Biological Sciences

Koch's Postulates

Koch's postulates are a set of criteria used to establish the causative relationship between a microorganism and a disease. They were developed by Robert Koch in the late 19th century and are still used today to determine the etiology of infectious diseases. The postulates state that the microorganism must be present in every case of the disease, isolated and grown in pure culture, and then shown to cause the disease when introduced into a healthy host.

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12 Key excerpts on "Koch's Postulates"

  • Book cover image for: Bacterial Pathogenesis
    eBook - ePub

    Bacterial Pathogenesis

    A Molecular Approach

    • Brenda A. Wilson, Malcolm Winkler, Brian T. Ho, Brenda A. Wilson, Malcolm Winkler(Authors)
    • 2019(Publication Date)
    • ASM Press
      (Publisher)
    6 IN THIS CHAPTER History and Relevance of Koch’s Postulates Early Germ Theory Koch’s Postulates: A Set of Criteria Used To Establish a Microbe-Disease Connection Challenges to Satisfying Koch’s Postulates Easier Said than Done… The First Postulate: Association of the Microbe with Lesions of the Disease The Second Postulate: Isolating the Bacterium in Pure Culture
    The Third Postulate: Showing that the Isolated Bacterium Causes Disease Experimentally in Humans or Animals
    The Fourth Postulate: Reisolating the Bacterium from the Intentionally Infected Animal Modern Alternatives To Satisfy Koch’s Postulates Detecting the Presence of the Pathogen Only in Diseased Tissues Eliminate the Pathogen and Prevent or Cure the Disease Comparative Infectious Disease Causation The Microbiota Shift Disease Problem Koch’s Postulates and Pathogenic Microbial Communities Keystone Pathogens and Microbial Shift Diseases Molecular Koch’s Postulates Concepts of Disease Varieties of Human-Microbe Interactions Views of the Human-Microbe Interaction Virulence as a Complex Phenomenon Selected Readings Questions Solving Problems in Bacterial Pathogenesis CHAPTER 6 Microbes and Disease ESTABLISHING A CONNECTION
    F elix, qui potuit rerum cognoscere causas ” [“Fortunate is he, who is able to know the causes of things.”]—verse 490, Book 2 of Georgics
    , Virgil (circa 29 BCE). Modern microbiologists seeking to cure previously intractable diseases have embraced the spirit of this quote by the famous Latin poet. Indeed, one of the most exciting areas of infectious disease research was kicked off by research into the cause of gastric ulcers and the discovery of their bacterial origins. For decades, physicians believed that gastric ulcers were a chronic condition caused by genetic predisposition and excess stomach acid production, which thus led to the conclusion that ulcers could not be cured and that it was only possible to treat the symptoms through bland diets and daily doses of antacids. The finding that most gastric ulcers are caused by a particular bacterium led at long last to a cure for ulcers—fortunate indeed for all chronic ulcer sufferers who now could go back to eating their favorite spicy foods. Now scientists are enthusiastically exploring the possibility that bacteria might be the cause of other chronic conditions, such as inflammatory bowel disease, cardiovascular disease, atherosclerosis, and certain cancers, which, if so, might also be curable. The problem is demonstrating that the bacterium is indeed the direct cause of the disease and not simply associated with the condition. Scientists have been grappling with this problem for over a century, and even today with a strong set of guidelines such as Koch’s postulates in hand, finding a clear-cut connection between microbe and disease is challenging. Today, researchers are applying modern molecular technologies to tackle the microbe-disease causation problem.
  • Book cover image for: Veterinary Epidemiology
    Chapter 1 indicated that there has been a transition from the idea that disease has a predominantly single cause to one of multiple causes. The former idea is epitomized by Koch's Postulates. Koch's Postulates The increased understanding of microbial diseases in the late 19th century led Robert Koch to formulate his postulates to determine the cause of infectious disease. These postulates state that an organism is causal if: (1) it is present in all cases of the disease; (2) it does not occur in another disease as a fortuitous and non-pathogenic parasite; (3) it is isolated in pure culture from an animal, is repeatedly passaged, and induces the same disease in other animals. Koch's Postulates brought a necessary degree of order and discipline to the study of infectious disease. Few would argue that an organism fulfilling the above criteria does not cause the disease in question; but is it the sole and complete cause? Koch provided a rigid framework for testing the causal importance of a microorganism but ignored the influence of environmental factors that were re-latively unimportant in relation to the lesions that were being studied. Microbiologists found it difficult enough to satisfy the postulates without concerning themselves with interactions between complex environmental factors. Therefore the microorgan-isms were assumed to be the sole causes of the diseases that the microbiologists were investigating. Dissatisfaction became evident in two groups. Some microbiologists thought that the postulates were too difficult to satisfy because there can be obstacles to fulfilling Koch's Postulates with some infectious agents that are causes of disease. Others thought that the postulates were insufficient because they did not specify the environmental conditions that turned vague associations into specific causes of disease. Furthermore, the postulates were not applicable to non-infectious diseases.
  • Book cover image for: Agency and Action in Colonial Africa
    eBook - PDF

