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- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Magic Bullets, Miracle Drugs, and Microbiologists
Magic Bullets, Miracle Drugs, and Microbiologists: A History of the Microbiome and Metagenomics by William C. Summers is an enlightening journey through the fascinating world of microbiology, exploring its history, challenges, and the revolutionary concept of the microbiome.
Summers draws from his unique perspective as both a practicing microbiologist and a historian of science, influenced by early microbiological literature and his own extensive career, presenting how our understanding of microbes evolved from concepts of simple germs to complex, essential elements of life. Summers skillfully ties together key players and eras in the microbial sciences into a concise narrative, from early microscopic observations to the revolutionary developments in genetic analysis and metagenomics, highlighting our ever-evolving understanding of the diverse microbial world.
Magic Bullets, Miracle Drugs, and Microbiologists is a compelling read for anyone interested in the profound impact of microorganisms on our world.
“Bill Summers artfully explains how, over the past century, scientists have synthesized new disciplines and embraced evolving technologies to develop new concepts about how germs behave in microbial communities and what their relationship is to the environment, human health, and epidemic diseases. Skillfully written in engaging prose, this book will be valuable to microbiologists, epidemiologists, medical historians, and geneticists seeking to better understand the historic roots of twenty-first century microbiology.”
— Powel H Kazanjian, University of Michigan Medical School and Author of Frederick Novy and the Development of Bacteriology in Medicine
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Table of Contents
Cover
Table of Contents
Title Page
Copyright Page
List of Illustrations
Foreword
Preface
Acknowledgments
About the Author
1 Introduction
A Scandalously Short History
Microbial Hubris
The Microbial World
Notes and References
2 Microbe Hunting before DNA
Notes and References
3 Magic Bullets and Miracle Drugs
Magic Bullets: Sulfa, Tyrothricin, and Streptomycin
Penicillin
The Golden Age
Notes and References
4 Hints of Trouble
Microbial Drug Resistance
Drug‐Fastness
Disinfection
Microbial Metabolism and Adaptation
Adaptation or Mutation?
Multiple Drug Resistance and Cross Resistance
Antibiotic Resistance in the Current Context
Notes and References
5 The Terrible Decade
Lassa Fever: 1969
Legionnaires Disease: 1976
AIDS: 1981
Lyme Arthritis: 1976
A Decade in Review
Notes and References
6 Loss of Innocence
Ribosomal RNA
Archaea and Extremophiles
Population Size and Diversity
Human Beings and Other Animals
Notes and References
7 The New Microbe Hunters
DNA Chemistry and Genetics
DNA Hybridization and Gene Comparisons
RNA AND DNA Sequence Analysis
Enzymes That Cut DNA Precisely
Plasmids: Carriers of New Genes
Amplifying Genes
In Vitro
Bioinformatics and Metagenomics
Notes and References
8 Global Microbiology
Tales of Three Biomes
Role of Bacteriophages
Human Microbiome
Notes and References
9 Emerging Diseases, Evolution, and the Microbiome
Plague: Microbial Evolution and a New Disease
Nipah Virus: Ecology of Disease
Influenza: Genetic Variation and Epidemics
Conclusion
Notes and References
10 The Future of the Microbiome Concept
In Conclusion…
Notes and References
Index
End User License Agreement
List of Illustrations
Chapter 2
FIGURE 2.1
Replica of one of Leeuwenhoek’s many single lens microscopes. The
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FIGURE 2.2
First image of a microbiome. Leeuwenhoek’s drawing of animalcules
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FIGURE 2.3
Image of some infusoria as drawn by von Ehrenberg in Die Infusori
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FIGURE 2.4
Petri dish with nutrient broth solidified by the addition of agar
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Chapter 3
FIGURE 3.1
Schematic Winogradsky column; the column is loaded with samples o
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Chapter 4
FIGURE 4.1
Gradient plate showing bacteria evenly spread on medium in which
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Chapter 5
FIGURE 5.1
Public health poster to educate the population in Africa about th
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Chapter 6
FIGURE 6.1
Logic for selecting the gene for 16S rRNA for microbial genealogy
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FIGURE 6.2
Tree of life proposed by Woese in 1987 based on evolutionary rela
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Chapter 7
FIGURE 7.1
Steps in metagenomic analysis from original sample to production
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Chapter 8
FIGURE 8.1
Graphical representation of global distribution of biomass by dif
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FIGURE 8.2
Metagenomic data display (simplified) of the ten most prevalent p
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Chapter 9
FIGURE 9.1
Ecological interrelationships in the emergence of Nipahvirus in M
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Chapter 10
FIGURE 10.1
N‐grams (8) showing the prevalence, by year, of the term “microb
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FIGURE 10.2
Journey to the center of Jules Microbiome.
