A heart failure drug shown effective in African-Americans stands to become the first ethnically targeted drug, if a Lexington biotechnology firm is successful in its bid for federal approval.
It would be the first drug targeted at patients on the basis of ancestry -- a dangerous precedent, some ethicists and activists say, because a new marriage of race and genetics could distract from the real causes of disease.
The tricky part of this emerging debate is that the drug, BiDil, seems to work, extending the lives of African-Americans who sustain heart failure. The latest trial of BiDil was halted last month by an outside panel that decided the drug was so effective it was unconscionable to let some patients continue to get a placebo instead of BiDil. An earlier trial found the drug was of relatively little benefit to white patients.
So, if the government doesn't approve BiDil, it would deny African-Americans treatment for a disease that strikes them earlier than whites, often with a deadly outcome; if it does approve it, some will accuse the government of racism and bad science.
''I think if people get one little inkling that there's a biological basis to race, we could potentially lose ground into understanding racial difference in disease," said JudyAnn Bigby, director of the Office for Women, Family and Community Programs at Brigham and Women's Hospital.
Bigby said that heart failure does seem to have different causes in black and white patients, but that to see genetics at the root would be an oversimplification. A slew of other factors contribute, including low income, which fosters bad eating and exercise habits and may restrict access to health care. ''Biology could be an excuse for not looking at the social basis of disease," she said.
No one involved with the study believes that race is the optimal way to distinguish who will respond to the drug and who will not. But, with the promise of the human genome project -- a medicine cabinet tailored to fit each patient's genome -- still a distant dream, researchers have begun to look to race as a rough marker for underlying genetic differences.
Race, already a good indicator for certain genetic diseases like Tay Sachs, which affects mostly Jews of Eastern-European descent, and sickle-cell anemia, which is concentrated among African-Americans, might help doctors understand who is at risk for a disease.
''There is no question that depending upon your geographic descent, your heritage, that we see different prevalences of diseases and risk factors," said Anne Taylor, a professor of medicine at the University of Minnesota Medical School and chairwoman of the BiDil study.
By searching for genetic similarities among patients who responded to BiDil, scientists may find that the drug works for non-African-American patients with the same genes, and better understand how and why the drug works at all, said Michael Loberg, chief executive officer of NitroMed, which makes BiDil.
The upside of NitroMed's attention to racial differences: The company went out of its way to find black patients for its trials. Even though heart failure strikes African-Americans younger than white Americans, only 4,000 black patients have ever participated in a heart failure study. BiDil's clinical trials accounted for 1,500 of those subjects.
''Given the prevalence of heart failure in African-Americans in the United States, they should always be included to know whether a given treatment is effective," said Bigby, who spends a lot of her professional life pushing for more minority participation in health studies.
BiDil isn't new. It's a combination of two generic drugs that were first tested for heart failure more than 20 years ago. The drug was rejected by the Food and Drug Administration in 1997 in part because the application was based on outdated studies, so researchers re-examined the data and showed that in the 395 blacks included in the old studies, it worked better than in whites.
In March 2001, NitroMed announced that it had received a letter from the FDA confirming, according to a company press release, ''that BiDil could potentially provide a survival benefit in African-American heart failure patients," and requesting a new drug trial to confirm the results. That trial was stopped last month.
The current debate has been building since the company announced it would seek approval for the drug, but erupted over the winter, when lawyer and bioethicist Jonathan Kahn wrote a 40-page paper in the Yale Journal of Health, Policy, Law and Ethics questioning how BiDil became an ''ethnic" drug.
If approval is given, ''you have the federal government giving its imprimatur, its stamp of approval, to using race as a biological category," Kahn, of Hamline University in Minnesota, said in an interview. ''To my mind, it's the road to hell being paved with good intentions."
Douglas Throckmorton, the acting director of the Center for Drug Evaluation and Research at the FDA, said the agency would ask the same questions of BiDil as it does of every drug: Does it work, and for whom?
''In other cases, that's led to descriptions of use in children, descriptions of use in women -- so extending that to ethnic descriptions in some sense falls within a sort of norm for the agency," Throckmorton said.
Others say that if the FDA approves BiDil as a drug for African-Americans, it will send science down a slippery slope, where race -- a social category -- will be confused with biology in the ensuing ''marketing spin."
''To a hammer, everything looks like a nail. To a geneticist or a pharmaceutical researcher, everything looks like a genetic problem," said anthropologist Michael Montoya of the University of California at Irvine, who believes that disparities in disease -- such as the prevalence of Type 2 diabetes in Mexican-Americans -- are based on environment rather than genetics.
To people who have heart disease, such a debate is irrelevant, as long as an effective drug reaches those in need.
''I don't care if a drug is just for minorities, I don't have a problem with that," said Laureston ''Butch" Layne, 49, who has had heart problems since 1985. The Massachusetts General Hospital dispatcher tried drugs, open-heart surgery, 41 attempts at shocking his heart back into a proper rhythm, and finally a heart transplant last September.
''When you go through what I went through," Layne said, ''any drug, even if it's a racial thing, you'd have to be crazy not to want to use it."