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Pharmacogenomics and Pharmacogenomics and American Indian American Indian Populations: Populations: Drug Development Drug Development in the in the Context of Health Context of Health DisparitiesDisparities

Morris W. Foster, Ph.D.Morris W. Foster, Ph.D.

Department of AnthropologyDepartment of Anthropology

University of OklahomaUniversity of Oklahoma

12th Annual Summer Public Health Research Videoconference on Minority Health

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The promise of The promise of personalized medicinepersonalized medicine

Will it really be Will it really be individualized?individualized?

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Instead of customized Instead of customized therapies for individuals, therapies for individuals, pharmacogenomics may just pharmacogenomics may just re-arrange the way in which re-arrange the way in which the economics of drug the economics of drug development development are calculated, using both are calculated, using both historicalhistorical and and marker-basedmarker-based groupings to determine groupings to determine potential markets.potential markets.

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Existing social groups Existing social groups will be characterized will be characterized by by differing differing frequenciesfrequencies of variants of variants that promote drug that promote drug response, while new response, while new groupings will be groupings will be based on the based on the presence presence or absence or absence of those of those variants.variants.

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To the extent that To the extent that frequencies of those frequencies of those variants differ by social variants differ by social identity, existing health identity, existing health disparities may be disparities may be exacerbated by the ways exacerbated by the ways in which in which pharmacogenomic drug pharmacogenomic drug development plays out, development plays out, while additional while additional disparities may be created disparities may be created among those assigned to among those assigned to new, marker-based groups.new, marker-based groups.

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This may result in two This may result in two kinds of kinds of pharmacogenomically-pharmacogenomically-relevant groupings:relevant groupings: (1) social groups that are (1) social groups that are genetically stereotyped genetically stereotyped (that is, differences in (that is, differences in frequencies are frequencies are misunderstood as the misunderstood as the presence or absence of a presence or absence of a variant among all group variant among all group members), andmembers), and

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(2) genotyped groups that (2) genotyped groups that are socially identifiable.are socially identifiable.

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Although not a Although not a pharmacogenomic drug, Bi-pharmacogenomic drug, Bi-Dil is an example of the way Dil is an example of the way in which identity-based in which identity-based disparities in the relative disparities in the relative frequency of disease frequency of disease incidence and drug response incidence and drug response can drive drug development can drive drug development and marketing.and marketing.

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The pre-existence of health The pre-existence of health disparities may shape the disparities may shape the ways in which ways in which pharmacogenomic drug pharmacogenomic drug development is mapped onto development is mapped onto social groups.social groups.

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How might the science of How might the science of pharmacogenomics play pharmacogenomics play out across a landscape of out across a landscape of social differentiation and social differentiation and health disparities? health disparities?

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American Indian/Alaska American Indian/Alaska Native (AI/AN) populations Native (AI/AN) populations make an interesting model make an interesting model for the groups that may be for the groups that may be affected or created by that affected or created by that intersection of science and intersection of science and society.society.

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AI/AN Populations - 1AI/AN Populations - 1 1.5% of total U.S. population 1.5% of total U.S. population

(approx. 4.5 million people)(approx. 4.5 million people)

1.9 million of whom receive their 1.9 million of whom receive their primary health care through IHSprimary health care through IHS

Significantly lower life Significantly lower life expectancy and significantly expectancy and significantly higher rates of heart disease, higher rates of heart disease, diabetes, etc.diabetes, etc.

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AI/AN Populations - 2AI/AN Populations - 2

Almost twice the percentage Almost twice the percentage of households below poverty of households below poverty as the general populationas the general population

Diversity of specific Diversity of specific ancestries (including ancestries (including European and African)European and African)

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Distribution of the Distribution of the benefits of benefits of pharmacogenomics pharmacogenomics dependsdependsboth on population both on population genetics genetics and market economics.and market economics.

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Do common drug response Do common drug response variants found in other variants found in other populations also exist in populations also exist in AI/AN populations? AI/AN populations?

– Yes, as will be the case in – Yes, as will be the case in all populations.all populations.

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Do some otherwise rare Do some otherwise rare drug response variants drug response variants occur at higher occur at higher frequencies in AI/AN frequencies in AI/AN populations? populations?

