Koch’s postulates in the 21st century

450px-Robert_Koch_berlinFor thousands of years, epidemics of contagious diseases were believed to be caused by the wrath of the gods, configuration of stars, or miasma. The association of specific microorganisms with disease came about as a consequence of the work of the German physician Robert Koch. He formulated a set of criteria that could be used to identify the pathogen responsible for a specific disease. These criteria came to be known as Koch’s postulates:

  1. The organism must be regularly associated with the disease and its characteristic lesions.
  2. The organism must be isolated from the diseased host and grown in culture.
  3. The disease must be reproduced when a pure culture of the organism is introduced into a healthy, susceptible host.
  4. The same organism must be reisolated from the experimentally infected host.

Koch applied these criteria to show that anthrax, a common disease of cattle, was caused by the bacterium Bacillus anthracis, and that tuberculosis in humans was caused by a different bacterial species. His postulates provided a framework for proving the role of microbes in disease. As a consequence of his work, the study of infectious disease was placed on a secure scientific foundation, which ultimately made possible rational treatment and control.

Despite the importance of Koch’s postulates in the development of microbiology, they have severe limitations, which even Koch realized. For example, he believed that cholera and leprosy were caused by microbes, but could not fulfill all four postulates. Furthermore, Koch knew that the putative agent of cholera, Vibrio cholerae, could be isolated from both sick and healthy people, invalidating postulate #2.

The limitations of Koch’s criteria are even more obvious when we consider viral diseases, which were not yet discovered when the postulates were formulated. Thomas Rivers, who has been called the ‘father of modern virology’, wrote:

”It is unfortunate that so many workers blindly followed the rules, because Koch himself quickly realized that in certain instances all the conditions could not be met. . . . Thus, in regard to certain diseases, particularly those caused by viruses, the blind adherence to Koch€™s postulates may act as a hindrance instead of an aid.€™€™

Many viruses do not cause illness in all infected individuals, a requirement of postulate #1. An example is poliovirus, which causes paralytic disease in about 1% of those infected. Further compromising postulate #1 is the fact that infection with the same virus may lead to markedly different diseases, while different viruses may cause the same disease. Postulates #2 and #3 cannot be fulfilled for viruses that do not replicate in cell culture, or for which a suitable animal model has not been identified.

The application of nucleic acid-based methods of microbial identification has made Koch’s postulates even less applicable. Polymerase chain reaction and high-throughput sequence analysis have revealed a great deal about microbes that are associated with pathology or disease, but proving causation has become even more difficult as the number of uncultivable viruses rapidly multiplies. Nucleic acid based detection methods are so sensitive that they detect small numbers of viruses that may occur in the absence of disease. The use of these new methods have lead to revised versions of Koch’s postulates that are fundamentally sound: both hepatitis C virus and human papillomaviruses were convincingly shown to be causative agents of hepatitis and cervical cancer, respectively, long before methods were developed for propagation of the viruses in cell culture.

Here are Koch’s postulates for the 21st century as suggested by Fredricks and Relman:

  1. A nucleic acid sequence belonging to a putative pathogen should be present in most cases of an infectious disease. Microbial nucleic acids should be found preferentially in those organs or gross anatomic sites known to be diseased, and not in those organs that lack pathology.
  2. Fewer, or no, copy numbers of pathogen-associated nucleic acid sequences should occur in hosts or tissues without disease.
  3. With resolution of disease, the copy number of pathogen-associated nucleic acid sequences should decrease or become undetectable. With clinical relapse, the opposite should occur.
  4. When sequence detection predates disease, or sequence copy number correlates with severity of disease or pathology, the sequence-disease association is more likely to be a causal relationship.
  5. The nature of the microorganism inferred from the available sequence should be consistent with the known biological characteristics of that group of organisms.
  6. Tissue-sequence correlates should be sought at the cellular level: efforts should be made to demonstrate specific in situ hybridization of microbial sequence to areas of tissue pathology and to visible microorganisms or to areas where microorganisms are presumed to be located.
  7. These sequence-based forms of evidence for microbial causation should be reproducible.