    Agency and Action in Colonial Africa

    Essays for John E. Flint

    • C. Youé, T. Stapleton, C. Youé, T. Stapleton(Authors)
    • 2001(Publication Date)
    19. Koch’s postulates are a series of procedures that should be followed to prove that a specific micro-organism is the causal agent of a specific infectious disease. The organism must be constantly present in the diseased tissue; the organism must be isolated and grown in pure culture; and the pure culture must be shown to induce the disease when injected into an experimental animal. Lester S. King, ‘Dr. Koch’s Postulates’, Journal of the History of Medicine and Allied Sciences, 7(1952), 350–61. 20. DSB, p. 430. For more on what Cranefield calls his ‘dark side’, see Crane- field, Science, p. 341, and Brock, Koch, pp. 4, 287, and 291. 21. Linda Bryder, Below the Magic Mountain: A Social History of Tuberculosis in the Twentieth Century (Oxford: Oxford University Press, 1988). 22. Brock, Koch, p. 239. 23. Robert Koch to Carl Salomonsen, no date. Cited in Brock, Koch, p. 237. 24. Cited in Brock, Koch, p. 237. 25. Watts, Epidemics, p. 256. 26. Cranefield, Science, p. 103. 48 Myron Echenberg 27. DSB, p. 425. 28. Cape Times, 3 December 1896. 29. The locale was at Kisiba, a German plantation on the west coast of Lake Victoria. Koch observed that the banana plantations abounded in rodents, and that when the native observed rats lying dead, they ‘fly from their huts’. Special correspondence from Berlin, reporting on Robert Koch’s address to the German Society for Public Hygiene of 7 July 1898, published in the British Medical Journal, 16 July 1898, 205–6. 30. Koch, as reported in the British Medical Journal, 16 July 1898, 205–6. 31. McNeill, Plagues, p. 111; see also Calvin W. Schwabe, Veterinary Medicine and Human Health, 3rd edn (Baltimore: Williams & Wilkins, 1984), p. 225. 32. DSB, p. 427. 33. McNeill, Plagues, pp. 111–13. The theory has been repeated in the historical literature. See John Iliffe, Africans: The History of a Continent, (Cambridge: Cambridge University Press, 1995), p.
  • Book cover image for: Germ Theory
    eBook - ePub

    Germ Theory

    Medical Pioneers in Infectious Diseases

    • Robert P. Gaynes(Author)
    • 2023(Publication Date)
    • ASM Press
      (Publisher)
    (10) . The postulates are known to most students who study microbiology as the guide to determination that a microorganism is the cause of a disease.
    The putative organism must be constantly present in diseased tissue. The organism must be isolated in pure culture. The pure culture must induce disease when injected into experimental animals. The same organism must be isolated from these diseased animals.
    The postulates are credited to Koch, but history shows that he was not the first person to develop the concepts (11) . Koch’s teacher, Jakob Henle, first proposed the guiding hypothesis but never had the means to actually test them. Later, Edwin Klebs, in 1877 and again in 1878, lectured on the criteria for causality from microorganisms (12) . Oddly, Koch did not rigorously adhere to the postulates in his anthrax work and could not adhere to them in his next triumph, human cholera, since humans are the only hosts, and no experimental animal model exists.

