Minority Health Conference: Genes, Race and Medicine

1. 12th Annual Summer Public Health Research Videoconference on Minority Health Minority Health Conference: Genes, Race and Medicine Pilar N. Ossorio University of Wisconsin-Madison Schools of Law and Medicine Visiting: UC Berkeley Boalt Hall School of Law

2. Individualized or Race-targeted Medicine???

3. The BiDil Story July 20, 2004

4. Popular Depictions of BiDil Current NewsRacial Pill Maker’s Sales Drop in Wider-than-expected-loss By Diverse and news wire reportsMay 31, 2006, 23:58 “… Despite low sales affecting stock market shares of the drug’s maker, NitroMed Inc., racially tailored drugs might be here to stay.” “The launch of the 10-month-old drug BiDil has been closely watched because it is expected to help usher in an era of “personalized” medicine, in which treatments are increasingly tailored to individuals’ genetic make-ups.”

5. Current news continued… “‘There are genetic differences between individuals…’ says Dr. Kenneth Edelin, associate dean of students and minority affairs at Boston University’s School of Medicine. “Asian doctors who treated Asian patients noticed these differences and subsequently tailored prescription to meet their needs.”’ “Edelin says the increased use of personalized medicine is here to stay because of how one group of people reacts to a drug in relation to another group. “‘The truth is we are different … and drugs can be individually tailored due to a specific problem based on genetic instructions.’”

6. Crestor • 04/02/06 Astra Zenica news release on Crestor • Data presented at the annual meeting of the National Hispanic Medical Association showed that, in Hispanic patients, Crestor reduced LDL-C more than atrovastatin at similar doses • Who is Hispanic? How could a doc use the info presented? • Does this mean that the drug works better in Hispanics than in non-Hispanic people? If not, then why the focus on Hispanics?

7. Race- & Ethnicity-targeted “Nutriceuticals” GenSpec Formulates the World's First Genetically Specific Vitamins and Weight Loss Supplements PR Newswire NEW YORK, Feb. 7 /PRNewswire/ -- GenSpec Labs, LLC. has announced that it has formulated the world's first genetically specific nutraceutical product line which effectively addresses the unique metabolic needs of African- Americans, Hispanics, and Caucasians…”

8. GenSpec continued… “While diet, exercise and regular medical exams can have a positive effect on an individual's overall health, these same studies indicate that genetics play a major role," says Vice President of GenSpec, Dr. Dexter Russell…

9. Common Mistakes • Health differences betweenracial, ethnic, national and other groups are treated as though they MUST be caused by genetic difference!!! • A genetic cause is inferred not demonstrated. • Mistake correlation for causation • E.g., story on “ethnic specific” vitamins, BiDil • Ignore non-genetic factors that affect healthor treatment responses • Ignore inter-individual differences, and all other differences that do not correlate with race/ethnicity

10. Common Mistakes • Treat all people of one racial, ethnic, national or other group as though they are all the same with respect to all important health determinants • Differences (genetic, cultural and otherwise) between individuals within groups are ignored • Who are the Hispanics? • Who are the Asians??? • Groups are treated as distinct and mutually exclusive (genetically, culturally, etc) • What about people who are black Hispanic? • What about people who are black Asian? • What about Chicanos of Ashkenazi Jewish descent? • Conflates ancestry, culture, socio-political categories

11. Differences Treated as Genetic Observed difference between racial/ ethnic groups in treatment outcome, drug response, disease course, side-effects, etc.is due to different frequencies of some causal allele among the different racial or ethnic groups

12. Biological≠Genetic

13. Biology≠ Genes • Not all biological variation is caused primarily by genetic variation • Not all genetic variation results in phenotypic variation • Mutations in non-coding and non-control regions of DNA • Mutations in genes that do not change the encoded protein • Do not assume causal relationship between genetic variation and between-group differences!

14. Sources of Biological Variation • Between groups • Different diets • Differential exposures to toxins • Differential access to health care • Differential exposure to physical risk • Differential access to power and control over one’s life • Differential exposure to racism and other stressors • Different allele frequencies (~5-15% of variable loci)

15. Between-Race Differences • Not necessarily due to genetic differences! • Group difference (racial or otherwise) is a difference in mean response profile or shape of the response profile (statistical, not categorical) • Lack of between-race differences may obscure important genetic risks/differences within a group

16. Sources of Biological Variation • Inter-individual variation • Diet • Age • Gender • Co-morbidities • Concomitant medications • Other exposures (toxins, stressors, dangers) • Genetics

17. Dietary Effects on Pigmentation R. Waterland & R. Jirtle, Molecular & Cellular Biology, 23(15): 5293-5300 (2003)

18. Mistakes (reminder) • Treat people of one racial, ethnic, national or other group as though they are all fundamentally the same • Differences (genetic, cultural and otherwise) between individuals within groups are ignored • “Will Tomorrow’s Medicines Work for Everybody?” • Absolutely not; no medicine works for everybody!

19. Inter-individual Difference in Drug Response Marked Interindividual Variability in Response to Selective Inhibitors of Cyclooxygenase 2 Fries et al., Gastroenterology 130: 55-64 (2006)

20. Why The Mistakes Occur… • Mistakes consistent with “folk notions” of race as • Fixed • Natural • Essential • Distinct and distinguishable groups • Categorically different/non-overlapping • Pervasively similar within group • “We all know that…”

21. Individualized Medicine≠Race-based Medicine

22. Individualized medicine • Do not treat statistical differences btwn groups as categorical differences! • Attend to the individual patient to identify risk • Family and personal medical history • Talk about personal circumstancese • Exposures, medicines and supplements taken, beliefs and treatment goals, etc. • When knowledge of the relevant allele matters for a tx decision, do a genetic test if one is available! • Ask about ancestry • Genes are not all!