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The race factor

Times Staff Writer

Washington

IT might be called the Bermuda Triangle of medical research: the intersection of genes, race and disease.

Politically dangerous yet medically alluring, it is drawing into its center a growing number of scientists, backed by the federal government and now joined by a respected African American institution in the nation’s capital.

This summer, Howard University Medical School in Washington announced it will begin building a first-of-its-kind gene bank. Although other gene banks would be larger -- such as Iceland’s DeCode project or the United Kingdom’s proposal to bank the DNA of about 500,000 Britons -- Howard University’s initiative is unique. It proposes to collect and store the DNA only of those who identify themselves as African American.

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Over the next five years, the project would gather the genetic codes, along with personal and family health histories, of about 25,000 people. Once up and running, Howard’s “biobank” could help solve the enduring medical mystery: why African Americans seem to fall ill with so many diseases -- hypertension, heart disease, prostate and breast cancer, asthma, glaucoma and obesity -- more frequently than do white Americans and most major ethnic groups in the United States.

At a time when the nation stews over the practice of racial profiling and debates whether race continues to have any real meaning, Howard’s biobank -- along with a welter of other initiatives -- points toward a provocative conclusion: that some racial differences are encoded in the genes, and those differences can make people of one skin color inherently more or less susceptible to certain diseases than people whose complexion is different. In short, in matters of health, it seems that race matters.

Racism and poverty have long been seen as the reasons for the disparities between the health of black and white Americans, and so the idea that genes might play a role raises deep suspicion. Some fear that race will again be seen as a meaningful dividing line, not just an anachronistic social distinction. Suddenly, they say, it might be fair game to look into the genes for more controversial racial divides in areas such as intelligence, criminality and addiction.

“Whether you’re African American, no matter what you are, when you talk about research on genetics, the antenna will go up. It will go up for anyone. It will go up even higher in the African American community,” says Dr. Floyd Malveaux, president of Howard University College of Medicine. “There’s a great deal of suspicion, and I think that’s healthy suspicion.”

But at hospitals and research institutions across the country, the linkage of genes, race and disease is met with less and less skepticism. Rates of common chronic ailments such as heart disease, diabetes and asthma are significantly higher among African Americans than among non-Latino whites (although Native Americans and Latinos actually suffer higher rates of diabetes than do African Americans). And death rates for such diseases show even greater racial disparities. African American women are more likely to suffer more aggressive forms of breast cancer than white women, are three to four times more likely to develop lupus and are up to nine times more likely to develop uterine fibroids. Obesity is 60% more prevalent in the African American population than among white Americans.

Researchers had long believed that the social, environmental and economic stresses of lower-income and minority status explained those differences, but they could not ignore a growing mountain of research. Studies that compared the incidence of disease among twins, blood relatives and spouses, and among African Americans in different economic strata, all suggested that inheritance plays a key role in the development, course and outcome of certain diseases.

“We know that genetic differences between groups with different racial identities are very minimal -- 99.9% of the genome is similar,” says Dr. W. Timothy Garvey, a University of Alabama diabetes researcher who launched one of the nation’s first genetic studies of disease and race, among the Gullah-speaking African Americans of South Carolina. “But there’s something about that 0.1% that is conferring some additional risk of certain diseases.”

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Tailoring drug research

In recent years, independent researchers and pharmaceutical company researchers have begun to identify broad differences in the ways that Caucasians and African Americans respond to certain medications, suggesting that fundamental physical processes -- not strictly environmental factors -- are at work.

Beta blockers, a mainstay in the treatment of hypertension, seem to lower blood pressure for three in five whites, but for only two in five African Americans. The drug Tamoxifen appears to work less well in preventing the recurrence of breast cancer in African American women than in white women. Another medication, called NitroMed, has shown early promise in treating African Americans -- but not whites -- with heart disease, and the company that developed it has begun clinical trials aimed at marketing the drug specifically to blacks.

The federal government seems to be jumping into the new line of research full force, motivated by commitments to increase the study of historically underserved groups and eliminate health disparities among different ethnic and racial groups by 2010. Howard expects to attract substantial funding from the National Institutes of Health to help underwrite the $18-million cost of its biobank, called GRAD (short for Genomic Research in the African Diaspora).

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And in mid-August, NIH awarded Cedars-Sinai geneticist Jerome I. Rotter $8.5 million to collect and study the genetic material and family histories of about 2,700 Mexican Americans, African Americans and Chinese Americans. With 11 centers across the country, Rotter’s study aims to discern how patterns of genetic differences that run along racial and ethnic lines may affect whether and how heart disease develops in different groups.

When it comes to medicine, says Rotter, “it is very foolish to be colorblind, because ethnic groups differ in their genes. Only to some scientists is this a confusing concept.”

Rotter acknowledges readily that, day in and day out, physicians and medical researchers engage in racial profiling. “In fact, it’s called good medicine,” Rotter says. It prompts scientists to focus on groups that are disproportionately affected by a disease, learning more efficiently about its mechanisms and potential treatments, Rotter says. And physicians, he adds, use it to assess their patients’ particular vulnerabilities and to give them better advice to stay healthy.

Studying the role of genes and ethnicity in health, says Rotter, is not a racist plot. “It’s the responsibility of a multiethnic society” to know if some groups are biologically more vulnerable to certain disease than others.

