To capture the full array of human variation, Georgia Dunston, a geneticist at Howard University in Washington, D.C., leads studies of common diseases such as prostate cancer and hypertension among people of African descent. “There’s knowledge inherent in these diseases, and we can unravel it if we can bring the right thinking to it,” she says. This portrait of Dunston is made up of faces spanning the continuum of human physical appearance.

Unethical science
Segregation wasn’t a bad thing for her education, Dunston said unexpectedly. Even after her home school district in Norfolk, Virginia, was opened up by court order, Dunston remained at the black school. She studied under dedicated black teachers, whose encouragement made up for the thinness of resources.

Her parents, a cook and a dishwasher, never finished high school. Georgia Mae blazed through at the top of her class and entered Norfolk State College on a scholarship when she was only 16. In 1965 she went to Tuskegee University in Alabama, enrolling in the master’s program in biology. She saw white teachers there for the first time.

Tuskegee’s fine record of educating African Americans may be overshadowed by a sorry biomedical episode, the Tuskegee Syphilis Study, which was still in progress during Dunston’s graduate education. Although she didn’t pay much attention at the time, the biological premise of the study was just the kind that she would battle later. In the 1930s researchers for the U.S. Public Health Service suspected that black people and white people might respond differently to syphilis infection. One way to find out was not to treat those who tested positive for the venereal disease and simply monitor their cases as they developed.

The project continued even after an effective treatment for syphilis—penicillin—became available. After the scandal of the Tuskegee study broke in 1972, U.S. health agencies overhauled the ground rules for human research. President Clinton apologized to black Americans for the study in 1997. To this day, Dunston and her Howard University colleagues find themselves addressing Tuskegee-inspired fears when they recruit Washington residents for genetic studies.

Dunston earned her Ph.D. in human genetics at the University of Michigan in 1972 and joined the Howard faculty as an assistant professor of microbiology. She also worked as a consultant in Washington for the Job Corps Sickle Cell Anemia Program. There she found a real-life controversy over purportedly black genes. Prompted by health officials with a dim sense of genetics, the testing of African Americans for sickle-cell disease was a social program that, like the Tuskegee study, backfired on the group it was meant to benefit.

Sickle-cell anemia, a dangerous deformity of hemoglobin in red blood cells, is not limited to blacks any more than cystic fibrosis is to whites. However, a skew in the prevalence of the sickle-cell gene puts African Americans at much higher risk of the disorder than other Americans—about one in 10 blacks are carriers. The numbers in those days were vague, but the issue was the same as the one debated today: Was a person’s racial background a sufficient substitute for his or her genetic vulnerability to a disease? Policymakers decided it was. Between 1970 and 1972 a dozen states and the District of Columbia passed laws mandating sickle-cell screening for African Americans.

Today the laws would be condemned as racial profiling. The stigma was made worse by a misunderstanding of the inheritance of the condition. Contrary to reports of premature deaths, carriers of the sickle-cell gene were in almost all cases healthy; because genes come in pairs, carriers had one normal copy of the gene, making normal hemoglobin. The sick, who were far fewer, inherited two bad copies of the gene from their parents.

Patients having the disease didn’t need to be screened for it, for most already knew. The carriers needed information about their status only if they were planning to have children, who would have a one-in-four risk of getting the disease. But the blood test that was used, the Sickledex test, could not tell people with the sickle-cell trait, called genetic heterozygotes, apart from those with sickle-cell disease, the homozygotes. Therefore black children who had positive results were misdiagnosed and their families unnecessarily frightened. Workers who tested positive lost their jobs in some instances because employers didn’t want to be held responsible for stressing their health.

When Dunston became involved, the federal government had taken over the program, and the coercive laws had been repealed. Proper genetic counseling was supposed to accompany voluntary testing. At the Job Corps center she gave talks to young black adults about the transmission of sickle cell, trying to correct misinformation and mistrust in a community with a long memory.

“A 10 percent frequency [of the trait] doesn’t define a group,” Dunston said. “People assumed that every black had it, as if homozygotes were out there in numbers. It did an injustice to the group because employers now had the power—the “science”—if they needed a reason not to hire someone.”

The great irony of the sickle-cell allele, said Robert Murray, head of Howard’s human genetics department, is that in its singular form “it is a beneficial disease gene, the only one there is.” The allele evolved in Africa, southern Asia, and around the Mediterranean (where many Caucasians carry it) because these zones are plagued with malaria. People who are sickle-cell carriers make hemoglobin that changes shape when the red blood cell is invaded by the malaria parasite, rendering the cell less hospitable to the pathogen. Murray, who advised the federal government on the issue in the early 1970s, recalls pointing out: “Forty percent of Nigeria has this trait. Why aren’t they dying?”

Dunston elaborated. “The gene conferred a biological advantage in an area where malaria was wiping out a lot of folk. We can look at the history of other variants in the same way. It’s all related to population history. The gene tells a history of a population much better than the phenotype [the gene’s outward expression] does.

“Sickle-cell testing was an example of tying genetics to disease in a way that was bad. But now we have an opportunity of getting a better rap for genetics, if you will. With the tools we have now, let’s define the gene not as the culprit or the pathological entity but as the unit interacting with the environment and as part of the science of variation. Variation is a light we can use to understand biology.”

Origins of the sickle-cell trait
One of the most clear-cut examples of environmental influence on the human genome is the sickle-cell trait. Although the blood disorder sickle-cell anemia was first described for medical science early in the 20th century, it was not until 1956 that researchers pinpointed its cause: a single change in a nucleotide in the gene that codes for the oxygen-carrying molecule hemoglobin.

