Biomedicine and Health: The Germ Theory of Disease
Biomedicine and Health: The Germ Theory of Disease
According to the modern germ theory of disease, infectious diseases are caused by the presence of pathogenic microorganisms within the body. In other words, the germ is that which gives rise to the development of disease. Today, in popular usage, the word “germ” generally refers to a pathogenic microorganism, but the term is also used by biologists to describe the earliest form of an organism, that is, something that serves as the basis of further development. Commonly used phrases like “the germ of an idea” retain the more general meaning of the word.
During the last 20 years of the nineteenth century, germ theory revolutionized both medical thought and the art of surgery, although the drugs, antibiotics, and vaccines that made it possible to treat or prevent many of the major epidemic diseases were not available until the twentieth century. Microbiologists proved that specific microbes caused specific diseases, and that these microbes multiplied in the sick and spread from one person to another.
By the beginning of the twentieth century, microbiologists had identified the microbial agents—bacteria, protozoa, fungi, and viruses—that cause many major infectious diseases in both humans and animals. Health reformers brought the lessons of germ theory to the public, teaching people how to organize their homes and lives in accordance with modern sanitary practices. Germ theory had important implications for the way in which people cleaned their homes, selected foods, prepared their meals, and even influenced the length of women's skirts.
Historical Background and Scientific Foundations
The evolution of the germ theory of disease can be traced to ancient speculations about the noxious entities that were thought to cause epidemic and endemic diseases. The Greek physician Hippocrates of Cos (c.460–375 BC), traditionally honored as the father of Western medicine, and his followers generally attributed infectious disease to poisonous vapors or “miasmas” that arose from swamps or putrid, decomposing materials. Health and disease depended on interactions between such atmospheric conditions and the four humors that made up the human body, a concept known as the atmospheric-miasmatic theory of disease. Other medical writers speculated that the noxious particles in disease-causing miasmas might actually be living entities. These mysterious little animals, seeds, worms, or “ferments” might be disseminated through the air or transmitted directly from the sick to others by means of contact (contagion).
Although the modern germ theory of disease has eclipsed its predecessors, the atmospheric-miasmatic theory of disease was generally more influential until the late-nineteenth century, when the relationship between microbes and disease was finally demonstrated and confirmed. It was vigorously defended by many of the great nineteenth-century public health reformers who argued that poor sanitary conditions, filth, and noxious air caused the epidemic diseases that flourished in the rapidly growing industrial cities of Europe. In practice, sanitary reforms that helped remove the filth that allegedly generated noxious vapors or miasma often helped reduce the toll of epidemic diseases in cities and towns.
Supernatural Theories of Disease
In ancient and primitive medicine, disease was often seen either as a form of punishment sent by the gods, or attributed to demons, ghosts, and evil spirits. Because it was thought to be caused by supernatural agents, magic was part of its diagnosis and treatment. Shamans, medicine men, diviners, and priests served as healers because of their special relationship to the supernatural. Such healers used divination, exorcism, magic spells, and nauseating drugs to drive away evil spirits.
Many folk beliefs persist and even flourish alongside modern medicine. Our vocabulary for illness still reflects these doctrines: we are “attacked” by disease, and we “fight off” infection until the disease is “expelled” from our system. Until the Renaissance (c.1300–c.1650) and Scientific Revolution (c.1500–c.1700), traces of older,
supernatural explanations for disease coexisted with speculations about miasma and contagion.
The supernatural also played a major role in the civilizations that developed in the period between about 3500 and 1500 BCE in Mesopotamia, Egypt, China, and India. According to the writings of ancient Mesopotamia, demons, devils, and evil spirits caused disease and misfortune, often as punishment for sins. A combination of exorcism and noxious drugs was used to drive out disease.
Medical writings from ancient Egypt reflect the belief that supernatural agents were associated with health and disease. Although humans were born healthy, their bodies were susceptible to many disease-causing threats, including intestinal putrefaction, worms and insects, noxious winds, spirits, and ghosts. Whatever the cause of illness, the cure involved driving the agents of disease from the body by purging or exorcism. In the ancient legends of India, gods and healers wrestled with the demonic forces that caused disease and pestilence. Ancient Hindu texts reveal a complex pantheon of gods and a vast array of demons capable of causing fevers, fractures, wounds, and poisoned bites.
According to the scholarly tradition of Chinese medicine, disease was caused by physical imbalance, and all therapies were directed towards restoring the body to a state of harmony. Scholarly Chinese physicians, however, cared for only a tiny fraction of the population. Most people assumed that demons and spirits, as well as imbalance, played a role in causing disease. Protective measures for dealing with magical forces included exorcisms, incantations, and talismans. Because the drugs used to drive out disease-causing demons were powerful poisons, instead of swallowing the drug the patient might wear the prescription or the drug itself as an amulet.
The intellectual traditions established by Greek philosophers, naturalists, and physicians became the foundations of Western philosophy, science, and medicine. But the ancient Greeks also ascribed disease to supernatural agents, a belief reflected in the Iliad and the Odyssey, epics traditionally attributed to the ancient Greek poet known as Homer (fl. ninth or eighth century BC). In these epic poems, the god Apollo has the power to heal the wounded and cause epidemic disease as a form of punishment. In contrast, Hippocrates (460–375 BC) rejected superstition, divination, and magic.
During the Middle Ages (AD 476–1453), Christian theologians explained disease as a test of faith or punishment for sin, but medical books still referred to devil-sickness and other disorders caused by elves, demons, flying venom, elf-shot, and worms. Although prayer was an accepted response to illness, medical writers like John of Gaddesden (1280–1361), physician to Edward II, prescribed charms, rituals, and amulets. An earlier medical writer, the remarkable Hildegard of Bingen (1098–1179), a German abbess, scientist, and philosopher, argued that healers should look for natural causes to explain even the most bizarre conditions, such as frenzy, insanity, and seizures. People might think a man was possessed by a demon, but Hildegard suggested that such behaviors might be caused by headache, migraine, or vertigo. Supernatural explanations of disease certainly did not disappear with the end of the Middle Ages and the dawn of the Renaissance, but they were generally abandoned by scholars and physicians.
Contagion, Miasma, and the GermTheory of Disease
Ancient and primitive ideas about contagion dealt with the general notion of transfer through contact, and were not directly related to modern germ theory. Just as heat and cold were transferred to neighboring bodies by contact, so too were putrefaction, uncleanliness, corruption, and disease thought to be transmitted. The Greeks seemed to ignore the concept of contagion; the Hippocratic approach analyzed disease in terms of the relationship and interactions between individuals and their environment—including weather conditions and other local circumstances, as discussed in Airs, Waters, Places.
