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

1. Only 1 percent of Americans can use the word “genome”.

2. Genome: A person's entire set of genes.

3. 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.

Genome?

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.

Our

Genome

Our Culture

Our Genome - Our Culture Co-evolution

Genes, Self and Group Identity

1. Genetic essentialism: Defining human identity in genetic terms

2. The concept of self is reduced to a molecular entity

3. Human beings are equated, in all their social, historical, and moral complexity, with their genes.

4. These new concepts profoundly challenge personal, philosophical, cultural, legal, and political issues of identity.

5. 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

Genes, Self and Group Identity

The Human Mosaic

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A species is divided into races when it can be regarded as an essentially discontinuous set of individuals. Jonathan Marks

Genetic Structure of Human Populations

Rosenberg et al Science 2002;298:2381-2385

“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.”

Africa Europe Middle East Central/

South Asia East Asia America

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.”

Genetic Variation

Black Britons find their African roots http://news.bbc.co.uk

Black Southern African Bantu-speaking population who assert Jewish ancestry: LEMBA men NEIL BRADMAN AND MARK THOMAS

http://www.ucl.ac.uk/tcga/ScienceSpectra

"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)

Who gets to decide who is a member of the group?

DNA Testing to Determine “Native American Identity”

DNA Analysis and the Cultural Affiliation of the Kennewick Man

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?

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/

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

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.

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?

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

Slow acetylators

Rapid 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

What we hear and read

• Racial differences in the response to

drugs – pointers to genetic differences.

N Engl J Med 2001 -----

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

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

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.

Genomics, Health Disparity and the

Problem of Race

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

Genetic factors contribute to virtually every human disease by way of increased

Susceptibility

Resistance

Affect the severity or progression of disease

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

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.

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

Estimated European Ancestral Proportion of 11 populations of African Descent

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

Genomics and Health Disparity

In the book – It ain’t Necessarily So – The dream of the Human Genome and other

Illusions by Richard Lewontin pp18-19

“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.”

Health Disparity

Has “Negro blood” become “black genes” (Wailoo 1997)

Prevalence of Diabetes by Mean BMI and Gender

in Populations of the African Diaspora

Body Mass Index

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Cooper R, Rotimi C, Kaufman JS, et al., Diabetes Care 1997

Body Mass Index

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Maywood

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

Prevalence of Hypertension (140/90 mmHg) by

Age in Rural and Urban Nigeria: Men and Women

Age in Years 25 35 45 55 65 75 85

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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.

The complex interwoven history of human species

Figure is by Clayton Ryder- The Scientist 16[1]:16, Jan. 7, 2002 Ricki Lewis (rickilewis@nasw.org)

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