Bioethics in Daily Life

1. Bioethics in Daily Life Day 3 ANT 4930 Prof. Connie J. Mulligan Department of Anthropology

2. This week - Race • Race • Is there a biological basis to race? • How have we evolved? • Global distribution of genetic and phenotypic variation • How different are we? • Genetic ancestry • Racial disparities in health • Required reading (also listed on course webpage, Day 2) • http://en.wikipedia.org/wiki/Race_and_genetics – Wikipedia entry on ‘Race and Genetics’ • http://www.pbs.org/race/000_About/002_04-background-01-07.htm - Race: The Power of an Illusion, interview with Alan Goodman • Sample Genetic ancestry report, intended for an African American audience • Video – African American Lives • Practice oral presentations

3. Next week – Genetic screening/genetic testing and ancestry estimation • Prenatal screening • Testing for personality, mate choice, etc • Genetic ancestry testing • Reproductive technologies • Who is the mother when egg and sperm are donated? • Required reading (also listed on course webpage, Day 3) • http://www.newsweek.com/2010/06/09/inside-information.print.html - Newsweek article, Americans want to know their genetic codes • http://www.technologyreview.com/blog/editors/25297/ - Genetic testing can change behavior • http://www.nature.com/ng/journal/v42/n10/pdf/ng1010-811.pdf - newborn genetic screening • http://www.nature.com/nature/journal/v466/n7308/pdf/466816a.pdf - Nature, Aug 12 2010, Genetic testing regulation • http://www.time.com/time/magazine/article/0,9171,1158968-2,00.html – Iceland genetics project • http://www.medicalnewstoday.com/articles/157335.php - Iceland/deCODE project - genes identified to date • Skim http://bioethics.georgetown.edu/pcbe/reports/beyondtherapy/ - Beyond Therapy: Biotechnology and the Pursuit of Happiness, report from the President’s Council on Bioethics, 2003 (353 pages) • Video – African American Lives • Four oral presentations

4. NPR show, Is there a biological basis for race? Talk of the Nation, Jan 15, 2010 http://www.npr.org/player/v2/mediaPlayer.html?action=1&t=1&islist=false&id=122620064&m=122620043

6. What is race? • Is race a purely cultural construct or is there some biological or genetic distinction between races? • There is no Caucasian gene, no African gene, no Asian gene • Is there one gene that distinguishes one race from another? No.

7. Human evolution and genetic variation • There are no ‘pure’ human stocks and there never were • No populations are more highly evolved than others • Human populations are too closely related to be considered subspecies • There is a continuum of genetic variation across the globe • Very little time has passed since anatomically modern human evolved, i.e. little variation within and between populations

8. A little terminology • Genetics is the study of heredity and variation of organisms • A gene is a piece of DNA that is responsible for the inheritance of a specific characteristic • eye color • ability to process lactate (drink milk) • Gene  protein Human karyotype (chromosomes)

9. What is DNA? • DNA is a blueprint to direct the production of proteins • Coding = genes (~3%) • Non-coding (~97%) • DNA can be thought of as a sequence of letters (nucleotide bases) • Adenosine = A • Guanine = G • Cytosine = C • Thymine = T Genetics, 2001, Hartl and Jones, Jones and Bartlett Publishers, Inc

10. What genes do we have? • No one has ever identified a gene for: • Intelligence • Athleticism • Musical ability • Language ability • Work ethic • Personality

11. What is a genetic variant? This genetic variant is a change from a C to a T

12. How do you interpret a genetic variant? • What does a C-to-T change mean? • Smarter, prettier, faster, stronger??? • No, just different • Most variants are neutral = no effect • Genes make up only ~3% of genome and genes make our phenotype

13. Human variation • There are differences between people • Phenotypically • Genetically • What do the differences mean? • Genetic differences are studied through molecular analysis • Does a variant have an effect? • Does it occur in a gene? • Does if change the protein? • What does the protein do? • Or is it just variation? Genetics, 2001, Hartl and Jones, Jones and Bartlett Publishers, Inc