Some Greek and Roman philosophers, poets, and architects thought that disease might be caused by little animals dwelling in swampy places, or by contact with the sick and with contaminated articles. For example, in his discussion of hygienic regulations for selecting building sites, the Roman architect Marcus Terentius Varro (116–27 BC) warned against swampy locations. Tiny animals living in swamps, so small as to be invisible, might enter the body through the mouth and nose and cause illnesses. More commonly, however, epidemic diseases were associated with comets, eclipses, floods, earthquakes, or major astrological disturbances that charged the air with poisonous vapors known as miasmata.
Medieval writers believed that corruption, alteration, or pollution of the atmosphere caused disease, but they were also quite concerned with contagion, in the biblical sense of the spread of disease and moral pollution by contact. This is clearly seen in the medieval attitude toward leprosy. This disease seemed to increase as Crusaders and pilgrims returned from the Middle East. More than any other disease, leprosy demonstrates the difference between the biological nature of illness and the attributes ascribed to the sick. The word “leper” is still commonly used to mean one who is hated and shunned by society. The leper, according to medieval interpretations of the Bible, was a dangerous source of physical and moral contagion. Merely standing downwind of one could endanger a healthy individual.
In the 1870s, Mycobacterium leprae, the bacillus that causes leprosy, was discovered by Norwegian physician Gerhard Hansen (1841–1912). To honor him (and avoid the stigma associated with the term leper), the disease was renamed Hansen's disease. Interestingly, research has shown that Hansen's disease is not very contagious. Many people who have extended and intimate contact with lepers, such as spouses, nurses, and doctors, do not contract the disease. Of course, this does not mean that leprosy was not more contagious in the past, but it does make it unlikely that the leper was ever as dangerous to others as medieval people believed.
Girolamo Fracastoro and the Seeds of Disease
Girolamo Fracastoro (1478–1553), poet, physician, mathematician, and author of On Contagion, Contagious Diseases and their Treatment (1546) has often been called the founder of the germ theory of disease. His medical classic Syphilis, or the French Disease, was published in 1530. This sexually transmitted disease probably made its first appearance in Europe at the end of the fifteenth century, shortly after Christopher Columbus (1451–1506) and his crew returned from their historic voyage to the Western hemisphere.
The disease was known by many names—the French called it the Neapolitan disease, the Italians called it the French disease, the Portuguese called it the Castilian disease. In India and Japan it was called the Portuguese disease. Eventually, syphilis, the name suggested by Fracastoro, was universally adopted. Whatever its name, the disease spread explosively throughout Europe in the sixteenth century, providing a compelling example of how an epidemic disease could be transmitted directly from person to person.
In On Contagion, a landmark publication in the history of germ theory, Fracastoro speculated about the existence of “contagions” or “seeds” of disease and compared the miasmatic theory of disease with contagion theory. Fracastoro argued that these seminaria, or “little seeds of disease,” served as the living contagion that caused epidemic disease. The seminaria were transmissible, specific for each disease, and capable of reproducing themselves. By carefully reviewing what was known about contemporary diseases, Fracastoro analyzed the kinds of evidence that seemed to support the miasma and the contagion theories. Some diseases, such as syphilis, were transmitted only by direct contact. Others were transmitted by direct contact and “fomites” (inanimate articles, such as clothing, that had been in contact with the sick). Some diseases were apparently transmitted by direct contact, by fomites, and by contagions or seeds capable of infecting new victims without any known direct contacts.
Despite his intriguing hypotheses, Fracastoro's writings share the ambiguity commonly found in the use of terms like contagion and miasma. Although the establishment of the germ theory of disease is often cast in terms of a conflict between contagion theory and miasma theory, until the late nineteenth century medical writers often used these terms interchangeably.
Microscopic Observations and Theoretical Considerations
Both Marcus Terentius Varro and Fracastoro speculated about minute living entities that might serve as the material basis of contagion, but these hypothetical entities were invisible until the invention of the microscope. Seventeenth-century microscopists were certainly able to see a new world teeming with previously invisible entities, including protozoa, molds, yeasts, and bacteria, but their observations had little or no impact on contemporary theories of disease. Nevertheless, Dutch microscopist van Leeuwenhoek's intriguing reports about the myriad “animalcules” (“little animals”) that could be found in sources as diverse as the human mouth, pond water, and semen provided new grounds for speculating about the role played by invisible living entities.
Using simple microscopes, van Leeuwenhoek studied plant and animal cells, spermatozoa, molds, and microbes, including various bacteria and pond infusoria, water from different sources, saliva, seminal fluid, and minerals. When told that animalcules had been found in the seminal fluid of a man with gonorrhea, van Leeu-wenhoek investigated semen from healthy men and animals including dogs, rabbits, birds, amphibians, and fishes. These investigations convinced him that the animalcules in semen were not related to venereal disease or putrefaction. These entities, he argued, were normal constituents of the fluid.
Experimental evidence that contagious human diseases could be transmitted by tiny parasites was first established by Giovanni Cosimo Bonomo's (1663–1696) studies of the “itch mite” (Sarcoptes scabiei). This tiny parasite, barely visible to the naked eye, causes scabies, a skin disease then commonly known as “the itch.” The itch mite can be transferred directly from person to person, or through bedding and clothing used by infested persons. However, it was not until the early nineteenth century that other minute parasites were implicated as the causative agents of specific diseases.
Agostino Bassi (1773–1856) is often credited with being the first to isolate a live disease-causing agent. In 1836, he demonstrated that a silkworm disease known as muscardine was caused by a parasitic fungus transmitted by direct contact between silkworms and indirectly by contaminated food. The causative agent, a parasitic fungus, was later named Botrytis bassiana in his honor. (The fungus has since been reclassified as Beauveria bassiana.) Bassi suggested that similar living agents might cause other contagious diseases. Inspired by his work, in 1839, Johann Lucas Schönlein (1793–1864) discovered a microscopic fungus that causes the contagious skin disease known as ringworm or favus. (Several species of fungi are known to cause ringworm; Trichophyton schoenleinii was named for Schönlein). An advocate of experimental laboratory research, Schönlein's influence was amplified by his clinical teaching and his role as founder of the German Congress of Nature Investigators and Physicians (1822).
Most eighteenth- and early-nineteenth-century physicians held a medical philosophy not very different from that of Hippocrates: Disease was the result of an imbalance in the body, generally caused by noxious influences in the environment or the patient's own misbehaviors. Attempts to attribute illness to disease-causing germs or microbes were generally dismissed as little better than ancient superstitions about disease-causing demons. Some early-nineteenth-century clinicians and epidemiologists, however, suspected that living germs might cause infectious disease. Based on his studies of the diphtheria epidemic of 1818–1820, French epidemiologist Pierre Fidèle Bretonneau (1778–1862) suggested that a specific living agent caused this disease.