Fredericks DN, & Relman DA (1996). Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clinical microbiology reviews, 9 (1), 18-33 PMID: 8665474

Lipkin, W. (2008). Microbe hunting in the 21st century Proceedings of the National Academy of Sciences, 106 (1), 6-7 DOI: 10.1073/pnas.0811420106

31 thoughts on “Koch’s postulates in the 21st century”

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  2. I think a very important factor is missing here. With the use of Lyme vaccines and Lepto vaccines, I know for sure that at least with these examples, that the vaccination is the conferer of disease! Yes, what Koch had no knowledge of was the fact that the antigen (in the case of Lymerix vaccines in humans and the Lyme vaccines in dogs..Osp A…all of the vaccines confer the pathology of the dis ease……that being the very interaction of the antigen with the immune cells of the victim vaccinated! Leptospirosis vaccines as well confer the pathology, some dogs dying within 48 hours of innoculation with the Lepto vaccines of renal failure the very “dis ease” of Leptospirosis, immune mediated complexes that form from the injection…….and sometimes the natural infection, react with the hosts immune cells and dis ease results. Serum sickness , glomerulnephritis, even a cytokine cascade can be induced as a result of administering a vaccine. The more injections the more immunopathology! Now, I see disease as the result of the hosts response to the injected invasion. Hyper and Hypo immune responses often the results of previous injection/infections by vaccines and the level of autoimmune dysregulation the earlier injections caused. The horrific realization is that we have so immune compromised individuals and mutated their previous (before vaccines) unadulterated innate immune system that well, the hubris of man, what can I say, we certainly have not done good work. Unless good work is being able to corrupt the immune system of life! So, Koch should have put the most aggressive species of death and destruction into his postulates, the vermin of man and the ignorance of his meddling with the immune system the creator gave us.Vaccinations are the largest conveyer of disease.

  3. These updated postulates sound plausible and interesting.
    Any idea how well accepted this has become and/or is likely to become accepted for widespread application?

  4. These updated postulates sound plausible and interesting.
    Any idea how well accepted this has become and/or is likely to become accepted for widespread application?

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  7. “the ignorance of [man’s] meddling with the immune system the creator gave us”

    I honestly cannot believe a doctor has written these words.  You are writing of Lyme vaccinations as evidence of the evils of man?  Have you not seen video or pictures of children in iron lungs or paralyzed due to polio?  Do you not remember the real fear of smallpox?  whooping cough?  The hubris of man (as you have put it) has likely saved loved ones of yours pain, suffering, and maybe life.

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  9. Do you even know where the poliovirus comes from??? Try reading the International Polio Conferences … because they didn’t even test the blood for what virus (or pesticides) were causing the paralysis. Not too scientific.

    Rhodes, A.J., Differential Diagnosis of Poliomyelitis in the Acute Stage
    Poliomyelitis, Papers and Discussions Presented at the Third International Poliomyelitis Conference, 1955
    pp. 69-80

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  11. very true may be doc have his own school of thought but vaccines are playing very vital role in saving human race

  12. Explain why polio goes away when you vaccinate against it (CDC, Progress toward global poliomyelitis eradication, 1999.)
    using sources that came out earlier than 1955.

  13. Are you an MD or microbio Ph.D doctor, or a homeopathic “doctor”? Your science is kind of (very) wrong.

    By their nature, vaccines are a balance between causing sickness and protecting against it. There will be people who react badly to, say, polio vaccines – but the majority will be saved.

    And we know who reacts badly to vaccines: immunocompromised people. But guess what? All those vaccinated people make it hard for polio to spread since most people are already immune, so immunocompromised people don’t have to be vaccinated!

    I’ve yet to meet someone who says “vaccines are bad” and is actually a respectable scientist.

  14. I think a better question to ask would be: what antigens are in the vaccine. Are “Coxsackieviruses, Group A& B, Echoviruses, and Enteroviruses” also considered with the ‘polio’ vaccine? If not.. then answer this…

    Notice on the Centers for Disease Control website, it says,
    “Poliomyelitis (polio) is a highly infectious disease caused by a virus
    that invades the nervous system.”