Guide
Cover Page
Table of Contents
Title Page
Copyright Page
List of Illustrations
Foreword
Preface
Acknowledgments
About the Author
Begin Reading
Index
WILEY END USER LICENSE AGREEMENT
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Magic Bullets, Miracle Drugs, and Microbiologists
A History of the Microbiome and Metagenomics
WILLIAM C. SUMMERS
Copyright © 2024 American Society for Microbiology. All rights reserved.
Copublication by the American Society for Microbiology and John Wiley & Sons, Inc.
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The right of William C. Summers to be identified as the author of this work/the editorial material in this work has been asserted in accordance with law.
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ISBN 9781683674771 (Paperback)
Cover Design: WileyCover Image: © Cavan Images/Getty Images, luchschenF/Shutterstock
List of Illustrations
Figure 2.1 Leeuwenhoek microscope
Figure 2.2 Leeuwenhoek Letter 39. First microbiome of mouth
Figure 2.3 Infusoria from von Ehrenberg
Figure 2.4 Petri dish with colonies
Figure 3.1 Winogradsky column
Figure 4.1 Gradient plate showing antibiotic resistance
Figure 5.1 Lassa fever and rat poster
Figure 6.1 Logic of 16S rRNA sequence analysis for genealogy studies
Figure 6.2 Woese’s revised tree of life based on 16S rRNA gene sequences
Figure 7.1 Metagenomic sequencing strategy
Figure 8.1 Graphical display of global biomass distribution by biological groups
Figure 8.2 Metagenomic data display (simplified) of the human gut microbiome
Figure 9.1 Nipah ecology
Figure 10.1 N‐grams for microbiome
Figure 10.2 Journey to the center of Jules Microbiome
Foreword
I’ve always thought of Bill Summers as a virologist. I was aware of his molecular biology research first on T7 bacteriophage and later, on herpes virus in collaboration with Wilma Summers. But on second thought, I realized that wasn’t quite right. Summers is a historian of science as well, and as a historian his research and books include both viruses and bacteria. Examples are: Summers WC. 1999. Félix d`Herelle and the Origins of Molecular Biology; Summers WC. 2022. The American Phage Group: Founders of Molecular Biology; and Summers WC. 2012. The Great Manchurian Plague, 1910–1911: Geopolitics of an Epidemic Disease (all published by Yale University Press, New Haven, CT).
In this book he takes on the story of how the diversity of the microbial world has come to be understood from its discovery over four centuries ago to our current concept of microbiomes. Central to this understanding are the experimental methods used to identify, describe, and classify microbes. Summers argues that this understanding was revolutionized in the decades of the 1960s and 1970s when microbiologists adopted genetic approaches in place of the traditional physiological, morphological, and pathological approaches to identify and classify microbes.
The present book includes both bacteria and viruses (and at times a few other denizens of the microbial world). Bacteria often predominate but bacteriophage and animal viruses also have an important role throughout. Summers gives credit for the beginning of the subject of microbiology to van Leeuwenhoek’s report of his microscope and what he saw in his letter to the Royal Society of 9 October 1675, but we are also reminded that Aristotle (384 BCE–322 BCE) should be acknowledged and given credit for his efforts to devise a comprehensive and rational classification scheme.
Once microbes were identified, Summers writes that “medical scientists sought microbial causes for every known malady, from cancer to mental disorders to heart disease and strokes. These hunters of microbes were remarkably successful. Many serious diseases of humankind turned out to be caused by microbes: tuberculosis, pneumonia, typhoid, cholera, polio, influenza… the list goes on and on.” Now at the end of the 20th century and in the 21st century, research again implicates microbes in the initiation or cause of chronic diseases. Helicobacter pylori and human papillomavirus are illustrations of two microbes that are the cause of peptic ulcers and cervical cancer, respectively. Other chronic diseases may be initiated by a virus or bacterial infection. Although not a direct cause, infection with hepatitis B virus and hepatitis C virus can lead to the disease of hepatitis.