English physician John Snow (1813–1858), famous for his studies of epidemic cholera, suggested that the causative agent of cholera was present in water contaminated by the fecal matter of the diseased—all too easy given the city's inadequate sewage system. By mapping
the areas in which residents died, Snow was able to identify the contaminated well that he believed was causing the outbreak. At his urging, city officials removed the pump handle, rendering it inoperable, and the epidemic was halted.
In 1840 Jacob Henle (1809–1885), a prominent German pathologist, physiologist, and anatomist, published On Miasmata and Contagia, a new analysis of contagious, miasmatic, and miasmatic-contagious diseases. While Henle's discussion of the question of contagion and miasma is superficially similar to Fracastoro's, the scientific knowledge and scientific instruments available to them and the three centuries that separated them infused very different meanings into their terminology.
Newly improved microscopes provided one of the most important technological innovations available to Henle and his contemporaries. Henle's critical analysis of outbreaks of various diseases suggested that malaria was a purely miasmatic disease, while smallpox, measles, typhus, influenza, dysentery, plague, and so forth were both miasmatic and contagious. Diseases such as syphilis, gonorrhea, and rabies were acquired only through contagion. After reviewing the work of Bonomo, Bassi, Schönlein, and others, Henle discussed the nature of the proofs that would be required to establish a causal relationship between microbes and disease.
Miasma was traditionally defined as something that mixed with and poisoned the air, but, Henle argued, no one had ever demonstrated the existence of miasma. It was simply assumed to exist because no other cause could be demonstrated. A more likely hypothesis, Henle asserted, was that contagia animate (living organisms) caused contagious diseases, because whatever the morbid matter of disease might be, it obviously had the power to increase in the afflicted individual. A poison or toxin, by contrast, might be powerful even at very small doses, but inanimate chemicals were not capable of multiplying beyond their original finite quantity.
The natural history of epidemics could be explained by assuming that a living agent emitted by sick individuals caused disease. If the lungs excreted this agent, it might pass to others through the air; if via the gastrointestinal tract, it could enter sewers and wells. Given the fact that the pus from smallpox pustules could be used to infect a multitude of people, the contagion that caused smallpox must be a living entity capable of multiplying within the body of the sick person. Chemicals remain fixed in amount; only living things have the power to reproduce and multiply.
Well aware of the difficulties confronting the germ theory of disease, Henle warned that finding some microorganism in the sick did not prove that it had a causal role. The agent must be isolated and cultured so that it was free from any toxins or traces of the diseased individual. But, at the time, obtaining pure cultures of microbes was virtually impossible.
Fracastoro, Henle, and others had suggested that the processes involved in putrefaction, fermentation, and infectious disease were fundamentally alike. Indeed, one of the most important steps in establishing the modern germ theory of disease was the demonstration that microscopic living agents were responsible for fermentation. “Ferments,” or “fermentation-granules,” had, of course, been used for thousands of years to produce beer, wine, bread, and other foods. Nevertheless, until the 1860s there was considerable controversy about whether the minute entities observed under the microscope were the product of putrefaction, fermentation, and disease, or the cause of such phenomena.
In the 1830s, German physiologist Theodor Schwann (1810–1882) and French engineer Charles Cagniard de la Tour (1777–1859) suggested that the growth of yeast might be the cause of fermentation. In Microscopical Researches into the Accordance in the Structure and Growth of Animals and Plants (1839), Schwann argued that because yeasts were actually cells, fermentation provided a practical model system for investigating the fundamental activities of all cells. In a series of experiments, Schwann challenged the theory of spontaneous generation and suggested that microorganisms cause the chemical changes involved in putrefaction and fermentation. Schwann predicted that fermentation could be successfully exploited as a model system for investigating the vital processes occurring in the cells of all plants and animals.
Despite the lucidity of Schwann's reasoning and the ingenious nature of his experiments and observations, the most famous chemists of this era, the Germans Justus von Liebig (1803–1873), Friedrich Wöhler (1800–1882), and Swede Jöns Jacob Berzelius (1779–1848) ridiculed his hypothesis. Liebig insisted that fermentation was a purely chemical process and that microorganisms were the product rather than the cause of fermentation, and even suggested that Schwann had substituted mysterious “vital phenomena” for the strictly chemical processes that caused fermentation. The French chemist and microbiologist Louis Pasteur (1822–1895) enthusiastically attacked Liebig's position and vigorously defended the hypothesis that the activities of organized beings known as microorganisms cause specific fermentations, as well as putrefaction and infectious disease.
Through his studies of fermentation, Pasteur discovered that changes in the population of microorganisms were associated with healthy and spoiled fermentations. After analyzing wine, beer, vinegar, and other fermentation processes, Pasteur suggested that microorganisms cause all fermentations and that specific microbes carry out different fermentations.
During the 1850s, Pasteur began his studies of spontaneous generation, designing experiments that would unequivocally disprove it. The question of spontaneous generation was an ancient and controversial one, but Pasteur argued that microbiology and medicine could not progress until those who supported it were totally crushed. His publications, lectures, and demonstrations refuting the spontaneous generation of microbes are landmarks in the establishment of the modern germ theory of disease.
The Spontaneous Generation Hypothesis
According to the ancient theory of spontaneous generation, living organisms could originate from nonliving matter. Many ancient peoples and cultures saw the whole world as a nurturing organism, capable of giving birth to living creatures. Under the right conditions, they believed, lifeless materials could be transformed into small creatures. For example, slime, mud, and manure, along with moisture and heat, were thought to generate insects, frogs, and mice.
The Greek philosopher Aristotle (384–322 BC) supported the doctrine of spontaneous generation and described the kinds of species generated from various substances. A combination of morning dew with slime or manure was thought to produce fireflies, worms, bees, or wasp larvae, while moist soil gave rise to mice. Seventeenth-century Flemish physician and alchemist Jan Baptista van Helmont (1579–1644) believed that mice could be produced by incubating a flask stuffed with wheat and old rags in a dark closet.
Questioning these ancient assumptions, the Italian physician Francesco Redi (1626–1697) initiated an experimental attack on the question of spontaneous generation. Redi tested various kinds of meats, both raw and cooked. Noting the way that different flies behaved when attracted to rotting meat, Redi suggested that maggots might develop from the objects deposited on the meat by adult flies. When rotting meat was carefully protected from flies, no maggots were found. Therefore, maggots and flies developed from eggs deposited on rotting meat by adult flies. Redi's Experiments on the Generation of Insects (1668) did not altogether destroy the doctrine, but the debate shifted away from insects and mice to the animalcules revealed by the microscope.
