Commentary: Two Threats to Precision Medicine Equity

Commentary Commentary: Two Threats to Precision Medicine Equity

Dayna Bowen Matthew, JD, PhD1

In January 2015, President Barack Obama Introduction unveiled the “Precision Medicine Initiative,” alities. Both hold that a new under- a nationwide research effort to help bring standing of genetics will result not an effective, preventive, and therapeutic First, achieving precision medi- only in remarkable improvements in approach to medicine. The purpose of the initiative is to bring a precise understanding cine equity will require scientists human health, but also in the better- of the genetic and environmental determi- and clinicians to fulfill their intel- ment of society overall.5 Both target nants of disease into clinical settings across lectual, moral, and indeed legal duty ways to distinguish “a given patient the United States.1 The announcement was coupled with $216 million provided to work against abusive uses of pre- from other patients” and propose to in the President’s proposed budget for a cision medicine science to advance do so “on the basis of genetic, bio- million-person national research cohort distorted views of racial group varia- marker, phenotypic, or psychosocial including public and private partnerships 6 with academic medical centers, research- tion. The prospect of using patients’ characteristics…” Both movements ers, foundations, privacy experts, medical genetic information to better predict emerged amidst rapidly develop- ethicists, and medical product innovators. and prevent disease could easily trav- ing technological and analytical ad- The Initiative promises to expand the use of precision medicine in cancer research and el down the slippery slope toward vancements that could accelerate the modernize regulatory approval processes eugenics – the immoral and deadly speed and expand the scope of their for genome sequencing technologies. In pseudo-science that gave racist and influence beyond our ethical and le- response, Congress passed the 21st Century Cures Act in December 2016, authorizing nationalist ideologies what Troy gal capacity to accommodate plans a total of $1.5 billion over 10 years for the Duster called a “halo of legitimacy”4 to “revolutionize” health care as 2 program. Although the Precision Medicine during the first half of the 20th cen- we know it.7 And both movements Initiative heralds great promise for the future of disease treatment and eradication, its tury. While precision medicine and are located contextually amidst a implementation and development must be eugenics may not seem similar, the disturbing surge in the social ac- carefully guided to ensure that the millions two movements share common- ceptance of prejudice, xenophobic, of federal dollars expended will be spent equitably. This commentary discusses two key threats to the Precision Medicine Initia- tive’s ability to proceed in a manner consis- tent with the United States Constitutional Precision medicine scientists must decisively improve and indeed transform health care requirement that the federal government denounce and distinguish this Initiative from delivery for all patients, regardless of race, shall not “deny to any person . . . the equal the pseudo-science of eugenics – the im- color, or national origin. Ethn Dis: 2019; protection of the laws.”3 In short, this com- moral and deadly pseudo-science that gave 29(Suppl 3):629-640; doi:10.18865/ed.29. mentary sounds two cautionary notes, in racist and nationalist ideologies what Troy S3.629 order to advance precision medicine equity. Duster called a “halo of legitimacy” during th 4 First, achieving precision medicine equity the first half of the 20 century. Second, Keywords: Equity; Eugenics; Ecological will require scientists and clinicians to fulfill to combat the social threat to precision Race; Racism their intellectual, moral, and indeed legal medicine, scientists must incorporate a duty to work against abusive uses of preci- comprehensive, ecological understanding 1 University of Virginia Law School, sion medicine science to advance distorted of the fundamental social and environ- Charlottesville, VA views of racial group variation. mental determinants of health outcomes in all research. Only then will the Precision Address correspondence to: Dayna Bowen Medicine Initiative live up to its potential to Matthew: [email protected]

Ethnicity & Disease, Volume 29, Supplement 3, 2019 629 Commentary: Precision Medicine Equity - Matthew and White supremacist ideology in lish the fit it has for its purpose nic minority groups experience.19 I the United States, and worldwide.8 not the betterment of physical call this the threat of social racism. During the early 20th Century types merely, but the establish- I discuss these two threats, begin- “[r]acism . . . provided the theoreti- ment of those types of greatest ning by illustrating the impact that cal framework for eugenic thinking. value to progressive civilization indifference to the threat of scientific In return, eugenics provided twisted . . . Those who seek to main- racism could have. Following this versions of science and public health tain the White race in its puri- section, the threat of social racism justifications for White supremacists ty within the United States are is explored in light of the evidence to advocate that forced steriliza- working in