Genomic Definition of Self and Group Identity: Implications for Biomedical Research

1. Genomic Definition of Self and Group Identity: Implications for Biomedical Research “2003 Summer Public Health Videoconference on Minority Health - UNC” Charles N. Rotimi, Ph.D. Director, Genetic Epidemiology National Human Genome Center College of Medicine, Howard University UNC – June 10, 2003

2. Genome? • Only 1 percent of Americans can use the word “genome”. • Genome: A person's entire set of genes. • Genome: All the DNA (genetic materials) contained in an organism or a cell, which includes both the chromosomes within the nucleus and the DNA in mitochondria.

3. Holy Grail? The human genome has been labeled the "Book of Man" and its decoding likened to the search for the Holy Grail. Is our genome synonymous with our humanness? Some view the genome as the core of our nature - determining both our individuality and our species identity.

4. Our Genome - Our Culture Co-evolution Our Culture Our Genome Who are we? How are we related? Why ill health? Why differential distribution of diseases?

5. Genes, Self and Group Identity • 1. Genetic essentialism: Defining human identity in genetic terms • The concept of self is reduced to a molecular entity • Human beings are equated, in all their social, historical, and moral complexity, with their genes. • These new concepts profoundly challenge personal, philosophical, cultural, legal, and political issues of identity. • These issues are described in more detail in The DNA Mystique by Dorothy Nelkin and M. Susan Lindee • http://www.cnr.edu/home/Honors/syllabus/F1999/bio489.html

6. Genes, Self and Group Identity We all have multiple identity We maintain Complex relationships A species is divided into races when it can be regarded as an essentially discontinuous set of individuals. Jonathan Marks

7. Genetic Structure of Human Populations Central/ South Asia Africa Europe Middle East East Asia America “the challenge of genetic studies of human history is to use the small amount of genetic differentiation among populations to infer the history of human migrations. Because most alleles are widespread, genetic differences among human populations derive mainly from gradations in allele frequencies rather than from distinctive diagnostic genotypes.” Rosenberg et al Science 2002;298:2381-2385

8. Genetic Variation Confusion 1. Group identity is confused with group ancestry. For example, the group identity “African Americans” does not reflect a single path of ancestry. 2. Self-identification is confused with more complex tapestry of ancestry. 3. Simplification of self and group identity. “If self- identity is complex, group identity is infinitely more complex.”

9. Black Britons find their African roots http://news.bbc.co.uk "Despite their long-term residence in different countries -- most Jewish populations were not significantly different from one another at the genetic level.” (M.F. Hammer, Proc. Nat'l Academy of Science, May 9, 2000) DNA Testing to Determine “Native American Identity” DNA Analysis and the Cultural Affiliation of the Kennewick Man Black Southern African Bantu-speaking population who assert Jewish ancestry:LEMBA menNEIL BRADMAN AND MARK THOMAS http://www.ucl.ac.uk/tcga/ScienceSpectra Who gets to decide who is a member of the group?

10. House of artist and Oshun priestess Suzanne Wenger, Oshogbo http://african.lss.wisc.edu/yoruba Suzanne Wenger in her Osogbo home in 2000. Photo Marty Wong http://www.friendsofnigeria.org/ Is a Diasporan African with genetic affinity to the Yorubas more Yoruba than Suzanne Wenger, the Austrian Anthropologist and Chief Priestess of the Oshun Goddess, the keeper of Beaded Comb, in Yoruba land even though she is white?

11. Genetic Variation • How may we interpret data describing human genetic variation today? • Variation is not discontinuous. • Pharmacogenomic differences can be 10 to more than 40-fold between individual within an ethnic group. • Variation between ethnic groups is rarely more than 2 to 3-fold • Human populations exhibits considerable genetic admixture

12. Pharmacogenomics The study of how inherited genetic variations affect an individual’s ability to response to a drug and the use of that knowledge in drug discovery and development. Genetic Variation may explain why one person may benefit from a drug while another person may suffer toxic effects from the same dosage of the same drug.

13. Variable Drug Response • How do we interpret differential drug response by “groups” when “group” definition is imprecise, fluid and time dependent? • Can we tell how an individual will respond based on group data? • What is the acceptable error rate? • Who decides this? • Will error rate be higher for some groups compared to others?

14. Slow acetylators Rapid acetylators Variable Drug Response • N-acetyltransferase 2 (NAT2) • Enzyme involved in the detoxification of many carcinogens and the metabolism of many common drugs. • NAT2 Variants • Slow acetylators 14% East Asia 34% African Americans 54% Caucasians Anti-tuberculosis drug – isoniazid is inactivated by acetylation and the capacity of individuals to inactivate the drug is dependent on their genotype at the NAT2 locus

15. What we hear and read • Racial differences in the response to drugs – pointers to genetic differences. N Engl J Med 2001 -----