In 1954 molecular biologist Anthony C. Alison had surmised that alterations in the hemoglobin molecule protected against death from malaria. The defense works like this: Having a single copy of the allele confers protection from severe malarial infection by somehow rendering the red blood cell less hospitable to the malaria parasite, Plasmodium falciparum. The downside is that someone with two copies of the allele suffers from sickle-cell anemia, an incurable blood disorder. When two copies of the altered hemoglobin gene are present, they cause the shape of the hemoglobin to change so much that the “sickled” blood cells don’t flow freely in the blood vessels, causing excruciating pain. A child of parents who each possess one copy of the sickle-cell trait has a one-in-four chance of inheriting both sickle-cell alleles—and thus getting sickle-cell anemia.

Of the five variants of the sickle-cell trait, four appear to have originated in Africa and spread through trade routes or the transport of enslaved Africans. The fifth, which is predominant in the Middle East and India, appears to have originated in Asia. The prevalence of the single copy of the gene varies, but in some malaria-prone pockets of India, Africa, and Saudi Arabia, up to 35 percent to 45 percent of the population have the trait. Malaria was confined to the Old World until about 500 years ago, when the malaria parasite gained a foothold in the New World with the arrival of Europeans and Africans. The disease was common in the United States prior to the introduction of DDT and the clearing of swamps.

Other variants of the hemoglobin gene also confer some protection against malaria. One of the most common causes thalassemia, a type of anemia that occurs more often in parts of Africa, the Mediterranean, the Middle East, and Southeast Asia than it does elsewhere.

Ancestry and Africa
The National Institutes of Health became the major funder of Dunston’s laboratories at Howard. In the 1980s she investigated why kidney transplants were being rejected at higher rates by black patients. The problem was that the tests for making immunologic matches between organ donors and recipients were based on “the majority population.” That is, the tissue samples for the antigen panels had come from European Americans and only scratched the surface of human antigenic variation. Antigens are flags on the surface of cells, and they trigger the immune response when the flags are foreign.

“These are genetically inherited characteristics,” Dunston said. “People thought that there were black tissue antigens and white tissue antigens—and I knew that wasn’t so.” Now that antigens are better understood, cross-racial transplants often make better matches than those from within a racial group because, as Dunston is quick to point out, it’s the individual response that counts, not the group’s.

In the 1990s, after two genes for familial breast cancer were identified, Dunston secured a NIH fellowship to study the alleles of breast cancer genes in the African American population. Making an ally of Francis Collins, she laid the groundwork for the National Human Genome Center at Howard University, which was launched in 2001. Its plan, she said, is to search out genes for disorders other than breast cancer, such as prostate cancer, high blood pressure, and diabetes, all of which affect blacks disproportionately.

“My role is not solving the puzzles and problems,” she said to me in her office. “I’m more of a conceptualizer. My strength is recognizing the deficits in our capacity to answer questions.”

I must have implied that she traded on her race with sponsors, because she said acidly: “We’re supposed to pride ourselves when we get government support? We don’t need to be included just because we’ve been excluded. It’s better for the science design of the project. When I’ve said that blacks have to be included, it’s not from the point of view of the social group. I’ve also said that whites as a group can’t serve as the only reference for whites.”

She shifted to the big picture. “Africa may be instructive to Europeans, but it may not be vice versa. Eleven hours of the total 12 hours on the evolutionary clock was spent in Africa. That’s where most human variation occurred. As it migrated out, the base was still there, the base of the diverse human group. The breadth of variation in African people is a tool to look at variation in all of humanity.

“Yes, there is a set of diseases that occur more frequently in blacks, but they’re complex diseases, involving multiple environmental factors and multiple genes too. The causes are tied to biology, not to race. There’s knowledge inherent in these diseases, and we can unravel it if we can bring the right thinking to it.”

In 2003 Howard announced it would establish a repository of genetic samples from 25,000 persons of African descent, an effort lately expanded to include people from West Africa and the Caribbean as well as people from the Washington, D.C., area. But Dunston and her colleagues were unhappy with the press coverage of the biobank plan, which she said focused on “collecting DNA on blacks. That’s only a small part. Other factors will come out of the research.”

She and her colleagues, it seemed, walked a fine line. They pursued the genetic mechanisms behind disease while maintaining that environmental and social factors—unhealthy diets, inactivity, poverty, stress, and other tolls of urban life—were just as important as genes in explaining the prevalence of disease. They denied race biologically but at the same time represented their race in the political competition for research dollars, and they objected when blacks were left out of studies. They called attention to their own work at Howard, then bristled at how the work was characterized by others. “We are gun-shy about other people’s definitions of what we are,” Dunston said.

Yet she has negotiated this minefield for 20 years without an explosion. “A couple of my colleagues say, ‘You’re the Martin Luther King of the group, not the Malcolm X.’ ” She has repeatedly arranged collaborations between Howard and the richer institutions in the neighborhood, such as Georgetown University, Johns Hopkins University, and NIH.

Howard, which has trained black doctors proudly for more than a century, rivals big institutions in quality, but its budget doesn’t compare, and its staff is stretched thin. There’s no padding in the place, no room for error in dealing with the medical establishment. Nor was there eagerness to deal with a medical reporter nosing around the campus and asking about their activities. After a time doors at Howard that had been open to me were quietly closed—except for one. All the more power to Georgia Dunston, I thought.