Race and medicine can mix without prejudiceA research team at the University of Minnesota School of Medicine recently unveiled the results of a medication tested only in black patients. The drug, called BiDil, is expected to receive FDA approval next year and will be marketed for use in African American patients with heart failure.
How the story of BiDil illuminates the future of medicine.
Sally Satel, MD
December 10, 2004
Dubbed the first "ethnic drug," BiDil was greeted with both excitement and apprehension. As the Boston Globe put it, "Heart Drug Seen Aiding Blacks: Research Findings Stoke Race Debate." The longstanding debate is between those who insist that race has clinically relevant biological dimensions versus those who claim that race is nothing more than a cultural construct. BiDil's moment in the spotlight, then, offers an opportunity to resolve some confusion over the relationship between race and genetics.
What is BiDil? It is a combination of two older drugs - isosorbide dinitrate and hydralazine - that dilate blood vessels and reduce blood pressure. When tested in a broad sample several years ago, it showed little benefit and failed to get FDA approval. When the trial data were later reanalyzed by race, however, the combination appeared to work better in black patients than in whites, though too few blacks were included in the study to be certain.
This prompted researchers to conduct an all-black study of BiDil which so successful it was halted months ahead of schedule to permit the patients on placebo to begin taking the drug. The striking results were published last Thursday in the New England Journal of Medicine. Of the patients who took BiDil (plus their standard medication regimen) only 16.4% required hospitalization for heart failure, versus 24.4% of the standard treatment group. Mortality differed as well - 6.4% taking Bidil died compared to 10.2% who got standard heart failure drugs plus a placebo.
The notion that certain groups respond differently to some medications comes as no surprise to geneticists, physicians and pharmacologists. In the 1950's public health doctors treating Canadian Eskimos for tuberculosis made an early observation that when they used standard-dose isoniazid, the infection persisted. Eventually the mystery was solved once it was recognized that the Inuits metabolized isoniazid so quickly that the usual (Canadian) dose had little impact. Last month, the prestigious journal Nature Genetics reported that at least 29 medicines have been shown to be either safer or more effective in certain populations because of genetic differences.
How is this possible when humans share 99.9% of their DNA, as the Human Genome Project has revealed? How can race-related variations be medically meaningful if we are so similar? Because that .1% difference means a great deal. After all, we share a large amount - 98 % - of our genetic makeup with chimpanzees. Or consider the DNA itself. The unshared amount residing in the .1% comprises over three million nucleotides - the building blocks of genes. A mutation of even a single nucleotide can cause the gene within which it is embedded to produce an altered protein or enzyme that determines disease or, theoretically, response to treatment.
Many genetic variations are embedded in that .1% and those variations tend to cluster by racial groups - that is, by people whose ancestors came from a particular geographic region. This is called population genetics - the uncontested fact that people who share a common lineage are more likely to have more gene variants in common with each other than with people whose ancestors are from a different group.
To be sure, noting that a patient is, say, African-American is a crude marker of biological identity. For most therapies - so far as we know - it is not important. But when it is, doctors should inquire about mixed heritage. And be as specific as possible. There is far more clinical value, for example, in distinguishing a white person who is Irish or of Ashkenazi Jewish descent from another who has Scandinavian roots.
The Association of Black Cardiologists recognized this from the start. It helped recruit almost 1100 patients for the BiDil study that took place in 161 research centers across the U.S. between 1999 and the summer of 2004. Is heart failure in blacks - or in any group for that matter - all about genes? No. As Keith Ferdinand, president of the Association of Black Cardiologists and one of the BiDil researchers, rightly reminds us "heart failure is a complicated illness - involving environmental factors, such as access to quality care, timely care, diet, income-level, stress."
But genetic factors do play a role. How much of a role they play in response to the drug is now being explored by the BiDil team as it examines responders for genetic markers that differentiate them from non-responders. This makes some people nervous. "Anything that invites the perception of African Americans as biologically different is a huge worry," said Dr. Gregg Bloche, who wrote the editorial on Bidil in last week's Journal.
How to dispel that worry? By taking pains to specify whether we mean social race or biological lineage when we talk about race-based therapeutics. Social race is the phenomenon constructionists have in mind - the idea that an individual himself and society's perception of him influences the ethnic or racial group with which he is identified. Biological race, however, is what BiDil's developers are concerned with - that is, race as ancestry.
Three years ago when BiDil trials were beginning, the one news story headline asked: Shouldn't A Pill Be Colorblind? This time around, the extensive - and predominantly optimistic - coverage of the BiDil story recognizes that diseases and treatments are not colorblind, so doctors and researchers should not be either.
Some day geneticists hope to be able to conduct genomic profiles of each individual, making group identity irrelevant - but until then, race-based therapeutics has its virtues.
Sally Satel, M.D., is a Resident Scholar at the American Enterprise Institute.