    What they neglect to say is what virus. In Fields Virology Second
    Edition, for example, it says on pg. 551, Ch 21, Polioviruses,
    Coxsackieviruses, Group A& B, Echoviruses, and Enteroviruses can all
    cause “polio”. So what is it?

    Polio was originally referred to as infantile paralysis. Though, the
    diagnostic label was renamed to aseptic meningitis. Source: Fields

    Also, it seems illogical to inject millions considering the following information:

    “Approximately 95% of persons infected with polio will have no symptoms.

    About 4-8% of infected persons have minor symptoms, such as fever, fatigue, nausea, headache, flu-like symptoms, stiffness in the neck and back, and pain in the limbs, which often resolve completely. Fewer than 1% of polio cases result in permanent paralysis of the limbs (usually the legs). Of those paralyzed, 5-10% die when the paralysis strikes the respiratory muscles. The death rate increases with increasing age.”


    Now – you have some explaining to do.

  15. “My science” is kind of wrong? I don’t have a copyright on it.

    If you can’t tell me the ’cause’ of polio, or how someone contracted polio, outside of telling me it’s some random virus, you owe it to yourself to do a bit more investigative work.

    Before the word “polio” was profited on — which was done so through the National Foundation for Infantile Paralysis and March of Dimes — there were very plausible explanations. But I want to start with a few contemporary sources for you because I’m going to guess this might be new to you.

    “Food was first recognized as a vehicle for the transmission of viruses in
    1914 when a raw milk-associated outbreak of poliomyelitis was reported.
    Additional milk-borne outbreaks were recognized after this time, but
    with the development of a vaccine for poliovirus, no outbreaks were
    reported in the developed world after the early 1950s.”
    “Viruses in Foods” (2006) by Sagar M. Goyal, pp. 1.

    “Poliomyelitis was the first reported foodborne viral disease, having
    been transmitted via raw milk as early as 1914. Raw milk predominated as
    the vehicle among the 10 outbreaks recorded through 1949, the last year
    in which foodborne poliomyelitis is known to have occurred in the United States or other reporting, developed countries.”
    “Foodborne Diseases” (1990) by Dean O. Cliver, pp 283.

    Now, let’s go back to the time where “polio” was running rampant. And I want you to ask yourself two very important questions: 1. When was milk first pasteurized on a massive scale? For that answer you may have to look into the dairy sciences… 2. What were some of the predispositions for getting ‘bulbar poliomyelitis’? (hint: removal of tonsils — what was given after the operation? another hint: ice cream (dairy))

    Mathews, F., Poliomyelitis Epidemic,
    Possibly Milk-Borne, In a Naval Station, Portland, Oregon. Am. J.
    Epidemiol. (1949) 49(1): 1-7

    Lieutenant Colonel David M. Goldstein, W.
    McD. Hammon, M.D., Dr. P.H., Henry R. Viets, M.D. An Outbreak of
    Polioencephalitis Among Navy Cadets, Possibly Food Borne. JAMA.

    Rosenow, E.C., An Institutional Outbreak
    of Poliomyelitis Apparently Due to a Streptococcus in Milk. The Journal
    of Infectious Diseases Vol. 50, No. 5/6 (May – Jun., 1932), pp.

    Aycock, W.L., Milk-borne epidemic of poliomyelitis. Amer. J. Hyg., 7: 791-803, 1927.

    Sabin, A.B., Poliomytlitis. Preventitive
    Medicine in World War II. Vol. 5 Communicable Diseases, Medical Dept.
    U.S. Army Government Printing Office. 1960, pp. 367-400.

    Knapp, A.C, E. S. Godfrey Jr., M.D., W. L. Aycock, M.D. An Outbreak of
    Poliomyelitis, Apparently Milk-borne. JAMA. 1926;87(9):635-639.

