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Germ Theory: Medical Pioneers in Infectious Diseases, SECOND EDITION From the ancient worlds of Hippocrates and Avicenna to the early 20th century hospitals of Paul Ehrlich and Lillian Wald to the modern-day laboratories of François Barré-Sinoussi and Barry Marshall, Germ Theory brings to life the inspiring stories of medical pioneers whose work helped change the very fabric of our understanding of how we think about and treat infectious diseases. In beautifully crafted narratives, author Robert Gaynes describes and presents compelling stories, including * How Edward Jenner, the pioneer of vaccination, faced down scores of naysayers * How a chance discovery led Louis Pasteur to the idea that the virulence of microbes can be altered * How scientists in France, the Netherlands, and Denmark produced penicillin during World War 2 while keeping their efforts hidden from the Nazis The second edition features three new chapters based on interviews with Nobel Laureates François Barré-Sinoussi and Barry Marshall, and former NIAID Director and medical advisor to seven U.S. presidents Anthony Fauci, detailing fascinating accounts from their careers, including their groundbreaking work in the areas of HIV, peptic ulcers, and COVID-19, respectively. Winner of a CHOICE Outstanding Academic Title award for its first edition, Germ Theory is required reading for anyone training or working in the field of infectious diseases or with an interest in microbes, the history of medicine, or how new discoveries can bring about paradigmatic shifts in thinking. Germ Theory, Second Edition was selected as a top community college title for December 2023 by CHOICE: The Top 75 Community College Titles: December 2023 - Choice 360
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Table of Contents
Cover
Title Page
Copyright Page
List of Illustrations
Foreword
Preface
Special Note
Acknowledgments
About the Author
1 Introduction
REFERENCES
2 Hippocrates, the Father of Modern Medicine
MEDICINE BEFORE HIPPOCRATES
HIPPOCRATES
NATURAL CAUSE FOR DISEASE
THE FOUR HUMORS AND DISEASE
THE COAN SCHOOL OF MEDICINE
FEVER AND THE FOUR HUMORS
THE FOUNDATION OF EVIDENCE‐BASED MEDICINE
THE HIPPOCRATIC OATH
THE HIPPOCRATIC CORPUS: EPIDEMICS
THE LASTING INFLUENCE OF THE HUMORAL THEORY ON MEDICINE
EVOLUTION OF THE HUMORAL THEORY THROUGH THE CENTURIES AFTER HIPPOCRATES
GALEN: HIS LEGACY
REFERENCES
3 Avicenna, a Thousand Years Ahead of His Time
BUBONIC PLAGUE IN THE MIDDLE AGES
MEDICINE IN THE MEDIEVAL ISLAMIC WORLD
ROLE OF TRANSLATION IN THE ESTABLISHMENT OF MEDIEVAL ISLAMIC MEDICINE
CHANGES TO MEDICAL EDUCATION IN MEDIEVAL ISLAMIC MEDICINE
AVICENNA, THE PRINCE OF PHYSICIANS
THE
CANON OF MEDICINE
BEGINNINGS OF EVIDENCE‐BASED CLINICAL TRIALS
THE CONCEPT OF CONTAGION
THE
CANON OF MEDICINE
’S INFLUENCE IN WESTERN MEDICINE
REFERENCES
4 Girolamo Fracastoro and Contagion in Renaissance Medicine
PLAGUE IN THE RENAISSANCE
SYPHILIS IN THE RENAISSANCE
STAGES OF SYPHILIS
GIROLAMO FRACASTORO: EARLY INFLUENCES
FRACASTORO’S EPIC POEM—
SYPHILIS SIVE MORBUS GALLICUS
FRACASTORO: ON CONTAGION AND CONTAGIOUS DISEASE
REACTION TO
DE CONTAGIONE
FRACASTORO AND THE COUNCIL OF TRENT
THE TUMULT OVER FRACASTORO’S BURIAL PLACE
THE REDISCOVERY OF
DE CONTAGIONE
REFERENCES
5 Antony van Leeuwenhoek and the Birth of Microscopy
THE DISCOVERY OF THE MICROSCOPIC WORLD
ANTONY VAN LEEUWENHOEK: EARLY INFLUENCES
VAN LEEUWENHOEK AND LENS MAKING
VAN LEEUWENHOEK AND THE ROYAL SOCIETY IN LONDON
REACTIONS TO VAN LEEUWENHOEK’S MICROSCOPIC DISCOVERIES
THE FIRST DESCRIPTION OF BACTERIA
VAN LEEUWENHOEK’S MICROSCOPES
MODERN INVESTIGATIONS INTO VAN LEEUWENHOEK’S MICROSCOPES
SPONTANEOUS GENERATION AND VAN LEEUWENHOEK
MICROORGANISMS AND DISEASE IN THE ENLIGHTENMENT
REFERENCES
6 The Demise of the Humoral Theory of Medicine
ANDREAS VESALIUS AND HIS CHALLENGE TO GALENIC ANATOMY
THE CHALLENGE TO GALENIC PHYSIOLOGY: WILLIAM HARVEY, THE DISCOVERY OF THE CIRCULATION OF BLOOD, AND THE SCIENTIFIC METHOD IN MEDICINE
MORGAGNI AND THE ANATOMIC BASIS OF DISEASE
THE PARIS SCHOOL OF MEDICINE
THE RISE OF MODERN HOSPITALS IN WESTERN MEDICINE
CONTAGION AND 18TH‐CENTURY MEDICINE
THE SANITARY MOVEMENT, CONTAGION, AND 19TH‐CENTURY MEDICINE
CONTAGIONISM VERSUS ANTICONTAGIONISM IN THE 19TH CENTURY
REFERENCES
7 Edward Jenner and the Discovery of Vaccination
THE DISEASE OF SMALLPOX
A SHORT HISTORY OF SMALLPOX
SMALLPOX IN THE 18TH CENTURY
CONTAGION AND SMALLPOX IN THE 18TH CENTURY
VARIOLATION AND THE “CONTROL” OF SMALLPOX
LADY MARY WORTLEY MONTAGU
EDWARD JENNER: EARLY INFLUENCES
MILKMAIDS, COWPOX, AND SMALLPOX
THE FIRST INOCULATION AGAINST SMALLPOX
PUBLICATION OF
AN INQUIRY INTO THE CAUSES AND EFFECTS OF THE VARIOLAE VACCINAE
REACTION TO
AN INQUIRY INTO THE CAUSES AND EFFECTS OF THE VARIOLAE VACCINAE
THOMAS JEFFERSON’S LETTER TO JENNER
VACCINATION AND THE ERADICATION OF SMALLPOX
GLOBAL APPLICATION OF VACCINATION
VACCINIA VIRUS IN THE CONTEMPORARY SMALLPOX INOCULATION
SUCCESS OF VACCINATION
REFERENCES
8 Ignaz Semmelweis and the Control of Puerperal Sepsis
THE DEVELOPMENT OF HOSPITALS IN WESTERN MEDICINE
THE TRAGEDY OF PUERPERAL FEVER
THEORIES ABOUT THE CAUSES OF PUERPERAL FEVER IN THE 18TH AND 19TH CENTURIES
ALEXANDER GORDON AND PUERPERAL FEVER IN ENGLAND
CONTAGION VERSUS INFECTION IN EARLY 19TH‐CENTURYMEDICINE
OLIVER WENDELL HOLMES AND PUERPERAL FEVER IN AMERICA
IGNAZ SEMMELWEIS: EARLY INFLUENCES
THE UNIVERSITY OF VIENNA HOSPITAL: A SHORT HISTORY
