- The Washington Times - Sunday, August 3, 2003

NEW YORK

When she learned about 15 years ago that she had high blood pressure, Gloria Taylor was surprised. She had always been the member of the family with low blood pressure.

“I actually didn’t believe it. I don’t want to believe it now,” Mrs. Taylor, 52, said the other day after a doctor’s appointment at Harlem Hospital Center in New York. Why her? Maybe her former eating habits, she speculates.

Scientists would love to know why black Americans like Mrs. Taylor run elevated rates of high blood pressure. And prostate cancer, obesity, asthma and diabetes.

But to find such answers about any racial group, many researchers say, scientists have to accept the idea of classifying people by race for biological studies. And that stirs a contentious debate among scientists and physicians who call race useless for biomedical research, and warn that using it risks lending scientific credibility to racism.

The issue isn’t new, but it resurfaced recently when genetic researchers at Howard University in the District proposed building a collection of DNA and other information from 25,000 people of African descent. The goal would be to find genes and non-genetic factors that explain the elevated rates of major common diseases in that population.

The Howard researchers aren’t alone at the crossroads of biological science and race:

cNitroMed Inc. of Bedford, Mass., is developing an experimental heart-failure drug called BiDil just for blacks. It has begun a study in 1,100 patients to follow up on prior research that indicated the drug works best in blacks. It’s not clear why that’s so, but NitroMed is collecting genetic data from study participants to look for clues, said CEO Michael Loberg.

• A Sarasota, Fla., company called DNAPrint Genomics said in June that its analysis of crime scene DNA had tipped police that a serial killer in southern Louisiana was an unidentified man of mostly black ancestry. Police had initially indicated they were looking for a white man, but they arrested a black suspect in late May and said DNA evidence linked him to the crimes.

• Scientists are seeking about 1,300 black Americans with schizophrenia and 5,000 relatives to look for genes that predispose people to the disease. The federally funded study focuses on American blacks because the unusually wide diversity in their DNA should make locating genes easier, said Rodney Go of the University of Alabama at Birmingham, a leader of the project.

To keep all this in perspective, it helps to realize that the DNA of any two persons of the same sex, no matter what race, is overwhelmingly the same, about 99.9 percent alike.

In fact, scientists say it’s quite possible for two persons of different races to resemble each other more in their DNA than two members of the same race. Research shows that the amount of DNA variation within a continent — Africa, Asia or Europe, for example — is far greater than the variation between continents, by about 9-to-1.

Challenging the idea

The whole idea of race has long been questioned by many scientists. It’s merely a social invention and “biologically meaningless,” a 2001 editorial in the New England Journal of Medicine declared. The American Anthropological Association in 1998 stressed that neighboring populations interbreed and that physical traits tend to vary gradually rather than abruptly over geographic areas. Moreover, knowing one trait, like dark skin, doesn’t unerringly predict the presence of others, like hair texture, the association said.

So “any attempt to establish lines of division among biological populations [is] both arbitrary and subjective,” the association said.

In fact, “most of what’s coming out of modern human genetics now tells us about our genetic brotherhood, and tells us there’s really nothing genetically that argues that one group is in any way superior or inferior to another,” says University of Utah geneticist Lynn Jorde.

“What comes out is we are all genetically similar, and there is a tremendous degree of overlap. There aren’t nice, neat categories you can put people into.”

Mr. Jorde calls it “the happy message.” But he also says that’s not the whole story about human DNA variation.

In fact, he notes, scientists have identified patterns of genetic markers that can reveal a person’s geographic ancestry — a term they prefer to “race,” which they say is ambiguously defined and connotes social aspects as well as biology.

Mr. Jorde, for example, has found that by looking at the overall pattern of details at 160 places in human DNA, a computer could identify whether DNA samples came from Europe, East Asia or sub-Saharan Africa. Others have made similar findings.

But with DNA from south India, which has had waves of migrations, some samples were classified as European and others Asian, showing not everybody is going to “fall neatly into these preconceived categories,” Mr. Jorde said.

Some scientists, in fact, use DNA to calculate what percentage of different ancestries individuals have. Given the intermixing of populations across human history, that makes more sense than assigning people a single race, says Mark Shriver, an assistant professor of anthropology and genetics at Penn State University.

Genes vs. environment

Scientists reported earlier this year that for a group of children from Alabama, the higher the calculated percentage of African ancestry, the less sensitive the body was to insulin, a finding of interest to diabetes researchers.

Scientists say DNA-based studies of ancestry can help them track down the underpinnings of disease and of a good or bad response to medications. The big disease targets are common disorders — high blood pressure, cancer, asthma and others — that appear to result from environmental triggers in combination with many susceptibility genes. These genes are actually specific variants of genes everybody has, and they are devilishly hard to identify.

The question is, if some population has a high rate of a particular disorder, how much of that is caused by an excess of these gene variants vs. environmental factors — everything from food to medical care?

At Howard, a historically black private university, the 2-year-old National Human Genome Center focuses on how DNA and the environment interact in disease susceptibility and treatment in black Americans and others of African descent.

