ViroLIEgy 101: Koch’s Postulates

I am starting a series of posts under the heading ViroLIEgy 101 in order to provide relatively short (by my standards) and concise explanations of key concepts regarding both germ “theory” and virology. I’m providing an overview on topics that are essential to the conversation that people may be confused with and have difficulty understanding, or areas that seem to be controversial when engaging in discussions with those defending the germ “theory” of disease.

In this inaugural edition of ViroLIEgy 101, I am focusing on Koch’s Postulates as they remain a sticking point for many. These criteria, developed and popularized by German bacteriologist Robert Koch during the late 1800s, are largely considered necessary to satisfy in order to prove that any microbe can cause disease. However, depending on who is asked or what source one turns to, there are ways in which those defending the germ “theory” have attempted to bypass these postulates using various excuses, such as claiming that the postulates are old and outdated, or that they refer only to bacteria rather than “viruses.” Let’s take a closer look at these postulates in order to see why they are just as relevant and essential today as they were when Robert Koch originally proposed them.

According to Merriam-Webster, a postulate is defined as a hypothesis that is advanced as an essential presupposition, condition, or premise of a train of reasoning. Taking this a step further, it is a logical statement that is assumed true so that a conclusion can be drawn. Postulates do not require any proof as what they state is obvious and stems from common sense.

At the time that German bacteriologist Robert Koch began devising his own logic-based postulates in the late 1870s that would eventually go on to become the standard by which to prove a microbe causes a disease, different aspects of these same logical requirements already existed. In some instances, Koch’s Postulates are referred to as the Henle-Koch Postulates as a version of these same criteria had already been proposed by Koch’s teacher, German pathologist Friedrich Gustav Jacob Henle. Koch would later modify and go on to popularize them. Henle was one of the early adopters of the unpopular idea that microbes caused disease, stating in his 1840 paper “Von den Miasmen und Contagien und von den miasmatisch-contagiösen Krankheiten” that the “material of contagions is not only an organic but a living one and is indeed endowed with a life of its own, which is, in relation to the diseased body, a parasitic organism.” According to Koch’s Postulates in Relation to the Work of Jacob Henle and Edwin Klebs, it is said that Henle knew that just finding an organism in a diseased host was not enough to prove causation. The only way to prove the “contagious” nature was to isolate (i.e. separate one thing from everything else) the microbe from the fluids and study it independently. However, Henle felt that this was an impossibility.

“In a discussion published in 1840, Jacob Henle, who was also a pathological anatomist, proposed a criterion for identifying external disease causes. This criterion conformed perfectly with the general strategy that Virchow subsequently discussed. Henle conjectured that many diseases may be caused by parasitic micro-organisms. However, he noted that even if one regularly found living organisms in contagious fluids within diseased bodies, one could still not infer that the organisms were more than harmless saprophytes. The contagion could still be the fluids themselves rather than the organisms. According to Henle, “one could prove empirically that [the organisms] were really effective only if one could isolate…the contagious organisms from the contagious fluids, and then observe the powers of each separately.” Henle was sceptical about the possibility of carrying out such a proof, and apparently he never tried to do so.”

In addition to Henle’s influence on Koch, it is stated that Edwin Klebs, a disciple of the father of modern pathology Rudolf Virchow (ironically, a disbeliever in germ theory), had set forth similar criteria in the early 1870s. Klebs noted that a microbe must be isolated to induce other cases of “infection” and then be observed acting upon the host. He felt that one could infer a causal relationship if different pathological processes, such as inflammation, were noted. As his papers were widely known and discussed, and Koch regularly cited Klebs work, it is argued that Koch was influenced by Klebs own logic-based approach.

In his 1872 paper, Klebs observed that “tracing the invasion and the course of the micro-organisms can make causality probable, but the crucial experiment is to isolate the efficient cause and allow it to operate on the organism.” In 1875, he observed that if one could show that “inflammation and other reactive changes follow, step by step, the spread of the schistomycetes, then it is logical to infer a causal relation rather than a simple coincidence.” Klebs pointed out that experimental evidence could support the same conclusion. To obtain such evidence, one must “isolate substances from the body and use them to induce further cases of infection.” Klebs claimed to have followed both approaches and to have obtained mutually supporting results. His papers and his procedures for establishing causality were widely known and discussed.”