SEMMELWEIS AND CHILDBED FEVER: A TALE OF TWO DIVISIONS
THE TRAGIC CLUE TO CHILDBED FEVER
PREVENTION OF CHILDBED FEVER: HAND WASHING
REACTION TO HAND WASHING
SEMMELWEIS’S DEPARTURE FROM VIENNA
THE RETURN TO HUNGARY
OPPOSITION TO SEMMELWEIS AND HIS THEORY
SEMMELWEIS’S LAST YEARS
REFERENCES
9 Louis Pasteur and the Germ Theory of Disease
LOUIS PASTEUR: EARLY INFLUENCES
PASTEUR THE CHEMIST AND THE DISCOVERY OF CRYSTALS
THE “DISEASES” OF FERMENTATION
PASTEURIZATION
SPONTANEOUS GENERATION AND LOUIS PASTEUR
DISEASES OF SILKWORMS AND THEIR ROLE IN THE GERM THEORY OF DISEASE
THE GERM THEORY OF DISEASE, PASTEUR, AND MEDICINE IN THE 19TH CENTURY
PASTEUR’S WORK ON ANTHRAX
THE DISCOVERY OF TOXIN PRODUCTION FROM ANTHRAX BACILLI
CHICKEN CHOLERA AND ATTENUATION OF MICROORGANISMS
PASTEUR AND THE ANTHRAX VACCINE
THE RABIES VACCINE
REACTION TO THE RABIES VACCINE
PASTEUR’S LAST YEARS
REFERENCES
10 Robert Koch and the Rise of Bacteriology
ROBERT KOCH: EARLY INFLUENCES
THE DISCOVERY OF ANTHRAX SPORES
IMPROVEMENTS IN MICROSCOPY
KOCH’S MOVE TO BERLIN
THE DEVELOPMENT OF PURE BACTERIAL CULTURES
THE DISCOVERY OF THE TUBERCLE BACILLUS
KOCH’S POSTULATES
THE DISCOVERY OF THE CAUSATIVE AGENT OF CHOLERA
THE RIVALRY BETWEEN KOCH AND PASTEUR
THE MISTRANSLATION OF A WORD
THE INSTITUTE OF HYGIENE
THE TUBERCULIN FIASCO
PUBLIC REACTION TO KOCH’S ANNOUNCEMENT
THE EFFECTS OF TUBERCULIN FAILURE ON KOCH
THE INSTITUTE FOR INFECTIOUS DISEASES IN BERLIN
CHOLERA IN GERMANY: A PUBLIC HEALTH TRIUMPH FOR KOCH
THE ROBERT KOCH INSTITUTE
THE 1905 NOBEL PRIZE IN MEDICINE
REFERENCES
11 Joseph Lister, the Man Who Made Surgery Safe
THE DISCOVERY OF ANESTHESIA
SURGERY BEFORE JOSEPH LISTER
HISTORY OF THE TREATMENT OF WOUNDS
JOSEPH LISTER: EARLY INFLUENCES
JAMES SYME IN EDINBURGH
MARRIAGE OF JOSEPH LISTER AND AGNES SYME
THE MOVE TO GLASGOW
THE CLUE TO WOUND INFECTIONS
ANTISEPTIC SURGERY
THE FIRST SUCCESS WITH ANTISEPSIS
ANTISEPSIS AND SURGICAL WOUNDS
PROBLEMS WITH CARBOLIC ACID
MOVE BACK TO EDINBURGH
REACTION TO SURGICAL ANTISEPSIS
ACCEPTANCE ON THE EUROPEAN CONTINENT
LISTERISM IN THE UNITED STATES
THE DEATH OF PRESIDENT JAMES A. GARFIELD
ANTISEPTIC SURGERY IN ENGLAND
ANTISEPSIS AND ASEPSIS IN SURGERY
LISTER’S OTHER ACCOMPLISHMENTS
HONORS AND ACCOLADES
DEATH OF LADY AGNES SYMES LISTER
LISTER’S LATER YEARS
REFERENCES
12 Paul Ehrlich and the Magic Bullet
EARLY INFLUENCES
EHRLICH’S DISCOVERY OF THE MAST CELL
FIRST MEETING WITH ROBERT KOCH
DOCTORAL DISSERTATION: THEORY AND PRACTICE OF HISTOLOGIC STAINING
THE CHARITÉ HOSPITAL IN BERLIN
IMPROVING THE IDENTIFICATION OF THE TUBERCLE BACILLUS
DEATH OF VON FRERICHS
BACK TO BERLIN
DISCOVERY OF THE DIPHTHERIA ANTITOXIN AND SERUM THERAPY
CELLULAR IMMUNITY AND HUMORAL IMMUNITY
STANDARDIZATION OF DIPHTHERIA ANTITOXIN
THE STEGLITZ INSTITUTE AND THE ROYAL PRUSSIAN INSTITUTE FOR EXPERIMENTAL THERAPY IN FRANKFURT
THE SIDE CHAIN THEORY—THE FIRST THEORY OF ANTIBODY PRODUCTION
THE MAGIC BULLET: THE DAWN OF CHEMOTHERAPY FOR INFECTIOUS DISEASES
THE NOBEL PRIZE
COMPOUND 606—SALVARSAN
THE PUBLIC ANNOUNCEMENT OF SALVARSAN AT THE CONGRESS OF INTERNAL MEDICINE IN APRIL 1910
TROUBLES INTRODUCING SALVARSAN TO HUMAN MEDICINE
AWARDS AND HONORS
LAST YEARS
REFERENCES
13 Lillian Wald and the Foundations of Modern Public Health
EARLY INFLUENCES
“BAPTISM OF FIRE”
WALD’S PROPOSAL: A NURSING SERVICE
THE LOWER EAST SIDE OF NEW YORK IN THE 1890S
THE PUBLIC HEALTH NURSE
TB AND THE NURSING SERVICE
SCHOOL NURSES INTRODUCED IN NEW YORK CITY SCHOOLS
THE HOUSE ON HENRY STREET
COLUMBIA UNIVERSITY AND THE DEPARTMENT OF NURSING AND HEALTH
NATIONWIDE INSURANCE COVERAGE FOR HOME‐BASED CARE
ESTABLISHMENT OF A NATIONAL PUBLIC HEALTH NURSING SERVICE
JOINT BOARD OF SANITARY CONTROL
WALD’S OTHER ACHIEVEMENTS AND ACTIVITIES
AWARDS AND HONORS
LATER YEARS
REFERENCES
14 Alexander Fleming and the Discovery of Penicillin
PROGRESS IN CHEMOTHERAPY OF INFECTIOUS DISEASES
THE BEGINNING OF SULFONAMIDES
THE BEGINNINGS OF THE PENICILLINS
ALEXANDER FLEMING: EARLY INFLUENCES
ALMROTH WRIGHT AND THE INOCULATION DEPARTMENT OF ST. MARY’S HOSPITAL
FLEMING AND THE FIRST WORLD WAR
THE DISCOVERY OF LYSOZYME
WORK ON ANTISEPTICS
THE DISCOVERY OF PENICILLIN: “THAT’S FUNNY”
A DECIDEDLY UNSTABLE SUBSTANCE
FIRST PRESENTATION OF PENICILLIN’S DISCOVERY
FIRST ATTEMPT TO PURIFY PENICILLIN
PRONTOSIL: EARLY WORK LEADS TO SUCCESS
THE DISCOVERY OF SULFANILAMIDE
RENEWAL OF INTEREST IN PENICILLIN
THE OXFORD TEAM
THE ISOLATION OF PARTIALLY PURIFIED PENICILLIN
PENICILLIN TESTING IN ANIMALS—MIRACULOUS RESULTS
THE FIRST HUMAN TRIALS OF PENICILLIN
THE FIRST PENICILLIN PATIENT: THE OXFORD POLICEMAN
PENICILLIN PRODUCTION IN THE UNITED STATES
LARGE‐SCALE CULTIVATION OF
PENICILLIUM
WARTIME PENICILLIN PRODUCTION IN THE UNITED STATES
PENICILLIN AND PATENTS
PENICILLIN USE IN ENGLAND
PUBLIC AWARENESS OF PENICILLIN: THE FLEMING MYTH
SECRECY IN WARTIME ENGLAND
PENICILLIN PRODUCTION DURING WORLD WAR II ON THE CONTINENT OF EUROPE
POSTWAR PENICILLIN PRODUCTION
THE NOBEL PRIZE
THE CHEMICAL STRUCTURE OF PENICILLIN
THE IMPACT OF PENICILLIN ON CHEMOTHERAPY OF BACTERIAL DISEASES
REFERENCES
15 Françoise Barré‐Sinoussi and the Discovery of the Human Immunodeficiency Virus
CLUES TO THE ETIOLOGIC AGENT OF AIDS
REVERSE TRANSCRIPTASE AND RETROVIRUSES
DISCOVERY OF THE FIRST HUMAN RETROVIRUS—HTLV‐1
EARLY INFLUENCES
SINOUSSI AND THE PASTEUR INSTITUTE
WORK AT THE NATIONAL INSTITUTES OF HEALTH IN THE UNITED STATES
RETURN TO FRANCE
ISOLATION OF A RETROVIRUS AT THE PASTEUR INSTITUTE
LYMPHADENOPATHY‐ASSOCIATED VIRUS (LAV)—THE CAUSE OF AIDS?