Even now, it is more complicated to associate a microorganism with a chronic disease when the organism is the initiator of the disease, but the actual pathology is influenced by additional factors, leading to cases when infection is more prevalent than clinical disease. There are a number of human diseases that fall into this category, still challenging “microbe hunters,” including multiple sclerosis and diabetes type 1. The association of viruses with these diseases comes mainly from animal models and immunological studies. In addition, there is increasing evidence to suggest that the herpesvirus, Epstein‐Barr virus, is associated with the cause of multiple sclerosis.
As I was writing this, I was reminded of poliovirus–an enteric virus–and the disease of poliomyelitis. Another example where the early tools for identifying and understanding the viral cause was clouded by its complex biology. An important observation in early studies of the paralytic disease leading to the development of the vaccines was that only about 1% of infected individuals experience neurodegeneration caused by the spread of the virus to the central nervous system. Infection of the central nervous system would be responsible for what could be considered the chronic disease of paralysis. Even more relevant might be that decades later some individuals develop post‐polio symptoms of muscle weakness and pain thought to be due to a deterioration of motor neurons; poliovirus is no longer present.
I am also reminded of poliovirus as an example of the near miraculous success of vaccines against this virus that have almost led to the eradication of the disease of poliomyelitis. An unstated corollary of Summers’ book is the importance and influence of vaccination on the threat of infectious diseases. As of 1980, extensive worldwide vaccination efforts led to the eradication of the disease of smallpox. Now in the 21st century in many countries (although there are definitely exceptions) there is almost no memory about the disease of paralytic poliomyelitis. The pandemics of plague are not a threat. Cases of measles had been rare in many countries, but there has been an increase in infections. Other serious diseases (tetanus, typhoid) are hardly known in many countries, and the importance of vaccination was often not recognized as one of the reasons for the absence of the disease, although that did change with the pandemic of SARS‐CoV‐2. Instead, there have been protests against vaccination. Perhaps this book will remind us that infectious diseases, known and emerging, remain a threat as cases of polio and measles are reappearing.
There have been protests against vaccination ever since Jenner’s vaccine against smallpox, but more recent objections have come from the “antivax” movement–objections to vaccination that seem to have become even more vociferous with the COVID‐19 pandemic. While Summers does not delve into the history of vaccines, per se, he does write about the devastation of infectious diseases such as plague, influenza, and others. Understanding microbial diversity and avoidance of microbiological hubris with respect to new and emerging pathogens are essential to our continued success in developing new immunological protections.
After a broad history of diversity in the microbial world and an introduction to the new metagenomic methods coming into widespread use in microbiology, Summers turns to the subject of the human microbiome and especially to the importance of the presence and diversity of the residents of the microbiome. In the past few years this has become a fascinating and explosive field—I believe it is just the beginning. Now the composition of our blood is a normal part of a medical exam—the residents of our microbiome should soon also become a routine part of an exam.
Through most of this book Summers focuses on microorganisms as disease‐causing agents. In the last chapter he may be hinting at the subject of his next book – the stable communities of microbes that are found in various physiological niches from deep sea corals to the human digestive track where they play crucial roles in health and disease.
Bill Summers writes that he was strongly influenced by Paul de Kruif ’s account of the heroes of microbiology, Microbe Hunters (1926) and later by The Microbial World (Roger Stanier, Michael Doudoroff, and Edward Adelberg, 1957). After reading Magic Bullets, Miracle Drugs, and Microbiologists, I am convinced that this book by Bill Summers will be an influence on some young readers to enter the field of microbiology.
Sondra Schlesinger
Professor EmeritusDepartment of Molecular MicrobiologyWashington University School of MedicineSt. Louis, MO
Preface
This book is the product of three contingencies: my half‐century career as a practicing microbiologist, my more recent career as a historian of science, and the recent flood of commentaries on pandemics, probiotics, and the politics thereof.