By studying people of African ancestry who live outside that continent, scientists can see how similar genetic backgrounds play out in a variety of environments to promote or suppress diseases, said researcher Charles Rotimi of the center.

Genes clearly aren’t all the whole story, because high blood pressure, diabetes and some other diseases are much more common in American blacks than in Africans despite the similar ancestry, Mr. Rotimi said.

One goal of the center, said Director Georgia Dunston, is to make sure American blacks will share the benefits of individualized medicine based on genetic markers.

Yet, Mr. Rotimi and Mrs. Dunston say, findings in American blacks will benefit everyone.

About 80 percent of the black American DNA pool is rooted in Africa, which provides an unusually wide variation to begin with, Mrs. Dunston said. Add to that the historical mixing-in of genes from people of European descent and American Indians, and you’ve got “a microcosm of human variation,” she said.

Mr. Go, of the University of Alabama at Birmingham, said the results of that history of the black American gene pool should also make it easier to pinpoint schizophrenia-related genes.

Howard University’s proposed “GRAD Biobank” — GRAD stands for Genomic Research in the African Diaspora — has not yet been funded beyond the planning stage. It would build up a large pool of participants by drawing on Howard’s medical clinics and physician networks, and later reaching overseas.

People in the databank would donate not only biological samples for DNA analysis, but also information on diet, lifestyle, access to health care, health beliefs and practices, and other factors considered environmental.

Racial health disparities

Those non-genetic factors aren’t always easy to assess. One focus of the center’s research is how the experience of racism affects the body’s functioning, Mr. Rotimi said, but “try measuring somebody’s reaction to racism.”

The Biobank proposal has some support among scientists. Utah’s Mr. Jorde said black Americans have been underrepresented in many aspects of medical research, and that studying that population’s DNA is “potentially a very good thing.”

Esteban Gonzalez Burchard, who directs the DNA bank at the University of California at San Francisco, also praises the effort. “I think it’s important, and I think we should do this in more populations,” Mr. Burchard said.

But others have reservations. Troy Duster, a sociologist at New York University who studies social implications of biological research, said the Howard plan has the potential to be useful. But he’s concerned that when genetic research is defined by racial groups, it seems to tell the public that race has more biological meaning than it actually does.

It’s “giving a false reality to racial classification systems at a genetic level,” Mr. Duster said.

What’s more, no matter how often scientists say racial differences in disease rates come from complex interactions of genes and environment, he said, a race-based DNA approach tends to focus research and funding priorities on the genetic differences. And that could make policy-makers overlook non-genetic, potentially fixable factors, he said.

At Howard, Mr. Rotimi emphasizes that the genome center is looking beyond DNA for the causes of racial health differences. “A huge chunk of health disparities is the result of social experience,” he said. “We don’t relieve the society of its responsibility to make the necessary changes to begin to reduce the health disparity.”

The reactions to the Howard proposal mirror the overall debate on using race in biomedical research.

“We give a lot of exaggerated emphasis to these concepts of black and white, Asian and so on,” says Richard Cooper, chairman of the department of preventive medicine and epidemiology at the Loyola Stritch School of Medicine in Maywood, Ill.

The roots of racial differences in U.S. rates for common diseases such as cancer, diabetes and high blood pressure are almost certainly environmental, he said. Black Americans have higher rates of a series of diseases that aren’t related at the gene level, he said, and he finds it hard to blame that on an unfortunate collection of unrelated, disease-promoting genes.

Scientists who support seeking genetic influences in racial health differences agree that genes aren’t the whole answer. So why focus on them? “We don’t know what the environmental triggers are” for the targeted common diseases, Mr. Go said. “So we want to get a handle on one piece and then study the other piece.”

And if race were abandoned as a category for research, the search for potential genetic factors in racial health disparities would have to stop, Mr. Burchard said.

“At this point we don’t know all the answers … Let’s not close the door yet,” he said.

Mr. Duster, meanwhile, worries that race-based DNA studies could go beyond studying diseases and unduly pin a genetic rap on blacks for crime. He suggested that “mindless” studies of people in prison could find statistical correlations between crime and particular genetic markers occurring frequently in blacks, for the simple reason that blacks are overrepresented in prison populations.

Even scientists sometimes confuse genetic markers with genetic explanations, he said, so “the danger is both real and present.”

Studying genes that affect behavior is a potential minefield, Mr. Jorde agreed. Behavior is complex, with lots of nongenetic influences, and any genetic component would involve many genes interacting in complicated ways, he said.

So in studies involving race, there might be a tendency to focus on differences in the frequency of a single gene variant and draw conclusions that reinforce stereotypes, which would be “grossly oversimplifying a very complex issue,” Mr. Jorde said.

Mr. Burchard acknowledges the risk that DNA data from biomedical research could be misused to fortify racism. But ignoring race brings the risk of passing up medical advances, he says.

And to him, “the risk of not looking under the hood … far outweighs the risk of potential misuses.”

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