    Poliomyelitis. Papers and Discussions
    Presented at the First International Poliomyelitis Conference. Third
    Session – Tuesday July 13, 1948. J.B. Lippincott Co., Chicago. p. 119.

    Aycock, W.L. and Luther, E.H., The occurrence of poliomyelitis following tonsillectomy. New Engl. J. Med., 200: 164, 1929.

    Aycock, W.L. Tonsillectomy in Poliomyelitis. JAMA. 1944;125(14):990. doi: 10.1001/jama.1944.02850320048022

    Francis T., Krill, C.E., Toomey, J.A.
    and Mack, W.N., Poliomyelitis following Tonsillectomy in five members
    of a family. JAMA. 1942;119(17):1392-1396. doi:

  16. I am double doctorate and in veterinary medicine and in naturopathic medicine. I have also an Honors Degree for NCSU in Microbiology, Medical Microbiology emphasis, a B.S. gradulate Magna Cum Laude, a second B.S. in Biology with PreMed Emphasis and Medical Technologist. Presented nomination for Public Health awards and worked for the NIEHS as research Scientist, Adjunct Professor for a Naturopathic College…….so I KINDA KNOW what I am talking about.
    The only one that supports vaccines, are the ones that have FAILED tp perform due diligence.
    See Dr. Suzanne Humphries video talks on vaccinations, she is an MD. a Nephrologist Board Certified. See what she has to say about vaccines…….
    That statement you made is unbelievebly ignorant, the only ones that say “vaccines are good” are those that have not performed due diligence.
    Dr. Jordan

  17. Adrian Thomson

    I looked at her site and CV she has veterinary qualifications but is obviously not a scientist. The mention of a doctorate in naturopathic medicine along with practising Homeopathy and Reiki removes any credibility and reveals her full blown anti science quackery.

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  19. Rieke has no credibility and should not be used to cheapen alternative sciences. Naturopathic science and homeopathy are just a different ideology in healing. So because you don’t believe in this form of healing does not mean that it is flawed. I myself will not even take main stream medicine serious for healing disease but look at it as a form of medicine that treats symptoms

  20. They changed the definition of polio as the vaccine trials started. This eliminated two thirds of the polio cases and the cases that came after are merely called meningitis

  21. Adrian Thomson

    A veterinary who uses homeopathy to treat animals should be charged with animal abuse. Homeopathy has never been shown to treat any real disease. Thankfully in the UK we are at last managing to stop the health service from funding homeopathy.

  22. Animals should not be treated with homeopathy. Though if you call it animal abuse then everyone who feeds their pets bagged, canned or man made dog food should also be held on animal cruelty charges. Some one like you wouldn’t understand that because you are an individual who is agenda drive. That being said, dogs and cats are made to eat animals, animals in the raw to be exact. The further from this natural state the more diseases these animals will get.
    So, if an animal is fed what is natural for them to eat then we can render the veterinarian useless and the profession should be stored in the ANALS (yes correct spelling for main stream health care animal or human) of history and quack medicine.

  23. If you actually knew anything about the nature, history and synthesis of vaccine, you would know without a doubt that, scientifically proven, vaccines in America CANNOT cause disease. Period. There are two types of vaccines: attenuated and inactivated. Attenuated used a live, highly weakened version of the virus. Their weakened state dramatically lowers their burst time, giving the immune system plenty of time to illicit a response, attack and kill the pathogen. Inactivated uses viruses whose genome have been destroyed by either physical (pasteurization, dry heat, etc) or chemical means. Without the genome, the virus has no DNA or RNA to incorporate into host cells, making them completely unable to infect, yet, the proteins in their capsids are still received as foreign and illicit an immune response, building the antibody reservoir in the host’s body in the event of an actual exposure, hence, immunity. America, through millions upon millions of dollars of research and the race against Polio determined inactivated vaccines would be used, as there is no risk of speeding burst times and live infection. Without vaccines, millions of people would die every year from otherwise eradicated illnesses.

  24. It’s literally named Poliovirus. Any medical journal will tell you that. There are also images of the shape and structure of the virus.

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