose concepts he has revitalized and substantially developed with consummate logic.—Harald Gaier, 199171

The Law of Cure

The fundamental patterns of the organism’s dynamism in disease were codified by Constantine Hering, following insights and suggestions by Hahnemann. “Hering’s Law,” also known as the “Law of Cure,” describes the movements of the vital force in the transition from acute to chronic disease and from chronic back to acute.

bbStephenson compiled and edited Hahnemannian Provings (1924-1959). A Materia Medica with Repertory (1963).

Hahnemann first suggested that a pattern exists in his 1828 Chronic Diseases:

•    A skin eruption is the first manifestation of the chronic disease, psora (more or less identical with scabies);

•    It is an outlet for the internal disease; the more serious it is, the better the internal organs are protected;

•    If it is suppressed by topical medications, the vital force is compelled to effect a transference of a worse form of morbid action to other and more important parts;

•    Latent psora will also erupt if the patient’s overall condition is worsened by an acute infection, overwork, poor nutrition, or suppressive allopathic treatment;

•    When psora is treated homoeopathically, the most recent symptoms are always the first to disappear, but the oldest ailments, and those which have been most constant and unchanged, among which are the local ailments, are the last to give way;

•    If symptoms from earlier stages of the patient’s illness, which had meanwhile disappeared, return during treatment, the cure is progressing well;

•    Reappearance of the skin eruption means that a favorable outcome is near.—Samuel Hahnemann, 182872

The next contribution was made in Hering’s Preface to the 1845 American edition of Hahnemann’s Chronic Diseases:

Every homoeopathic physician must have observed that the improvement in pain takes place from above downward; and in diseases, from within outward. This is the reason why chronic diseases, if they are thoroughly cured, always terminate in some cutaneous eruption ...

The thorough cure of a widely ramified chronic disease in the organism is indicated by the most important organs being first relieved; the affection passes off in the order in which the organs had been affected, the more important being relieved first, the less important next, and the skin last.

This ... accounts for numerous cutaneous eruptions consequent upon homoeopathic treatment, even where they never had been seen before; it accounts for the obstinacy with which many kinds of herpes and ulcers remain upon the skin, whereas others are dissipated like snow. Those which remain do remain because the internal disease is yet existing.'1

Hering returned to this question in 1865: “The quintessence of [Hahnemann’s] doctrine is to give in all chronic diseases, i.e., such as progress from without inwardly, from the less essential parts of our body to the more essential, from the periphery to the central organs, generally from below upwards—to give in all such cases by preference such drugs as are opposite in the direction, or way of action, such as act from within outward, from up downward, from the most essential organs to the less essential, from the brain and the nerves outward, and down to the most outward and the lowest of all organs, to the skin.”74

And again in 1875: “In all chronic and lingering cases the symptoms appearing last, even though they may appear insignificant, are always the most important in regard to the selection of a drug; the oldest are the least important; all symptoms between them have to be arranged according to the order of their appearance. Only such patients remain well and are really cured who have been rid of their symptoms in the reverse order of their development.”75

The Law of Cure, in its final formulation, holds that as disease passes from acute to chronic, the symptoms move from the surface to the interior, from the lower parts of the body to the upper, and from the less vital organs to the more vital. Under correct treatment, symptoms disappear in the reverse order of their appearance, moving from the upper parts of the body to the lower, from the interior to the surface, and from the more vital organs to the less vital.76

Of the Law’s four parts the one most often encountered in the curative process is: symptoms disappearing in the reverse order of their appearance. Next is: symptoms moving from more important to less important organs. Third is: symptoms moving from within outwards. Fourth in importance is: symptoms moving from above downwards.77

Any chronic disease, therefore, occurs in stages. Since most are generated out of preexisting acute disease, cure is often ac-

complished when the chronic ailment is transformed back into an acute one. No genuine cure can abort the disease’s stages of development but must recapitulate them in the reverse order. The natural progression and stages of illness must be respected by both physician and patient. Otherwise the body’s own curative efforts are thwarted, with dire results.

The Law of Cure also provides guidance for treating “mental” illness. The mind/brain is simultaneously one of the “uppermost,” “innermost,” and most vital organs; the suppression of “physical” symptoms can (and does) shift illness into the mental sphere.

The parallel is more than superficial between this Empirical concept of the chronic disease process and the “fundamental bio-genetic law” of Ernst Haeckel (1834-1919)—that development of the embryo recapitulates the evolutionary sequence through which the species has passed.

This Law has a central role in homoeopathic practice, as the patient’s past medical history is crucial for correct prescribing and forjudging the progress toward cure. It is also used to criticize allopathy, whose incorrect procedures suppress acute conditions and convert them into chronic ones. References to improper allopathic treatment figure frequently in accounts of homoeopathic cases:

A violation of the law of metastasis is responsible for nearly all chronic ailments, and the cause of the severity and obstinacy of many acute attacks of sickness.—Homoeopathic Physician, 189078

Many forms of suppression will be brought out by the homoeopathic remedy, such as the reappearance of skin eruptions suppressed by various ointments, catarrhal complaints, and gonorrheal discharges suppressed by injection, followed by rheumatic troubles. Leucorrheal discharges stopped by local treatments are followed by ovarian and uterine troubles.—A. Dwight Smith, 195279

Discharges through the skin, skin eruptions, and dermatolo-gic “diseases” are modes adopted by the body to rid itself of in-

ternal toxins. Blocking these discharges with ointments, or excising them, are pernicious sources of subsequent chronic disease:

M. W., age three, had a rash on the cheek when two