If we contrast Edwin Klebs own postulates with Robert Koch’s, we can see that the steps that Klebs outlined are very similar to what Koch proposed in 1890 while speaking to the Tenth International Congress of Medicine in Berlin. They both dealt with observation, isolation, and experimentation.

Edwin Klebs Postulates 1877

1. Anatomical investigations of diseased organs
2. The isolation and cultivation of disease germs
3. The initiation of new cases of the same disease by conveying germs to healthy animals

Robert Koch’s Original Postulates 1890

1. The parasite occurs in every case of the disease in question, and under circumstances which can account for the pathological changes and clinical course of the disease
2. After being fully isolated from the body and repeatedly grown in pure culture, can induce the disease anew
3. It occurs in no other disease as a fortuitous and nonpathogenic parasite

While there are slightly different ways of stating the criteria that make up Koch’s Postulates, there is a commonality in all of them, and typically a fourth postulate, added by plant biologist E. F. Smith in 1905, is presented along with Koch’s original three criteria. Thus, Koch’s Postulates are regularly written as follows:

Koch’s Postulates

1. The microorganism must be found in abundance in all cases of those suffering from the disease, but should not be found in healthy subjects.
2. The microorganism must be isolated from a diseased subject and grown in pure culture.
3. The cultured microorganism should cause the exact same disease when introduced into a healthy subject.
4. The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

When going through each of the postulates, it is clear that they are logic-based and rely on common sense. As stipulated by the first postulate, it is logical to assume that, if a microbe were to cause disease, it should only be found in those with the disease while not found in those who are without disease. The presumed pathogen should also not be absent in cases of the disease or found in cases of different diseases. With the second postulate, it is reasonable to require that, when experimenting with an assumed pathogen, one is working with nothing but the pathogen in question in order to rule out contaminants and confounding variables that may influence the results. As for the third postulate, insisting that the same exact disease is established when a healthy host is subjected to a pure source of the presumed pathogen is entirely rational and should be the expected outcome. If no disease is produced or different symptoms are observed, then the presumed pathogen can hardly be the cause of the specific disease being investigated. Finally, it is sound reasoning to require that, if a healthy host does come down with the same disease, the same presumed pathogen should be able to be isolated from the newly sickened host. If it is not, then this would show that the presumed pathogen was not necessary to cause disease and that the experimental procedure or some other confounding variable was likely to blame.

While being entirely logical, the postulates also lend themselves to the concept of falsifiability, which means that they offer a way to disprove that a microbe causes disease. As the postulates are logical and assumed true, anything that goes against them would be considered false. For example, the stipulation highlighted in bold above in the first postulate states that the disease-causing agent “should not be found in healthy subjects.” This means that if a microbe that is assumed to be pathogenic is found in healthy hosts, it is falsified as a pathogen as it is found not causing disease. Sometimes, this stipulation is left out of the postulates due to the concept of asymptomatic carriers. However, the very idea of an asymptomatic carrier goes against logic and creates an unfalsifiable concept where the assumed pathogen is able to be found in both the sick and the healthy. There is no way to disprove a microbe as a pathogen if it is found both causing disease and not causing disease. Koch himself denied that bacteria can ever be found in healthy tissues and stated in 1890 that the microbe should not be found in a nonpathogenic form. Thus, even though he did not always practice what he preached, Koch understood the importance of falsifiability and the logic behind the requirements.

Due to their scientific nature, Koch’s Postulates serve as a valuable common sense complement to the steps of the scientific method. In fact, they closely align with the scientific method, as noted by virologist Peter Duesberg who stated that they “are science or at least a scientific method.” Koch’s logical criteria are based upon observation and experimentation, and they crossover with the steps of the scientific method in a few other ways as well. As already discussed, falsifiablity, i.e. the capacity to be shown to be wrong is built into each postulate (sick or healthy, pure or impure, ablity or inability to recreate disease or isolate the same microbe). In order to satisfy the postulates, it is required to identify the causative agent in order to be used as an independent variable prior to experimentation so that it can be determined if it is responsible for producing the disease. Reproducibility is also required to ensure the accuracy of the results. These are all core tenets of the scientific method.

Koch’s logical and experimental methods are designed to be used in order to prove a cause-and-effect relationship between a specific microbe and a specific disease. They serve as the overall guide to experimental design as well as a test for the validity of the conclusions, as stated in a 1979 editorial in the American Review of Respiratory Disease.

