Koffi N. Maglo Koffi N. Maglo Associate Professor, Department - - PowerPoint PPT Presentation

Grouping Humans into Race in Population Grouping Humans into Race in Population Genomic Research: Genomic Research: Historical Historical, Conceptual and Empirical , Conceptual and Empirical Considerations Considerations

Koffi N. Maglo Koffi N. Maglo

Associate Professor, Department of Philosophy Associate Professor, Department of Philosophy University of Cincinnati University of Cincinnati

(CCTST Conference, March 13, 2015) (CCTST Conference, March 13, 2015)

Importance of Biological Systematic Importance of Biological Systematic Principles in Genomic Informatics Principles in Genomic Informatics

“… “… In In some some [academic] [academic] programs, programs, systematics systematics has has been been eclipsed eclipsed by by the the […] […] disciplines disciplines of

• f genomics

genomics and and bioinformatics, bioinformatics, which which focus focus entirely entirely on

• n molecular

molecular data. data. These These trends trends are are unfortunate unfortunate because because stronger stronger emphasis emphasis

• n
• n sound

sound training training in in systematic systematic principles principles could could help help forestall forestall the the uncritical uncritical and and frequently frequently ill-conceived ill-conceived proliferation proliferation

• f
• f

phylogenetic phylogenetic applications applications by by [population] [population] geneticists, geneticists, molecular molecular biologists biologists and and users users

• f
• f the

the systematic systematic “toolbox”…” “toolbox”…” (Schuh (Schuh & & Brower Brower 2009:19-21) 2009:19-21)

“ “If If we we look look at at enough enough genes, genes, the the genetic genetic distance distance between between Ithaca Ithaca and and Albany Albany in in New New York York or

• r Pisa

Pisa and and Florence Florence in in Italy Italy is is most most likely likely to to be be significant, significant, and and therefore therefore scientifically scientifically proven… proven… The The inhabitants inhabitants of

• f

Ithaca Ithaca and and Albany Albany might might be be disappointed disappointed to to discover discover that that they they belong belong to to separate separate races.

• races. People

People in in Pisa Pisa and and Florence Florence might might be be pleased pleased that that science science had had validated validated their their ancient ancient mutual mutual distrust distrust by by demonstrating demonstrating their their genetic differences” (Cavalli-Sforza 2000:25). genetic differences” (Cavalli-Sforza 2000:25).

Million Biologically Real Human Races? Million Biologically Real Human Races?

Four Questions Four Questions (see Maglo 2010, 2011)

(see Maglo 2010, 2011)

1) 1) The The natural/biological natural/biological reality reality question question: : did did the the human human evolutionary evolutionary history history lead lead to to a a natural natural division division of

• f our
• ur species

species into into subspecies, subspecies, the the so-called so-called biological races? biological races? 2) 2) The The correspondence correspondence question question: : do do genetic genetic taxa taxa correspond correspond to to racial racial identities identities defined defined at at a a social/political level? social/political level? 3) 3) The The utility utility question question: : d do

• racial

racial groupings groupings (genomic (genomic

• r social) have clinical utility?
• r social) have clinical utility?

4) 4) The The permissibility permissibility question question: : is is it it morally morally permissible to use race in biomedicine? permissible to use race in biomedicine?

The Invention of The Invention of R Racial Classification and acial Classification and the Natural Reality Question the Natural Reality Question

Francois Francois Bernier Bernier (1620-1688), (1620-1688), French French physician, physician, introduced introduced the the concept concept of

• f race

race in in the the classification classification of

• f

humans humans in in 1684 1684 in in his his essay essay “A “A New New Division Division of

• f the

the Earth Earth according according to to the the Different Different Species Species or

• r Races

Races who who Inhabit Inhabit it it.” .” He He used used skin skin color color as as a a primary primary characteristic characteristic to to define define human races. human races. Carolos Carolos Linnaeus Linnaeus (1707-1778), (1707-1778), Swedish Swedish botanist botanist and and naturalist naturalist acclaimed acclaimed for for his his hierarchical hierarchical biological biological classification classification system system and and binomial binomial nomenclature, nomenclature, recognized recognized in in 1758 1758 four four human human “varieties” “varieties” as as Homo Homo sapiens sapiens europaeus europaeus, , Homo Homo sapiens sapiens afer afer; ; Homo Homo sapiens sapiens asiaticus asiaticus, Homo sapiens , Homo sapiens americanus americanus

