Koch's postulates

Related article: Detecting bacteria

Microbiologist Robert KochAuthor of Koch's postulates, a set of rules for establishing a relationship between a causative microbe and a disease. Koch's belief that only one pathogens causes one disease has now been called into question as multiple postulates are increasingly considered out of date. was born in 1843. Koch's postulatesCentury-old criteria designed to establish a causal relationship between a causative microbe and a disease. Koch's belief that only one pathogen causes one disease has now been called into question as multiple postulates are increasingly considered out of date. are a series of ground rules to determine whether a given organism can cause a given disease. Koch theorized that a pathogen must be:

For all their lingering influence, Koch's postulates never anticipated the era of the human metagenome in which thousands of difficult or impossible-to-culture species of bacteria contribute to a single disease state. Koch's century-old ideas have held science back from understanding how chronic disease occurs because they make no provision for these facts.

The Marshall Pathogenesis is consistent with mounting evidence that Koch's postulates no longer apply to discerning the vast amounts of microbes in the human body.

Legacy of Koch – a false sense of confidence

According to T.D. Brock at the American Society of Microbiology,1) attempts to rigidly apply Koch’s postulates to the diagnosis of viral diseases may have significantly impeded the early development of the field of virology. It also impeded the understanding of chronic disease.

In 1932, Razumov noted a large discrepancy between the viable plate count and total direct microscopic count of bacteria taken from aquatic habitats,2) yet his work was dismissed, underestimate, or both – undoubtedly because it was not consistent with Koch's postulates.

The faithful adherence to Koch's ideas about disease has led researchers to overestimate their comprehension of how pathogens cause disease.

For most of the twentieth century, the predominant feeling about the treatment, control and prevention of infectious diseases was optimism.

Mitchell L. Cohen 3)

In 1931, Henry Sigerist wrote, “Most of the infectious diseases … have now yielded up their secrets…. Many illnesses … had been completely exterminated; others had [been brought] largely under control….”4) Between 1940 and 1960, the development and successes of antibiotics and immunizations added to this optimism, and in 1969, Surgeon General William H. Stewart told the United States Congress that it was time to “close the book on infectious diseases.”5)

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With “victory” declared, increasing emphasis was directed at the “non-infectious” diseases such as cancer and heart disease. Often, research on infectious disease or activities on their prevention and control were de-emphasized and resources were reduced or eliminated. As recently as the 1980s, pharmaceutical companies, believing that there were already enough antibiotics, began reducing the development of new drugs or redirecting it away from antibiotics.6) 7)

Still valid?

Robert Koch created a series of ground rules to determine whether a given organism can cause a given disease.

When someone talks about imbalance of humors of the miasmic origin of disease, I always detect among listeners the amused tolerance a parent gives to an explanation from his 3-yr-old son. A discourse on Koch’s postulates, on the other hand, is treated with great solemnity. In this light, my premise that there is no more dangerous half-truth among students of disease today than the postulates of Koch may be considered sacrilegious.

Robert P. Hanson 8)

As early as the 19th century, researchers realized that viruses invalidate Koch’s postulates because they require another living cell in order to replicate.

The fact that scientists are still trying to apply Koch’s postulates to bacteria is causing an even greater array of problems. For one, bacteria in the L-form (also known as cell wall deficient bacteria) cannot be easily grown in the lab and can only be studied in conditions that mimic those of the human body. As Gerald Domingue, Professor Emeritus at Tulane University states, “When it comes to L-form bacteriaDifficult-to-culture bacteria that lack a cell wall and are not detectable by traditional culturing processes. Sometimes referred to as cell wall deficient bacteria., Koch’s postulates cannot be fulfilled because it is impossible to duplicate all the variables involved in disease expression.”

It is already widely accepted that some species of bacteria cause disease despite the fact that they do not fulfill Koch’s Postulates since Mycobacterium leprae and Treponema pallidum, (which are implicated in leprosy, and syphilis respectively) cannot be grown in pure culture medium.

Another problem with the postulates - and perhaps its most significant liability - is that the rules fail to successfully account for horizontal gene transfer. Horizontal gene transferAny process in which a bacterium inserts genetic material into the genomes of other pathogens or into the genome of its host. is a process in which organisms swap genetic material, a common biological process which blurs the distinction between one organism and the next. Recall that Koch postulated that one pathogen caused one disease.

Rethinking Koch

Life has changed since the 1880s when Robert Koch elucidated his guidelines, later to be called Koch’s postulates, for determining whether a microorganism is the cause of a disease. The horse-drawn buggy bumping over dirt roads has been replaced by the computer-assisted automobile speeding along paved highways. It would be absurd to expect modern cars to abide by traffic rules and standards designed for horse-drawn carriages. Yet, many continue to hold Koch’s postulates as the unchanging standard for determining causation in medicine, despite a revolution in biotechnology and leaps in medical knowledge. Recent findings based on the application of new technologies, especially in the fields of microbiology and infectious disease, demand a renewed dialogue on proof of causation and revised guidelines for defining a causal relationship between a microbe and a disease.

David N. Fredricks and David A. Relman9)

Koch's contributions were substantial, but his ideas preceded any understanding of genetics or of horizontal gene transfer and made no provision for organisms that were not genetically distinct.

The blind adherence to Koch's postulates precludes a more nuanced understanding of disease: it is in fact a group of genetically indistinct organisms, a metagenomic microbiota, which may cause and drive chronic disease.

In a 2005 Lancet paper, Brogden et al. point to the existence of dozens of polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites.10) In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease. This topic is discussed further in the article Successive infection and variability in disease.