Seventeenth-century microscopists discovered a new world teeming with previously invisible molds, yeasts, worms, and protozoa. Some naturalists thought that these minute entities might be the living molecules, or “monads” postulated by German mathematician and philosopher Gottfried Wilhelm Liebniz (1646–1716). Others thought that the “infusoria” were tiny plants and animals spontaneously generated in pond water, broth, and other nutritive media. Van Leeuwenhoek, however, was quite sure that his animalcules must have descended from parents like themselves.
Louis Joblot (1645–1723) confirmed some of van Leeuwenhoek's observations and, in 1718, published an illustrated treatise that described the microscopic animalcules found in various infusions. Joblot carried out a series of experiments to prove that living beings were not spontaneously generated. After boiling nutrient broth, Joblot divided it into two parts. One flask was sealed and the other left uncovered. The open flask was soon teeming with animalcules, but the sealed vessel was not. If the medium in the sealed flask was exposed to air, infusoria soon appeared.
Joblot's experiments were repeated with many variations by other naturalists, but the results were not consistent. In support of spontaneous generation, the French naturalist Georges Buffon (1707–1788) and the English microscopist John Turberville Needham (1713–1781) attacked Joblot's work. When Needham repeated Joblot's experiments, all his flasks swarmed with microscopic life. According to Needham, vitalism and the doctrine of spontaneous generation were entirely compatible. In An Account of Some New Microscopical Discoveries (1745), Needham argued that a powerful vegetative or vital force remained in matter that had previously been part of a living being. Therefore, the decomposition products of plants and animals served as the “living atoms” from which microscopic living beings arose.
Needham's conclusions and experimental methods were directly challenged by the Italian physiologist Laz-zaro Spallanzani (1729–1799). By heating a series of flasks for different lengths of time, Spallanzani determined that various sorts of microbes differed in their susceptibility to heat. Further experiments suggested that microorganisms entered the medium from the air. Convinced that a great variety of little “eggs” must be disseminated through the atmosphere, Spallanzani concluded that air could either convey germs to the infusions or assist their multiplication once there.
Although Spallanzani's experiments answered many of the questions raised by advocates of spontaneous generation and proved the importance of rigorous sterilization, his critics claimed that his methods destroyed the all-important “vital force” needed for spontaneous generation.
During the nineteenth century, the design of experiments for and against spontaneous generation became increasingly sophisticated. Theodor Schwann repeated many of Spallanzani's experiments, but added the refinement of heating the air as well as the medium. Heinrich Schröder (1810–1885) and Theodor von Dusch (1824–1890) filtered air through a tube of cotton wool, a process that presumably would not destroy the “vital principle.”
For all practical purposes, Pasteur and Irish physicist John Tyndall (1820–1893), best known for his studies of light scattering or Tyndall effect, won the debate by proving that the existence of germs in the air was the critical issue in an experimental test of spontaneous generation. Although Pasteur acknowledged that it is logically impossible to prove a universal negative, he effectively demonstrated that, under present conditions, microbes arise only from preexisting microbes.
One of the most vigorous defenders of spontaneous generation was Félix Archimède Pouchet (1800–1872), Director of the Natural History Museum in Rouen, a member of many learned societies, and a respected zoologist. In his dispute with Pouchet, Pasteur argued that all so-called evidence in favor of spontaneous generation was the result of flawed techniques and that the existence of germs in the air was the critical experimental issue. Pasteur and Pouchet created considerable drama by taking air and dust samples from mountaintops, glaciers, cathedrals, the tomb of Ramses II, and hospital wards. Perhaps the most convincing demonstrations involved Pasteur's simple “swan neck flasks”—glass vessels with long curved necks. In 1862 the Academy of Sciences honored Pasteur with a prize for his studies of spontaneous generation.
Tyndall introduced further experimental refinements to study the germ-carrying capacity of the air and the efficacy of various sterilization methods. These studies were described in his Essays on the Floating Matter of the Air in Relation to Putrefaction and Infection (1881). Tyndall discovered that some germs formed heat-resistant spores. To overcome this problem, he developed a method known as fractional sterilization or tyndallization.
Louis Pasteur and Diseases of Animals
After studying the nature of fermentation, Pasteur was asked to investigate a disease threatening the French silk industry. This led to research on other animal diseases and finally to rabies in humans. Pasteur's study of chicken cholera showed that it was possible to prepare weakened strains of various microbes in the laboratory and use them as protective vaccines. In a well publicized demonstration, Pasteur proved that a laboratory vaccine could protect farm animals from anthrax, a disease that primarily attacked sheep and cattle. The anthrax bacillus could also cause severe skin ulcers and a deadly pneumonia in humans.
Pasteur hoped his work on animal vaccines would be extended to human diseases, but he thought it would be unethical to experiment on humans. One way of escaping this ethical dilemma was to study rabies, a disease that was fairly common in animals and invariably fatal in humans. Although he could not identify a specific microbe in preparations of materials capable of transmitting rabies, in 1885 he demonstrated that his vaccine could protect human beings who had been bitten by rabid dogs or wolves. Pasteur's success in saving 9-year old Joseph Meister from almost certain death brought worldwide acclaim. Within a year thousands of desperate people came to Paris to receive the rabies vaccine. The rabies vaccine brought Pasteur international fame and led to the establishment of the Pasteur Institute.
Germ Theory, Joseph Lister, and Antiseptic Surgery
Historical studies of the acceptance of germ theory suggest that different professional communities—surgeons, physicians, sanitarians, veterinarians—developed somewhat different concepts of germ theory and its practical implications. However, germ theory clearly had a profound impact on the practice of surgery and preventive medicine long before it provided actual cures for infectious diseases.
Surgery had been revolutionized in the 1840s by the introduction of anesthesia, but many patients survived painless operations only to die of postsurgical infections. The search for antiseptics and disinfectants has been part of folklore, medicine, and surgery throughout history. As Florence Nightingale (1820–1910), pioneer of modern nursing and sanitary reform often said, most of these agents were useless, except when their noxious odor forced people to open the windows.