14. Genetic variation in humans around the world • Phylogenetic analysis of non-coding, neutral region • 1st divergence • African cluster = common human origin • Subsequent divergences • People from around the world are mixed together • No divisions based on race or geography Cann et al., Nature, 1987

15. What about sickle-cell anemia? That’s only in Africans! • Not so. Sickle cell anemia is correlated with areas of malaria, i.e. Africa, Asia, and Europe • Sickle cell anemia protects against malaria = positive selection Genetics, 2001, Hartl and Jones, Jones and Bartlett Publishers, Inc

16. But we look different! • We can see differences between people • e.g. dark-skinned, light hair, etc • But, only a few genes determine skin color, hair color, etc. so it doesn’t take many variants to make us look different • The differences are literally only ‘skin deep’ • Skin color is controlled by levels of melanin • Three main candidate genes for melanin production

17. Skin color • Skin color shows some geographic patterning • Does it correlate with race? Distribution of different skin colors in indigenous populations of the world (Jobling et al. 2004)

18. What about another phenotype, like the ability to drink milk/digest lactose?Is there geographic patterning that matches race categories? Frequency of lactase persistence around the world Fig 13.10, Jobling et al. 2004

19. It seems like we see some phenotypes patterned across the world in ways that could possible correlate with race • But, only a few genes determine skin color, hair color, etc. so those genes aren’t representative of the entire genome • 88% of skin pigment variation is apportioned among populations (Relethford 2002) • In contrast, only 10-15% of average genetic variation is apportioned among populations • Furthermore, only skin pigmentation shows a good correlation with geography, or latitude (Parra 2007) • Variation in hair and iris color is much more restricted • Most humans have dark hair and irises • Red and blond hair are mainly found in Europe • Lighter iris colors (blue, green, hazel) are mainly found in Europe, and some in the Middle East, North Africa, West Asia and South Asia (Sturm and Frudakis 2004) • So, we’re talking a handful of genes that control skin pigmentation that correlate with geography, and possibly race • Is that enough to say there’s a biological or genetic basis to race? • What if we look at neutral (non-gene-encoding) DNA?

20. Using current analytic methods and huge datasets, we can distinguish between populations in astonishing detail, far beyond ‘races’ A statistical summary of > ½ million genetic variants from 1,387 Europeans based on principal component axis one (PC1) and axis two (PC2). Small colored labels represent individuals and large colored points represent median PC1 and PC2 values for each country. PC axes are rotated to emphasize similarity to the geographic map of Europe.AL, Albania; AT, Austria; BA, Bosnia-Herzegovina; BE, Belgium; BG, Bulgaria; CH, Switzerland; CY, Cyprus; CZ, Czech Republic; DE, Germany; DK, Denmark; ES, Spain; FI, Finland; FR, France; GB, United Kingdom; GR, Greece; HR, Croatia; HU, Hungary; IE, Ireland; IT, Italy; KS, Kosovo; LV, Latvia; MK, Macedonia; NO, Norway; NL, Netherlands; PL, Poland; PT, Portugal; RO, Romania; RS, Serbia and Montenegro; RU, Russia, Sct, Scotland; SE, Sweden; SI, Slovenia; SK, Slovakia; TR, Turkey; UA, Ukraine; YG, Yugoslavia. (Novembre et al. Nature, 2008)

21. What about differences in disease rates? • Lots of evidence that African-Americans and Hispanics suffer disproportionately from diabetes, obesity, high blood pressure, some types of cancer, etc. • Unclear how much is due to environment and how much to genetics • Popular press – may focus on ‘racial’ differences • Research and clinical practice – unclear that ‘racial’ differences exist or are sufficiently large to affect treatment • Starting to dissect population differences in disease and response to treatment Source: National Center for Health Statistics (2004)

22. Complex disease rates vary worldwideExample - Differences in cancer rates and types

23. Heredity? Behaviors? Other Factors? • Study people who move from one country to another • Result – exposure to risk factors for cancer vary by geographic location • Japan – low rate of colon cancer • US – low rate of stomach cancer • When Japanese move to the US, their rate of colon cancer increases and stomach cancer decreases • Obviously no correlation with ‘race’ --National Institutes of Health

