Embracing the “Trial and Error” approach in drug discovery
March 13, 2014
Humans are ecosystems, just like the kefir yoghurt
March 23, 2014
by Marija (Masha) Zecevic
Back in 2001, in Tuscany, while attending the most bizarre conference of my PhD years, I cornered Lynn Margulis into a small talk. Few months before the event in Cortona, I had read James Lovelock’s book on the Gaia hypothesis and I was spellbound by it. No way I was going to let the creator of the endosymbiosis theory and a close collaborator of Lovelock get away without a conversation!
I remember Dr. Margulis telling me, among other things, about kefir. Kefir, also know as “the champagne of the Caucasus Mountains” is a live symbiotic food naturally selected during the past three thousand years by the long-lived Caucasians (1). Some go far and speculate that kefir is the reason why there are so many ultra-centennials in Georgia.
According to Margulis, kefir isn’t just any yoghurt that only happens to be made and commonly eaten in the Caucasus region. It is a live culture composed of over 20 different types of organisms including bacteria, fungi and yeast. Almost all attempts to propagate the live cultures outside of Georgia and manufacture kefir elsewhere have failed after few passages. “That’s because kefir is not a mixture of microorganisms but it is a specific super organism by itself” Margulis told me, “you cannot take it apart and reassemble. It has to live its own life”.
Are humans a bit like kefir?
After all, for each human cell there are 10 cells from microorganisms that too are part of our body. Our genes are outnumbered 100 to 1 by microbial genes. The NIH funded Human Microbiome Project has successfully characterized the composition and diversity of microbial communities which inhabit ins and outs of the human body. It turns out most of our fellow microorganisms are good for us and each human has a specific population that does not change much with time.
In a recent PLOS paper, medical mycologist Mahmoud Ghannoum studied the Candida infection in the oral mucosa of babies and immunocompromised HIV patients. Ghannoum group showed that Candida is kept in check in normal subjects not by the host’s immune system but rather by a fellow fungus cohabiting the oral cavity call Pichia. The healthy fungal rivalry keeps the overall oral ecosystem under control and if Pichia levels fall low, as is the case in people with HIV, Candida takes over causing the condition called thrush. In animal models, a Pichia derived extract has anti-fungal properties able to kill Candida and possibly give source to novel therapeutic anti-micotic agents.
Humans are not just the result of our own genome but also of our microbiome, that is the genetic elements of tens of thousands of microorganisms with whom we live in symbiosis and make us what we are.
How wonderful it is to think that the new frontier in drug discovery will be the manipulation of human microbiome.
There are many companies today that are venturing into this area with powerful new techniques and innovative approaches. Although, as a proof that the theory is solid, it might be sufficient to look at an old hypothesis that has recently been tested in properly designed clinical trials generating surprising evidence of efficacy: fecal transplantation.
But fecal transplantation is a topic that is complex and too much fun to talk about in this post so I’ll leave it for another time.
(1) Dazzle Gradually: Reflections on the Nature of Nature, By Dorion Sagan, Lynn Margulis