On this date in 1843, Robert Koch, the founder of modern microbiology was born. And on December 10, 1905, one day before his 62nd birthday, he was awarded the Nobel Prize in Physiology or Medicine for his work on tuberculosis.
But what many microbiologists are more familiar with are the Koch’s postulates, four criteria needed to establish a causal relationship between microbe and disease. These are:
- The microorganism must be found in individuals suffering from the disease, but in not healthy individuals,
- The microorganism must be isolated from a diseased individual and grown in pure culture,
- The cultured microbe should cause disease when introduced into a healthy individual, and
- The microbe must be isolated from the inoculated individual and identified as the same microbe from the original source.
Now, more than a century after Koch’s time, how do these postulates hold up?
We now know that most microorganisms cannot be isolated and grown in pure culture using our current methods, some microbes cannot exist outside of a host (and therefore cannot be cultured), and that the same microbe may cause symptoms in one person but not in another (H. pylori for example is asymptomatic in most people). These examples are thus contrary to Koch’s second and third postulate.
David Fredricks and David Relman of Stanford University School of Medicine revisited Koch’s postulates just over a hundred years after Koch put forth his postulates. In 1996, Fredricks and Relman suggested some revisions to account for the growing knowledge of microbiology in the context of molecular biology. Based on nucleic acid sequence, these revisions focus on using DNA (or RNA) sequence to identify suspected pathogens. These revisions include:
- A nucleic acid sequence belonging to the suspected microbe should be present in most cases of infection. These sequences should be found in higher numbers in locations known to be diseased and not in organs that are not diseased,
- Fewer (or no copies) of pathogen-associated nucleic acid sequences should be in hosts or tissues without disease,
- When the infection resolves, the copies of pathogen-associated nucleic acid sequences should decrease or disappear altogether,
- Correlation between copy numbers of the microbial sequence and severity of disease likely indicates a causal relationship,
- The microbe inferred from the nucleic acid sequence should be consistent with known characteristics of that group of organisms,
- Sequences found in tissues should be verified at the cellular level either by direct observation of microorganisms in the tissue or in situ hybridization at the site(s) of tissue pathology, and
- The sequence data as evidence for microbe-disease causation must be reproducible.
Today, Fredricks and Relman’s postulates incorporate technologies and methodologies that were unimaginable or only a pipe dream in Koch’s time. While Koch’s postulates may not completely hold true for all microorganisms, his work laid the foundation necessary to propel much of modern microbiology.