Racial Classification and The Natural Racial Classification and The Natural Reality Question (cont’d) Reality Question (cont’d)

Immanuel Immanuel Kant Kant (1724-1804), (1724-1804), German German philosopher, philosopher, used used Buffon’s Buffon’s rule rule (=interbreeding (=interbreeding resulting resulting in in fertile fertile

• ffspring)
• ffspring) to

to affirm affirm in in 1777 1777 the the unity unity of

• f the

the human human species species and and to to demonstrate demonstrate that that human human races races are are not not “natural “natural divisions” but artificial ones. divisions” but artificial ones. Yet Yet Kant Kant claimed claimed likewise likewise that that skin skin color color corresponds corresponds to to an an intrinsic intrinsic property property and and provides provides a a necessary necessary and and sufficient sufficient criterion criterion to to determine determine racial racial membership.

• membership. He

He identified four human races. identified four human races.

Racial Classification and the Natural Racial Classification and the Natural Reality Question (cont’d) Reality Question (cont’d)

Johann Johann F Friedrich riedrich Blumenbach Blumenbach (1752-1840), (1752-1840), German German physician physician and and naturalist, naturalist, combined combined multiple multiple characteristics characteristics in in [1781] [1781] 1795 1795 to to identify identify five five “continental” races but maintained that: “continental” races but maintained that: 1) 1)Racial differences are due to environmental causes Racial differences are due to environmental causes 2) 2)Racial Racial groups groups are are not not discrete discrete but but gradate gradate into into each each

• ther.
• ther.

3) 3)Divisions Divisions of

• f humans

humans into into races races are are not not natural natural but but artificial. artificial. 4) 4)Some Some racial racial categorizations categorizations may may however however be be more more robust than others. robust than others.

Race Concept, Natural Classification and Race Concept, Natural Classification and Evolutionary Theory Evolutionary Theory

Charles Charles Darwin Darwin (1809-1882), (1809-1882), British British naturalist naturalist and and the the author author of

• f the

the Origin Origin of

• f Species

Species (1859) (1859) and and the the evolutionary evolutionary theory, theory, claimed claimed in in 1871 1871 in in his his essay essay the the Descent of Man Descent of Man that: that: 1) 1)Characteristics Characteristics used used to to classify classify humans humans are are superficial. superficial. 2) 2)Racial Racial classifications classifications are are meaningless meaningless because because they they do not map evolutionary relationships. do not map evolutionary relationships. 3) 3)The The race race concept concept should should be be abandoned abandoned in in human human classification in favor of the sub-species concept. classification in favor of the sub-species concept.

Race Concept, Natural Reality, and Race Concept, Natural Reality, and Darwinian Classification Darwinian Classification

In In phylogenetic phylogenetic systematics systematics and and evolutionary evolutionary classification, classification, a a grouping grouping of

• f organisms
• rganisms is

is considered considered real or natural if it meets the following criteria: real or natural if it meets the following criteria:

• Common

Common descent descent (phylogenetic/cladistic (phylogenetic/cladistic => => monophyletic monophyletic grouping grouping = = comprises comprises all all and and only

• nly the

the

• ffspring of a common ancestor)
• ffspring of a common ancestor)

1) 1) Genetic Genetic similarity/degree similarity/degree of

• f differentiation

differentiation (similarity due to shared ancestry) (similarity due to shared ancestry)

The The revival revival of

• f the

the debate debate over

• ver race

race defined defined primarily primarily as as continental continental group group at at the the turn turn of

• f the

the 21 21st

st

century century was was partly partly due due to to the the need need to to connect connect theoretical theoretical “bench” “bench” inquiries inquiries to to bedside bedside health health concerns, concerns, that that is is the the lab lab to to the clinic. the clinic.

