WASHINGTON — Drugs like BiDil, which target a particular racial or ethnic group, do not represent the best approach for looking at health disparities, Dr. Francis S. Collins said at a meeting sponsored by the Department of Health and Human Services and the Office of Minority Health.
“It is a good thing that we have a drug that treats individuals with congestive heart failure and clearly improves their survival,” said Dr. Collins, director of the National Human Genome Research Institute, in Bethesda, Md. “But are we sure this drug would not have benefited other groups?”
The original clinical trial for BiDil (fixed-dose isosorbide dinitrate and hydralazine) seemed to show that only African Americans clearly benefited from the drug, but “it was a relatively modest-sized study, and there could very well have been some benefit in others,” he said. “Are we sure this has anything to do with being African American, or could it be that since African Americans tend to have heart failure on the basis of hypertension, that this [study] says this drug works for hypertensive heart failure and not as well for heart failure from coronary artery disease, which is perhaps more common in other groups?”
With responders lumped into the category of a racial group, “there's a real risk that this will be interpreted as, 'Oh, well, that means black people really are biologically different. After all, there is this drug that only works for them,'” said Dr. Collins. “That is unjustified by the science that's been done here.”
More drugs like BiDil may be coming, but “I don't think this is where we want to go,” he said, noting it would be preferable to ask why the drug works for some and not for others. “What specific DNA variants are responsible for the variation in response? Let's check the individuals and find out whether they're likely to respond to the drug or not, and not use this murky and potentially misleading and damaging proxy called race, and pretend we're practicing really upscale medicine. We can do better than that.”
Part of the problem with using racial groups to explain health disparities is that race is hard to define, Dr. Collins noted.
“First you have to decide exactly what you mean by race. Race has so much baggage; it carries with it connotations of history and discrimination, culture and society, and dietary practices. It carries a little bit of ancestral geography, of course, but that is probably in the minority of what most people are actually thinking of when the term race appears in the census,” he said.
Another problem with separating people into races is that the genetic makeup of all humans is actually quite similar, said Dr. Collins, who leads the Human Genome Project. He noted that people are 99.9% the same, genetically speaking.
“We are much more alike … than most other species on the planet. There's more diversity in a small group of chimpanzees living on one hillside than there is in the entire human race, because we're so new on the scene.”
Most of the variation in the human genome over the last 100,000 years “relates to the ways in which those genes were spread as those people migrated out of Africa to other parts of the world,” he said. And although genomics may play a role in the reasons for health disparities, “it is almost always in concert with environmental factors.”
When new mutations have occurred, for the most part they appear and then disappear, said Dr. Collins. One exception to that, however, is any mutation that gave people a selective advantage. Skin color is an example.
“If you're dark skinned in a northern climate where there's not as much sun exposure, you're likely to get rickets, and someone with rickets will have a difficult time in childbirth. If you have light skin at the equator, you're going to end up with a very high risk of skin cancer,” he said. The way in which lighter-skinned people evolved from their starting point as black Africans just proves that “we white people are actually mutants,” he said.
Now that the Human Genome Project and other private groups have decoded the human genome, researchers are focusing on the 0.1% of the genome that varies among individuals. Dr. Collins is managing the International HapMap Project, a cooperative effort among researchers in six countries to build a catalog of human genetic variation.
“In the space of just 3 years, the HapMap has delivered this remarkable picture of how DNA variation has occurred across all chromosomes,” he said. “This has been a gold mine of information for people trying to unravel the genetic contributions of diabetes, heart disease, mental illness, blindness, and a whole host of conditions that fill up our hospitals and our clinics.” If medical researchers want to know how genetic variation affects predisposition to illness, “we're going to need more data, and the good news is, in another 2 or 3 years, we're going to have a lot more data on this subject and will be much more poised to do something about it,” he said.