    THE DISCOVERY OF THE CAUSATIVE AGENT OF CHOLERA

    Fresh from his achievement on the etiology of tuberculosis and with an improved salary, laboratory, and prestige, Koch was eager to test his newfound success. The chance came quickly. In 1883, a cholera epidemic hit Egypt. Concern across the continent of Europe flared; the worry was that it might begin in European cities. Koch remembered the Hamburg epidemic in 1866. He believed that he had developed the techniques to contain the devastating illness and, quite possibly, find the etiologic agent.
    A small port city, Damiette, in Egypt became the first city to announce the outbreak in 1883, but soon cholera was spreading throughout the country. Egyptian officials contacted France and Germany for help. Both countries sent delegations. In a way it was a national competition. Pasteur directed the French delegation in absentia. His young but trusted assistant, Louis Thuillier, and Émile Roux were on the ground in Egypt 1 day earlier than the German delegation. Koch, Georg Gaffky, Bernhard Fischer, and Hermann Treskow formed the German Commission, as it was known. The German team came well equipped to study cholera. A number of inoculations to animals failed to produce an animal model. Cultures of patients’ blood, liver, spleen, or liver also failed to produce any bacterial colonies. Koch had dissected a number of victims of the disease and found a characteristic organism only in the intestines. As Koch described the curious microorganism, it was not as a straight rod, but a little bent, like a comma. The bending could be so great that the organisms resembled half‐circles. But Koch could not be certain that this strangely shaped bacterium was the cause of the horrible disease. There were masses of bacteria in the intestine. Although this comma‐shaped bacillus was noted only in cholera victims, for Koch, the answer was still not clear. Unfortunately for Koch, the outbreak disappeared in Alexandria, Egypt, where the German Commission was working. Koch had no fresh material for culture. He did, however, track the disease through epidemiological studies to ascertain the effectiveness of quarantine measures. He correlated the disease incidence with the rise and fall of the Nile waters and made studies on the relationship of cholera to the water supply and with meteorological conditions.
  • Book cover image for: Case Studies in Public Health
    • Theodore H. Tulchinsky(Author)
    • 2018(Publication Date)
    • Academic Press
      (Publisher)
    th century. These postulates, developed based on experience with anthrax and tuberculosis, served to provide a rational scientific framework for evidence of causation in the study of infectious diseases for their prevention and treatment. Koch realized these criteria were not fulfilled in the case of cholera where the organism may be present in humans without causing the disease, and this was later seen as even more of a problem for viral diseases. Later, they were seen as too rigid, limiting identification of the multiple factors that together cause many diseases especially noncommunicable diseases. But even for infectious diseases there are multiple factors as well as the “causative organisms” such as poverty, poor nutrition, lack of access to health care, and other social inequalities not only in the incidence of disease but even more so in the severity of an infectious disease.
    Later definitions of association and causation required more complex criteria especially in regard to noncommunicable diseases with multiple risk factors. The criteria of evidence of association/causation as proposed by Bradford Hill in the 1950s for smoking and lung cancer were based on evidence of strength of association; consistency; specificity; temporality; biological gradient; plausibility; coherence, experiment, and analogy; and even more so on complex social and environmental factors in origins of disease in populations.
    However, the Koch–Henle postulates continue to be basic tools for providing evidence of causation of disease as in the identification of Helicobacter pylori as the major cause of chronic peptic ulcer disease in the early 1980s by Robin Warren and Barry Marshall (see Chapter 22 ). The finding of the causative bacteria H. pylori led to simple and inexpensive diagnostic and curative treatment. Since the early 1980s this development has resulted in emptying surgical wards of gastrectomy and vagotomy cases as well as medical wards of many patients suffering from peptic ulcers. Helicobacter pylori is considered to be present in half the world’s population and a cause of gastric cancer. As sanitation and living conditions improved in the 20th century, gastric cancer incidence gradually declined in many countries. The simple diagnosis for H. pylori
  • Book cover image for: Germ Theory
    eBook - PDF