harmony with the precision medicine seems yet unable tion, anti-miscegenation laws, and ideals of eugenics. Asiatic ex- to incorporate. The conclusion offers state-sponsored segregation would clusion and Negro repatriation some preliminary recommendations. advance the ‘health of the race.’”9 are expressions of the eugenic White Americans had for more than ideal.” – Earnest Sevier Cox 9, p138 two centuries developed an under- Scientific Racism standing of the races as biologically The possibility of incorporat- Threat distinct groups marked by inherited ing information encoded in the attributes of inferiority and superi- human genome to address threats In 2002, the Institute of Medi- ority.”10 Eugenics, named from the to human health could easily ap- cine published a landmark consensus Greek word meaning “well-born,” is peal to perverse notions of selective report, Unequal Treatment: Confront- “the study of self-directed human he- reproductive breeding. Moreover, ing Racial and Ethnic Disparities in redity and breeding [that] promise[s] the notion of biological hierarchies Health Care, which reviewed the em- to raise the general welfare by re- could extend to tolerate, if not jus- pirical literature, considering more producing better individuals”9 Ar- tify legalized social and economic than 600, peer-reviewed studies and thur Caplan famously recounts racial hegemony. Minority popula- identifying dramatic and troubling the deadly cruelty that eugenicists tions share a deep concern14,15 that health disparities across a broad va- visited upon Jews during the Ho- precision medicine’s basis in genome riety of diseases and illnesses. It con- locaust,11 and Dorothy Roberts10 science may be misused to resurrect cluded that in America, racial and poignantly traces the movement’s the backwards and hateful asser- ethnic minorities tend to receive a cruel inspiration that institution- tions of racialized science.10 Since lower quality of health care than non- alized White supremacy in Racial the 1970’s, the White power move- minorities, even when access-related Integrity Laws,12 enacted across the ment16 in America has consolidated factors, such as patients’ insurance United States to protect whiteness an escalating campaign of terror that status and income, are controlled.20 from race-mixing. Eugenics pro- sadly continues to claim adherents In the wake of Unequal Treatment, vided the biological justification for among geneticists today.8,17,18 I call the Center for Health Equity Re- viciously legalized sterilization of the this the threat of scientific racism. search and Promotion describes re- poor and mentally ill,13 and intel- Second, if precision medicine searchers engaged in identifying the lectually fueled the discriminatory science fails to fully incorporate causes of observed disparities as well doctrines that instituted the Post- knowledge of the ecological influ- as interventions to eradicate them, Reconstruction, segregated social ences of structural discrimination as second and third “generation”21 order in America that persists today. and prejudice on the epigenetic and researchers, respectively, and preci- ecological outcomes shared among sion medicine and genomics could “The Negro problem is part many minority populations, the ge- contribute to these efforts. However, of the greater problem of he- netic revolution may indeed exac- a group of geneticists have assailed redity. When eugenics seeks to erbate the disproportionate adverse the work of all generations of dis- eliminate the unfit and estab- health effects that racial and eth- parities researchers as unscientific,22

630 Ethnicity & Disease, Volume 29, Supplement 3, 2019 Commentary: Precision Medicine Equity - Matthew asserting that the field is driven by zations, genetic determinists report that focus on human evolution, ge- an ideological commitment to polit- “[t]he results are the same irrespec- netic determinists assert that endoga- ical correctness rather than rational tive of the type of genetic markers mous mating patterns have persisted fact.23 These critics represent a scien- employed, be they classical systems, from prehistoric times to the most tific threat to the potential of preci- restriction fragment length poly- recent US census: “[A]dmixture be- sion medicine. They, like eugenicists, morphisms (RFLPs), microsatellites, tween races has occurred over many resort to scientifically unsupported or single nucleotide polymorphisms centuries. Nonetheless, during the and plainly degrading explanations (SNPs)” These studies, they say, same period of time, as well as cur- of observed differences among racial consistently find populations clus- rently, mating patterns are far from populations in ways that amount to tered into five groups: “The African random. The tendency toward en- positing genetic inferiority of mi- branch [including] three sub-Saha- dogamy is reflected within the 2010 nority populations.24,25 This form ran populations, . . . the Caucasian Census, which allowed individuals of racialized medicine could pro- branch [which] included Northern to report themselves to be of a single foundly distort precision medicine Europeans and Northern Italians; race or of mixed race – 69.1% of research first by causing a dangerous the Pacific Islander branch [includ- subjects reported being of one race, re-focus on assertions of biological ing] Melanesians, New