24. Pharmacogenomics • Goal of research is to use genetic differences to benefit the population and the individual • Pharmacogenomics is the idea that a health plan can be tailored to an individual’s unique genetic structure • Currently, only look at broad categories, such as ‘race’ • Blacks are more likely than whites to suffer side effects from certain antidepressant drugs • Blacks have a higher frequency of one variant that reduces the liver’s ability to break down certain tricyclic antidepressant drugs, so individuals with that variant will suffer more side effects • Blacks may need lower levels of certain antidepressants (e.g. Prozac) • Blacks have a higher frequency of a genetic variant that increases the speed at which a newer class of antidepressants (Prozac) take effect • Black males may process testosterone more quickly, resulting in stronger bone and an increased risk of prostate cancer • Whites experience more side-effects with warfarin, a blood-thinning drug, than Blacks

25. Devilish details • Warfarin example • 8% Whites carry a genetic variant that causes trouble with warfarin, blood-thinning drug • 2-3% Blacks carry same mutation • Would your doctor make a different diagnosis or propose different treatment based on knowledge of your race? No. • Difference is only significant when looking at populations, not when looking at an individual

26. "Nobody would make clinical decisions based on a racial profile. Race is a very crude predictor of any sort of differential response to medication” Dr. Bruce Pollock, chief of geriatrics and neuropsychiatry, University of Pittsburgh, Department of Psychiatry

27. If not race, what then? • Doctors should base all diagnoses and treatments on all available information • They should take detailed family histories that capture the full range of an individual’s genetic and ethnic make-up • Not a single indicator, like race

28. What about forensics? • Forensic scientists can look at a skeleton and determine, with some accuracy, if the individual was Black, White, Asian, Native American, etc • How is that possible?

29. Bottom line • The vast majority of the human genome does not match racial categories • However, there are phenotypes that can be used to distinguish between races • Furthermore, if we use enough genetic variants, and variants that are maximally informative in a geographic sense, we can distinguish between populations from different races, different continents, different countries

30. How to read a journal article • What are the parts of a journal article?

31. Parts of an article – some of this information is very field-specific and may not be true outside Bioanthropology • What is an abstract? • What information goes into an Intro? • What information goes into Results? • What information goes into Disc?

32. Parts of an article • What is an abstract? • A summary of points presented in skeletal form • Opportunity for authors to specify what they think are the most important points • What information goes into an Intro? • What information goes into Results? • What information goes into Disc?

33. Parts of an article • What is an abstract? • What information goes into an Intro? • Background info • Foreshadows Discussion • All Intro material should be followed up later in article • What information goes into Results? • What information goes into Disc?

34. Parts of an article • What is an abstract? • What information goes into an Intro? • What information goes into Results? • Just Results • No interpretation, no discussion • What information goes into Disc?

35. Parts of an article • What is an abstract? • What information goes into an Intro? • What information goes into Results? • What information goes into Disc? • Interpretation and significance of results • Opportunity for authors to focus on what they think is most important about their results • Should pick up on info in Intro • Can be very dependent on what topics are currently ‘hot’ so Discussion can become outdated even if Results are still relevant

36. How to read a journal article • Note year of publication • Anything more than 5 yrs old is fairly old in my field • Note authors • Have you read anything else by this lab? • Author et al. Year is the best way to refer to a paper • Refer to articles this way in Questions/Comments, Journal Analysis, exam, etc • General strategy for an article outside of your field • Read Abstract, then Intro and then Disc • M&M is usually too complicated unless you want a specific piece of info • Results is generally pretty cut and dried • Re-read abstract after you read paper • See what authors presented as the take-home message

37. How to remember and understand a journal article • Take notes while reading • Re-read article until you really understand it • Make summary notes when you are finished reading • What was purpose of study? • What questions were being asked? • What were final answers? • What was unique about the study? • What is the next step? • Write notes on paper itself or on notecards or electronically