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“Evildoers”

For many, the main motivation to better understand the factors behind ethnic differences is the troubling health disparities among groups in this country. Many of those disparities are likely due to varying access to health care and to other economic factors. But most existing medicines were tested in clinical trials in which most of the participants were white; if there are genetic differences in how various ethnic populations respond to drugs, they could be widening the gap in health outcomes.

Esteban Gonzalez Burchard has a quick and affable way of speaking that seems to suddenly slow and turn serious when he explains the subject of his research: why Hispanic populations suffer such dramatically different rates of asthma and respond so differently to asthma drugs. In the United States, Puerto Ricans have a higher rate of asthma than any other ethnic group and tend to respond poorly to albuterol, the leading asthma drug, while Mexican Americans have a low rate of the disease and are effectively treated with medications. It’s a perplexing epidemiology riddle as well as a public-health puzzle that affects thousands of lives. Says Burchard, “When a Puerto Rican kid takes albuterol, he is just not getting the same bang for his buck as any other kid.”

Like many other areas of genomic research, Burchard’s work is at an early stage, and the challenges he faces point up the difficulty of determining the role that ethnic differences play in diseases. Hispanics are extremely diverse culturally and socially; genetically, they have varying mixtures of African, European, and Native American ancestry. But by teasing out the relative contribution of each ancestral group in a particular population (Mexicans, for example, tend to have far smaller genetic inheritance from African ancestors than Puerto Ricans do), Burchard attempts to zero in on specific genetic factors.

Most recently, Burchard, a physician and assistant professor of medicine and biopharmaceutical sciences at the University of California, San Francisco, identified specific genetic variants that seem to be associated with a lesser response to albuterol in Puerto Ricans; in Mexicans, the same variant seemed to have no connection to albuterol. While such a finding might seem ambiguous and inconclusive, it’s suggestive to Burchard that some still unidentified factor is behind the ethnic difference. And Burchard says that that is just the point: he might not have yet found the smoking gun, but “I can smell the smoke.”

The opportunities created by looking at ethnic differences in medicine are “far bigger than BiDil,” says Burchard. Health disparities among racial groups are invaluable clues to untangling underlying genetic and environmental factors that could make it possible to design safer and far more effective drugs. And it is essential that those clues be followed, says Burchard. “We do see racial differences between populations and shouldn’t just close our eyes,” he says. “Unfortunately, race is a politically charged topic, and there will be evildoers. But the fear should not outweigh the benefit of looking.”

Whether BiDil, with its complicated history and decades-long evolution into a race-specific drug, is the right way to begin making sense of race, medicine, and genetics is debated. Jonathan Kahn, a law professor at Hamline University in Saint Paul, MN, who has written extensively about the history of BiDil and the legal issues surrounding it, maintains that the reasons that the drug is being marketed to African Americans have far more to do with business and patent issues than medical ones. And yet, says Kahn, if the FDA approves the drug exclusively for blacks, it “lends credence to the misguided idea that race is somehow genetic.”

Indeed, much of the controversy over BiDil is really about the message that the drug’s approval will send to the general public. No one claims that the drug will work only for African Americans; nor does anyone pretend to have identified specific genetic factors exclusive to black patients that account for the drug’s effectiveness. Like racial categories themselves, the group of patients whom BiDil will benefit remains ambiguous. But here the disagreement starts: is it worthwhile to use race as a crude, stopgap approximation, or is giving the pill only to black patients a dangerous shortcut to genetic profiling that many in the public will, intentionally or otherwise, misconstrue?

There is no easy answer to the question of how to best balance medical expediency with social consequences. But the real danger of BiDil as a race-based medicine could be in its potential to turn the public’s understanding of complex genomic research on differing drug response and disease susceptibility among populations into a simple black-and-white issue.

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