Robert Koch was another “giant of microbiology”, who made several big advances in bacteriology towards the end of the 19th century. So numerous were his acheivements I am sure he will feature in future articles on this website.

In this article I want to review his 4 “postulates”, which he published in 1890. There was a reasonable amount known then about micro-organisms, but little to prove a causal link between them and a specific disease entity. The “miasma theory” still predominated. The four postulates were designed to establish “proof of causation”.

Koch’s postulates were as follows:

• The micro-organism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy hosts. This is not always true as we are aware as there are lots of micro-organisms which can both colonise and cause disease in the host.
• The micro-organism must be isolated from a diseased organism and grown in pure culture. We know that some organisms are very difficult to grow outside the host, Treponema pallidum being an example.
• The cultured micro-organism should cause disease when introduced into a healthy hosts. We are also aware that this does not always hold up as progression from colonisation to infection depends not only on the micro-organism, but also on host immunity.
• The micro-organism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

I think Koch did pretty well with the postulates, considering just how little was known about “germ theory” at the time.

A modern day version of Koch’s postulates has since been published by Fredricks and Relman in 1996, to take into account new knowledge and molecular techniques. They are as follows:

• 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.
• Fewer, or no, copies of pathogen-associated nucleic acid sequences should occur in hosts or tissues without disease.
• 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.
• 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.
• The nature of the microorganism inferred from the available sequence should be consistent with the known biological characteristics of that group of organisms.
• 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.
• These sequence-based forms of evidence for microbial causation should be reproducible.

The modern postulates are “politically correct”, but to be honest I find them tedious and difficult reading. I think I prefer the original postulates by Robert Koch, flawed as they were…..

Click here for a 2 minute biography about Robert Koch and the discoveries that he made.

Michael

p.s. I recall being taught Koch’s postulates in what I think was the first ever microbiology lecture I attended. In my hungover and sleep deprived student days, it must have made an impact for me to remember it!