“Robert Koch, described a logical and experimental process that could be used to prove (by systematic elimination of alternative possibilities) a cause-and-effect relationship between a specific micro-organism and a specific disease. His ideas have been condensed into an elegantly simple and concise set of principles, commonly known as Koch’s postulates, which have served the discipline of bacteriology both as an over-all guide to experimental design and as a test of the validity of conclusions.”

For two centuries, Koch’s Postulates have stood as the “gold standard” for establishing the microbiological etiology of “infectious” disease. They are considered so essential that, according to a 2015 paper by Ross and Woodyard, the postulates are “mentioned in nearly all beginning microbiology textbooks” and “continue to be viewed as an important standard for establishing causal relationships in biomedicine.” Lester S. King, a Harvard educated medical doctor who authored many books on the history and philosophy of medicine, wrote in his 1952 paper Dr. Koch’s Postulates that Koch’s contribution was in “forging a chain of evidence which connected a specific bacterium and a given disease.” King stated that this chain was so strong and so convincing “that his principles have been exalted as “postulates” and considered a model for all future work.” The Robert Koch Institute stated that Koch’s success was due to “the precision with which he developed and applied his scientific methods as well as his logical construction of the chain of evidence.”

However, even though the postulates are logical, align with aspects of the scientific method, and are accepted as the “gold standard” causation criteria, there have been many attempts to dismiss them as being nonessential in proving a microbe causes disease. During the “Covid-19 pandemic,” various “fact check” articles came out seeking to minimize and disparage the use of Koch’s Postulates, such as this article by Reuters published in March of 2021. It attempted to rationalize Robert Koch’s bending of his own logical criteria in order to claim that it is acceptable to disregard them altogether. It is true that it was realized early on by Koch and his contemporaries that these logical rules could not be satisfied. Koch himself found the tuberculosis and cholera bacteria in healthy individuals, thus failing his first postulate. For his experiments with anthrax, Koch utilized impure cultures that he claimed were “pure” simply because he found no evidence of contamination when he examined the cultures with a microscope as he had no technique at the time that ensured purity, thus failing his second postulate. He was unable to recreate the cholera disease experimentally utilizing pure cultures of the comma bacillus in animals and even in himself, thus failing his third postulate.

In the paper “The Germ Theory of Disease,” Dr. Herbert Snow pointed out that “not a solitary germ yet discovered has succeeded in fulfilling all these conditions” and that “no single microbe put forward by bacteriologists as the cause of a disease has yet complied with more than one.” According to the textbook Infectious Diseases (Fourth Edition), the evidence that was gathered by Koch and his contemporaries could not be “fit” to the postulates, and as more and more evidence was acquired, it became rather clear that fulfilling Koch’s Postulates was implausible.

“It became apparent almost immediately that there were instances where causation was very likely but the postulates could not be made to ‘fit’ the evidence. Koch himself believed Vibrio cholerae to be the cause of cholera, but because the organism had also been isolated from otherwise healthy carriers his second principle was breached. As time passed, more and more examples emerged that stretched the utility of Koch’s postulates right up to – and indeed beyond – the limit of plausibility.”

In fact, it was due to the inability to actually fulfill Koch’s Postulates when looking for a bacterial cause of a disease that the very concept of the “virus” was born, as noted by Fields Virology.

“These studies formalized some of Jacob Henle’s original ideas in what are now termed Koch’s postulates for defining whether an organism was indeed the causative agent of a disease. These postulates state that (a) the organism must be regularly found in the lesions of the disease, (b) the organism must be isolated in pure culture, (c) inoculation of such a pure culture of organisms into a host should initiate the disease, and (d) the organism must be recovered once again from the lesions of the host. By the end of the 19th century, these concepts became the dominant paradigm of medical microbiology. They outlined an experimental method to be used in all situations. It was only when these rules broke down and failed to yield a causative agent that the concept of a virus was born.”

As the inability to satisfy the postulates showed that microbes do not cause disease, germ “theory” defenders have tried to disregard the postulates by claiming that they are outdated, too strict, and are no longer necessary. They claim that we now know that asymptomatic “infections” occur, that “viruses” and some bacteria cannot be grown in pure culture, and that human experimentation is unethical, and animals can not be “infected” with certain microbes. The Reuters article claimed that the postulates were devised at a time “when germ theory was still controversial and before the discovery of viruses” which means that Koch’s Postulates, as originally written, are outdated and no longer apply. Thus, “modern criteria” such as those proposed by Thomas Rivers and Austin Bradford Hill, which are not Koch’s Postulates, are accepted in its place.