CONTROVERSY DEVELOPS: LAV OR HTLV‐3?
CLAIMS AGAINST PATENTS FURTHER CONTROVERSY
BARRÉ‐SINOUSSI AND THE WORLD OF AIDS PATIENTS
BARRÉ‐SINOUSSI AFTER DISCOVERY OF HIV AT PASTEUR INSTITUTE
THE NOBEL PRIZE
COLD SPRING HARBOR, 2019
AWARDS AND HONORS
REFERENCES
16 Barry Marshall and
Helicobacter pylori
in Peptic Ulcer Disease
CAUSES OF PEPTIC ULCER DISEASE, CIRCA 1980
COMPLICATIONS OF PEPTIC ULCER DISEASE
CURVED BACTERIA ON GASTRIC BIOPSIES
EARLY INFLUENCES
FIRST STUDY ON PEPTIC ULCERS AND GASTRIC BACTERIA
GROWTH CHARACTERISTICS OF THE UNIDENTIFIED CURVED BACILLI FROM THE STOMACH OF PATIENTS
FIRST PRESENTATION OF THE ASSOCIATION OF
HELICOBACTER PYLORI
AND PEPTIC ULCER DISEASE
ATTEMPT TO FULFILL KOCH’S POSTULATES
PHYSICIAN SELF‐EXPERIMENTATION
NATURAL HISTORY OF
H. PYLORI
DISEASE
A DIFFICULT YEAR, 1984
A BOOST FROM AN UNEXPECTED SOURCE
THE MOVE TO THE UNITED STATES: RESEARCH AT THE UNIVERSITY OF VIRGINIA
THE TIDE TURNS
A WATERSHED YEAR, 1994
H. PYLORI
AND GASTRIC CANCER
INFECTIOUS AGENTS AND OTHER CHRONIC DISEASES
AWARDS AND HONORS
THE NOBEL PRIZE
CHALLENGES REMAINING
CONCLUSIONS
REFERENCES
17 Anthony Fauci
EARLY INFLUENCES
FAUCI AND THE NATIONAL INSTITUTES OF HEALTH
CHIEF RESIDENCY
BREAKTHROUGH IN VASCULITIS TREATMENT
FAUCI AND AIDS
FAUCI NAMED DIRECTOR OF THE NIAID
OPENING THE DOOR OF THE AIDS ACTIVIST COMMUNITY
ADVISING U.S. PRESIDENTS ON INFECTIOUS DISEASES
HIGHLY ACTIVE ANTIRETROVIRAL THERAPY FOR HIV
CREATION OF PRESIDENT’S EMERGENCY PLAN FOR AIDS RELIEF (PEPFAR)
PEPFAR’S SUCCESSES
A SERIES OF NEW INFECTIOUS DISEASE THREATS IN THE 21ST CENTURY
COVID‐19 PANDEMIC
FAUCI AND THE WHITE HOUSE CORONAVIRUS TASK FORCE
DR. FAUCI AND PRESIDENT TRUMP
OPERATION WARP SPEED
COVID‐19 VACCINE HESITANCY
POLITICS OF COVID‐19
DEVELOPMENT OF COVID‐19 VARIANTS
COVID‐19 AND HERD IMMUNITY
POST‐COVID CONDITION (LONG COVID)
LESSONS FROM THE COVID‐19 PANDEMIC
AWARDS AND HONORS
DR. FAUCI’S LEGACY
REFERENCES
18 Conclusions
THE DEVELOPMENT OF ANTIBIOTIC RESISTANCE
THE NEED FOR A NEW PARADIGM IN ANTIMICROBIAL TREATMENT
THREATS FROM NEW OR REEMERGING PATHOGENS
STRENGTHENING PUBLIC HEALTH
THE CHALLENGE OF VACCINES
REFERENCES
Index
End User License Agreement
List of Tables
Chapter 7
TABLE 7.1 Impact of immunizations, 1900 to 1999
Chapter 10
TABLE 10.1 Results of treatment with tuberculin
Chapter 12
TABLE 12.1 Some early recipients of the Nobel Prize
List of Illustrations
Chapter 2
FIGURE 2.1 Hippocrates.
FIGURE 2.2 Washington on His Deathbed, 1851. Junius Brutus Stearns (1810–188...
Chapter 3
FIGURE 3.1 Avicenna. G. P. Busch sculpture.
Chapter 4
FIGURE 4.1 Girolamo Fracastoro. Portrait by Titian from the National Gallery...
Chapter 5
FIGURE 5.1 Antony van Leeuwenhoek. Portrait by Jan Verkolje from the Rijksmu...
Chapter 7
FIGURE 7.1 The Cow Pock—or—the Wonderful Effects of the New Inoculation! Dra...
Chapter 8
FIGURE 8.1 Maternal mortality, which was nearly all from puerperal sepsis, a...
Chapter 9
FIGURE 9.1 Louis Pasteur.
Chapter 10
FIGURE 10.1 Robert Koch.
Chapter 11
FIGURE 11.1 Joseph Lister.
Chapter 12
FIGURE 12.1 Paul Ehrlich (left) and Sahachiro Hata (right).
FIGURE 12.2 (Left) Before treatment of syphilis. (Right) After successful tr...
Chapter 13
FIGURE 13.1 Lillian Wald as a young nurse in uniform.