As a teenager I was strongly influenced as were many of my contemporaries by Paul de Kruif’s account of the heroes of microbiology, Microbe Hunters (1926). A bit later I encountered a textbook with the title The Microbial World (Roger Stanier, Michael Doudoroff, and Edward Adelberg, 1957) which presented microbiology as a comprehensive science and a title that suggests some sort of global unity of microbes. These two ideas, not quite themes, are the two guiding principles in this book: 1) history matters and 2) microbes are, indeed, ubiquitous co‐inhabitants of our planet.
I also have drawn upon my understanding of the broad fields of microbiology, infectious diseases, and epidemiology to center this account of the changing views of the microbial world on the decades of the 1960s and 1970s as a paradigm shifting period when both human history with new microbial challenges and scientific progress coincided to change our understanding of this unseen world. Serious “new” diseases such as Legionnaires’ disease, Lassa fever, Lyme disease, and a bit later, AIDS, emerged and invaded the public consciousness. At the same time, amazing new genetic approaches such as direct gene analysis by DNA and RNA sequencing provided the new technologies that would change our earlier views of the microbial world.
Prior to these decades, now perhaps seen as infected with microbiological hubris, we were comfortable in our belief that we understood our microbial neighbors, had antibiotics to keep them in their place, and could look forward to a time without major epidemics and other contagious disease disasters. But, to quote that philosopher, Yogi Bera, “It’s tough to make predictions, especially about the future.”
This book, then, is a historical look at the understanding of our microbial world from its seventeenth century discovery of animalcules to the current appreciation of the diverse microbiomes that are an integral part of our planet, and in some ways a cautionary tale, highlighted by the recent COVID‐19 pandemic, to be mindful of the mysteries of microbiology yet to be solved.
Acknowledgments
An earlier version of chapter 4 appeared in Summers WC. 2007. Microbial drug resistance: a historical introduction, p 1–10. In Wax RG, Lewis K, Salyers AA, Taber HW (eds). Bacterial Resistance to Antimicrobials. 2nd Ed. CRC Press, Boca Raton, Florida.
I am greatly indebted to many generous mentors, kind colleagues, and generations of Yale students who helped me develop my thoughts on matters treated in this book. I thank Wilma P. Summers, G. Nigel Godson, Sondra Schlessinger, Adam Lauring, and Susan Spath for special help on various aspects of this work. Thanks also to Megan Angelini, my very helpful and diligent editor, for her cheerful and astute advice in bringing this work to publication.
About the Author
William C. Summers is a retired Professor of History of Medicine, of Molecular Biophysics and Biochemistry, and of Therapeutic Radiology and in the Program of History of Science and Medicine at Yale University where he was a faculty member from 1968 until his retirement in 2017. His formal education at the University of Wisconsin included mathematics, molecular biology, and medicine and he received the MD and PhD in 1967. He began his laboratory work on bacteriophages in 1963 and expanded to study animal viruses in the 1980s. In addition to studies on the molecular biology and genetics of cancer and viruses, his scholarship has included history of medicine and science, and the relations between science and the humanities. He has held visiting positions in Sweden, the United Kingdom, Stanford, Columbia University, Hubei Medical College, and the National University of Singapore. His previous historical books include Félix d'Herelle and the Origins of Molecular Biology; Reconceiving the Gene: Seymour Benzer's Adventures in Phage Genetics (edited); The Great Manchurian Plague of 1910–1911: The Geopolitics of an Epidemic Disease; and The American Phage Group: Founders of Molecular Biology.
1Introduction
A SCANDALOUSLY SHORT HISTORY
Microbiome! Who, these days, hasn’t heard about “the microbiome”? From TV pitches to “support gut health” to complex explanations in high‐end magazines about new understanding of the myriad human‐microbe interactions, some apparently essential for our existence as living, breathing organisms. For those of us of a certain age, microbes, aka “germs” were mainly to be casually washed away a few times a day from our grubby little hands before meals and after using the bathroom. How did “microbes” become a central concern in modern life, and what is the history of this recent interest? This question is the theme of this book.
