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January 15, 2005 | The FDA is on the verge of approving the first "ethnic medicine" — a heart disease drug called BiDil that is particularly effective in African-Americans. Some see this as a belated effort to redress long-standing health inequalities in the United States. Others view it as a treacherous first step en route to racial discrimination in the name of personalized medicine.

BiDil is a combination of two drugs that elevate nitric oxide (NO) levels, which yielded poor results in early trials conducted in a mixed population. NitroMed, based in Lexington, Mass., obtained a new patent on the therapy targeted specifically to African-Americans. The rationale: African-Americans experience double the risk of heart disease than whites, are less responsive to conventional drugs, and exhibit lower physiological NO levels.

With support from the Association of Black Cardiologists and the Congressional Black Caucus, NitroMed launched A-HeFT, a Phase III trial of 1,050 African-American patients. (The company assuaged concerns of patients and physicians, for whom an African-American-only trial rekindled memories of the shameful Tuskegee syphilis experiment.) The trial was halted last summer, as doctors recorded a striking 43-percent reduction in heart attacks in patients taking BiDil (Taylor, A. et al. N Engl J Med 351, 2049; 2004).

BiDil's success has intensified debate about the use of race in genetics. In a genetics workshop last October*, David Goldstein (University College London) said that before approving BiDil the FDA "should first require a very substantial and serious pharmacogenetic effort to see if genetic determinants ... might explain the [population] difference." Goldstein would like to see more research into environmental determinants before pushing a medicine onto a particular ethnic group. "Race for prescription is only an interim solution to carry us through a period of ignorance until we find the underlying causes," Goldstein says.


PRESSURE: Manuel Worcel 
What is so bad about using self-identified racial groupings for targeting drugs? Genetic variation within and between different populations generally exists as a continuum rather than discrete clusters. "We are all Africans beneath our skin; we all moved out of Africa at some point," cautions Charles Rotimi of the National Human Genome Center at Howard University. Slaves were brought to America from vast swathes of Africa — hardly common ancestry — and the subsequent European admixture among African-Americans is well documented.


'Very Complicated' 
Such nuances are unlikely to overturn popular racial designations. What happens when the wide-ranging frequencies of gene markers across different populations produce aberrant statistical correlations with traits rather than diseases? "This is going to happen," warns Francis Collins, director of the National Human Genome Research Institute. "People are studying all manner of things, from athletic abilities to how you score on an IQ test. Variations will be discovered that have very tiny contributions to those very complicated and very environmentally driven circumstances. You can imagine how misrepresentation of early data, before [they have] been validated, could be a profoundly negative moment for the field of complex genetics."

Manuel Worcel, NitroMed's chief medical officer, acknowledged that not all African-Americans respond to BiDil, and he believes that environmental factors, including smoking, diet, and socioeconomic status, play a key role in the differential symptoms and drug response of African-Americans. Although the company is beginning to analyze DNA samples from heart-disease patients, he bristles at the notion of waiting until such pharmacogenetic data are available. To postpone the use of BiDil, which reduces hospitalizations by close to 40 percent, would be "a disservice" to his patients. Drugs are approved based on clinical events — why should BiDil be an exception?

NitroMed has come under considerable scrutiny for championing BiDil as an "ethnic medicine." Bioethicist Jonathan Karp charged: "Medical researchers may use race as a surrogate to get at biology in drug development, but corporations are using biology as a surrogate to get at race in drug marketing." Many people, however, feel BiDil is long overdue. Howard University bioethicist Charmaine Royal quotes Martin Luther King Jr.: "Of all the injustices that exist, inequality in health is the most shocking and the most inhumane."* 




For reprints and/or copyright permission, please contact  Terry Manning, 781.972.1349 , tmanning@healthtech.com.