However, these excuses put forth to try and explain away the postulates only reinforces that the postulates, as originally devised by Robert Koch, absolutely worked as intended. By failing to satisfy the logic-based rules, microbes as the cause of disease was scientifically disproven. Thus, researchers and “fact checkers” have been trying to either dismiss, work around, or completely revise the postulates (i.e. logic) in a “modern” context in order to continue to try and “fit” the evidence to make the germ “theory” of disease work. Being unable to falsify the hypotheses and being unwilling to change in the face of contradictory evidence are the very hallmarks of pseudoscience.

Regardless of the excuses, the main “infectious” disease institutions in the world still maintain that Koch’s Postulates, as originally devised, must be satisfied in order to prove that any microbe, including “viruses,” are the cause of a disease. For instance, the WHO stated, during the original “SARS epidemic” in 2003, that all of Koch’s Postulates must be satisfied:

“Conclusive identification of a causative must meet all criteria in the so-called “Koch’s postulate.” The additional experiments needed to fulfil these criteria are currently under way at a laboratory in the Netherlands.”

https://web.archive.org/web/20210105005624/https://www.who.int/csr/don/2003_03_27b/en/

On April 16th, 2003, the WHO outlined exactly what steps are required in order to prove a microbe causes disease:

“The 13 laboratories have been working on meeting Koch’s postulates, necessary to prove disease causation. These postulates stipulate that to be the causal agent, a pathogen must meet four conditions: it must be found in all cases of the disease, it must be isolated from the host and grown in pure culture, it must reproduce the original disease when introduced into a susceptible host, and it must be found in the experimental host so infected.”

https://www.who.int/news/item/16-04-2003-update-31—coronavirus-never-before-seen-in-humans-is-the-cause-of-sars

As can be seen, these are Koch’s original postulates. These are not the revised “modern” versions supplied by Thomas Rivers, Austin Bradford Hill, or anyone else for that matter. In agreement with the WHO on the importance of Koch’s Postulates, the CDC’s own field manual published in 2018 titled Optimizing Epidemiology–Laboratory Collaborations, stated that Koch’s postulates form the basis of proof that an emerging agent is the etiological cause of a disease. Each of the postulates was considered necessary to satisfy as just finding an agent does not mean that it is the cause of disease:

“In field investigations that involve emerging pathogens, Koch’s postulates form the basis of proof that an emergent agent is the etiologic agent. Therefore, the interpretation should consider the successful fulfillment of each of Koch’s postulates. Just because an agent is found does not necessarily mean it caused the disease.”

https://www.cdc.gov/eis/field-epi-manual/chapters/Epi-lab-Collaboration.html

Various virologists have also agreed with both the WHO and the CDC that fulfilling Koch’s Postulates is necessary. In 2012, Zaki et al. stated that Koch’s Postulates were important to determining if their “virus” was the causative agent of severe respiratory disease:

“Epidemiologic investigations, active case findings with the use of updated case definitions, and syndrome surveillance in combination with sensitive diagnostic tests will be key to monitoring the present situation and — if necessary — to intervene in a potential outbreak. It will be equally important to test whether HCoV-EMC fulfills Koch’s postulates as the causative agent of severe respiratory disease.”

Zaki MERS “Coronavirus” Paper (2012)

This was backed up by virologist Ron Fouchier, the lead researcher for the 2003 “SARS” paper claiming fulfillment of Koch’s Postulates, who stated (wrongly) that it was KOCH’S Postulates that were fulfilled for “SARS” while speaking about the need to once again fulfill them for MERS:

Ron Fouchier on the New Coronavirus: We Need to Fulfill Koch’s Postulates

“For starters, we’ll find out whether animals get sick from this virus. You can isolate a virus from a patient, but that does not mean they died from it; to show that it causes disease you need to fulfill Koch’s postulates. That’s what we did for SARS, and it’s what we hope to do here; we’ve applied for emergency ethical approval.”

https://www.sciencemag.org/news/2012/09/ron-fouchier-new-coronavirus-we-need-fulfill-kochs-postulates

This was echoed by researchers in 2020 when discussing the fact that “SARS-COV-2” had not fulfilled Koch’s Postulates. According to Zhou et al., the experiments to fulfill the postulates had not been carried out:

“However, there are still many urgent questions that remain to be answered. The association between 2019-nCoV and the disease has not been verified by animal experiments to fulfil the Koch’s postulates to establish a causative relationship between a microorganism and a disease. We do not yet know the transmission routine of this virus among hosts.”