Guineans and while 2.4% reported being of more differences among human popula- Australians; the East Asian branch than one race.29 These figures, genetic tion groups that simply do not ex- including Chinese, Japanese and determinists say, highlight the strong ist,26 drawing attention away from Cambodians; and the Native Ameri- deviation from random mating in productive second and third gen- can branch [which] included Ma- the United States. They explain that eration research needed to eradicate yans from Mexico and the Surui and “gene flow from non-Caucasians health disparities among underrep- Karitiana from the Amazon basin.”27 into the US Caucasian population resented populations,27 and second While acknowledging that these cat- has been modest.”23 This surprising by suppressing policy solutions that egorizations have been blurred by line of reasoning leads to the conclu- might improve and lengthen lives. migratory patterns, genetic deter- sion that despite “modestly” higher I will discuss these two aspects of minists place fundamental impor- rates of admixture among Blacks and the scientific racism threat in turn. tance on these findings,28 which they Asians, African Americans largely interpret to have a profound impact reflect African origins from a ge- The Distractive Threat of on racial health disparities between netic perspective and Whites remain Scientific Racism Black and White Americans. Despite largely and genetically Caucasian. the fact that these researchers “cate- Dr. Esteban Gonzalez Burchard Many who attribute the problem gorize Africans as those with primary is among the genetic determinists of health disparities to genetic varia- ancestry in sub-Saharan Africa; [in- who conclude that recent genetic tions among the races define “race” as cluding] African Americans and Af- studies of population substructure a group that is ancestrally connected ro-Caribbeans. . . [and] Caucasians have produced clusters of genetic in- to one of five population groups [as] those with ancestry in Europe formation that can be used to iden- based on their primary continent and West Asia, including the Indian tify an individual’s self-described of origin, a theory first advanced by subcontinent and Middle East,”28 geographic ancestry. As is common racial topologist Johann Blumen- they believe they have found mean- among this group of researchers, bach in 1795. These are people who ingful pathways to ascribe genetic Burchard quickly extrapolates from believe one’s genes determine one’s variations that exist among ancestral what is known about genetic dif- race. Hence, I call them “genetic de- population groups to self-identified ferentiation for the few diseases terminists.” Citing a human popula- racial groups in the United States. where scientists have identified spe- tion genetic study as exemplary of To connect modern American ra- cific variations, to assert the prom- many that confirm these categori- cial groups to the population studies ise of solving much more complex

Ethnicity & Disease, Volume 29, Supplement 3, 2019 631 Commentary: Precision Medicine Equity - Matthew and uncertain connections between racial and ethnic health disparities, self-categorizations, both from the other diseases that occur disparately distracting from generating effective research and public policy points of among American racial groups. Bur- interventions to eradicate inequi- view.”23 The threat to precision med- chard writes, “there are at least 15 ties, and therefore ultimately serving icine this view represents includes an million genetic polymorphisms and to widen rather than narrow ineq- oversimplification of diagnostic and an undefined subgroup of these that uity in population health outcomes. therapeutic decisions that will be im- underlie variation in normal disease Dr. Satel flatly and incorrectly precise and inaccurate.36 Even worse, traits. . . . [One] need change only a claims the problem of racial and eth- the biologization of race threatens single base pair to cause many well- nic health disparities is a “myth,”24 to mislead or exploit those most in known inherited diseases such as turning an epidemiological phenom- need of medical interventions37 to sickle cell . . . or increase risk of com- enon into a “civil rights problem” by erase inequities that have produced mon disorders such as Alzheimer’s.”30 ignoring confounding variables. She racial health disparities that by one Dr. Satel is another researcher sees racial disparities such as the fact estimate, unnecessarily cost more whose work exemplifies the mis- that White women more frequent- than 84,000 lives each year.38 How- take common to genetic determin- ly suffer osteoporosis, while Black ever the most dangerous adherents ists, who similarly fail to appreciate women suffer greater numbers of to this school regard racial equality that genomic variations are neither uterine fibroid tumors, as evidence as “tripe.” 39 This version of scientific as common nor as deterministic as of biological or genetic differences. 