A ‘theory of everything’ for disease?

Theoretical physicists have long sought a grand “theory of everything,” which would account for all the physical phenomena in the universe by unifying Einstein’s general relativity with the so-called standard model based on quantum mechanics.

In recent years, some biomedical scientists, including School of Medicine immunobiologists Richard A. Flavell, Ph.D., and Ruslan M. Medzhitov, Ph.D., have proposed that deeply understanding inflammatory processes might provide similar unifying insights into a great range of seemingly dissimilar chronic diseases: heart disease, cancer, type 2 diabetes, Alzheimer’s disease, and more.

Thanks to a $10 million grant from the Blavatnik Family Foundation, a charitable organization started by American industrialist and philanthropist Leonard Blavatnik, Flavell and Medzhitov will now have the opportunity to put their ideas to the test. “The Blavatnik Family Foundation is proud to support breakthrough scientific discoveries that accelerate the impact of biomedical research,” Blavatnik says. “The theory proposed by Drs. Flavell and Medzhitov represents a paradigm shift in the science of chronic diseases and may lead to new prevention strategies, treatments, and even cures for many disorders.”

The healthy human body regulates its own tissues and organs to maintain key physiological variables in a beneficial balance, a steady state that scientists call homeostasis. The body even gets some outside help from microbes, or commensal microorganisms, that reside on the skin and in the digestive tract and play a part in maintaining core body temperature, blood pressure, blood sugar, sleep patterns, and a host of metabolic processes needed for fitness and survival.

When infection or tissue damage occurs, the body’s innate immune system activates inflammatory mechanisms that help to combat these dangers and restore a proper balance, at least in the short term. Flavell, chair and Sterling Professor of Immunobiology, and Medzhitov, the David Wallace Professor of Immunobiology, postulate that these same inflammatory mechanisms can have a cumulative damaging effect on homeostatic controls—an effect they believe is a root cause of many serious health disorders. With the new grant from the Blavatnik Family Foundation, the scientists plan a detailed study to define the molecular links between inflammation, commensal microorganisms, and chronic disease.

Yale President-elect Peter Salovey expressed the University’s gratitude to the Blavatnik Family Foundation for what he called “an extremely generous and far-sighted” contribution. “The research now under way in the Medzhitov and Flavell laboratories has the potential to transform our understanding of human biology and our approaches to the most intractable diseases. This grant will accelerate their work at Yale’s Department of Immunobiology, which is world-renowned for leading major advances in innate and adaptive immunity,” Salovey said.

Medzhitov and Flavell, both of whom are Howard Hughes Medical Institute investigators, have led pioneering studies on the control of inflammation by the innate immune system.

Medzhitov is widely recognized for classic studies he conducted in the late 1990s with the late Charles A. Janeway Jr., M.D., that clarified the functions and importance of the innate immune system, work for which he received a Blavatnik Award for Young Scientists in 2007. In February, Medzhitov and Flavell were jointly awarded the 2013 Vilcek Prize for Biomedical Science.

Robert J. Alpern, M.D., dean of the School of Medicine, believes that a unified theory of inflammation and chronic disease will be a game-changer. “This work offers a whole new way to look at the causes of many chronic illnesses, including cardiovascular disease, type 2 diabetes, autoimmune diseases, asthma and allergies, neurodegenerative diseases such as Alzheimer’s disease, and cancer,” Alpern says. “A few years from now, I am optimistic that we will be in a position to develop new therapeutics that can broadly impact human health and quality of life.”

The founder and chair of Access Industries, Leonard Blavatnik is deeply committed to supporting innovation in biomedical research and higher education. In 2007, the Blavatnik Family Foundation established the Blavatnik Awards for Young Scientists, awarded through the New York Academy of Sciences, to recognize innovative and high-impact accomplishments in the life sciences, physical sciences, mathematics, and engineering. Blavatnik has supported the Broad Institute at Harvard University and MIT, and he has provided seed funding at Harvard for highly promising, early-stage research in the life sciences. In 2010, he contributed more than $115 million to the University of Oxford to establish the Blavatnik School of Government.