Race and the Genome

Less than three percent of the human genome consists of genes whose products are expressed to create our minds and bodies, and less than one percent of these genes produce visible characteristics like skin color. Yet history has been marked by discrimination based on the visible, but biologically negligible, differences called "racial" characteristics.

Which puts the new National Human Genome Center at Howard University, and its director and founder Georgia Dunston, professor and chair of microbiology and director of human immunogenics for the university, in the odd position of making the scientific case against the biological importance of race while pressing for efforts to increase inclusion of Africans and African-Americans in genetic research, both as researchers and participants.

Dunston's lab is currently conducting research on West Africans and on African-Americans, looking for genes for diabetes and prostate cancer, both of which disproportionately affect people of African descent. The center was conceived in the early nineties, but it was not until 1998 that Dunston gained enough funding to hire new staff and significantly increase lab capacity.

"Statistics show that 85 percent of human variation is within whites or blacks, not between them," says Dunston. "The category of 'black' or 'white' is spurious and the differences that are observable provide no basis for partitioning groups." There are, however, differences that relate to particular genetic lineages, so it is important for all groups seeking to benefit from genetic research to participate in it.

Dunston came to genomic research via her interest in transplantation, a field that provides another illustration of the superficiality of racial differences. In order to match tissues, researchers look at an immune system component called the Major Histocompatibility Complex. A match of six HLA antigens in this system means an organ is compatible. Quite frequently, cross-racial transplants provide better matches than those from the same racial groups.

Because racism continues to play a role in how African-Americans are treated, and because genetic research has often been used in attempts to prove racial inferiority, Dunston fought hard to ensure that the traditionally black Howard University would play an important role in the Human Genome Project. Creating a center for genomic research at Howard increases the university's ability to train black researchers and attract more into the field, while conducting research that could benefit African-Americans.

"The human genome project is a major event of our time and one important [if not the essential] characteristic of the genome is sequence variation," says Dunston. "Populations vary in their patterns of genetic variation, and what I proposed with others at Howard was that we need to have a resource that [allows examination of] the variation in the African-American population."

"Since the African population is the oldest group, there has been more time for the accumulation of variations," she adds, which is another reason to focus on it. Variation provides a species with the ability to survive in a wide range of circumstances, so, as Dunston points out, diversity is a key to human development and survival.

The very first human DNA to be sequenced by the human genome project came from a group of European families, selected because their genetic history had already been reported and their pedigrees detailed. This provided only the broad outlines of the genome; the genes sequenced in later phases came from many different racial and ethnic groups.

Dunston wanted to create a similar basic resource for Africans. "My goal was to provide a reference on the spectrum of variation in the African population," she says. Though an early attempt to get NIH funding for this project failed, she has been able to collect much of the data she sought through a project to study diabetes in Africa, which grew out of a fellowship she did at the National Human Genome Research Institute.

"Francis Collins had spent five months working in a missionary hospital in Nigeria and he was intrigued with the difference in clinical presentation of type II diabetes between Africa and the United States," says Dunston. In America, type II diabetes is usually associated with obesity, which itself causes many health problems and makes it difficult to determine which problems are related to the diabetes and which to the obesity. In Africa, however, type II diabetics are often lean.

"[Collins] knew I was interested in building capacity at Howard and studying African genetics so he suggested a collaboration. I considered it totally from heaven," says Dunston.

The admiration is mutual. "The promise of genomics for unraveling the mysteries of diseases like diabetes and prostate cancer is profound," says Collins. "It would be tragic indeed if these advances did not reach populations at particularly high risk. Thus, involving African-American populations in genetic studies on conditions such as this is critical to the future. Dunston and her able team are making dramatic inroads into an area of inquiry which has previously been underserved. The quality of their research, and their attention to community concerns, is exemplary."

The study, Africa America Diabetes Mellitus (AADM), focuses on West Africa, since most African-Americans trace their lineage to slaves captured on the coast from Senegal to Angola. Genetic material has been collected at five sites: three in Nigeria, two in Ghana. A genome-wide scan of these samples to find genes related to type II diabetes is currently being conducted.

Charles Rotimi, now associate professor and director of genetic epidemiology at Howard, was recruited by Dunston in 1999. "Going to West Africa gives us an opportunity to understand type II diabetes with less noise from the environment," says Rotimi. He adds, "We're not just doing 'helicopter science.' In fact, one of our criteria for determining which investigators to collaborate with there was that we would help improve the infrastructure so that when we left, they would continue the work."

In previous genetic research in the developing world, scientists have been criticized for taking samples and sometimes even patenting genes from local people without offering them any medical benefits in return for their participation.

Concerns about exploitation, about the potential use of genetic testing to discriminate against African-Americans and to further racist ends, have inspired an approach at Howard that puts ethics front and center. Charmaine Royal is assistant professor of genetics and principal investigator for what is called "GenEthics" research at Howard. "To understand the ethical, legal, and social implications of genetic research, you need different perspectives," says Royal. "Howard brings a lot of that from its history. The needs of a community have to be factored into the research and no one can do that better than people who are from the community themselves."

The history of medical experimentation on black slaves in the United States, and the infamous Tuskegee syphilis study by the U.S. Public Health Service, which denied treatment to infected subjects for 40 years and ended only in 1972, has given rise to a great deal of skepticism among African-Americans both about science in general and about participating in medical studies.

As a result, even now, a federally funded study of health and nutrition found that 86 percent of whites were willing to have genetic tests done as part of the research, but only 74 percent of blacks agreed. Royal recently published a paper in the Annals of Epidemiology on how Howard successfully recruited 43 African-American families for a prostate cancer study, which had strict eligibility requirements. To participate, four males in the family had to have had prostate cancer, and at least one had to have been diagnosed before age 65.

The most fruitful source of referrals turned out not to be mass media campaigns or pamphlets distributed at barber shops, churches, or health fairs, but physicians and tumor registries. This suggests that having an existing, trusting relationship with a doctor or with the health care system, and being invited to participate in a study centered at a traditionally black college and run by mainly black researchers, were factors allowing recruitment in the community of even the most difficult to find families.

Dunston says, "We can't deny history, but we can't be guided by fear. If you don't participate, you can't expect [designer medicine] to be designed for you. The greatest protection against what happened in the past is for us to have the knowledge and to be in the arena."

One of the main goals of Dunston and her colleagues is to recruit more African-American students into scientific careers, an area where currently they are a tiny minority. For example, only about four percent of medical school faculty members are black, and only 26 of 1,500 NIH funding panel members.

For her part, Dunston credits a high school biology teacher and a series of mentors for encouraging her natural interest in "asking why" for her start on the road to a scientific career. Neither of her parents were high school graduates, and so were unfamiliar with the trajectory of this type of work. "I remember my mom telling me that people would often ask her, 'What is Georgia Mae doing now?' and all she could tell them was 'She is still going to school!'"

Dunston sees her work on the genome as having implications beyond the medical. "We've grown up in a culture that says variation is abnormal," she says. "The genome is trying to teach us a whole new way of looking at it: variation is the instrument that allows us to become who we are. Variation is like our vision, you can't see without contrast."

On the recent publication of the data from the Human Genome Project, she says, "Publishing the human genome sequence is right up there with the printing of the Bible, and making knowledge available and open to the public. The new knowledge will challenge old ways of thinking about ourselves that are unhealthy and too limiting for self-recognition at the genome level of life."