A Grant for a Genius

Commit his name to memory – Sarkis Mazmanian is well on his way to changing the world. The medical microbiologist is one of 23 people to receive the prestigious 2012 MacArthur Fellowship – by popular name the Genius Grant – for his pioneering research of microbes. The title and $500,000 unrestricted monetary award is given to game changers in disciplines ranging from fiction writing to geochemistry.

Focusing on the potential use of bacteria to improve health, Mazmanian and his team at the California Institute of Technology study how beneficial microbes can be harnessed as therapies. With no exaggeration, the work that he and his team of researchers have done in identifying microbes as a positive contributor to the body’s immune system has created a paradigm shift in the field of preventive medicine. Mazmanian’s research has made a measurable impact on finding treatments for multiple sclerosis(MS), staph infection and inflammatory bowel disease.

“I had this simple thought, but I think it was revolutionary in its simplicity,” Mazmanian said. “If I was a bacteria and I was going to intelligently design an activity – and I only lived inside of humans – then I could either passively live there and use the nutrients in that host or I could learn ways to improve the health of that host because the healthier the host is, the more I will thrive, and the better environment I will have.” With that idea, he shifted the thinking within the field of medical microbiology from “all bacteria arebad to some of these bacteria may be good.”

One small step for this man, but in hindsight, one big step for mankind. In a summary of the direction and rationale of his work Mazmanian stated: “The Western world is experiencing a growing medical crisis. Epidemiologic and clinical reports reveal a dramatic increase in immune disorders: inflammatory bowel disease, asthma, type 1 diabetes and multiple sclerosis. Emboldened by the ‘hygiene hypothesis’ proposed two decades ago, scientists have speculated that lifestyle changes (vaccination, sanitation, antibiotics) have predisposed developed societies to these disorders by reducing bacterial infections.

However, the hypothesis remains without explanation as our exposure to most bacteria does not result in disease. Mammals are colonized for life with 100 trillion indigenous bacteria, creating a diverse ecosystem whose contributions to human health remain poorly understood. In recent years, there has been a revolution in biology toward understanding how (and more importantly, why) mammals harbor multitudes of symbiotic bacteria.

We have recently demonstrated for the first time that intestinal bacteria direct universal development of the immune system; thus fundamental aspects of mammalian health are inextricably dependent on microbial symbiosis. Furthermore, it is now clear that all of the diseases in question astonishingly involve a common immunologic defect found in the absence of symbiotic bacteria. As we have co-evolved with our microbial partners for eons, have strategies used against infectious agents reduced our exposure to health-promoting bacteria, ultimately leading to increased disease?

We propose that the human genome does not encode all functions required for health, and we depend on crucial interactions with products of our microbiome (collective genomes of our gut bacterial species). Through genomics, microbiology, immunology and animal models, we wish to define the molecular processes employed by symbiotic bacteria that mediate protection from disease.

Advances in the past year have now made it possible to mine this untapped reservoir for beneficial microbial molecules. Ultimately, understanding the immune mechanisms of these symbiosis factors may lead to natural therapeutics for human diseases based on entirely novel biological principles.”

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