16. The Medicalization of Race: Scientific Legitimization of a Flawed Social Construct. Serious negative consequences of a physician’s assumptions about a patient’s race Case 1: An 8-year-old boy, phenotypically European, presented with acute abdominal pain and anemia (hematocrit, 0.21). Although his body temperature was only 37.9 °C, surgery was considered. A technician found red corpuscles with hemolytic characteristics on a smear. Surgery was canceled after the results of a subsequent sickle preparation were found to be positive, and the child was treated for previously undiagnosed sickle cell anemia. His parents were from Grenada and were of Indian, northern European, and Mediterranean ancestry. Ritchie Witzig – Ann Int Med 1996;125:675-679

17. The Medicalization of Race: Scientific Legitimization of a Flawed Social Construct. “---Ethnic boundaries are dynamic and imprecise, and it is dangerous to assume that any person possesses a certain health variable just because that person is a member of a particular ethnic group. The common thread between ethnicity and race is that both are social constructs and subject to ethnocentric biases. Ritchie Witzig – Ann Int Med 1996;125:675-679

18. Pharmacogenomics Future use of drug therapy will not depend on the imprecise indicators as race or ethnicity, but on the individual patient’s genotype. The idea, then, is not to eradicate or ignore differences but to redefine or move beyond race to more precise categories of difference with justification for establishing such differences. M. Rothstein and P. Epps, Pharmacogenomics 2001,1:104-108 In this regard, pharmacogenomics may help deconstruct the present concept of group definition including race. For example, if you are defining a group with adverse reaction to chloroquine-like drugs for the treatment of malaria, I will not be in the same group as my mother.

19. Genomics, Health Disparity and the Problem of Race Genetic factors contribute to virtually every human disease by way of increased Susceptibility Resistance Affect the severity or progression of disease Of all the forms of inequality, injustice in health is the most shocking and the most inhuman. The Rev. Martin Luther King – Chicago, March 25, 1966

20. Genomics and Health Disparity • ---genetic explanation reifies racial and ethnic classifications by reinforcing the notion of biological difference rooted in genetics. --- leads to stigmatization of racial and ethnic minorities and to research strategies that divert attention from confronting the multidimensional ways in which racism, not race, influence patterns of disease. • Lundy Braun: Perspective in biology and medicine 2002

21. Can Genetic Variation Explain Health Disparity ----The historical, anthropological, and linguistic definitions of “populations” with which genetic findings are correlated represent superficial understandings of the dynamic history of present-day ethnic populations and how these populations were formed--- Current research emphasis on genetic explanation for diseases disparities is problematic, since race and ethnicity are social, not genetic, categories comprised of individuals whose ancestry is highly diverse. Lundy Braun: Perspective in biology and medicine 2002.

22. Estimated European Ancestral Proportion of 11 populations of African Descent Populations Proportion Charleston, SC 11.6±1.3 Philadelphia 12.7±1.5 Baltimore 15.5±2.6 Detroit 16.3±2.7 Houston 16.9±1.5 Maywood, IL 18.8±1.4 New York 19.8±2.1 New Orleans 22.5±1.6 Jamaica 6.8±1.3 Used 9 autosomal DNA markers; these are either population specific alleles or show frequency difference > 45%; Para EJ Am J Hum Genet 1998; 63:1839-51

23. Genomics and Health Disparity “In America, race, ethnicity, and social class are so confounded, and the reality of social class so firmly denied, that it is easy to lose sight of the general setting of class conflict out of which biological determinism arose. Biological determinism, both in its literary and scientific forms, is part of the legitimating ideology of our society, the solution offered to our deepest social mystery, the analgesic for our most recurrent social pain. In the words of Charles Darwin, quoted on the title page of The Mismeasure of Man, “If the misery of our poor be caused not by the laws of nature, but by our institutions, great is our sin.” In the book – It ain’t Necessarily So – The dream of the Human Genome and other Illusions by Richard Lewontin pp18-19

24. Health Disparity Has “Negro blood” become “black genes” (Wailoo 1997)

25. Prevalence of Diabetes by Mean BMI and Gender in Populations of the African Diaspora Men 14 Women 12 US UK UK 10 Caribbean US 8 Prevalence of Diabetes 6 Caribbean 4 2 West Africa West Africa 0 20 22 24 26 28 30 32 Body Mass Index Cooper R, Rotimi C, Kaufman JS, et al., Diabetes Care 1997

26. Prevalence of Hypertension by Mean Body Mass Index Among Populations of the African Diaspora North America Caribbean West Africa Cooper R, Rotimi C. et al. AJPH. 1997

27. Prevalence of Hypertension (140/90 mmHg) by Age in Rural and Urban Nigeria: Men and Women .6 Urban .5 .4 Prevalence .3 Rural .2 .1 0 25 35 45 55 65 75 85 Age in Years

28. Health Disparity and the Problem of Race Health disparity is not new and is the result of multiple factors with deep roots in social, political and cultural practices. It is not an American phenomenon but a global one. Some of the largest disparity in health occur among persons of similar ancestry living in the same continent. Epidemiological data coming out of Africa, Central and South America are good examples.

29. The complex interwoven history of human species The continuous interaction between human groups makes it very unlikely to have genes or alleles that are population specific. Unlike geographical separations, differences in allele frequencies are gradual, without discontinuities between clusters Figure is by Clayton Ryder-The Scientist 16[1]:16, Jan. 7, 2002Ricki Lewis (rickilewis@nasw.org)