Chapter 14
FIGURE 14.1 Bacinol 2, a building named in honor of the site of efforts in D...
FIGURE 14.2 Alexander Fleming’s image on a European postage stamp.
Chapter 15
FIGURE 15.1 One of the very first photographs of the AIDS virus, taken on 4 ...
FIGURE 15.2 Banner for Françoise Barré‐Sinoussi outside her laboratory at th...
Chapter 16
FIGURE 16.1 One of the early images taken from the work of Drs. Robin Warren...
Guide
Cover Page
Title Page
Copyright Page
List of Illustrations
Foreword
Preface
Special Note
Acknowledgments
About the Author
Table of Contents
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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Germ Theory
Medical Pioneers in Infectious Diseases
SECOND EDITION
ROBERT P. GAYNES, MD
Copyright © 2023 American Society for Microbiology. All rights reserved.
Copublication by the American Society for Microbiology and John Wiley & Sons, Inc.
No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted by law. Advice on how to reuse material from this title is available at http://wiley.com/go/permissions.
The right of Robert P. Gaynes to be identified as the author of this work has been asserted in accordance with law.
Limit of Liability/Disclaimer of WarrantyWhile the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties or merchantability of fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The publisher is not providing legal, medical, or other professional services. Any reference herein to any specific commercial products, procedures, or services by trade name, trademark, manufacturer, or otherwise does not constitute or imply endorsement, recommendation, or favored status by the American Society for Microbiology (ASM). The views and opinions of the author(s) expressed in this publication do not necessarily state or reflect those of ASM, and they shall not be used to advertise or endorse any product.
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Library of Congress Cataloging‐in‐Publication Data Applied for
ISBN 9781683673767 (Paperback);ISBN 9781683673774 (Adobe PDF);ISBN 9781683673781 (e‐Pub)
Cover image: Front, top row, left to right: Antony van Leeuwenhoek, Anthony Fauci, Louis Pasteur, Françoise Barré‐Sinoussi (courtesy of Institut Pasteur, credit: François Gardy); bottom row, left to right: Robert Koch, Lillian Wald, Barry Marshall, Alexander Fleming (courtesy of the Wellcome Collection, CC BY 4.0); back cover, top row, left to right: Ignaz Semmelweis, Avicenna, Paul Ehrlich, Edward Jenner; bottom row, left to right: Edwin Chadwick, Girolamo Fracastoro, Hippocrates, Joseph Lister. Background and spine image: electron microscope schematic (courtesy of David Eccles [Gringer] CC BY‐SA 3.0).Cover design: Debra Naylor, Naylor Design, Inc
List of Illustrations
Chapter 1
Opener An Early Microscope. Courtesy of the National Library of Medicine (image ID A022153).
Chapter 2
Opener Hippocrates. Line engraving. Courtesy of the Wellcome Collection (reference 4235i).
1 Hippocrates. Courtesy of the National Library of Medicine (NLM image ID B014575).
2 Washington on His Deathbed, 1851. Junius Brutus Stearns (1810–1885), American painter. Oil on canvas, 37 1/4 by 54 1/8 in. The Dayton Art Institute; gift of Robert Badenhop, accession number 1954.16.
Chapter 3
Opener “Avicenna” stamp from Iran, 1950.
1 Avicenna. G. P. Busch sculpture. Courtesy of the National Library of Medicine (NLM image ID B01242).
Chapter 4
Opener Hieronymus Fracastorius [Girolamo Fracastoro]. Line engraving by N. de Larmessin, 1682. Courtesy of the Wellcome Collection (reference 2086i).
1 Girolamo Fracastoro. Portrait by Titian from the National Gallery (inventory number NG3949).
Chapter 5
Opener Portrait of Antony van Leeuwenhoek by Jan Verkolje from the Rijksmuseum (accession number SK‐A‐957).
1 Antony van Leeuwenhoek. Portrait by Jan Verkolje from the Rijksmuseum (accession number SK‐A‐957).
Chapter 6
Opener Portrait of Edwin Chadwick. Courtesy of the National Library of Medicine (image ID B08321).
Chapter 7
Opener Oil painting of Edward Jenner. Courtesy of the Wellcome Collection (reference 47332i).
1 The Cow Pock—or—the Wonderful Effects of the New Inoculation! Drawing by James Gillray, 1756 to 1815. Courtesy of the National Library of Medicine (NLM image ID A021551).
Chapter 8
Opener Engraving of Ignaz Semmelweis by Jenő Doby (1894).
1 Maternal mortality, which was nearly all from puerperal sepsis, at the Vienna General Hospital, by division, 1841 to 1848.
Chapter 9
Opener Photograph of Louis Pasteur. Courtesy of the National Library of Medicine (image ID B020570).
1 Louis Pasteur. Courtesy of the National Library of Medicine (NLM image ID B020574).
Chapter 10
Opener Photograph of Robert Koch. Courtesy of the National Library of Medicine (image ID B016696).
1 Robert Koch. Courtesy of the National Library of Medicine (NLM image ID B016691).
Chapter 11
Opener Photograph of Joseph Lister. Courtesy of the National Library of Medicine (image ID B017424).
1 Joseph Lister. Courtesy of the National Library of Medicine (NLM image ID B017429).
Chapter 12
Opener Photograph of Paul Ehrlich. Courtesy of the National Library of Medicine (image ID B07744).
1 Paul Ehrlich (left) and Sahachiro Hata (right). Courtesy of the Hata Memorial Museum, Shimane.
2 (Left) Before treatment of syphilis. (Right) After successful treatment of syphilis with Neosalvarsan, 1915. Used with permission of the Mütter Museum of the College of Physicians of Philadelphia, Philadelphia, PA.
Chapter 13
Opener Oil painting of Lillian Wald by William Valentine Schevill. Courtesy of Look and Learn History Picture Archive (record ID npg_NPG.76.37).
1 Lillian Wald as a young nurse in uniform.
Chapter 14
Opener Photograph of Sir Alexander Fleming. Courtesy of the Wellcome Collection, under license CC BY 4.0 (https://wellcomecollection.org/works/k4ezny6h).
1 Bacinol 2, a building named in honor of the site of efforts in Delft, The Netherlands to produce penicillin during World War II and the drug produced by The Netherlands Yeast and Spirit Factory.
2 Alexander Fleming’s image on a European postage stamp.
Chapter 15
Opener Photograph of Françoise Barré‐Sinoussi. Courtesy of Institut Pasteur ‐ photo François Gardy.
1 One of the very first photographs of the AIDS virus, taken on 4 February 1983. A view of a section of a T lymphocyte infected with the virus isolated from an affected patient with generalized lymphadenopathy syndrome, which precedes AIDS. Photo by Charles Dauquet, courtesy of Institut Pasteur.
2 Banner for Franc¸oise Barré‐Sinoussi outside her laboratory at the Pasteur Institute, Paris, congratulating her after winning the Nobel Prize in Physiology and Medicine in 2008.
Chapter 16
Opener Photograph of Barry Marshall.
1 One of the early images taken from the work of Drs. Robin Warren and Barry Marshall of a gastric biopsy showing curved bacteria later identified as Helicobacter pylori. Image courtesy of Barry Marshall.
Chapter 17
Opener Photograph of Anthony Fauci.
