Date:
Location:
Speaker: Mary-Claire King, American Cancer Society Research Professor of Genetics and Medicine, University of Washington School of Medicine
The Harvard University Tanner Lectures for 2006 were delivered by Mary-Claire King, American Cancer Society Research Professor of Genetics and Medicine at the University of Washington School of Medicine. Dr. King is known world-wide for her discovery of the inheritable BRCA 1 and BRCA 2 gene mutations, which indicate a high likelihood of breast and ovarian cancer. Dr. King spoke November 15th and 16th on "Genomics, Race, and Medicine," and participated in a seminar discussion on Friday, Nov. 17th. The first lecture was opened by Steven Greenblatt, Chair of the Tanner Committee. After reviewing the life of Obert Tanner, the founder o the Tanner Lectures, and giving a short history of the Tanner Lectures at Harvard, Prof. Greenblatt introduced Harvard University Provost Stephen Hyman, who presented a short overview of Mary-Claire King's many contributions to the fields of genomics and medicine. While King is justifiably famous for her discovery of the breast cancer gene, she has explored, and continues to explore, other links between genetics and disease, including current research into genetic causes of deafness and of schizophrenia.
Prof. King began her lecture by focusing on the controversial concept of race. The reality of race, she said, is that there is only one race, human. There are no significant genetic boundaries within the human species. An appropriate metaphor for humanity would be to think of us all as part of one ocean: individual drops from different parts of the ocean have different qualities, but the drops can circle, spread, and intermingle. At the same time, Prof. King, went on, the concept of distinct races does have some reality in biology when “race” is understood correctly, and is thus not merely a social construct. While humans have 93% of our genetic structure in common, computer analysis has discovered that about 4% of our genetic variation is both continent-wide and continent-specific. A computer analysis run by Marcus Feldman, and published in Science in 2002, demonstrated this: Feldman gave a computer program, Structure, the data from about 1000 people, from about 50 different ancestral populations, who had been genotyped for 377 highly variable genetic markers. No additional information about the ancestral origin of these people was included in the information the computer was given. When Structure was asked to divide them into three groups on the basis of allele frequency difference, it divided the genetic types into distinct groups whose respective ancestral origins were, in fact, in the continents of Africa, Eurasia, and East Asia/Oceania. When the program was asked to further divide the data into four groups of similar make-up, it split people whose ancestral origin was East Asia off from those from Oceania, and when asked to split the sample into five groups, then split America from Oceania. Prof. King stressed that this exercise was only successful in this regard because the people chosen for analysis had very specific and uniform ancestral origins—or example, all four grandparents from Sweden—rather than having a geographically heterogeneous background, as most Americans have. Within this constraint, though, the analysis revealed objective genetic distinctions which correspond generally to commonly conceived racial divisions. Prof. King concluded that there are, then, genetic differences which correspond to geographical area, being held by all those and only those whose ancestors are linked to a particular continent. This 4% variation may be thought of as the genetic basis of race.
This is not surprising: our oldest alleles are all African, since that is where the human species originated. This accounts for the 93% of shared genetic material. After these oldest alleles had originated, there followed, some 50,000 to 60,000 years ago, several waves of migration as humans spread across Asia to Australia, to Asia, and then, 30,000 years ago, into the Americas. Then, 10,000 years ago, the development of agriculture led to a massive population growth, and many new alleles appeared, some specific to one small population, or even one family, and some spreading continent wide. Every mutation compatible with life probably occurs in one person per generation, so it is natural that variety would develop with time and increasing population; still, King stressed, most of our genetic structure is common across all humans, and originated in our common African origin.