British surgeon Joseph Lister's (1827–1912) introduction of the antiseptic system in the 1860s was a key factor in the evolution of modern surgery. Like most doctors, Lister initially believed that infection was caused by the entry of noxious air into a wound. After learning about Pasteur's studies, Lister began a series of experiments on the relevance of germ theory to surgical infection. Having tested many disinfectants, Lister found that carbolic acid was effective and did not cause excessive damage to normal tissue. For many years, Lister endured the apathy and ridicule of the conservative medical community, but by the end of the century his methods had won general recognition. Few Americans are familiar with his work today, except in advertisements for Listerine. In 1879 this antiseptic, named after the famous physician, was first sold to doctors and dentists as a general antiseptic and
ROBERT KOCH (1843–1910)
Robert Koch (1843–1910) was born in a small village in the Harz Mountains, the third of 13 children born to Herrmann Koch, a mining administrator, and his wife Mathilde. When Koch began his medical studies at the University of Göttingen, the faculty included many eminent scientists, including Jacob Henle (1809–1885), a prominent German pathologist, physiologist, and anatomist, who was studying the relationship between bacteria and disease. After passing his state medical examinations in 1866 Koch studied clinical medicine and attended lectures presented by Rudolf Virchow (1821–1902), Germany's leading pathologist and the founder of cellular pathology. During the Franco-German War of 1870, Koch volunteered for the medical service.
Although forced to earn a living as a country doctor, Koch devoted much of his time to the study of natural history, photography, public health, hygiene, bacteriology, and microscopy. His first successful research project was his 1876 demonstration that a specific bacillus causes anthrax. In 1905 he was awarded a Nobel Prize for the greatest achievement of his career, the discovery of the tubercule bacillus, Mycobacterium tuberculosis. During the last years of his life, Koch continued to conduct research that he hoped would lead to a cure for tuberculosis. Two years after his death, Germany's Institute for Infectious Diseases became the Robert Koch Institute.
mouthwash. Listerine has been advertised to the public as a germ killer since the 1920s.
Very different from Louis Pasteur in training, temperament and his approach to medical science, German physician Robert Koch (1843–1910) was most successful at formulating the principles and techniques of modern bacteriology.
Koch's study of anthrax provided the first rigorous demonstration of the relationship between a specific germ and an important disease. Although anthrax is primarily a disease of sheep and cattle, it can cause severe, localized skin ulcers known as malignant pustules in humans, as well as gastric anthrax, and a virulent pneumonia known as wool-sorter's disease. Koch's rigorous analysis of the complex life cycle of Bacillus anthracis explained many aspects of the disease's transmission. Although Koch demonstrated the bacterial etiology of anthrax and the critical problem of spore formation, it was Pasteur who developed a preventive vaccine and demonstrated its effectiveness in 1881 in a highly publicized trial.
Despite studies of germs and disease carried out by Koch and Pasteur, critics of the germ theory continued to argue that microbes were nonspecific and easily transformed into different types. The apparent generation of new forms in the laboratory, Koch contended, was not proof of transformation of type, but evidence of contamination. Clearly, Koch and other supporters of germ theory realized that it would be impossible to say that a specific germ caused a specific disease if microbes did not exist as distinct species. Growing bacteria outside the animal body and obtaining pure strains, therefore, became Koch's obsession. After many unsuccessful experiments, he concluded that it would be impossible to construct a universal medium in which all microbes could grow. Koch found that he could convert nutrient broths into a jelly-like consistency with agar, a material used in Asian cuisine. A simple, but very effective device for culturing microbes on agar gel was introduced by Koch's associate, the German bacteriologist Richard Julius Petri (1852–1921).
In contrast to Pasteur, who had taken rabies, a dramatic but relatively rare threat to human life, as his greatest challenge, Koch chose tuberculosis. His goal was to prove that tuberculosis was an infectious disease, identify the causal agent, and find a way to prevent or cure the disease. Koch presented his preliminary report on tuberculosis to the Physiological Society of Berlin on March 24, 1882. Accounts of Koch's discovery of the tubercle bacillus and speculation about a possible cure quickly appeared in newspapers throughout the world.
To understand the excitement generated by Koch's research on tuberculosis, it is essential to appreciate the way in which this dread disease permeated nineteenth century society. When Koch began his work, epidemiologists estimated that tuberculosis caused one of every seven human deaths. Even in the 1940s, pathologists commonly found evidence of tuberculosis when performing postmortem examinations of persons who had not been diagnosed as tubercular during their life. The impact of the disease on society was amplified by the fact that it was particularly likely to claim victims in what should have been their most productive adult years.
Not unlike AIDS in the 1980s, tuberculosis seemed to claim the lives of all too many young artists, writers, composers, and musicians. The romantic myth of a link between artistic creativity and tuberculosis was dispelled by the discovery of the tubercle bacillus in the sputum of impoverished slum dwellers and in the air of filthy tenements and factories. As in the case of AIDS, the connection between creativity and the disease was coincidental, but the association between the pathogen and the poor was a very real indictment of fundamental inequities in society.
Mycobacterium tuberculosis was isolated from the tissues of patients suffering from a bewildering array of clinical conditions known as phthisis, consumption, scrofula, miliary tuberculosis, and others. Thus, after decades of controversy as to the nature of the disease and whether it was contagious, Koch's discovery vindicated the unitary theory of tuberculosis. That is, the same pathological agent caused very different clinical patterns, depending on the patient's age, health, and other factors. Pulmonary tuberculosis, the most common form of the disease, provided the most efficient means of transmission, because its victims coughed up large quantities of germ-laden sputum. In poorly ventilated, dirty, dusty tenement rooms, tubercle germs remained viable for months.
During his studies of tuberculosis in the 1880s, Koch formalized the criteria needed to prove unequivocally that a particular germ causes a specific disease. First presented in 1883, these milestones of medical microbiology are now known as Koch's postulates.
First, Koch stipulated, it is necessary to find the microbe invariably associated with the disease. Rigorous proof of a causal relationship required complete separation of the microbe from the diseased animal or plant and all possible contaminants. After the suspected pathogen had been grown as a pure laboratory culture, it should be introduced into healthy specimens. If the disease was then induced with all its typical symptoms and properties, the investigator could conclude that the microbe was truly the cause of the disease. A fourth postulate is often included in this list: the researcher should be able to culture the causative microbe from the infected specimen.
Despite the rigor of Koch's investigations of the tubercle bacillus, not all scientists were willing to accept the idea that a single germ could be responsible for such a complex enigma. Rudolf Virchow (1821–1902), Germany's most respected pathologist, insisted that pulmonary tuberculosis and miliary tuberculosis were different diseases. Questioning the value of Koch's work on the “so-called tubercle bacillus,” Virchow argued that if the microbe were as widespread as Koch asserted, the true cause of tuberculosis could not be a specific germ, because only certain individuals became consumptives. Advocates of germ theory objected that one might as well say that bullets did not kill, because not every soldier on the battle field was killed by them.