1 President George W. Bush presenting Anthony Fauci with the 2008 Presidential Medal of Freedom at the White House.
Chapter 18
Opener Illustration of Candida auris, presented in the CDC publication, Antibiotic Resistance Threats in the United States, 2019 (medical illustrator: Stephanie Rossow). Courtesy of the CDC‐Phil (image ID 23239).
Foreword
This second and considerably expanded edition of Germ Theory: Medical Pioneers in Infectious Diseases by Robert Gaynes is an important and timely contribution. The germ theory is foundational to the scientific understanding of the microbial world and the threats it poses to our society and even our species. In this work the author has undertaken the ambitious task of tracing the origins, development, and impact of this idea across two and a half millennia. His sweeping, panoramic study ranges from ancient Greece to the present. Today we find ourselves in the precarious position of being subject to increasingly numerous zoonotic pathogens, as the ever‐lengthening list of emerging and reemerging diseases from Avian flu to Zika to Ebola and COVID‐19 reminds us. Especially in this context, Germ Theory provides a compelling account of how medicine has evolved—and is still evolving—in its understanding of infectious diseases and the tools it deploys to control them.
The organizational approach of the study is biographical. Each of the book’s eighteen chapters explores the role of a key figure in understanding the role of microorganisms as causes of disease and promoting an array of strategies to combat them—vaccination, sanitation, public health, antibiotics. The figures, including Edward Jenner, Louis Pasteur, and Anthony Fauci, are well known. But in each case Gaynes has skillfully deepened our understanding of the process of scientific discovery and of the difficulties confronting those who propose innovative and unorthodox ideas. Scientists, physicians, historians, and other specialists will find original and illuminating material here, including the author’s interviews with a number of the recent protagonists of the narrative. At the same time, however, the biographical approach humanizes the subject matter and helps to make complex scientific concepts accessible to the general reader new to the field. The author succeeds throughout in conveying the excitement and importance of the topic while avoiding jargon and obscurity. He also eschews any sense of linear triumphalism, carefully choosing instead to present the challenges and the dangers of the present with sobering clarity. Extremely well written and presented with the authority of an author who is himself a leading medical scientist, this work deserves a wide readership.
FRANK M. SNOWDEN, PHD
Andrew Downey Orrick Professor Emeritus of History,Yale University;former Chair, Program in History of Science and History of Medicine,Yale University
Preface
History is simply the biography of the mind of man; and our interest in history, and its educational value to us, is directly proportionate to the completeness of our study of the individuals through whom this mind has been manifested. To understand clearly our position in any science today, we must go back to its beginnings, and trace its gradual development.
Sir William Osler
The first edition of this text was inspired by the reception my 2008 seminar received from members of the Emory Infectious Disease Division. I presented the history of our field by way of short biographies of some of the people who changed it. The seminar began at the initial stages of Western medicine in ancient Greece and ended with the discovery of penicillin and the beginnings of modern antimicrobial therapy. Faculty, fellows, postdoctoral students, residents, and medical students all appreciated the seminar and commented on their lack of acquaintance with the historical roots of their chosen discipline. A presentation at the Centers for Disease Control and Prevention (CDC) some months later yielded similar comments from those in public health.
In the midst of the COVID‐19 pandemic, few would question the importance of the germ theory of disease and its effects on our world. Building on the first edition, this second edition includes a more complete discussion of the origin of the germ theory, including the research of Codell Carter, Margaret Pelling, Michael Worboys, and others who contend that the germ theory notion had its more probable beginnings in the practices of quarantine, first for leprosy and later for bubonic plague. Chapter 6 now includes a discussion of the sanitary movement and contagion in 19th‐century medicine. Chapter 14 still highlights the work of Fleming, Florey, Chain, Heatley, and others in England and America on the discovery of penicillin; it adds compelling stories from continental Europe—in France, the Netherlands, and Denmark during World War II. Scientists in these countries attempted to produce penicillin while keeping their efforts secret from the Nazis. The Danish story is told for the first time in English thanks to Dr. Peder Worning’s help with the translation of Danish documents recently declassified.
The first edition ended with the story of penicillin and its wide‐scale distribution in the mid‐1940s, ushering in the modern antibiotic era. The second edition attempts to remedy the truncation of the first edition in the mid‐20th century noted by one reviewer (1). I have added three new chapters to recognize the developments relating to the germ theory of disease that have unfolded in the last 75 years. Notably, I have interviewed Dr. Françoise Barré‐Sinoussi, 2008 Nobel laureate for the discovery of HIV, the most important new pathogen discovered in the last 75 years; Dr. Barry Marshall, 2005 Nobel laureate for discovering the link between Helicobacter pylori and peptic ulcer disease, opening the concept that microorganisms can trigger diseases that were long considered chronic; and Dr. Anthony Fauci, Director of the U.S. National Institute of Allergy and Infectious Diseases, dubbed America’s Top Infectious Disease Doctor. Fauci is well known in the U.S. for his public information on COVID‐19 but has made numerous other contributions to the field of infectious diseases and immunology. All three of these noteworthy individuals are quoted from my interviews with them and have reviewed their chapters for accuracy. It was an honor to have spoken to them. I hope I have been able to place their contributions to the germ theory of disease in context to the exciting and challenging times that we face.
I chose to weave the narrative of the origins of the germ theory of disease through short biographies of 13 men and 2 women who changed the very fabric of our knowledge. Guided by others who followed a similar path—notably Sherwin Nuland, author of Doctors: The Biography of Medicine—I selected the biographical approach to humanize further the persons who made the significant discoveries. I also chose this style to enhance accessibility, as this book is intended not just for physicians or students of medicine but to be accessible to anyone with an interest in microbiology, infectious diseases, medical history, and, to a degree, biography. The stories of these medical pioneers demonstrate both the impact of their early life influences on their innovations and their frustrations with their societies’ inability to accept some of the greatest discoveries in the history of medicine. The biographical approach illustrates how change in medical thought has occurred. Since paradigm shifts in our scientific thinking will continue, the study of historical transformations functions to encourage a requisite open‐mindedness to new shifts in medical thinking.
ROBERT P. GAYNES, MD
1. Ewald PW.
2013.
Q Rev Biol
88:
151.
Special Note
An essential part of the American Society for Microbiology’s (ASM) mission is to embrace inclusive diversity in the STEM community, including in its book publications. Being inclusive enhances innovation, broadens the health research agenda, and furthers scientific advancement. ASM and this book's author are committed to promoting and advancing the microbial sciences through the elevation, embodiment, and sustainability of inclusive diversity with equity, access, and accountability (IDEAA).
ASM and this book's author also acknowledge that the history of science, including the history of germ theory, has been focused through a narrow lens and as a result historically excluded and underrepresented individuals were either barred entry to the field, allowed to participate in limited or special capacity, and/or had their contributions completely overlooked, in order to perpetuate the status quo. This approach and practice across history has resulted in low diversity in the field, which is reflected in the profiles contained herein. ASM’s goal is that we continue advancing the microbial sciences through IDEAA. By doing so, we will begin to mitigate the lack of diversity in the field and thus ensure future historical profiles will reflect the large diversity of scientists making impacts at all levels, including those rare, paradigm‐shifting contributors such as Lillian Wald and Françoise Barré‐Sinoussi who are focused on in this text.