24 racism has serious medical, legal, they suppose. Thus, this group mis- This view precludes Satel and health and policy implications. Dr. Satel’s understands the context in which providers who share her medical work provides ready fodder for the these variations can be important. myopia from taking a comprehen- arguments of eugenicists and White Satel infamously proclaimed, “I am sive approach to improving patient supremacists with whom she, no a racially profiling doctor,” and as- health outcomes, dismissing the doubt, does not identify ideologi- serted that “the .1 percent of human social determinants that have been cally. Nevertheless, Dr. Satel’s scien- genetic variation [by race] is a medi- shown to have a substantial impact tific errors are useful to racists. For cally meaningful fact” and “[n]ot on health outcomes, entirely from the example, when she cites fatalism as surprisingly, many human genetic provider’s concern.34 This perspec- an explanation for minorities’ disin- variations tend to cluster by racial tive robs underrepresented minority terest in medical treatment, ignoring groups…31 Satel has worked for years communities of the opportunity for egregious historical research abuses with a group of physicians inter- precision medicine to be precisely as well as persistent contemporary ested in the genetic association be- tailored to reflect the environmen- discrimination in medicine40 that tween dopamine transporter protein tal, social, and clinical determinants readily explains patient preferences, (DAT1) alleles and cocaine-induced that affect their health, and prompts she dangerously diverts away from paranoia; Satel and her group appear providers and researchers to reach fashioning effective, evidence-based to have had a special interest in iden- for and privilege plainly incorrect interventions to reduce disparities. tifying racial differences in gene cod- explanations for disease disparities. When she cites “magical thinking” ing for DAT1, focusing their study The arguments of genetic deter- as a reason that minorities avoid on comparisons of Black and White minists obscure the hard work of cancer treatment while ignoring patient samples.32 This effort seems parsing apart the true impact that ge- the simple fact that a majority of to have been largely fruitless,33 but netic differences may have on popu- White as well as Black Americans Satel’s research orientation poses a lation health,35 and instead rest on a believe in the devil,41,42 she espous- grave threat to the efficacy and integ- presumed understanding that “from es the type of biased analysis that rity of the Precision Medicine Initia- both an objective and scientific (ge- aligns squarely with the worst scien- tive. Satel’s views can lead to a false netic and epidemiologic) perspective tific racism, even if unintentionally. understanding of the true causes of there is great validity in racial/ethnic In their preface to Race:

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The Realities of Human Differ- The Policy Threat of Scientific cohort study in which he reviewed ences, Sarich and Miele argue: Racism the Missouri Department of Health’s maternally linked birth-death certif- “We present what we believe Applying genetic determinists’ icate database.46 Kistka studied live is compelling evidence to sup- view to a selected health disparity singleton births from the cohort, fo- port the propositions that race problem can demonstrate the prac- cusing on the recurrence of preterm is a valid biological concept, and tical import of their approach. The delivery in the same mother. His that human variations – that is, increase in the incidence of preterm hypothesis was that genetic factors, the differences among individu- birth presents an alarming public independent of environmental ones, als and groups, whether in ath- health problem in the United States. increase the risk for extreme preterm letic competition, IQ tests, or Preterm infants currently account birth and its recurrence at a similar the competition to lead a satisfy- for between 50% and 70% of all gestational age in Black mothers ing and successful life, however neonatal morbidity and mortality, as compared with Whites. Indeed, each individual or group may and poor birth outcomes have been Kistka did find that Black moth- define it – reflect both genetic recognized as important predictors ers had a higher relative risk rate of and environmental factors. On of adult disease and illness, particu- preterm and extreme preterm births matters of social policy, we are larly adult cardiovascular health for than Whites (3.71 and 2.99, respec- both individualists. We oppose African Americans.45 Most impor- tively). Moreover, while Black and any governmentally sanctioned tantly for the purpose of this analy- White mothers both showed limited benefits or handicaps being ap- sis, the disparate incidence of low variation in the week of gestation plied solely on the basis of group birthweight babies between Blacks for recurrent preterm birth, Black membership. Rather, we argue and Whites is well-documented. mothers were at increased risk for re- for policies that help each in- This case is therefore ideal for com- current preterm birth and for Black dividual do the best he or she paring the approaches of genetic multiparous mothers, recurrent pre- can and wants to do. Both of us and environmental determinists to term births occurred two weeks ear- benefited from programs that analyze and address health inequity. lier than for Whites and were more foster and reward talent and Zachary A.F. Kistka,46 a research- likely to repeat during the same ges- performance, and we support er studying the frequency and re- tational week than Whites. Kistka making them open to anyone currence of preterm (and therefore) and his research team reasoned that who is qualified – Period!” 