IOM Explores Gene-Environment Interplay

Is biology destiny? That’s the question the Institute of Medicine (IOM) set out to investigate at its annual meeting this fall in Washington, DC. In exploring the interaction of genes and environments, panelists presented a healthy dose of behavioral research, the importance of which biologists and geneticists increasingly realize they can’t overlook.

The IOM, which describes itself as “adviser to the nation to improve health,” is a component of the National Academy of Sciences (NAS), a prestigious independent organization that conducts science policy studies for the U.S. government and other sponsors. Many APS Fellows have been elected to membership in the NAS and the IOM.

At first glance, the conference title, “Is Biology Destiny? The Interaction of Biological, Behavioral, and Social Determinants of Health,” might produce a yawn. We all know by now that: a) it’s not a question of nature vs. nurture anymore, but both, and b) multiple variables need to be factored into the health equation. But we know little about the mechanisms behind this multi-faceted process works. This gap in knowledge was at the heart of the conference. The panelists not only presented cutting-edge research, they expounded on the nature of the interdisciplinary teamwork in which they engaged.

Biology tells us that early development is built into our bodies, but significant adversity during the first three years of life can cause major impairments to development over the lifespan. Jack Shonkoff, Harvard University, reviewed findings that demonstrate a far-reaching relationship between negative childhood experiences and risk factors for both depression and heart disease in adulthood. Shonkoff noted that the public policy arena is saturated with correlational data on low socioeconomic status and poor health, but knowledge of the mechanisms is scant.

On a more microscopic level, APS member Bruce McEwen, The Rockefeller University, touched upon a theme that is increasingly familiar: the plasticity of our brain and how that is modulated by experience. Among other brain regions, the hippocampus, involved in memory, is particularly malleable in the face of stress: it turns out that stress, and its corresponding hormones, including cortisol, stunts neurogenesis, the growth of new cells in adulthood. The hippocampus also shrinks in individuals experiencing depression, post-traumatic stress disorder, sleep deprivation, chronic inflammation, and surprisingly, low self-esteem. On the other hand, short-term stress produces short bursts of cortisol, enabling the “flight or flight” response, which can be essential to survival.  So cortisol acts in a biphasic manner depending on the environment: it both offers protection and causes damage. McEwen stressed the need to look at the cumulative effects of environmental mediators and how they embed in early life.

Encompassing both behavior and genetics, Frances Champagne, Columbia University, discussed biological implications of individual differences in maternal care. Using rodent models, Champagne, who will be speaking at the 2009 APS Convention in San Francisco, has shown that pups licked and groomed more by their mothers more effectively cope with stress. This, in turn, is expressed in the pups’ genes (by way of decreased methylation and the behavior therefore gets passed onto the next generation. Conversely, positive social experiences later in life (e.g., an enriched environment) can alter the effects of an early experience of insufficient grooming. Although changes to the epigenome are a kind of cellular memory of an environmental effect, it’s important to remember that they don’t always dictate later behavior.

Elizabeth Blackburn, a genetics researcher at University of California, San Francisco (UCSF), gave a particularly exciting talk on her work on telomeres, sections of repetitive DNA at the end of chromosomes that protect the chromosomes from destruction. While their degradation is a natural part of aging, stress and behavior can also affect them. Blackburn partners with APS member Elissa Epel, also at UCSF, to look at the relationship between stress and telomeres and the overall impact of this interaction on health. Through studies showing that, for example, caregivers of dementia patients under a great deal of stress have shorter telomeres and smaller amounts of telomerase (the enzyme that produces telomeres), they have presented a strong case for a causal relationship. This undeniably demonstrates the necessity of incorporating behavior into considerations of genetic variability.

Other panels throughout the day focused on more macroscopic topics such as demographic and sociological perspectives on health, interdisciplinary work on health disparities, and the public perception of research. Such multilevel, dynamic processes round out the picture of health and how we can improve it. One panelist, Leon Eisenberg of Harvard Medical School, summed up the conference perfectly: trying to separate out nature and nurture in health research is like asking how much of a rectangle is due to its height and how much is due to its width. The two are fundamentally intertwined, as are behavior and biology.