ASM and this book's author recognize that there are many more stories across the field that we might not have represented within this text. We invite the reader to share stories and feedback on individuals whom we should include as integral players and add to the historical record in the next edition. In the interest of ASM’s IDEAA mission we also encourage the reader to view the below resources to help foster the next generation of microbiologists:
Article: Inclusive Approaches to Mentoring Historically Underrepresented Groups,
https://asm.org/Articles/2022/June/Inclusive‐Approaches‐to‐Mentoring‐Historically‐Und
Webinar: Strengthening Career Pathways in Science for Underrepresented Groups,
https://asm.org/Webinars/Strengthening‐Career‐Pathways‐in‐Science‐for‐Under
Meeting: Annual Biomedical Research Conference for Minoritized Scientists (ABRCMS),
https://abrcms.org/
Acknowledgments
Having benefited from the feedback of a number of generous individuals, I want to thank Kirvin Gilbert, Lisa Macklin, James Curran, Alicia Hidron, Elissa Meites, Abeer Moanna, Mark Mulligan, David Rimland, Michael Schlossberg, Robert Rosman, Peter Rogers, and Harold Jaffe for their patience, sage advice, and encouragement.
I am particularly indebted to Drs. Françoise Barré‐Sinoussi, Barry Marshall, and Anthony Fauci for their willingness to be interviewed and their subsequent review of their respective chapters for accuracy. I also want to recognize the love and support from my children, Sara and Matthew, and most of all, my wife, Sherry.
I hope that this final product will impart to the reader the knowledge, understanding, and passion that I discovered in writing it.
About the Author
Robert P. Gaynes, MD, is a Professor Emeritus of Medicine (Infectious Diseases) at Emory University School of Medicine, where he continues to teach the history of medicine.
After graduating magna cum laude from the University of Illinois in Urbana, Dr. Gaynes earned his medical degree from the University of Chicago Pritzker School of Medicine with honors in 1979. He completed a residency in internal medicine at Michael Reese Hospital in Chicago. After serving for 2 years in the Epidemic Intelligence Service at the Centers for Disease Control and Prevention (CDC), he returned to complete a fellowship in infectious diseases at the University of Chicago Hospitals and Clinics. In the 1980s, he served as an Assistant Professor of Medicine and Hospital Epidemiologist at the University of Michigan Hospitals in Ann Arbor, MI.
From 1989 to 2009, Dr. Gaynes worked at the CDC in several positions in the Division of Healthcare Quality Promotion and for over a decade as Chief of the Surveillance Activity in the Hospital Infections Program and as the Director of CDC’s National Nosocomial Infection Surveillance System.
From 2009 to 2022, he served as an attending physician and the Chair of the Infection Control Committee, Antimicrobial Stewardship Committee, and COVID‐19 Vaccine Planning Committee at the Atlanta VA Hospital. As Professor of Medicine at Emory University School of Medicine during this period, Dr. Gaynes lectured on various infectious disease topics and taught courses on the history of medicine. He has authored or coauthored more than 150 papers and book chapters on infectious disease topics.
Board certified in Internal Medicine and in Infectious Diseases, Dr. Gaynes is a Fellow of the Infectious Diseases Society of America. In addition, he is a reviewer for numerous scientific journals and served on the Editorial Board of Infection Control & Hospital Epidemiology.
He is a husband, father, and grandfather who enjoys history, racquetball, gourmet cooking, and travel.
1Introduction
What is the greatest contribution that medicine has made to humanity? In 2007, more than 11,000 readers of the British Medical Journal were surveyed to answer that question. The answers were (in order): (i) public health sanitation; (ii) discovery of antibiotics; (iii) discovery of anesthesia; (iv) discovery of vaccination; (v) discovery of the structure of DNA; and (vi) discovery of the germ theory of disease (1). Of the greatest contributions ever made to medicine, four of the top six were either the discovery of the germ theory of disease or innovations that were a direct result of that discovery. While the answers to this provocative question can be argued, the germ theory remains one of the most important contributions in the 2,500‐year history of Western medicine and a relatively recent one—only 150 years old.
Modern society has taken for granted the value of public health sanitation; the vanishing of vaccine‐preventable diseases such as smallpox, measles, and polio; and the existence of antibiotics to treat infectious diseases. In the 1970s, we even had the hubris to declare infectious diseases “conquered.” However, infectious diseases have emerged or reemerged to devastate our modern world. I didn’t realize when I made my decision to go into the specialty of infectious diseases in 1978, my last year of medical school, that I would be witness to this emergence. I thought that antibiotic treatments could actually cure people, not just treat them. Unlike chronic illnesses such as diabetes, bacterial pneumonia or a urinary tract infection, once treated with antibiotics, could be cured. I was not alone in this thinking.
I entered the specialty at a time when it was believed that medical science had nearly done it all—that there would be little left to do since we had such powerful agents for treating and curing infectious diseases. I recall my first meeting of the Infectious Diseases Society of America in 1981, when one of the foremost authorities in the field told the audience that “all infectious disease doctors would be doing in the next decade would be culturing each other.” This complacency would be short‐lived; such complacency has always been short‐lived in medicine. During the same meeting, James Curran, at the time working at the Centers for Disease Control (CDC) and now recently retired as dean of the Rollins School of Public Health at Emory University, was scheduled to describe the first cases of what would soon be called AIDS (acquired immunodeficiency syndrome). Curran was the last of four speakers in a session that began with 150 people in the audience. But word of these cases had spread through the conference. By the time Curran spoke, over 1,000 people had crammed into a room at a downtown hotel in Chicago, IL. Even though the attendees at the meeting were told that infectious diseases were “conquered,” the infectious disease community of doctors, microbiologists, and public health officials had clearly recognized that something new was happening.
Many new diseases, such as AIDS, hepatitis C virus, hantavirus, SARS (severe acute respiratory syndrome), MERS (Middle East respiratory syndrome), Zika, and COVID‐19 infection, have been described in the last 40 years. The microorganisms that cause these diseases were not actually new—they clearly existed before medical science became aware of them. In some cases, new techniques were developed to identify organisms that had always been there but that we could not detect. More often, the novelty for many of the new diseases is not the emergence of a new microorganism but the novel way the pathogen found its way into humans. Microorganisms are now thought to trigger diseases long considered to be chronic in nature, including peptic ulcers, numerous cancers, arthritis, type 1 diabetes, and others. In 1981, no one imagined how one of these newly emerged diseases, AIDS, which is caused by human immunodeficiency virus (HIV), would change the human landscape of entire continents, alter our conceptual framework of how we treat or even think about an infectious disease, and completely confound our understanding of the human immune system and vaccine development. Additionally, the upheaval caused by a virus causing respiratory disease that began in China at the end of 2019 was almost unimaginable until it spread rapidly through the world, resulting in the worldwide COVID‐19 pandemic, a story that is still being scripted at the time of this writing.
