Koch’s Postulates

Synonyms

Henle–Koch postulates

Definition

A set of criteria used to identify the specific pathogen that causes an infectious disease.

Characteristics

Koch’s postulates are attributed to Robert Koch, who received the 1905 Nobel Prize in Medicine or Physiology “for his investigations and discoveries in relation to tuberculosis.” Jakob Henle was a professor at the University of Göttingen when Koch enrolled as a student there in 1862, and Henle was one of the early proponents of the idea that contagious diseases were caused by microorganisms. In the early days of bacteriology, there were numerous heated arguments over the identity of pathogenic agents. The presence of commensal microorganisms alongside pathogenic microorganisms often resulted in the misidentification of the real disease-causing organism. At that time, there was also a school of thought which held that there were no true bacterial species, but rather that a bacterium could adopt nearly limitless morphologies and physiologies, which would allow it to cause tuberculosis, anthrax, food spoilage, or other problems depending on the particular form adopted by the bacterium. It was against this backdrop that Koch proposed the following three criteria for identifying a microbiological cause of disease:

• 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. It occurs in no other disease as a fortuitous and non-pathogenic parasite.

• 3. It, after being fully isolated from the body and repeatedly grown in pure culture, can induce the disease anew” (as translated by Thomas M. Rivers).

Koch famously applied these principles as he isolated Bacillus anthracis and Mycobacterium tuberculosis and identified them as the causes of anthrax and tuberculosis, respectively. By establishing a theoretical framework for determining cause and effect, Koch’s postulates had a profound effect on infectious disease research. Within a few decades, the identities of dozens of new pathogens were revealed. Yet these precepts had obvious limitations arising from the simple fact that not all pathogens can be propagated in pure form as autonomous living organisms. Viruses were the first such examples to be considered by the scientific community, and it was soon apparent that Koch’s postulates had to be revised to accommodate the scientific discoveries of the twentieth century. Over the years, since Koch’s postulates were first postulated, many investigators have articulated a revised set of criteria to permit the systematic evaluation of viruses, prions, serum cholesterol, tobacco smoke, chromosomal translocations (Chromosomal Translocation), and other factors as the underlying cause of a disease, contagious or otherwise.

In 1976, Alfred S. Evans proposed the following ten criteria as a “unified concept” for disease causality, which could be applied to either chronic or acute diseases:

• 1. Prevalence of the disease should be significantly higher in those exposed to the putative cause than in case controls not so exposed.

• 2. Exposure to the putative cause should be present more commonly in those with the disease than in controls without the disease when all risk factors are held constant.

• 3. Incidence of the disease should be significantly higher in those exposed to the putative cause than in those not so exposed as shown in prospective studies.

• 4. Temporally, the disease should follow exposure to the putative agent with a distribution of incubation periods on a bell shaped curve.

• 5. A spectrum of host responses should follow exposure to the putative agent along a logical biologic spectrum from mild to severe.

• 6. A measurable host response following exposure to the putative cause should regularly appear in those lacking this before exposure (i.e., antibody, cancer cells) or should increase in magnitude if present before exposure; this pattern should not occur in persons so exposed.

• 7. Experimental reproduction of the disease should occur in higher incidence in animals or man appropriately exposed to the putative cause than in those not so exposed; this exposure may be deliberate in volunteers, experimentally induced in the laboratory, or demonstrated in a controlled regulation of natural exposure.

• 8. Elimination or modification of the putative cause or of the vector carrying it should decrease the incidence of the disease (control of polluted water or smoke or removal of the specific agent).

• 9. Prevention or modification of the host’s response on exposure to the putative cause should decrease or eliminate the disease (immunization, drug to lower cholesterol, specific lymphocyte transfer factor in cancer).

• 10. The whole thing should make biologic and epidemiologic sense.

The correct identification of the cause of a cancer is essential, because the cause can either be avoided, thereby preventing cancer, or the cause can be targeted through drug design, thereby curing the cancer. It is also clear that if one invests preventive or drug design efforts into the wrong cause, then one will have accomplished naught. Obvious limitations of Koch’s postulates arise when one attempts to apply them to noncontagious diseases, when suitable animal models for reproducing the disease do not exist, or when there is an inordinately long latent period between initial exposure to the causal agent and the disease’s manifestation. These circumstances often apply to the development of cancer. The ability of a pathogenic agent to cause cancer is also dependent upon the presence or absence of various tumor suppressors, which causes some individuals to be more susceptible to developing cancer than others. For these and other technical reasons, it is often unwise to dogmatically invoke Koch’s postulates in an effort to disprove a particular agent as a cause of disease. An infamous controversy arose in the late 1980s and early 1990s when Koch’s postulates were invoked in an attempt to disprove that HIV-1 caused AIDS, although that pathogenic link is now universally accepted. Koch’s postulates are of great historical significance because they marked the application of logic and reason to the field of pathology. As many scholars have noted, it is unwise to insist upon the application of the original postulates when we now know that there are pathogenic mechanisms that do not conform to the lifestyles of protozoa, fungi, or bacteria. It is the rigorous application of logic and reason to the elucidation of the cause of disease which remains as the lasting legacy of Koch’s postulates.