43 low-weight births between Black and their “data suggest that the proposed White mothers, holds a genetic de- genetic component of preterm birth These authors’ political objectives terminist view of health disparities. may be a greater etiologic contributor are as unabashed as their assertions Recently, Kistka explained, “allele than has previously been recognized about Africans’ average cranial vol- frequencies of functional gene vari- because racial differences in preterm ume and related racial difference in ants differ between geographical iso- birth severity and recurrence per- intellectual ability are foolish. These lates. This difference in functional sisted in [their study] cohort, even biological assertions are affirmatively gene variants would therefore be ex- after adjusting for known medical harmful to minority health. Dr. Satel pected to be reflected [sic.] by race. and socioeconomic confounders.”46 appears to have fallen silent concern- Indeed a number of polymorphisms In contrast, biological anthropol- ing health disparities in recent years. in inflammatory markers as a func- ogist Christopher Kuzawa compared In the interim, some disparities have tion of race or ethnicity have been the incidence of low birthweight improved slightly but many have identified in association with pre- infants born to Blacks and Whites not,44 and the danger presented by term labor.” Kistka set out to test the by reviewing evidence from existing scientific racism persists. An analy- strength of this asserted association studies to critically evaluate the evi- sis of its policy impact is illustrative. by conducting a population-based dence for developmental and epigen-

Ethnicity & Disease, Volume 29, Supplement 3, 2019 633 Commentary: Precision Medicine Equity - Matthew etic links between early life environ- vation that “[t]he first line of evi- and environmental, as well as epi- ments and adult disease disparities. dence is the generally low heritability genetic,47 factors play in Kuzawa’s Kuzawa’s analysis was based on his of birthweight,” finding that studies understanding of racial disparities “growing appreciation that environ- based on twin registries generally re- and the role that biological factors mental influences contribute to adult port heritability between .2-.4, with serve in Kistka’s conclusions, is evi- health disparities by influencing bio- national studies reporting estimates dent in their recommendations. Ku- logical processes and responses across of .31 confirming this range. Kuzawa zawa concluded his study by observ- the life cycle.”45 Kuzawa aimed to next reviewed studies of monozy- ing that the “emerging epigenetic evaluate the contribution of mater- gotic twin pairs to observe the asso- model of health disparities points to nal stress as a biological pathway ciation between lower weight twins social and economic change as key to cardiovascular health disparities and their elevated risk for adverse to addressing racial differences in between Black and White Ameri- changes that put them at risk for dia- disease burden and underscores the cans. His study discussed the role of betes and hypertension later in life, need to implement . . . interventions “developmental and epigenetic pro- finding that “genetic correlations do across the life-course.” Kuzawa’s list cesses as underlying mechanisms” not fully account for the associations is long – improving access to ad- that contribute to racial disparities with adult disease risk.” Finally, equate prenatal care and nutrition in heart disease. However, Kuzawa’s Kuzawa offered his support for the buffering stress to improve lactating, definition of race differed from “developmental origins of health and improving social support through the Kistka’s clinical classification: disease” (DOHaD) model, which maternity leave, and other far reach- emphasizes the biological and devel- ing solutions. In contrast, Kistka’s “[W]e choose to use the term opmental mechanisms that associate discussion remarkably concludes ‘race’ because many of the so- early life conditions such as malnu- with no hint of an intervention re- cial forces we discuss as under- trition, stress, and maternal stress sponding to his disparities findings.48 lying determinants of health with modifications in the weight Kistka and other genetic determin- disparities, such as discrimina- and condition of infants, later their ists suggest nothing to improve the tion, economic inequalities, risk of developing adult diseases, and health outcomes of minorities.49 or segregated neighborhoods hence the disparate outcomes that represent the unique lived real- are seen between Blacks and Whites Summary: The Scientific ity of race as a socially defined throughout the life cycle. Kuzawa Racism Threat and imposed system in the US. concluded that, “[w]hereas group . . . [W]e emphasize that we membership and continental race are I see six exemplary, though non- define race as a socially con- poor predictors of genetic variation, exhaustive, threats that scientific rac- structed category that has bio- these same categories are directly ism presents to the precision medi- logical implications, rather than related to the social and structural cine movement. First, it perpetuates a genetically justified criteria for