Consider the vast changes wrought by HIV. In sub‐Saharan Africa, HIV has completely altered the human demographics. For many decades, even centuries, before HIV, infectious diseases were the leading cause of death in Africa, but the deaths were childhood deaths. Malaria, infectious diarrhea, measles, and other childhood infectious diseases took their toll on the youngest inhabitants. As tragic as it sounds, most children in Africa did not see their first birthday, a fact that was simply accepted. The dynamic was high birth rates and high childhood death rates. In the course of a generation, HIV became the leading cause of death in Africa, but the deaths were not childhood deaths. The mortality rates among adults from HIV exceeded even the highest childhood mortality rates. In 2007, according to the Joint United Nations Program on HIV/AIDS, 60% of all HIV infections in the world were in Africa, even though Africa has only 12% of the world’s population. In 2007, the life expectancy in Africa was 47 years with HIV and 62 years without HIV. In 2022, Africa remains the most severely affected region, with nearly 1 in every 25 adults (3.4%) living with HIV and accounting for more than two‐thirds of people living with HIV worldwide (https://www.who.int/data/gho/data/themes/hiv‐aids#cms). The medical, economic, social, and political effects of this one infectious disease are so great that the capacity to cope with its burden is stretched thin and, in many cases, has nearly collapsed. Curran was a witness to AIDS during its first 40 years in our modern world and described it this way:
When you walked in the Castro district [of San Francisco] in the early 1990s, AIDS was palpable. The same thing is still true in some African cities. The hospital wards of African hospitals are filled with AIDS patients, sometimes two to three to a bed with young adult people dying. An AIDS death prior to antiretroviral therapy was a horrible process for most people. They lost weight, became demented, had unremitting diarrhea, Kaposi’s lesions all over themselves, and people did not want to be near them. (J. Curran, unpublished data)
In Africa, while mortality for HIV‐positive patients has improved since 2007 (see chapter 17, PEPFAR Successes), this kind of lonely, horrific death still occurred more than 420,000 times in 2021. HIV has forced a change in our social attitudes. Consider the sexual attitudes before HIV appeared. For centuries, syphilis was the most feared sexually transmitted disease since it could not be effectively treated until the 20th century. During the early 1900s, this disease became treatable with arsenic‐based compounds. The concern about syphilis virtually disappeared with the introduction of penicillin. In the 1960s and 1970s, people had the perception that there were no incurable sexually transmitted pathogens. True, genital herpes existed and was a concern. While genital herpes was incurable, it did not cause death and could be treated with medicines. Sexual health could simply be managed by a visit to the doctor. Along came HIV. Once its sexual transmissibility was established, we were faced with a sexually transmitted pathogen that not only could not be handled by a trip to the doctor but also caused death. Sexual practices and attitudes changed. Among adolescents, for example, the rate of unprotected sex has decreased (2). But relentless efforts are needed for each new generation to implement these behavioral interventions.
The medical community itself has been forced to change its thinking because of HIV. Biologically, the silent nature of the infection, i.e., the long incubation period of years, even decades, leaves us with tens of millions of human incubators. Many HIV‐positive individuals do not even know that they are infected. When the CDC reported the first five AIDS cases in 1981, an estimated 250,000 people were already infected with HIV in the United States alone. HIV has a silent, long incubation period followed by a lingering illness. Infectious disease physicians were just not equipped to face a chronically ill patient population in such vast numbers. The appearance of HIV/AIDS forced a complete reexamination of what we thought we knew about treating infectious diseases. Contrast HIV to influenza, which crashes into a community and leaves in a few short weeks. With HIV, an infectious disease becomes a chronic illness.
As the established paradigms for treating vast numbers of AIDS patients broke down for infectious disease doctors, public health officials struggled with the time‐honored models they had used for monitoring infectious diseases. When a new infectious disease enters a community, it is often called an epidemic. The Merriam‐Webster dictionary defines an epidemic as the occurrence of more cases of a disease than would be expected in a community or region during a given period of time. With some infectious diseases, an epidemic is easy to spot. Often, making the determination that more cases of an infectious disease have occurred than would be expected in a region can be challenging. One initial and basic approach used in public health to make this determination is development of an epidemic curve, a technique I learned on my first day of work at the CDC. After a known exposure, the number of cases of an infectious disease is plotted against the time of onset of illness among individuals with the disease to graph an epidemic curve. The shape of the epidemic curve might suggest the mode of transmission of the infectious agent. An epidemic curve where all the cases show signs of infection at nearly the same time and the number of cases quickly tapers off suggests that an infectious agent was transmitted from a common source, e.g., contaminated food at a picnic. With a different type of infectious disease, e.g., influenza, the curve may show an initial or index case, followed by two cases, then four, then eight, etc., until all individuals who are susceptible in a community have acquired the infection and the number of new cases decreases. This shape of an epidemic curve suggests person‐to‐person transmission of an agent. There are combinations of shapes in epidemic curves, but the overall shapes of these curves are the same. The number of cases goes up and then comes back down. In public health, the goals are to shorten the epidemic or work to prevent the problem or a similar problem from occurring, i.e., decrease the width and/or height of the epidemic curve and prevent the occurrence of any epidemic curves in other communities. This is the infectious disease epidemic paradigm. Doctors and public health officials were accustomed to this approach. In fact, we thought we were pretty good at it. HIV was different. HIV produced a chronic infectious disease, one in which the virus entered the body, remained silent (although it could be transmitted) for years, and then produced a lingering disease in which the virus did not disappear in an individual while he or she remained alive, even during treatment. The curve measuring HIV cases went up but did not come back down. Other viruses, such as hepatitis B or C virus, had long incubation periods before illness developed and were known before HIV. However, only a portion of patients initially infected with hepatitis B or C developed chronic illness, although we continue to grapple with people with chronic liver disease from hepatitis B and C. The rapid spread of HIV was coupled with an almost completely ineffective immune response from a person who had the virus. The virus was not eliminated by antibody production. In fact, HIV went on to damage the very immune system we had always thought would eliminate a pathogen. HIV’s ravage of the immune system left the person susceptible to other infectious agents that he or she would normally not be susceptible to, so‐called opportunistic infections. In the first few years of AIDS, it was invariably fatal within 4 years of an AIDS diagnosis. No one was prepared to deal with an infectious agent that could produce disease like this. The mentality of the medical community had to change to deal with a chronic infectious disease. Public health turned to the chronic disease experts for guidance on how to predict, moderate, and control it. We could not cure HIV and move on to something else. In the United States, we have been somewhat comforted by the success of treatment of HIV, which has improved dramatically since the mid‐1990s. Life expectancy of adults with HIV infection who take combination antiretroviral drug therapy may now be near that of life expectancy of individuals without HIV infection (3). Still, treatment does not cure the individual. Indeed, intermittent treatment often leads to changes, i.e., mutations, in HIV that result in treatments that are ineffective or more difficult to administer, a problem that has troubled infectious disease management since the advent of modern antimicrobial therapy. Success in HIV treatment in the United States and elsewhere remains challenging and expensive. In Africa and other less developed regions, the prospect of treatment has improved since 2010 but there are still more than 27 million people in Africa with HIV. The cost of drugs and the infrastructure to deliver and monitor drug treatment will remain substantial. The “what goes up must come down” or epidemic thinking will not solve HIV or other endemic infectious diseases, such as tuberculosis or malaria, in Africa. We have had to reconsider our infectious disease treatment/prevention model to one that effectively approaches chronic or endemic infectious diseases. According to Curran, “this model is far less heroic, but arguably more important. And that’s why there needs to be a change in thinking” (Curran, unpublished).
Nowhere has HIV challenged our conceptual framework more than in the development of an HIV vaccine. The world desperately needs an effective immunization for HIV as the means to control or even eliminate AIDS. Immunizations have been one of the most effective methods for control of disease, even eradicating the scourge of smallpox. The traditional approach to immunization formulation is to kill or inactivate a pathogen and inject it into people. Vaccines formulated in this way rely upon duplicating a successful human immune response to the natural exposure of a pathogen. Following the discovery of HIV as a causative agent of AIDS in 1983, the expectation was to rapidly develop a vaccine but, as of 2022, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV. We still do not have a complete understanding of immune responses required to protect against HIV acquisition (4). The traditional methodology of vaccine development has not worked for HIV.
