Message from the Director
Genomes, Race & Medicine
Huntington F. Willard, PhD
Every so often, a single issue arising at the interface of genome science and public policy gets to the very heart of what the IGSP is about. That's exactly what a drug named BiDil does.
BiDil is a combination of two cardiovascular drugs that its marketer, NitroMed, has been testing exclusively in African Americans for the treatment of heart failure. Why? Because data first collected in the 1980s found that while BiDil had little therapeutic effect in the overall population, it might be of benefit to African Americans.
"Pharmacogenetics represents one of the first and most promising opportunities to bring advances in genomics to the practice of medicine."Last summer, NitroMed halted Phase III clinical trials of BiDil in African Americans because the survival benefit conferred by the drug was so significant (43 percent better in patients versus controls) that the company wanted all patients in the trial to receive it. The drug (and the data) are now under consideration by the Food and Drug Administration (FDA).
This is potentially welcome news for the patients involved. But as new IGSP Center Director David Goldstein (see cover story) and I tried to point out in a recent op-ed (The Boston Globe, January 17), BiDil raises a number of thorny questions. First, how is a physician to decide who among her patients is African American? As we now know from studies of the human genome in many populations worldwide, no more than 10 or 15 percent of our genetic variation can be attributed to our geographic or racial origins. Further, the degree of contribution of an ancestral African genome varies widely among the modern genomes of those who self-identify as African Americans. And if, as many social and life scientists contend, the concept of race is biologically meaningless, then how does one account for BiDil's startling efficacy in the African American population?
As I frequently maintain, the IGSP is uniquely positioned to tackle these questions from a science and a policy perspective. Goldstein's arrival and the creation of the Center for Population Genomics and Pharmacogenetics will enable us to go beyond the crude proxy of race and get at the genetic and environmental roots of why different people respond differently to the same medications. Pharmacogenetics represents one of the first and most promising opportunities to bring advances in genomics to the practice of medicine. The effects are measurable, and the implications for physicians and their patients could be immediate.
Our challenge is even bigger. In an era when the safety of several blockbuster drugs is being questioned, it is incumbent upon us to provide new tools to ensure that individual patients are getting the right drug at the right dose at the right time. Going forward in combination with other stakeholders in translational and clinical research at Duke, there are opportunities for genome sciences to contribute to the burgeoning field of pharmacovigilance: the detection, prevention and assessment of adverse drug reactions. Who's to say that some fraction of the heart attacks linked to Vioxx and Celebrex don’t have a genetic basis? We should find out.
BiDil appears to be one of those cases where a specific population stands to benefit from a particular drug. However, we need to consistently remind ourselves – and the FDA – that pigmentation will never serve as a generally reliable means upon which to deliver healthcare. We need to perform the extensive genome-wide studies that will be needed to find precisely what gene(s) in our
genome are responsible for the BiDil effect. Treating patients effectively will always be more than a skin-deep proposition, and science alone is unlikely to provide all the answers we need. At Duke, we are fortunate to have scholars from across the campus engaged in major efforts to measure and interpret the social and cultural consequences of the intersection of race, ethnicity and genomics.
Beyond issues of race, more general questions of population admixture—the exchange of genes among once-isolated populations—are not limited to humans. Understanding and preserving biodiversity, whether among giant tortoises in the Galapagos or loblolly pines in Duke Forest, increasingly depends upon a thorough understanding of the genomic complement of various species in the context of their peculiar ecosystems. Here again, Goldstein's expertise in population genomics will only enhance Duke's ability to make an impact in this area and further strengthen an already-impressive core of evolutionary genomics investigators in the Department of Biology.
In clinical medicine, the contribution of single genes to a variety of disorders is increasingly appreciated. Now comes the hard part: figuring out the complex genomic underpinnings of common diseases and drug responses and understanding the structure and dynamics of our population along with those of thousands of other species. The IGSP's network of highly interde- pendent Centers will be greatly enhanced by the new Center for Population Genomics and Pharmacogenetics. It brings us one step closer to our goal: understanding and improving life, and leading and engaging society in the Genome Revolution.
Huntington F. Willard
Director