Microbes (a name coined by a French surgeon in the latter part of the nineteenth century) by their nature are not visible to the naked eye, so they were unknown until the mid‐seventeenth century when high‐powered glass lenses were employed to magnify these tiny objects. The microscope was simply a handy magnifying glass arranged to look at things up‐close (1). An amateur scientist from Delft, in the Dutch Republic (at that time science was done by amateurs with regular day jobs because there was no such career path as “scientist.”) became very skilled at making lenses and microscopes and recorded his many observations over a period of a half‐century (1676–1723). The various objects that Antonie van Leeuwenhoek (1632–1723) observed, he called “little animals” (animalcules) because he viewed them as simply tiny versions of the known animals of common experience.
Leeuwenhoek’s work became widely known and appreciated, but it took over a century for others to understand just where these animalcules fit into the schemes of life that were being formulated, and what they might be doing in the many environments where they were found. The 19th century was a time of intense expansion in scientific knowledge in many fields; new theories of chemistry, new technologies, new philosophies of nature, and new questions fueled this expansion. The stories of the germ theories of disease and the debates over the living nature of microbes as the agents of fermentation and related everyday processes are by now almost folk tales.
The heroic figures of Louis Pasteur (1822–1895) and Robert Koch (1843–1910) as discoverers of microbes as the causes of many here‐to‐fore mysterious diseases of both humans and other animals paved the way for the “microbe hunters” of the twentieth century. In the early years of that century, medical scientists (by now “scientist” had become a legitimate job description) sought microbial causes for every known malady, from cancer to mental disorders to heart disease and strokes. These hunters of microbes were remarkably successful. Many serious diseases of humankind turned out to be caused by microbes: tuberculosis, pneumonia, typhoid, cholera, polio, influenza… the list goes on and on (2).
Not only were microbes important in causing diseases, it was found that the animal body had a mechanism to deal with these invading microbes: the immune system. For many diseases, the body could react, over time, and develop powerful defenses against a later infection with the same or a related microbe. In a way, the body learned from its first encounter. The way this immunological learning works has taken nearly a century to unravel. But even before this process was completely understood, the phenomenon of immunity was quickly exploited to devise preventative measures. A deliberate infection (under mild conditions, it was hoped) could be used to induce this immunological protection against later, more dangerous, natural infections. Historically, smallpox was the human scourge most widely prevented by this inoculation procedure. Later, in 1796 Edward Jenner (1749–1823) introduced a novel variation on smallpox inoculation when he recognized that a related but benign infection with material from animals with cowpox induced immunity to smallpox just as well as a mild case of smallpox itself. This kind of immunization became known as “vaccination,” a name derived from vacca, Latin for a cow.
In addition to the development of immunizations against many microbes, from the early years of the twentieth century the pharmaceutical chemists were developing drugs to suppress microbial diseases. Some of these drugs were quite successful. One such drug made from arsenic and called Salvarsan became the first really useful treatment for the dreaded syphilis. The real “breakthrough” and the real start of this account came in the mid‐decades of the twentieth century with the discovery of several drugs with broad use against many different microbes, drugs such as the sulfa drugs. These drugs were based on the known metabolic reactions shared by many microbes but not their animal hosts. But the main event turned out to be the recognition that various microbes compete with each other in the environment and have evolved toxins to destroy their competitors. In 1928, famously, Alexander Fleming (1881–1955) in London observed a case of this microbial antagonism on some of his accidentally contaminated culture plates of bacteria that had been invaded by a mold. The mold, Penicillium notatum (now called P. chrysogenum), a common bread mold, produced a soluble substance, a chemical that Fleming partially isolated and showed would inhibit the growth of certain disease‐causing bacteria. He named this substance penicillin. Because it was from a biological source, the mold, and because it was useful to inhibit other organisms, penicillin became known as an “antibiotic” to be distinguished from the antimicrobial agents produced in the lab by chemists (3). For various technical reasons, it took nearly15 years to produce and purify enough penicillin to show that it was clinically useful to treat microbial infections. Fleming’s discovery, expanded on by others, about microbial antagonism led the former microbe hunters to become antibiotic hunters. Many new and useful antibiotics were discovered, tested, and brought into routine clinical use. There was hardly an infection known to medicine for which a useful antibiotic could not be found. Thus begins our story.