For those who accepted the relationship between the tubercle bacillus and the disease, Koch's discovery stimulated hope that appropriate medical guidance might break the chain of transmission and help victims in the early stages of disease. On the other hand, physicians' ability to detect previously undiagnosed infections immediately increased the apparent numbers of cases and, therefore, the public perception of its prevalence and threat. Public health reformers called for systematic campaigns to isolate the sick, break the chain of transmission, and solve fundamental social problems related to poverty and housing.
In 1890, the year that Germany hosted the Tenth International Medical Congress, Koch announced that he had found a substance that could inhibit the growth of the tubercle bacillus in laboratory cultures and in guinea pigs. Given the preliminary nature of his findings, Koch may have been somewhat reluctant to discuss these studies in public, but he was apparently under considerable pressure from government officials. After preliminary tests in humans, Koch published a progress report in which he specifically referred to tuberculin as a “therapeutic agent.”
As soon as Koch announced his preliminary studies of tuberculin, newspaper articles proclaimed it a cure for tuberculosis. Both scientists and patients flocked to Germany, hoping to obtain Koch's remedy. Before tuberculin's safety and efficacy had been properly tested, Koch was awarded Germany's Grand Cross of the Red Eagle and other honors. When it became apparent that tuberculin was not a cure, however, public opinion rapidly turned against him. Tuberculin did not cure the sick, but, it did become a diagnostic tool for detecting early tuberculosis infections. In 1905 Koch was awarded the fifth Nobel Prize for medicine or physiology in recognition of his pioneering work.
In the 1990s public health authorities found themselves dealing with significant increases in tuberculosis, often in association with AIDS. The resurgence of the diesease and the global emergence of virulent, multidrug resistant strains of Mycobacterium tuberculosis reflect the misplaced optimism that led to the neglect of the public health system needed to control tuberculosis and other infectious diseases.
Health Reformers and the GermTheory of Disease
By the 1880s, American health reformers like Ellen G. White (1827–1915), the spiritual leader and prophetess of the Seventh-Day Adventist Church, and John Harvey Kellogg (1852–1943), physician-in-chief of the Adventists' highly successful Battle Creek (Michigan) sanitarium, had incorporated the germ theory of disease into their gospel of wellness. In his popular lectures and writings, Kellogg advocated natural therapies, vegetarianism, and “biologic living,” which included fresh air and exercise. Impressed by the new science of bacteriology, Kellogg supported his doctrines by presenting a horror show of the germs and dirt found in meats coming from the slaughterhouse.
Often referred to as the Adventist prophetess of health, Ellen White told her followers that she received her revelations from the Creator of the laws of hygiene. Therefore, in addition to theological issues, her visions provided detailed advice about health, disease, food, drink, clothing, and other practical aspects of healthfulliving. In 1905 White published The Ministry of Healing, a book that summarized and clarified her teachings about the healing of body, mind, and soul.
White warned readers that rapid industrialization and urbanization had become a dangerous source of pollution, filth, overcrowding, corruption, and disease. Those seeking health were advised to learn the laws of life, study human anatomy and physiology, and bathe frequently. Women were told to exercise in fresh air and maintain scrupulous cleanliness of home, body, and clothing. Dress reform, a frequent target of ridicule, was actually an important aspect of health, according to White, because tight corsets inhibited the movement of the lungs and the circulation of the blood, and long skirts swept the ground, where they collected dirt and germs. Uncleanliness allowed germs to grow, poisoned the air, leading to death and disease. White argued that the virtues of vegetarianism were evident in biblical teachings and in scientific research that proved that the tissues of domesticated animals were swarming with parasites, including the germs that caused tuberculosis, cancer, and other fatal diseases. Milk was only safe to drink if sterilized by pasteurization and even bread had to be baked very thoroughly to kill the yeast germs.
Building on the foundations built by Pasteur, Koch, and others, microbiology exploded and splintered into numerous subdisciplines. Physicians and scientists were fascinated with the search for the microbial agents of disease and the toxins that some of them produced, as well as the implications of these discoveries for preventing and curing epidemics. As the nature of infectious diseases became more clearly understood, ancient doctrines about the body's mysterious healing powers could be investigated in the light of new theories. Given the ubiquity of germs, it was obvious that the human body must be equipped with powerful weapons to fight off microscopic invaders. The successful use of vaccinations for smallpox, anthrax, rabies, and other diseases helped establish the new science of immunology.
The Latin term immunitas, from which we get the word “immunity,” originally referred to a legal exemption, but the concept obviously applied in medicine as well as law. Even during the most deadly of epidemics, some people escaped infection and others recovered without complications. Moreover, those who had survived one attack of a disease were usually unaffected during later epidemics. The germ theory of disease allowed scientists to demonstrate that the virulence of infectious diseases varied with many factors, including the way in which the germ entered the body and the host's physiological status. Moreover, it was clear that protective vaccines could take advantage of the body's own defense mechanisms.
By the end of the nineteenth century, the fundamental question concerning scientists investigating the immune response was: Is immunity based on humoral or cellular agents? According to the humoral theory, immunity depended on the induction of “factors,” now known as antibodies, which circulate in the blood. German bacteriologist Emil Adolf von Behring (1854–1917) and Japanese physician Shibasaburo Kitasato (1853–1931), proponents of the humoral theory, proved that they could induce antibodies in experimental animals for therapeutic human use.
In the late 1880s, microbiologists discovered that the bacteria that cause diphtheria and tetanus kill by releasing deadly toxins into the bloodstream. Behring and Kitasato carried out a series of experiments that resulted in a new therapeutic approach to these diseases they called serum therapy. At the time, serum (the fluid portion of the blood that remains when blood cells and clots are removed) was often used as a synonym for immune serum, antiserum, or antitoxin.
Immune serum was prepared from the blood of animals that had been inoculated with diphtheria or tetanus toxin. The serum of animals that survived this challenge contained antibodies that could be used to protect other animals or humans. To provide sufficient quantities of immune serum, horses were used as “antitoxin factories.” Today, when no preventive vaccines or drugs are available for a particular disease, serum, or specific fractions of the blood (usually gamma globulin), from people who have survived a disease may be used as a source of antibodies.
When Behring won the first Nobel Prize in physiology or medicine in 1901, the Nobel Committee honored him for creating a “victorious weapon against illness and deaths.” In his Nobel Lecture, “Serum Therapy in Therapeutics and Medical Science,” Behring described serum therapy as a powerful and perhaps universal therapeutic approach that might lead to a complete triumph over all infectious diseases. Unfortunately, although serum therapy saved many lives and stimulated the establishment of a new scientific disciple known as immunology, it did not provide a universally effective weapon in the battle against germs.