    Germ Theory

    Medical Pioneers in Infectious Diseases

    • Robert P. Gaynes(Author)
    • 2023(Publication Date)
    • ASM Press
      (Publisher)
    Visitors traveled from all over the globe to his labo- ratory to learn and consult. In May 1883 the German Exposition of Hygiene and Public Health was held in Berlin. Koch presented his laboratory techniques for plat- ing pure cultures, disinfection, and staining. The Exposition carried Koch’s name and, more importantly, his techniques across the globe. Koch’s techniques were a break with the past. His methods were simple and transparent. Importantly, they could be easily repeated in other laboratories, in marked contrast to those of Pasteur, who often kept his methods secret, even from his laboratory assistants. KOCH’S POSTULATES An 1884 Koch publication titled “The Etiology of Tuberculosis” contained a more expansive explanation of his work on isolating the tubercle bacillus but is best remembered as the formal presentation of what we now call Koch’s postulates (10). The postulates are known to most students who study microbiology as the guide to determination that a microorganism is the cause of a disease. The putative organism must be constantly present in diseased tissue. The organism must be isolated in pure culture. The pure culture must induce disease when injected into experimental animals. The same organism must be isolated from these diseased animals. The postulates are credited to Koch, but history shows that he was not the first person to develop the concepts (11). Koch’s teacher, Jakob Henle, first proposed the guiding hypothesis but never had the means to actually test them. Later, Edwin Klebs, in 1877 and again in 1878, lectured on the criteria for causality from micro- organisms (12). Oddly, Koch did not rigorously adhere to the postulates in his anthrax work and could not adhere to them in his next triumph, human cholera, since humans are the only hosts, and no experimental animal model exists.
  • Book cover image for: Plant Disease Management
    eBook - ePub

    Plant Disease Management

    Principles and Practices

    • Hriday Chaube(Author)
    • 2018(Publication Date)
    • CRC Press
      (Publisher)
    Chapter 6Diagnosis of Plant Diseases

    I. Diagnosis—Its Concept and Scope

    Diagnosis is derived from a Greek word "diagignoskein" which means to distinguish (from "dia" through, and "gignoskein", to know). The conceptual validity of diagnosis is often a topic of discussion amongst the scientists. It is argued, whether diagnosis is an art or science or both. According to McIntyre and Sands,1 diagnosis is an art. They have very rightly argued that diagnosis is done by precept and experience. Even today whenever a diseased sample is brought to the diagnostician, he examines the symptoms and makes an intuitive judgement as to its nature. Thus, visual observations based on experience, precept, and intuitive judgement is still the most widely used method employed for identification of diseases.