HIV has been the most visible pathogen that has changed the concept that infectious diseases could be conquered, a concept that, according to Curran, “is now not credible” (Curran, unpublished). We have every reason to believe that other microorganisms might find their way into humans as we carelessly expand our way into previously undisturbed ecosystems. A new pathogen emerging anywhere in the world is cause for worldwide concern. The most obvious example is SARS coronavirus‐2 (SARS‐CoV‐2). The rapid geographic dispersal of this virus causing COVID‐19 infection is a clear reminder of how small our world has become. But there are other worries that shake our notion that infectious diseases have been subjugated.
The complacency that led us to the notion that we have conquered infectious diseases was due to our apparent successes—immunizations and antibiotics. Until HIV, development of vaccines was a major success of our modern medical world. The chief difficulty was administering the vaccines to the people who needed them. Vaccines were and still are underutilized. But immunizations can only prevent illness. Antibiotics treat illness. From the discovery of the first antibiotic, medical science and microorganisms have been in a constant struggle. Since the beginning of modern antibiotic therapy, resistance to antibiotics has steadily increased, and it is increasing faster than we can discover new therapies. Recent discoveries of vancomycin‐resistant Staphylococcus aureus and bacteria containing enzymes called carbapenemases that degrade some of the most potent antibiotics, the carbapenems, are but two examples of the difficulties facing contemporary treatment of infectious diseases. But we cannot simply blame the appearance of antibiotic‐resistant pathogens on clever, evolutionary tricks of microorganisms.
The widespread resistance among bacteria is a problem largely of our own making. Antibiotic use leads to antibiotic resistance. While it is blatantly obvious, most health care providers generally ignore this statement. Our infectious disease treatment paradigm involves use of broad‐spectrum antibiotics, usually without specific knowledge of the offending pathogens. There is hidden harm that occurs as a result of this antibiotic exposure. Sometimes a pathogen causing an infection will begin susceptible to the agent but become resistant to it during therapy. But often, antibiotic resistance is actually the result of collateral damage. The resistance develops among pathogens that are not responsible for the infectious syndrome manifested by the patient. Humans normally harbor bacteria in the mouth, the colon, the skin, and other sites. The normal bacterial flora in humans is immense and often protects the body when harmful bacteria invade. When powerful antibiotics destroy much of the normal, protective bacteria, the void is filled by small numbers of resistant bacteria that we all may harbor. These resistant subpopulations of bacteria are given a chance to proliferate after antibiotic therapy. The resistant organisms may not even cause damage to the person treated with broad‐spectrum drugs, but this person may become a reservoir or a human factory of a silent source of resistant organisms to those around him. Infection control efforts often fail since no one may be aware that the recently treated individual harbors antibiotic‐resistant organisms. The number of people colonized but not infected with a resistant organism may be 50 times greater than the number of people who have an infection with a resistant organism. This so‐called iceberg effect, where most of the resistance problem is hidden below the surface where we cannot see it, has been best described for hospitals, but resistance has become a problem outside hospitals. Community‐acquired methicillin‐resistant S. aureus (MRSA) infecting large numbers of patients who had not been in hospitals has been described in recent years. MRSA can be spread from one person to another. Our attempts to limit spread of this organism through infection control efforts appear to have been largely ineffective. Current attempts at hospital‐based efforts to control MRSA are controversial and may be too little, too late, since so many MRSA infections now occur outside hospitals. Indeed, determining the effectiveness of control measures for MRSA or other resistant microorganisms is complex. Ultimately, the reservoir of the resistance will be found to involve exposure to antibiotics, perhaps in a person’s distant past or in another person who served as the source of the MRSA.
The proliferation of antibiotic‐resistant organisms is challenging the current tenet of infectious disease practice—use broad‐spectrum antibiotics to “kill the bugs” with little or no concern for the collateral damage of antibiotic resistance. We have abused one of our greatest medical treasures, antibiotics. Abuse of antibiotics has opened the door to a new era with untreatable antibiotic‐resistant infections, a post‐antibiotic era. Pharmaceutical companies are not going to bail us out of this problem, since most have limited or even eliminated antibiotic drug discovery programs, largely because of economics. For example, from 2019–2022 there were no new antibacterial antibiotics approved by the Food and Drug Administration in the United States (https://www.fda.gov/drugs/new‐drugs‐fda‐cders‐new‐molecular‐entities‐and‐new‐therapeutic‐biological‐products/novel‐drug‐approvals‐2022). While some progress has been made in the last 25 years, finding new antibiotics has been time‐consuming, difficult, and expensive, with no guarantee of success.
The dilemmas from newly emerging infectious diseases—HIV, an often fatal, chronic infectious disease, and SARS‐CoV‐2, which have stressed, to the breaking point in some places, our ability to prevent infection, find treatment, and provide it to millions; HIV vaccine failures that require a complete reassessment of the concepts of the human immune response; untreatable, antibiotic‐resistant infections that portend a post‐antibiotic era; and the unsettling notions that new pathogens like SARS‐CoV‐2 or a microorganism that causes disease even worse than COVID‐19 infection will likely emerge, and that a problem that emerges in one corner of the globe can be rapidly transported anywhere in the world—have forced the medical and public health community to scrutinize itself. Medical science must reconsider all approaches to detecting and diagnosing emerging infectious diseases, to developing vaccines, to discovering new antibiotics, and to using wisely the precious few antibiotics that we have.
Where do we start? Before we can figure out where we should go, we should examine how we got here. We should look back to our initial advances in understanding infectious diseases. Appreciating how major contributions were made by some of the greatest doctors in history will help us reconsider our approaches to the practice of infectious diseases. Just as economists and policymakers look back to the Depression to develop policies to relieve us from economic woes, we should examine the history of infectious diseases. Historians debate the best approach to study the past. Thomas Carlyle, a well‐known historian in the mid‐1800s, once wrote, “The history of the world is but the biography of great men” (5). As an amateur historian, I have chosen to view history this way in order to detail the lives of 13 men and 2 women who were pioneers of our current conceptual framework of infectious diseases. Here, I must make a few qualifying remarks. First, the conceptual framework for the practice of infectious diseases is from Western medicine. This book is largely limited to Western medicine. Some readers may have a limited appreciation for the Eurocentric approach. Yet while my purpose is not to glorify Eurocentric concepts, Europe is where our conceptual framework for the practice of infectious diseases medicine was conceived. Contributions from other cultures, as germane as they are to a holistic perspective on the method of discovery, were largely ignored by Western medicine—often to its detriment. Second, there will be those who question the choice of the individuals who were included. While I doubt that one can argue against those included in this book, the persons excluded from any discussion will no doubt generate controversy. I have chosen individuals whose contributions were essential to understanding the origins of our approach to the practice of infectious diseases medicine and whose stories were compelling to me. I will admit to small detours into anecdote to better understand the person. The influences on the lives of these discoverers, often early influences, the era in which they lived, their personalities, and, in many cases, their daring, permitted these individuals to make extraordinary contributions even when those contributions were not initially well received. Discoveries made by an individual need to be accepted into the practices of the community before they can actually become advances. As we shall see, at times, the discovery had little impact until the practices of the community were reevaluated. These reexaminations provide lessons and, perhaps, some hope as we are forced to look introspectively toward our own practice of infectious diseases medicine.
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