Russian zoologist Élie Metchnikoff (1845–1916) discovered special white blood cells called phagocytes that seemed to consume and destroy disease-causing microbes, along with damaged or malignant cells. These cells, he believed, had evolved as one of the body's special defense mechanisms. Phagocytes, he said, were even more important than serum factors in the body's battle against infection. Metchnikof was awarded a Nobel Prize in 1908 for this discovery, sharing the podium with German medical scientist Paul Ehrlich (1854–1915), who was honored for contributions to the new science of immunology.
Sulfa Drugs and Antibiotics
Despite the success of serum therapy and preventive vaccines, in the early twentieth century few drugs were available to treat infectious diseases. In 1910 Ehrlich's work on an arsenical compound led to the discovery of Salvarsan, a drug that was effective against the spirochetes that cause syphilis. Ehrlich called Salvarsan a “magic bullet,” because it destroyed spirochetes without significant harm to the patient. Ehrlich hoped to synthesize or discover other drugs that would destroy virulent germs when the body was not fast or effective enough in making its own “bullets” or antibodies.
Unfortunately, many chemicals that kill germs in the test tube are also harmful to patients. Finally, in the 1930s German bacteriologist and pathologist Gerhard Domagk (1895–1964) discovered that a red dye called prontosil was effective against streptococcal and staphylococcal infections. The so-called sulfa drugs that resulted from this discovery raised hopes, but despite the synthesis and testing of thousands of sulfonamide derivatives, few were both safe and effective.
In 1928 Alexander Fleming (1881–1955) discovered that the mold Penicillium notatum produced a substance that inhibited the growth of certain bacteria. Fleming was unable to purify or perform clinical tests of his crude “mold juice.” During World War II (1939–1945), Australian pathologist Walter Florey (1898–1968) and German-born British biochemist Ernst Boris Chain (1906–1979) isolated penicillin and proved that it was effective against streptococci, staphylococci, pneu-mococci, and the bacteria that cause syphilis and gonorrhea. The large-scale production of penicillin became a major priority during the war. In 1945, the Nobel Prize for medicine or physiology was awarded to Fleming, Florey, and Chain for the discovery of penicillin.
Penicillin was greeted with great hope and enthusiasm around the world as a revolutionary new therapeutic agent. Stimulated by its success, within the next decade researchers discovered streptomycin, neomycin, chloramphenicol, aureomycin, erythromycin, nystatin, and other valuable drugs. Streptomycin, a product of Streptomyces griseus, was especially valuable, because it was effective against tuberculosis.
Ukranian-born American biochemist Selman A. Waksman (1888–1973), who discovered streptomycin, neomycin, and several other interesting antibiotics, defined these drugs as compounds produced by microorganisms that inhibit the growth of other microorganisms. Most antibiotics are the products of fungi, like Penicillium notatum, but soil bacteria belonging to the actinomycete group studied by Waksman also produced important antibiotics.
By the 1960s, many physicians were convinced that antibiotics had eliminated the threat of bacterial diseases and that viral diseases could be eradicated by vaccines. This optimistic belief was discredited by the rise of multidrug-resistant microbes and the emergence of new diseases, including AIDS, Lyme disease, and the Ebola viral hemorrhagic fever.
Modern Cultural Connections
The unsolved “anthrax letters” mystery of 2001 and the threat of bioterrorism emphasize the importance of enhancing public understanding of microbiology and germ theory. The anthrax bacillus, for example, which can be disseminated in the form of spores, has been called the ideal biological weapon. Popular books like Ken Alibek's Biohazard and Richard Preston's The Cobra Event raised awareness and fear of potential bioterrorism, but television and print media often confuse and mislead the public. Scientific illiteracy is clearly very common; too many people do not know difference between viruses and bacteria, or antibodies and antibiotics.
In an era of emerging infectious diseases and multidrug-resistant microbes, public health workers find it difficult to maintain a balance between keeping the public informed of real risks and creating an atmosphere of fear and hysteria. Because of widespread and often irrational fear of germs, many twenty-first-century consumers seek out antibacterial soaps, sponges, detergents, hand sanitizers, and products that claim to kill germs on telephones, handrails, doorknobs, and in the air. Companies that sell such products typically use the ambiguous term “germ,” which could mean bacteria, virus, or other microbe. Fear of contamination is triggered by news reports of food poisoning, or of children who become sick after visiting petting zoos or touching pet turtles.
Scientists warn consumers that creating a germ-free home or environment is impossible. Germs are unavoidable and, except for specific pathogens, are usually innocuous for people with normal immune systems. Tests of antibacterial products designed to exploit the fear of germs suggest that they have little or no impact on whether or not people contract colds, flu, or food poisoning. As demonstrated by the pioneers of germ theory and antiseptic surgery, the best defense against infection is frequent hand washing with soap and water.
By 1890 Louis Pasteur was sure that the germ theory of disease had earned the right to be seen as a revolutionary new science that had transformed human understanding of infectious diseases. The list of germs shown to be responsible for major threats to the public health was already impressive by the turn of the century: anthrax, cholera, diphtheria, gangrene, gonorrhea, leprosy, plague, pneumonia, scarlet fever, tetanus, tuberculosis, typhoid fever, and so forth. At the beginning of the twenty-first century the list is, of course, much
longer, as is the list of the infectious agents that cause them. New forms of infectious agents, viroids and prions, have been added to the ranks of pathogenic bacteria, protozoa, fungi, and viruses, extending the scope of the germ theory of disease and creating new challenges and opportunities for understanding the relationship between germs and human health.
Primary Source Connection
The germ-theory explanation of the greatest modern disease pandemic, AIDS, is denied by fringe groups and a few pop-culture heroes, despite conclusions from expert scientists who have spent years doing specialized research on the HIV virus and AIDS.
FOO FIGHTERS, HIV DENIERS
A platinum-selling alt-rock group may be endangering their fans by promoting a dangerous myth.
Some rock stars want to free Tibet. Others want to save Mumia. The Foo Fighters, on the other hand, want their fans to ignore accepted medical wisdom about AIDS.
The multimillion-album-selling alternative rock outfit has thrown its weight behind Alive and Well, an “alternative AIDS information group” that denies any link between HIV and AIDS. In January, Foo Fighters bassist Nate Mendel helped organize a sold-out concert in Hollywood to benefit the group. Foo fans were treated to a speech by Alive and Well founder Christine Maggiore, who believes AIDS may be caused by HIV-related medications, anal sex, stress, and drug use, and implies that people should not get tested for HIV nor take medications to counter the virus. Free copies of Maggiore's self-published book, “What If Everything You Thought You Knew About AIDS Was Wrong?,” in which she declares “there is no proof that HIV causes AIDS,” were also passed out to the concert-goers.
HIV experts are alarmed by the possible impact of the Foo Fighters' embrace of Maggiore's theories on their potentially gullible young fans.