– Probably, as again will be – Probably, as again will be the case in all populations.the case in all populations.

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Do those otherwise rare Do those otherwise rare variants occur at different variants occur at different frequencies frequencies between tribal- and between tribal- and village-specific village-specific populations?populations?

– Probably. – Probably.

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When will we learn the When will we learn the answers to the previous answers to the previous three questions? three questions?

– Probably after we learn – Probably after we learn similar information for similar information for other populations, due in other populations, due in part to internal cultural part to internal cultural reasons and in part to reasons and in part to external economic external economic reasons.reasons.

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Pharmacogenomics is Pharmacogenomics is itself the construction of a itself the construction of a particular cultural particular cultural context, and there will be context, and there will be barriers to its use when barriers to its use when transferred to other transferred to other cultural contexts, with cultural contexts, with respect both to world view respect both to world view and to historical and to historical relationships with the relationships with the culture that created the culture that created the

technology.technology.

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Like many other Like many other populations that populations that experience health experience health disparities, AI/AN disparities, AI/AN populations have a lesser populations have a lesser economic capacity to: economic capacity to: (1) attract investments in (1) attract investments in targeted drug discovery targeted drug discovery and and (2) pay for access to (2) pay for access to cutting-edge cutting-edge diagnostics and drugs.diagnostics and drugs.

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If common genetically If common genetically targeted drugs do apply, targeted drugs do apply, it is likely that many it is likely that many tribal health facilities tribal health facilities and tribal members will and tribal members will be unable to afford the be unable to afford the diagnostic tests and what diagnostic tests and what will probably be the will probably be the higher costs of new higher costs of new drugs.drugs.

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If otherwise rare drug If otherwise rare drug response variants exist response variants exist at higher frequencies at higher frequencies for some AI/AN for some AI/AN populations, will drug populations, will drug companies companies “personalize” “personalize” therapies for those therapies for those variants?variants?

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Whether or not AI/AN Whether or not AI/AN populations are populations are pharmacogenomically pharmacogenomically unique, existing health unique, existing health disparities will be disparities will be compounded by the advent compounded by the advent of pharmacogenomics.of pharmacogenomics.

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If otherwise rarer variants If otherwise rarer variants exist at higher frequencies exist at higher frequencies for for somesome members of members of somesome AI/AN populations, will this AI/AN populations, will this contribute to a perception contribute to a perception that AI/AN people generally that AI/AN people generally respond differently to drugs? respond differently to drugs? That is, will differences in That is, will differences in frequency be translated as frequency be translated as presence or absence?presence or absence?

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Does the basis for that Does the basis for that perception already exist due perception already exist due to health disparities to health disparities between AI/AN populations between AI/AN populations and others?and others?

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The IHS, for example, The IHS, for example, can be conceptualized can be conceptualized as an example of as an example of ancestry-based ancestry-based medicine.medicine.

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If pharmacogenomic If pharmacogenomic drugs are provided or drugs are provided or developed for AI/AN developed for AI/AN people through that people through that identity-specific lens, the identity-specific lens, the potential for potential for confounding the social confounding the social and the biological is and the biological is considerable.considerable.

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At the same time, the At the same time, the economic, cultural, and economic, cultural, and other challenges that other challenges that AI/AN people face in AI/AN people face in having access to having access to pharmacogenomic pharmacogenomic benefits may most benefits may most effectively be addressed effectively be addressed through the identity through the identity portal.portal.

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For example, the most For example, the most effective argument for effective argument for developing drugs developing drugs targeted to response targeted to response variants that are variants that are disproportionately found disproportionately found in AI/AN populations is in AI/AN populations is probably that of a shared probably that of a shared AI/AN identity, not a AI/AN identity, not a shared genotype among shared genotype among those individuals those individuals affected.affected.

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The ideal solution may The ideal solution may be to insist on an be to insist on an identity-neutral identity-neutral pharmacogenomics. pharmacogenomics. But is that goal as But is that goal as unrealistic as truly unrealistic as truly personalized personalized medicine?medicine?

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The engagement The engagement between between pharmacogenomics and pharmacogenomics and historical, social groups historical, social groups and identities may be and identities may be unavoidable.unavoidable.

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