MICROBIAL HUBRIS
What microbes do we know about, and, how do we know them? Two problems confronted the early microbe hunters: what methods are available to hunt microbes, and how should we classify, describe, and catalog our quarry. The first question is primarily one of laboratory technology, the second is practical as well as philosophical.
The microbiologists of the nineteenth century employed several basic techniques: inoculation of suspect material into various experimental animals, usually guinea pigs or mice and the watch for changes in health, appearance, or behavior. The affected animal was then dissected to look for both macroscopic and microscopic traces of the suspect microbes. A more focused method was to smear suspect material on a surface of some substance that was both free of known microbes, i.e., was “sterile” and was believed to support the growth of a microbe if it was present. These sterile culture surfaces were sometimes gelatin or agar surfaces that had been sterilized in an oven, or sometimes just the cut surface of a potato. The gelatin or agar was supplemented with sugars, meat broth, or other “nutrients” that the microbe hunter believed (or guessed) was needed by the microbe to grow and flourish on the surface. If the conditions were right, a microbe that landed on the surface and started to grow would eventually form a visible “colony” of all the millions progeny of the original microbe, a colony of identical descendants, a so‐called pure culture. Some of these microbes could then be observed under the microscope, tested in other ways, and eventually characterized and identified as either a known type or as a new, unknown, isolate. For a long time, basically up until the molecular revolutions of the 1970s, the main way microbes were described and characterized was by their size, shape, and appearance of their colonies, as well as their chemical properties as identified by their staining with various dyes, their growth or non‐growth on culture media of varying nutritional composition, or by their reaction with known antibodies (the molecules of the immune system that had been stimulated by specific known microbes to produce these identifying tools). With these rather simple and universally available technologies, the microbe hunters could be reasonably confident that microbes found in nature in one part of the world or by one laboratory could be compared with microbes found elsewhere.
With descriptions and characterizations of microbes in hand, the microbe hunters had to decide how to organize their collection. In the very early days in the nineteenth century, they relied on microscopic size and shape plus visible appearances of the colonies on various culture setups. As chemical and cultural technologies advanced and the relationship between the conventional classifications of Carl Linnaeus (1707–1778) and the evolutionary principles of Charles Darwin (1809–1882) were recognized, new microbial taxonomic systems developed. By about 1920, consensus was developing around certain principles, and several groups of microbiologists came together to produce what very soon became the standard authority on bacterial classification (viruses and non‐bacterial parasites were more complex and controversial). Under the leadership of David H. Bergey (1860–1937), a professor at the University of Pennsylvania, Bergey's Manual of Determinative Bacteriology was first published in 1923 (4). The very term “determinative” indicated that this was a source for information to determine what kind of bacterium one had just isolated. This manual, and its many subsequent updates, provide microbiologists with a consensus classification system, approved methods for characterizing bacterial isolates, and standardizations to insure inter‐laboratory comparisons and identifications. Bergey’s Manual (for short) integrates bacteria into the general biological classification scheme derived from the eighteenth‐century views of Linnaeus, the so‐called binomial classification that assigns hierarchical groupings down to the final categories of genus and species. Species, is, of course, considered the individual identification that defines the biological specificity. It is worthwhile to note, however, that the species concept is not without its critics, and modern biology struggles to come to grips with the species concept as more and more examples are found that don’t neatly fit. In microbiology, virus classification in particular, seems resistant to this traditional view.