“Clearly, more research is needed on the factors that contribute to HIV infection and the development of AIDS,” says Dorcus Crumbley of the Centers for Disease Control and Prevention's National Center for HIV, STD, and TB Prevention. “However, the conclusions of more than two decades of epidemiologic, virologic, and medical research are that HIV infection is transmissible through sexual contact, injecting drug use, perinatally, and from receiving blood or blood products … (and) the scientific evidence is overwhelming that HIV is the cause of AIDS.”
Adds Crumbley: “The myth that HIV is not the primarycause of AIDS … could cause (HIV-positive people) to reject treatment critical for their own health and for preventing transmission to others.”
“When it comes to such a complex health topic, it behooves the band to have really researched what they are endorsing,” says Diane Tanaka, an attending physician at the Children's Hospital of Los Angeles, where she works with a large population of high-risk and HIV-infected low-income youth. “(The Foo Fighters) have a big responsibility in terms of (their) public role and the impact that they can have on young people. Is this band willing to take responsibility for a young person engaging in risky, unprotected sex because of information they've gotten from the (Foo Fighters) or from Alive and Well?”
Alive and Well is one of several fringe groups that deny a link between HIV and AIDS. Similar theories have been put forth over the years by various far-right groups and anti-Semitic conspiracy theorists, and other so-called “HIV-refuseniks.”
“Your risk of being hit by lightning is greater than that of contracting HIV through a one-time random sexual contact with someone you don't know here in America,” says Maggiore, an HIV-positive Southern California resident with no formal training in medicine or the sciences. “And if (a young person) were to get a positive diagnosis, that does not mean they've been infected withHIV.” The HIV-AIDS connection, maintains Maggiore, has been promoted by greedy drug companies. Mendel says he was won over by Maggiore's book, and passed it around to the rest of the band, which includes former Nirvana drummer Dave Grohl. Mendel says that he would steer anyone considering an HIV antibody test toward Maggiore's group.
“If you test positive, you are pretty much given a bleak outlook and told to take toxic drugs to possibly ward off new infections,” says Mendel.
With the other band members on board, Mendel aims to use the Foo Fighters' celebrity to get the message out to a broad audience. The Foo Fighters plan additional benefit shows, and have placed a banner ad on their Web site linking to Alive and Well. Mendel says that he does not have HIV, nor does he have any friends with HIV besides Maggiore, who has remained asymptomatic.
The most recent numbers from the Joint United Nations' HIV/AIDS Program estimate that 16.3 million people worldwide have died of AIDS-related causes since 1981. Medical research in the United States indicates that as many as 25 percent of the nation's estimated 40,000 annual HIV infections occur among 13- to 21-year-olds. Maggiore, however, maintains that worldwide HIV infections and AIDS deaths are exaggerated by the CDC and the World Health Organization, even in regions like sub-Saharan Africa, where two-thirds of the world's HIV-infected people live.
Maggiore's message has apparently penetrated the minds of at least some Foo aficionados. She says she has heard from many Foo fans since the show—one of whom, she says, now works at the Alive and Well office.
“AIDS is a toxic disease caused by either long-term recreational drug abuse or short-term anti-HIV medications,” writes a 22-year-old member of the Alive and Well-affiliated Students Reappraising AIDS on the Foo Fighters' Web-based message board. “HIV is not spread sexually, nor is it the cause of any disease.”
Other fans are less impressed. Damian Purdy, a 21-year-old Winnipeg, Canada resident and devoted Foo Fighters fan, is outraged by the band's position. “By supporting this, the Foo Fighters have entered an arena that they have no business being in. The truth is that a rock concert is not the appropriate platform for these views to be expressed. I think the Foo Fighters have more influence than they realize,” he says.
For his part, Mendel remains convinced that the media and the medical establishment are keeping the truth about HIV and AIDS from the public. The Foo Fighters, he insists, will continue to use their celebrity to bring “light to the issue.”
Is he worried that the group might be endangering the lives of some of its listeners?
“I'm absolutely confident that I'm doing the right thing,” Mendel answers. “No, I wouldn't feel responsible for possibly harming somebody. I (feel) I'm doing the opposite.”
Silja J.A. Talvi
talvi, silja j.a. “foo fighters, hiv deniers : a platinum-selling alt-rock group may be endangering their fans by promoting a dangerous myth,” mother jones (february 25, 2000).
See Also Biomedicine and Health: Antibiotics and Antiseptics; Biomedicine and Health: Bacteriology; Biomedicine and Health: Galen and Humoral Theory; Biomedicine and Health: Immunity and the Immune System; Biomedicine and Health: Prions and Koch's Postulates; Biomedicine and Health: Virology; Physics: Microscopy.
Alibek, Kenneth, and Stephen Handelman. Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World—Told from Inside by the Man Who Ran It. New York: Random House, 1999.
Brock, Thomas D. Robert Koch: A Life in Medicine and Bacteriology. Madison, WI: Science Tech Publishers, 1988.
Conrad, Lawrence I., and Dominik Wujastyk, eds. Contagion: Perspectives from Pre-modern Societies. Brookfield, VT: Ashgate, 2000.
Debré, Patrice. Louis Pasteur. Baltimore, MD: Johns Hopkins University Press, 2000.
Drexler, Madeline. Secret Agents: The Menace of Emerging Infections. New York: Penguin Books, 2002.
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Lechevalier, Hubert A., and Morris Solotorovsky. Three Centuries of Microbiology. New York: Dover, 1974.
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Sagan, Dorion, and Lynn Margulis. The Garden of Microbial Delights. A Practical Guide to the Subvisible World. New York: Harcourt, 1988.
Silverstein, Arthur M. A History of Immunology. New York: Academic Press, 1989.
Tomes, Nancy. The Gospel of Germs: Men, Women, and the Microbe in American Life. Cambridge, MA: Harvard University Press, 1998.
Vandervliet, G. Microbiology and the Spontaneous Generation Debate During the 1870s. Lawrence, KS: Coronado University Press, 1971.
Talvi, Silja J.A. “Foo Fighters, HIV Deniers: A Platinum-selling Alt-rock Group May Be Endangering Their Fans by Promoting a Dangerous Myth,” Mother Jones (February 25, 2000).
Office of Science & Technology Policy and the National Science & Technology Council, Committee on Science, Subcommittee on Biotechnology. “The Microbe Project: A Portal to U. S. Federal Efforts in Microbial Research.” http://www.microbeproject.gov (accessed May 6, 2008).
Lois N. Magner
"Biomedicine and Health: The Germ Theory of Disease." Scientific Thought: In Context. . Encyclopedia.com. 11 Mar. 2019 <https://www.encyclopedia.com>.
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