New Koch

By Dale Bredesen, M.D., Chief Science Officer for Apollo Health

In the search for cures for diseases such as Parkinson’s, Alzheimer’s, and multiple sclerosis, a major impediment has been the lack of understanding of the cause of these and other neurodegenerative conditions. What starts the process, and what drives it? We’ve heard everything from misfolded proteins and protein aggregates to prions to free radicals to amyloid to tau to type 3 diabetes, and on and on, without any of these theories leading to successful treatment. One of the repeated suggestions is that these diseases may result from infections, and the method by which the medical community decides whether a specific organism causes a disease is to use Koch’s postulates, first published in 1890 by Robert Koch and used to show that tuberculosis is caused by Mycobacterium tuberculosis.  

To satisfy Koch’s postulates, four criteria must be met: (1) The microorganism must be found in diseased but not healthy individuals. (2) The microorganism must be cultured from the diseased individual. (3) Inoculation of a healthy individual with the cultured microorganism must recapitulate the disease (of course, this is typically done in animals). (4) The microorganism must be re-isolated from the inoculated, diseased individual and matched to the original microorganism. But it’s a new era, and we need a new Koch — what worked for a simple disease like tuberculosis has not worked for more complex diseases like Parkinson’s, Alzheimer’s, and MS, as recent findings have revealed: in MS, it was discovered that exposure to a Herpes virus, Epstein-Barr virus (EBV, which causes mononucleosis), predates many cases of MS. Even more convincingly, antibodies to one of the EBV proteins (EBNA1) were found to react against a normal brain protein, GlialCAM. But here’s the problem: if you take 1000 people at random, 940 of them will have been exposed to EBV, but only one will develop MS — why? This is not at all in keeping with Koch’s postulates.

More recently, a bacterium in the gut microbiome called Desulfovibrio was found to be associated with Parkinson’s disease, but once again, Koch’s postulates were not satisfied since this same bacterium is found in people without Parkinson’s as well, just at lower levels.

In the case of Alzheimer’s, multiple organisms have been implicated, from Herpes simplex virus to the P. gingivalis of periodontitis to HHV-6A (another Herpes virus), to Chlamydia pneumoniae, as well as others (and possibly the SARS-CoV-2 of COVID-19). So it’s time for new guidelines, new Koch — if we can truly understand what roles these various organisms, and the immune responses to them, play in complex diseases like Alzheimer’s, we have a much better chance of developing cures.