Zhou “SARS-COV-2” Paper (2020)

This same sentiment was reiterated by Zhu et al. who admitted that they had not fulfilled Koch’s Postulates and that these experiments remained to be completed:

“Although our study does not fulfill Koch’s postulates, our analyses provide evidence implicating 2019-nCoV in the Wuhan outbreak. Additional evidence to confirm the etiologic significance of 2019-nCoV in the Wuhan outbreak include identification of a 2019-nCoV antigen in the lung tissue of patients by immunohistochemical analysis, detection of IgM and IgG antiviral antibodies in the serum samples from a patient at two time points to demonstrate seroconversion, and animal (monkey) experiments to provide evidence of pathogenicity.”

Zhu “SARS-COV-2” Paper (2020)

This inability to fulfill Koch’s Postulates for “SARS-COV-2,” or even ones modified to make things easier for the researchers, in order to prove causality was admitted by Hongzhou Lu, the President of Shenzhen Third People’s Hospital:

“But the mystery has not been completely solved yet. Until there is a formal published scientific manuscript, the facts can be argued, particularly regarding causality despite these facts having been officially announced. The data collected so far is not enough to confirm the causal relationship between the new‐type coronavirus and the respiratory disease based on classical Koch’s postulates or
modified ones as suggested by Fredricks and Relman.”

https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25678

In chapter one of the fifth edition of Plant Pathology, it is stated that Koch’s rules are, in fact, possible to implement with all “pathogenic” microbes, even though they are not always easy to carry out. However, it states that in the cases where culture or purification of the pathogen is not yet possible and the pathogen cannot be reintroduced to produce the disease, Koch’s Postulates cannot be carried out. Thus, the acceptance of these microbes as the actual causes of the diseases they are associated with is considered tentative, and it is assumed that further improvement of techniques of isolation, culture, and inoculation of pathogens will someday prove that these assumptions are justified.

“Koch’s rules are possible to implement, although not always easy to carry out, with such pathogens as fungi, bacteria, parasitic higher plants, nematodes, most viruses and viroids, and the spiroplasmas. These organisms can be isolated and cultured, or can be purified, and they can then be introduced into the plant to see if they cause the disease. With the other pathogens, however, such as some viruses, phytoplasmas, fastidious phloem-inhabiting bacteria, protozoa, and even some plant pathogenic fungi that are obligate parasites of plants (such as the powdery mildew, downy mildew, and rust fungi), culture or purification of the pathogen is not yet possible and the pathogen often cannot be reintroduced into the plant to reproduce the disease. Thus, with these pathogens, Koch’s rules cannot be carried out, and their acceptance as the actual pathogens of the diseases with which they are associated is more or less tentative. In most cases, however, the circumstantial evidence is overwhelming, and it is assumed that further improvement of techniques of isolation, culture, and inoculation of pathogens will someday prove that today’s assumptions are justified.”

It is clear to see that, contrary to what the defenders of the germ “theory” want you to believe, Koch’s Postulates are still relevant today and fulfilling all of the postulates is considered necessary in order to prove any microbe can cause disease. Without fulfilling Koch’s logical rules, the “pathogenic” designation is tentative and awaits to be proven in the future. The defenders of germ “theory” do not want to accept this as they know full well that no bacterium has satisfied all four steps of Koch’s Postulates. They also know that, as stated by virologist Thomas Rivers, “it is obvious that Koch’s Postulates have not been satisfied in viral diseases.” Thus, they want you to believe that the postulates are outdated and do not pertain to “viruses.” However, the postulates apply to all microbes and are not outdated. This was summed up brilliantly by virologist Peter Duesberg when he was questioned whether Koch’s criteria are outdated and unable to be used to establish HIV as the cause of AIDS:

“Koch’s postulates are pure logic. Logic will never be “out of date” in science.”

-Peter Duesberg

This article originally appeared on ViroLIEgy’s Antiviral Substack.