    II. Koch’s Postulates

    In the 19th century, when criteria for determining causality of disease were hotly debated, a set of useful rules was developed in 1882 by Robert Koch and further modified by E. F. Smith2 to demonstrate pathogenicity of microorganisms. These rules became known as Koch's Postulates, and they are widely applied in plant pathology. These rules are (1) the microorganism must be constantly associated with the disease, i.e., a macroscopic as well as microscopic observations of host symptoms and if present, signs of the pathogen, (2) the microorganism must be isolated from diseased host and grown in pure culture, i.e., isolation and purification of the pathogen, (3) the specific disease must be reproduced when the microorganism from the pure culture is inoculated into the host, and (4) the same microorganism must be recovered from the inoculated diseased host.
    These rules have proved very useful to identify most of the diseases caused by biotic agents. However, the modification of rules have been necessary for mesobiotic agents and/or for pathogens that do not reproduce independently of the living cells. For example, the Koch's Postulates for viruses3
  • Book cover image for: Phytomycology and Molecular Biology of Plant Pathogen Interactions
    • Imran Ul Haq, Siddra Ijaz, Iqrar Ahmad Khan, Imran Ul Haq, Siddra Ijaz, Iqrar Ahmad Khan(Authors)
    • 2022(Publication Date)
    • CRC Press
      (Publisher)
    International Journal of History Philosophy of Medicine 6:10603
  • Goad, D.M., Y. Jia, A. Gibbons, Y. Liu, D. Gealy, A.L. Caicedo and K.M. Olsen. 2020. Identification of novel QTL conferring sheath blight resistance in two weedy rice mapping populations.
    Rice
    13:1–10
  • Göhre, V. and S. Robatzek. 2008. Breaking the barriers: Microbial effector molecules subvert plant immunity.
    Annual Review of Phytopathology
    46:189–215
  • Grimes, D.J. 2006. Koch’s postulates-then and now.
    Microbe-American Society for Microbiology
    1:223
  • Haas, B.J., S. Kamoun, M.C. Zody, R.H. Jiang, R.E. Handsaker, L.M. Cano, M. Grabherr, C.D. Kodira, S. Raffaele and T. Torto-Alalibo. 2009. Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans.
    Nature
    461:393–398
  • Heuberger, A.L., F.M. Robison, S.M.A. Lyons, C.D. Broeckling and J.E. Prenni. 2014. Evaluating plant immunity using mass spectrometry-based metabolomics workflows.
    Frontiers in Plant Science
    5:291
  • Höfler, M. 2005. The Bradford Hill considerations on causality: A counterfactual perspective.
    Emerging Themes in Epidemiology
    2:1–9
  • Hogenhout, S.A., R.A. Van der Hoorn, R. Terauchi and S. Kamoun. 2009. Emerging concepts in effector biology of plant-associated organisms.
    Molecular Plant-microbe Interactions
    22:115–122
  • Iriti, M. and F. Faoro. 2008. Ancient plant diseases in Roman Age.
    Acta Phytopathologica et Entomologica Hungarica
    43:15–21
  • Johal, G.S. and S.P. Briggs. 1992. Reductase activity encoded by the HM1 disease resistance gene in maize.
    Science
    258:985–987
  • Johnston-Monje, D. and J. Lopez Mejia. 2020. Botanical microbiomes on the cheap: Inexpensive molecular fingerprinting methods to study plant-associated communities of bacteria and fungi.
    Applications in Plant Sciences
    8:e11334
  • Jones, S., B. Yu, N.a. Bainton, M. Birdsall, B. Bycroft, S. Chhabra, A. Cox, P. Golby, P. Reeves and S. Stephens. 1993. The lux autoinducer regulates the production of exoenzyme virulence determinants in
    Erwinia carotovora
    and
    Pseudomonas aeruginosa
    .
    The EMBO Journal
  • Book cover image for: Research Methodology in the Medical and Biological Sciences
    • Petter Laake, Haakon Breien Benestad, Bjorn R. Olsen(Authors)
    • 2007(Publication Date)
    • Academic Press
      (Publisher)
    In the following sections, the principal traditional issues concerning reason, method, evidence and the object of science (the world) are discussed. The glue of the world: causation A pivotal task of the biomedical sciences is to find the causes of phenomena, such as disease. However, what is the implication of saying that something is the cause of a disease? According to Robert Koch (1843–1910), who was awarded the Nobel Prize in physiology or medicine for finding the tuberculosis bacillus in 1905, a parasite can be seen as the cause of a disease if it can be shown that the presence of the parasite is not a random accident. Such random accidents may be excluded by satisfying the (Henle–) Koch postulates: • The organism must be found in all animals suffering from the disease, but not in healthy animals. • The organism must be isolated from a diseased animal and grown in pure culture. • The cultured organism should cause disease when introduced into a healthy animal. • The organism must be reisolated from the experimentally infected animal. As became clear to Koch, these criteria are elusive. If such postulates are con-sidered to be general criteria for something to be a cause in the biomedical sci-ences, causation is unlikely. Acknowledging that overly stringent criteria for causation minimize the chance of identifying causes of disease, the British medical statistician Austin Bradford Hill (1897–1991) outlined tenable minimal conditions germane to establishing a causal relationship between two entities. Nine criteria were presented as a way to CHAPTER 1 2 determine the causal link between a specific factor (such as cigarette smoking) and a disease (such as emphysema or lung cancer): • Strength of association : the stronger the association, the less likely the relation-ship is due to chance or a confounding variable.
  • Book cover image for: Pioneers In Microbiology: The Human Side Of Science
    • King-thom Chung, Jong-kang Liu(Authors)
    • 2017(Publication Date)
    • World Scientific
      (Publisher)
    105 Chapter 13 Robert Koch (1843 – 1910): The Great Medical Microbiologist “One should first investigate the problems with attainable solutions. With this knowledge thus gained, we can proceed to the next attainable objectives”. “I have undertaken my investigations in the interest of public health and I hope the greatest benefits will accrue from there”. “If I think today of all of praise which you have heaped upon me, I must, of course, immediately ask myself if I deserve it. Am I really entitled to such homage? I guess that I can, with a clear conscience, accept much of the praise you have bestowed upon me. But I have really done nothing else than what you yourself are doing every day. All I have done is work hard and fulfill my duty and obligations. If my efforts have led to greater success than usual, this is due, I believe, to the fact that during my wanderings in the field of medicine, I have strayed on the paths where the gold was still lying by the wayside. It takes a little luck to be able to distinguish gold from dross, but that is all”. — Robert Koch Pioneers in Microbiology: The Human Side of Science 106 Source : https://en.wikipedia.org/wiki/Robert_Koch (US Public Domain image) Introduction Robert Koch is an important figure in the history of combating human diseases. His “Koch’s postulates” serve as the gold standard for identifying disease agents. Many infectious dis-eases such as acquired immunodeficiency syndrome (AIDS), Hanta virus pulmonary syndrome, and the avian flu are threat-ening us today, as well as reemerging threats from the past such as tuberculosis and hemorrhagic diarrhea. Therefore, it is worthwhile to recall how we battled diseases in the past. The past may give leads for the future. Background and Education Robert Koch was born to Hermann Koch and Mathilde Julie Henriette Biewend on 11 December 1843 in Klausthal, Harz, an 13 Robert Koch 107 old mountain town of some 10,000 inhabitants, 50 miles south of Hannover, a part of Prussia.
  • Book cover image for: Humans, Animals and Biopolitics
    eBook - ePub