THE MICROBIAL WORLD
All in all, however, microbiologists during the middle decades of the twentieth century could culture away, finding, and naming organisms from their environment and their patients, following Bergey and discovering ever more examples that fit nicely into the niches of Bergey’s groups and flow charts. Identification of new germs or recognition of known germs as causal agents of disease or perhaps even useful processes (think wine and cheese) was one thing, finding treatments or modifiers of microbial growth and pathogenicity was another. Although the French chemist Pasteur was famous for his pioneering work on various immunological approaches, introducing many useful inoculations (i.e., vaccines) and the serum from animals (and even humans) which contained the antibodies induced by these vaccines to treat or prevent some microbial infections, science was usually unable to find effective treatments for some of the most troublesome infections. The German chemist, Paul Ehrlich (1854–1915) took another, more direct, approach. Ehrlich noted that the stains used to characterize and visualize them were often the same compounds that could kill these microbes. The specificity of the staining reactions coupled with their lethal action suggested to Ehrlich that it might be possible to find specific chemicals that could treat specific infections. His first success in 1910 was the development of a compound (now known to be a mixture of related compounds) that contained arsenic called arsphenamine, also known as Salvarsan or compound 606, that could successfully treat both syphilis and African sleeping sickness (African trypanosomiasis). Because this chemical was both effective and highly specific, Ehrlich employed the metaphor of the “magic bullet,” a phrase that has become part of our vernacular discourse (5). Salvarsan became the first example of what became known as chemotherapy. It was several decades, however, before the next magic bullet was produced in the form of the sulfa drugs (introduced in 1935). These drugs would prove to be the first in a long line of small molecule drugs that effectively targeted diverse bacterial species.
After Fleming’s discovery of penicillin and the recognition of the microbial complexity of ecosystems such as soil, the discovery and isolation of several other antibiotics soon followed. Streptomycin, isolated in 1943 from the soil microbe Streptomyces griseus, was the first such antibiotic that was broadly effective and showed only rare side effects in humans. Others were discovered rapidly based on the same principles: actinomycin (1940), cephalosporins (1945), chlortetracycline (1945), and chloramphenicol (1947). Immediately following WWII when penicillin was introduced and sulfas were used to control infections, both penicillin and streptomycin were hailed as “wonder drugs” or “miracle drugs” and flowed like water across the medical landscape of the developed world. Infections that were previously feared as a death sentence, pneumonia in the elderly, tuberculosis, sepsis, typhoid fever, gonorrhea, and syphilis, all fell victim to the curative powers of the new miracle drugs being produced by the microbe hunters and their friends, the pharmaceutical chemists.
The new antibiotics were so successful and apparently so innocuous that they became the “go‐to” answer for every medical encounter. As we now know, this selective pressure (pace Darwin) led to microbial population shifts and the massive problems with drug resistance that are now commonplace. Still, acute infectious diseases seemed controlled, something to be treated with the ever‐new generations of antibiotics being discovered… up to a point. Between 1935 and 1968, 12 new classes of antibiotics were introduced but between 1969 and 2003, only two more (6).
The clinician, however, when confronted with a potential infection as well as a patient clamoring for one of the new “wonder drugs” simply pulled out the syringe and provided a dose of penicillin. The patient got well but whether or not it was due to the penicillin was never an issue… it was another score for the power of antibiotics. Antibiotics, it seemed to many, heralded the end to the scourges of infectious diseases of life on Earth, animal and plant alike. Soon, however, two biological realities changed all that: microbial diversity and genetic variation.
With the widespread use of antibiotics, as Darwin predicted, selection for resistant variants became the norm. Secondly, microbial diversity, long considered a naturalists hobby, revealed the vast array and abundance of microbes just waiting for ecological opportunities to show themselves in new, sometimes troublesome environments. These developments coincided with a rather abrupt change in microbiological technologies from morphological and physiological methods to genetic methods, all occurring in the few decades just after mid‐twentieth century.
Microbiologists, both in the lab and in the clinic, were justly proud of their early twentieth century successes at identifying the causal microbes underlying many of the prevalent animal and plant diseases. The discovery of antibiotics also was an accomplishment that led to optimism for a future free of sickness and death from major infections. Indeed, as several noted physicians have recently recalled, microbiology in the 1950s and early 1960s was marked by a kind of scientific hubris: we conquered the microbial world. This attitude, perhaps justifiably, led to a general malaise in the field of medicine known as “infectious diseases.” This book traces some of the events, both in the lab and in the clinic, that upended this optimistic outlook in the 1960s and 1970s. With the emergence of unknown new infectious diseases and the recognition of our ignorance of the vast majority of unknown members of the microbial world, we again lost our innocence as scientists and clinicians and now grapple with the new concept of microbiomes and the powerful new technologies of metagenomics.
NOTES AND REFERENCES
1. New understanding of the science of optics in the early seventeenth century produced both microscopes as well as telescopes, another device with lenses arranged to look at things far away.