Race Concept, Health and Continental Cluster Race Concept, Health and Continental Cluster

Prevalence of Hypertension in the US

Health, US, 2003 and 2006

Continental Races according Continental Races according (Risch et al. 2002; (Risch et al. 2002; Burchard et al. 2003 Burchard et al. 2003) )

No Phylogenetic Human Races No Phylogenetic Human Races ( (See Long & Kittles 2003

See Long & Kittles 2003)

)

Race as a Sampling-Artifact

[Gradients of Human Genetic Diversity (Serre & Paabo 2004)]

Race as a Sampling-Artifact (cont’d)

[Gradients of Human Genetic Diversity (Serre & Paabo 2004)]

Statistical Values of Continental Race Statistical Values of Continental Race

(Rosenberg et al. 2002, 2005; Rosenberg 2011) (Rosenberg et al. 2002, 2005; Rosenberg 2011)

World = 5 World = 5 World = 7 World = 7 Variation within Variation within population population 93.2 93.2 94.1 94.1 Variation among regions Variation among regions 4.3 4.3 3.6 3.6 Region variation over Region variation over within pop. variation within pop. variation 0.046 0.046 0.038 0.038

FST 0

0.15 0.05 0.25

No to little

Differentiation

Moderate Large Very Large

Clines (77%) vs. Cluster/Race (2%) Clines (77%) vs. Cluster/Race (2%)

[Going the Distance: Human Population Genetics in a Clinal World [Going the Distance: Human Population Genetics in a Clinal World (Handley et al. 2007)] (Handley et al. 2007)]

Pair-wise Fst Covariates Isolation by Distance (IBD) Cluster/Race 0.01 0.0077 0.0002 0.05 0.0385 0.001 0.1 0.077 0.002 0.15 0.1155 0.003 0.2 0.154 0.004 0.25 0.1925 0.005 0.3 0.231 0.006

“ “

Ancestry Ancestry varies varies from from population population to to population, population, and and from from individual individual to to individual.

• individual. Any

Any attempt attempt to to characterize characterize the the genetic genetic history history of

• f all

all African- African- Americans Americans (or (or any any human human population, population, for for that that matter) matter) by by a a single single number number is is futile.” futile.” (Relethford (Relethford 2012; 2012; see see also also Tishkoff et al. 2009) Tishkoff et al. 2009)

Race/Cluster and the Challenges of Population- Race/Cluster and the Challenges of Population- Targeted Personalized Genomic Medicine Targeted Personalized Genomic Medicine

Prevalence of Hypertension in African and European Populations

Cooper, RS et al, BMC Med 2005

The The prevalence prevalence of

• f frequently

frequently tested tested variants, variants, CYP2C9 CYP2C9 and and VKORC1, VKORC1, for for warfarin warfarin dosing dosing varies varies across across subpopulations subpopulations ( (Limdi Limdi et et al., al., 2008; 2008; Ramirez Ramirez et et al.

• al. 2012;

2012; Perera et al. 2013). Perera et al. 2013). Race Race accounts accounts for for 14.2 14.2 of

• f the

the variation variation in in response response to to warfarin. warfarin. After After controlling controlling for for pharmacogenetic pharmacogenetic factors, factors, race race accounts only for 0.3 of the accounts only for 0.3 of the variation (Kahn 2013). variation (Kahn 2013).

Race, Wafarin and Genomic Medicine Race, Wafarin and Genomic Medicine

Sticking Points Sticking Points

Sticking Sticking Point Point #1 #1: : Race Race research research needs needs to to be be constantly constantly subjected subjected to to clear clear and and objectively

• bjectively accepted

accepted rational rational taxonomic taxonomic principles principles and and not not to to blind bioinformatics and nebulous metaphysical commitments. blind bioinformatics and nebulous metaphysical commitments. Sticking Sticking Point Point #2 #2: : I It t is is crucial crucial for for clinicians clinicians to to understand understand that that race race is is not not a a natural natural biological biological grouping grouping but but a a mere mere instrumental instrumental grouping grouping in in

• rder to avoid the reification of this concept in the clinic
• rder to avoid the reification of this concept in the clinic.

. Sticking Sticking Point Point #3 #3: : Statistical Statistical values values of

• f race

race are are generally generally vanishing vanishing when when relevant relevant covariates covariates are are controlled controlled for for in in population population genomic genomic and and pharmacogenomic research. pharmacogenomic research. Sticking Sticking Point Point #4 #4: : Although Although race race may may be be a a relevant relevant problem-solving problem-solving tool tool under under some some well-controlled well-controlled biomedical biomedical situations, situations, its its clinical clinical use use for for therapy therapy choice choice is is problematic problematic and and may may require require clear clear ethical ethical guidelines. guidelines.