    Humans, Animals and Biopolitics

    The more-than-human condition

    • Kristin Asdal, Tone Druglitro, Steve Hinchliffe, Kristin Asdal, Tone Druglitro, Steve Hinchliffe(Authors)
    • 2016(Publication Date)
    • Routledge
      (Publisher)
    Thus, a central characteristic of Robert Koch’s medical bacteriology also reveals itself in the animal experiment. Fundamental questions relating, for example, to pathogenesis, are not elucidated in any depth. Instead, they are dealt with only implicitly in the techniques Koch employed to observe and manipulate various objects within the laboratory, such as bacteria, experimental animals, et cetera. 34 When viewed at closer quarters, even the famous postulates turn out to be nothing more than a historiographical construct of Koch’s students; the criteria Koch himself applied to proving the existence of bacterial aetiologies varied from case to case. If we make a point of comprehending the romantic idea of parasitical disease entities as a theory without practice, the discipline of medical bacteriology – in particular in its animal-experimental work – reveals itself to be a practice without theory. Instead of pursuing a systematic discussion on the problem of disease, medical bacteriology contented itself with the question of correct investigative techniques. Notes 1 This text is a translation from an earlier German version, published as ‘Das Maß der Krankheit: das pathologische Tierexperiment in der medizinischen Bakteriologie Robert Kochs’ (Gradmann, 2005). 2 References to Canguilhem are to German translations throughout the text. 3 For an introduction to the animal experiment in medicine, see Opitz (1968), Rupke (1987), Bynum (1990) and Löwy (2000)
  • Book cover image for: A New History of Vaccines for Infectious Diseases
    eBook - ePub

    A New History of Vaccines for Infectious Diseases

    Immunization - Chance and Necessity

    • Anthony R. Rees, Anthony Robert Rees(Authors)
    • 2022(Publication Date)
    • Academic Press
      (Publisher)
    Their discoveries when exposed would rock the world of medicine and provide an understanding of disease causation that would confirm and complement the earlier work of Jenner on the efficacy of vaccines. As the discoveries of Pasteur and Koch unfolded their critics pointed to earlier discoveries that had preempted the concept that microorganisms are the cause of communicable diseases. The Italian physician Hieronymus Fracastori, whose 1546 paper was said to have made the first scientific statement on the nature of infection or contagion (he did not distinguish between the terms), described it as something that “passes from one thing to another.” He compared contagion to the emanations of an onion and although he used the term “seminaria,” or seeds, there was no suggestion from him that these “seeds” of disease were living organisms, described variously as “small imperceptible particles” that might be “hard” or “viscous.” 1 300 years later, Koch's mentor Jacob Henle was credited by some with the discoveries made by Pasteur and Koch. As the Italian-American medical historian, Arturo Castiglione, put it in 1941, Henle's essay published in 1840 2 (describing his supposed discovery) was “… the best pre-Pasteurian statement of the microorganismal causes of infectious diseases,” 3 a view summarily debunked by Howard–Jones in 1977 who comments: “Although Henle maintained that miasmatic diseases could develop contagions and vice versa, he conceded that a miasm-"i.e. that which contaminated"-was little more than a concept, and that it was not possible to say to which of the natural kingdoms it belonged or, indeed, whether it belonged to any of them.” 4 But there was a much more credible attribution that both Pasteur and Koch acknowledged and whose observations clearly colored their own research discoveries. The remarkable set of observations was made by the French physician and researcher Casimir Davaine
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