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===== Notes and comments =====

Premature post-mortems of infections' role in chronic disease

Ethics and infectious disease. Selgelid MJ. Bioethics. 2005 Jun;19(3):272-89. PMID: 16167406

The development of antibiotics in the 1940’s and the hugely successful Salk Polio vaccination program in the 1950’s, and other developments such as the discovery of DDT, led the medical community to believe that infectious disease would soon be defeated through medical progress.43 As early as:

1948 U.S. Secretary of State George C. Marshall declared at the Washington, D.C., gathering of the Fourth International Congress on Tropical Medicine and Malaria that the conquest of all infectious diseases was imminent. Through a combination of enhanced crop yields to provide adequate food for humanity and scientific breakthroughs in microbe control, Marshall predicted, all the earth’s microscopic scourges would be eliminated.44

In 1955 the World Health Organization decided to ‘eliminate all malaria on the planet’ via the eradication of mosquitoes with DDT. ‘Few doubted that such a lofty goal was possible: nobody at the time could imagine a trend of worsening disease conditions; the arrow of history always pointed towards progress.’45 ‘By 1965, more than 25,000 different antibiotic products had been developed; physicians and scientists felt that bacterial diseases, and the microbes responsible, were no longer of great concern or of research interest.’46 In 1967 U.S. Surgeon General William H. Stewart was so convinced of success that he told a White House gathering of health officers ‘that it was time to close the book on infectious diseases and shift all national attention (and dollars) to what he termed “the New Dimensions” of health: chronic diseases.’47 ‘In 1972, the Nobel laureate Macfarlane Burnet concluded that “the most likely forecast about the future of infectious disease is that it will be very dull.” ’48 Fields such as bacteriology and parasitology appeared less important and subsequently fell out of vogue in the medical scientific community. The rise of medical ethics thus occurred at a time when it was popular – though perhaps hubristic – to think that infectious disease would no longer be a central concern of medicine. This presumably explains at least part of the neglect on the part of those concerned with medical ethics.

43 See Garrett, op. cit. note 27, pp. 30–52, esp. pp. 30–31.

44 Ibid., pp. 30–31.

45 Ibid., p. 31. Not only did it fail, but this program was somewhat counterproductive. DDT-resistant mosquitoes returned in higher numbers than before; and misuse of medication promoted drug-resistant strains of malaria. By ‘1975 the worldwide incidence of malaria was about 2.5 times what it had been in 1961 . . . A new global iatrogenic form of malaria was emerging – “iatrogenic” meaning created as a result of medical treatment. In its well-meaning zeal to treat the world’s malaria scourge, humanity had created a new epidemic’ (p. 52).

46 Ibid., p. 36.

47 Ibid., p. 33.

48 Gewen, op. cit. note 8.

L. Garrett. 2000. Betrayal of Trust: The Collapse of Global Public Health. New York. Hyperion: 474.

B. Gewen. ‘The Great Influenza’ and ‘Microbial Threats to Health’: Virus Alert. The New York Times March 14, 2004, available at: https://www.nytimes.com/ 2004/03/14/books/review/14GEWENT.html.

===== References =====

1)
Brock TD. (1999). Robert Koch: a life in medicine and bacteriology. American Society of Microbiology Press, Washington
2)
Grice EA, Kong HH, Renaud G, Young AC, Bouffard GG, Blakesley RW, Wolfsberg TG, Turner ML, Segre JA, NISC Comparative Sequencing Program. A diversity profile of the human skin microbiota. Genome Res. 2008 Jul;18(7):1043-50. doi: 10.1101/gr.075549.107. Epub 2008 May 23.
[PMID: 18502944] [PMCID: 2493393] [DOI: 10.1101/gr.075549.107]
3)
Cohen ML. Changing patterns of infectious disease. Nature. 2000 Aug 17;406(6797):762-7. doi: 10.1038/35021206.
[PMID: 10963605] [DOI: 10.1038/35021206]
4)
Sigerist, H. E. The Great Doctors 372 (Dover Publications, New York, 1971).
5)
Garrett, L. In: AIDS in the World (eds Mann, J. M., Tarantola, D. J. M. & Netter, T. W.) 825–839 (Harvard Univ. Press, Cambridge, Massachusetts, 1992).
6)
Culotta E. Funding crunch hobbles antibiotic resistance research. Science. 1994 Apr 15;264(5157):362-3. doi: 10.1126/science.8153617.
[PMID: 8153617] [DOI: 10.1126/science.8153617]
7)
Bax RP. Antibiotic resistance: a view from the pharmaceutical industry. Clin Infect Dis. 1997 Jan;24 Suppl 1:S151-3. doi: 10.1093/clinids/24.supplement_1.s151.
[PMID: 8994797] [DOI: 10.1093/clinids/24.supplement_1.s151]
8)
Hanson RP. Koch is dead. J Wildl Dis. 1988 Apr;24(2):193-200. doi: 10.7589/0090-3558-24.2.193.
[PMID: 3286904] [DOI: 10.7589/0090-3558-24.2.193]
9)
Fredricks DN, Relman DA. Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates. Clin Microbiol Rev. 1996 Jan;9(1):18-33. doi: 10.1128/CMR.9.1.18.
[PMID: 8665474] [PMCID: 172879] [DOI: 10.1128/CMR.9.1.18]
10)
Brogden KA, Guthmiller JM, Taylor CE. Human polymicrobial infections. Lancet. 2005 Jan 15-21;365(9455):253-5. doi: 10.1016/S0140-6736(05)17745-9.
[PMID: 15652608] [PMCID: 7119324] [DOI: 10.1016/S0140-6736(05)17745-9]