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A complex relationship

Although racial profiling makes things appear simple, Rotter and others say the relationship among genes, race and disease is complex, and will remain so even after much study. First, there is the definition of race in a society in which people of different races and ethnicities have intermixed for generations. Second, there is the challenge of finding patterns of genetic variation in large groups of individuals when each one has about 30 million places to look (that is the number of sites in each human’s 3 billion base pairs of DNA that are known to vary from person to person).

And then there is the nature of the diseases that seem to strike some ethnic groups harder than others. A few, such as sickle-cell anemia, Tay-Sachs disease and cystic fibrosis, are caused by a single genetic mutation occurring in the same place on the chromosomes every time, and geneticists have located and identified hundreds of these. But many of the common chronic diseases that affect blacks disproportionately are what geneticists call complex-gene disorders.

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That means that they may develop from the interaction of two or more genetic variations or from the interaction of a single gene mutation and factors in an individual’s environment, such as social or physical stresses, exposure to pollutants or diet. There is strong evidence that asthma, obesity, inflammatory bowel disease and depression -- all complex diseases that appear to strike African Americans disproportionately -- have some genetic basis. But in most cases, they may need some external push to manifest themselves.

In his hunt for the cause of diabetes, Garvey seems to be among the small number of scientists not only to have found a gene implicated in a complex gene disorder, but also to have found a clear racial divide between those who have it and those who don’t.

Garvey, who was the lead researcher of the University of South Carolina’s Project Sugar, already has built a small version of the gene bank and family registry that Howard aims to create. Project Sugar has stored genetic samples and medical histories of about 1,146 African Americans with a family history of diabetes along South Carolina’s Sea Islands. Garvey also has collected the same information from about 400 Africans in Sierra Leone -- the population from which the Sea Islands’ Gullah-speaking African Americans are descended.

In 10% of both populations, Garvey found a gene variation that promotes an individual’s ability to use carbohydrates as a principal source of energy, and thus to store dietary fats as body fat. This so-called thrifty gene may have helped many who have it to survive long periods of famine. But in circumstances in which food is plentiful and diets are rich in fat, it can lead to severe obesity. Garvey could find no evidence of this gene variation, called Uncoupling Gene 3, in white and Native American groups he checked for comparison.

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Garvey’s find underscores the importance of environment in triggering a gene’s effects. But the fact that it appears to be found in only Africans and African Americans -- albeit in a small percentage -- is important too, Garvey says. It might give some future physician clues as to who might be advised to get tested and what dose of prevention should be dispensed to the person who tests positive, Garvey says.

“This is an example of why race may be important,” says Garvey. “At least you could counsel people that if you have this gene, it’s very important you don’t consume a high-fat diet.”

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Looking to the future

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The actual balance of genes and environment in these complex diseases remains a subject of debate. Even as he presides over Howard’s ambitious biobank project, Malveaux believes that environment will trump genes after all the research is done.

“I do believe the primary basis and the overwhelming majority of the issues contributing to these disparities have to do with social status and access to health care. I don’t feel that genetics is playing a major role,” Malveaux says. But, he adds, institutions such as Howard need to be participants in such research to ensure that African Americans are being represented and to guarantee that, should improvements in treatment and diagnosis result, Howard graduates and researchers will be ready to use them in the communities they serve.

Some people have taken Howard University to task for its biobank project, and fear the new line of research will begin a slippery slope to racial prejudice.

New York University sociologist Troy Duster says scientists still know too little about which genes do what to use such a biobank well. So when they see a particular genetic variation and a disease in the same racial population, they may wrongly conclude that the gene is causing the disease. The two may only be coincidentally related.

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“We’re into a kind of high-tech phrenology -- where you draw a correlation between the size of the head and structure of the cheekbones and criminal behavior. People now consider that laughable,” Duster says.

Untangling the complex relationship among genes, disease and race now is possible for two reasons. First, the effort to map the human genome has shed light on the structure and function of many genes and other “candidate” locations along the genome, where scientists believe the basis for certain diseases will be found.

Second is the advent of a science called bioinformatics. With supercomputers, massive data storage banks and parallel processing of information, it is becoming possible not only to find a needle in a haystack “about the size of Washington, D.C.,” according to Rotter. These technological advances also allow scientists to sift for the same needle in thousands of different haystacks of equal size, and find broad patterns in the population.

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Legacy of suspicion

But first comes the hard work of gathering those genes -- and all the relevant supporting information -- and storing them in one place. In any population, that can be a daunting challenge. But when the population has been a historical victim of exploitation, abuse and discrimination, suspicion and reluctance compound the task of recruiting participants.

In Rotter’s study of heart disease and Garvey’s of diabetes, a shared history of a disease has helped many participants overcome initial skepticism. But even in these cases it is a daily struggle, says Ida Spruill, Project Sugar’s project coordinator. In seven years of recruiting for Project Sugar, Spruill has been reminded regularly of the notorious Tuskegee Institute syphilis study, in which for 40 years the U.S. Public Health Service tracked 399 African American sharecroppers with venereal disease without informing them of the results or treating their infection.

The memory of the Tuskegee experiments, which ended in 1972, has left a legacy of suspicion among potential study recruits, including her own family, says Spruill. “I don’t want to be bothered; they just want to use us,” they tell her when she makes rounds through the community.

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“Our population has been exploited in the past, so I take it personally,” says Spruill, an African American who is one of 10 siblings -- five of whom have diabetes.

“When people talk to me about being used, I don’t run from it,” says Spruill. “ ‘You’re correct,’ I say. ‘But this is an opportunity to make it right. Make a difference and don’t complain.’ ”


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