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.