Dr. King then went on and asked whether knowledge of these genetic racial groupings would actually be useful as a tool for medical diagnosis. Does race link to specific diseases, and would knowledge of the genomics of race help in either diagnosis or cures? We know that humans developed physical differentiations in response to their new environment, and in a few cases we can see a link between racial variation and a specific vulnerability. As people moved north from Africa, for example, they encountered darkness. There wasn’t enough light to synthesize vitamin D, so Europeans developed melanocortin receptor genotype variations. The “wild type”-- the normal type-- is found in Africans, and the variation in those who settled in the darker northern climate. These skin changes in northerners, though, have also made them more vulnerable to melanoma. Thus, when Europeans moved to a climate with more sunshine—Australia—they experienced a relatively high incidence of skin cancer, with the resulting prescription that they should wear hats. Another case where genomic information may be helpful is in the treatment of chronic congestive heart failure. Results in repeated trials using two treatments, ace inhibitors and vasodilators, were initially inconsistent as to which of these was more effective. Analysis has now shown that those who self-identify as black and those who self-identify their race as white respond differently to the two common treatments--whites do better on the ace inhibitors, and blacks on the vasodilators. We do not as yet know, however, if this is a difference whose origin lies in a genetic difference. Since participants were identified as white and black not by genetic analysis but on the basis of self-identification, and it is possible that is not a genetic difference but difference arising from other socio-economic or cultural factors which explains the different responses. Prof. King suggested ways in which a possible genetic origin of the difference in response could be investigated, and the specific location of the genetic difference, if there is one, could be identified. Given what we already know about genetic mapping, we have a basis for investigating probable locations for such a difference, and finding it could be useful in determining future treatment options.
Still, King again stressed, while there are some instances of race-linked disease and corresponding differences in treatment according to race, there are very few continent-wide and continent-specific genetic differences overall, and so racial differences are unlikely to result in widespread and significant differences in medical diagnosis or treatment. Other mutations which are correctly correlated to disease are likely to be much more specific than the continent-wide, continent-specific variations of race. Some mutations occur within very small populations, within families, or within individuals; others are found across all continental ancestries.
Dr. King’s talk was followed by comments from Prof. Jennifer Hochschild, Henry LaBarre Jayne Professor of Government and Professor of African and African American Studies at Harvard. Prof. Hochschild discussed some of the moral and political questions which the study of genomics engenders. What would we gain or lose, she asked, if we had complete genomic information? What is it that people want from such information? Will what we in fact learn about ourselves satisfy us in the way we hoped it would? Prof. Hochschild hypothesized that our reasons for being interested in such information are various, and range from practical concerns about our future health to the desire to augment the feeling of having roots. People often feel that knowing their genetic history will tell them who they are. Presumably such information will bring surprises, though, and people may occasionally find their sense of themselves confounded. Many will find inter-racial genetic mixes which they had not expected. When Henry Louis Gates did genomic research into his ancestral origin, he found his ancestors included North Europeans. Those who felt rootless may find roots, on the other hand, as when an orphan discovered that her family hailed from Sierra Leone, and reported a hitherto unknown sense of belonging.
On the whole, suggested Hochschild, the results will be beneficial for individuals. Information is useful, and disaggregating data is informative for individuals who emerge from the aggregate with unique individual profiles. Such information may also illustrate the nature of identity—some who find they are genetically multi-racial might embrace that identity, and others might reject it. This would suggest that identity depends on a choice, sometimes made by others, and sometimes by the individual. Identity is thus, Hochschild argued, more metaphysical than physical. This result may be positive —people might feel loyalties to more than one group, and might be less tolerant of racial exclusion and hierarchy. Whites might accept race as a mere social construction when see their whiteness is not biologically based. The whole endeavor also produces insight into our conflicted goals: on the one hand, the United States is supposed to provide people freedom and a chance to start over, but on the other, we want to identify ourselves with an ancestral past.
However beneficial it may be for individuals, though, genomics may have bad results for groups. Prof. Hochschild argued that if we dilute minority groups by disaggregating them into discrete, complex individuals, that may undermine policies to combat racial discrimination, since group identity might cease to carry weight. Targeting funding towards a particular group in order to raise its status becomes moot if that group loses its cohesion as a recognized, distinctive entity. The federal government now allows self-identification as multi-racial on its census, but in other areas acknowledges specific racial groups as the target of its policies, and these movements may be in conflict. Or, genetic knowledge might lead to generalizing about specific groups, as when we associate certain diseases with Ashkenazy Jews. It could lead to more discrimination, if DNA analysis shows some groups to be more or less intelligent, more or less violent., etc. The politics of social classification becomes murky, and genomics may have unforeseen consequences.
Lively discussion ensued among audience members and presentation participants, on the role of he scientist in society, the concept of race, and generally the possible ethical and social ramifications of genomic research.