manifestations of inequality that inaccurate notions of human popula- classifying human variation.”45 impact the development of respon- tions. For example, researchers such sive biological systems. A wealth of as epidemiologist Nancy Krieger have Kuzawa and his team plainly as- evidence now shows that the social definitively challenged the unscien- serted that low birthweight reflects and economic experiences of race tific descriptions of artificial human both environmental and genetic have profound influence on adult groups that Kistka and other genetic factors but quickly concluded that health and beginning in childhood, determinists employ.50 Krieger faults genetic correlations did not fully ex- can have effects that are both chron- their use of the term “Caucasian,” a plain the associations documented ic and cumulative in their impact.” factually and scientifically inaccurate between birthweight and race. More- Perhaps the most striking differ- term coined by 18th century racial over, Kuzawa began with the obser- ence between the role that biological topologist Johann Blumenbach, who

634 Ethnicity & Disease, Volume 29, Supplement 3, 2019 Commentary: Precision Medicine Equity - Matthew incorrectly assumed that Europeans best explains why scientific racism is The Threat of Social were the original humans and hu- a dangerous threat. It redirects pre- Racism man life emanated from the Cauca- cious research and policy resources sus region of Russia. Second, scien- away from innovative interventions A second threat to the precision tific racism advances the mistaken that might genuinely aid in eradicat- of precision medicine is the pos- notion that phenotype is equivalent ing health inequalities, giving false sible exclusion of racism itself as an to genotype. In other words, the comfort that ideologically driven re- important determinant of health. self-reported racial categories that search has proved that real solutions David Williams et al define racism genetic determinists rely upon are a are not needed. Thus, inaction is the as “an organized social system in function of observed traits that arise deadliest threat of scientific racism. which the dominant racial group, out of gene expression, rather than Scientific racism inspires vigor- based on an ideology of inferiority, traits that are heritable because they ous opposition to policies aimed at categorizes and ranks people into are a function of gene frequency. reducing disparities such as efforts social groups called “races” and uses Third, scientific racism overlooks the to increase physician workforce di- its power to devalue, disempower, well-documented fact that 99.9% versity or even data collection that and differentially allocate valued of humans are genetically identical measures the relative health of ra- societal resources and opportuni- and ignores the vast variability with- cial and ethnic groups. Perhaps the ties to groups defined as inferior.”54 in people groups that is far greater most pernicious view of this group In order for precision medicine than the variability among people is their attack on the “assumption” to realize its full potential at the groups.51 Fourth, it confuses gene that health gaps can be closed. Fun- population level, the design of stud- frequency with gene expression. The damentally, those who characterize ies and the topics of the clinical in- notion that genetic variability ac- health disparities as a “myth” dis- terventions that result from those counts for medically important dif- tance themselves and other health studies must not only avoid reifying ference in disease outcomes among providers from the responsibility race as a genetic concept, but also racial and ethnic groups depends on to address health disparities by de- understanding race as a reflection the frequency of genetic variants or risively calling those of us who be- of the societal and individual iden- alleles underlying the susceptibility lieve that disparities are associated tity constructions that impose social of diseases. While a rare set of mu- with structural racism “the dispar- consequences on groups of people tations that have frequencies of less ity-equals-racism crowd.”53 These based on societal status. Research- than 2% do show race-specific vari- theorists pronounce, “questions ers should follow the example set by ance, the vast majority of diseases about societal leveling: how to ex- historical epidemiologists, 55 sociolo- have complex mutations that cannot ecute it; whether to pursue it at all gists, 56 philosophers, 57 and hosts of be superficially explained by genetic and, if so, in which domains – are physicians58 who have reasoned that determinants. Fifth, scientific rac- best left to politicians, voters, and racial disparities in health status and ism exhibits what researchers Dar- social welfare policy experts.” The outcomes derive from interplay be- Nimrod and Heine describe as an es- circularity of this view – that social tween complex social forces such as sentialist bias.52 They document that determinants do not cause dispari- economic disadvantage, institutional using the cognitive heuristics that ties, but to the extent that they con- and interpersonal discrimination, simplistically organize people into tribute to disparities they are not a structural barriers to healthy life stable, immutable, groups for whom scientific concern – leaves nothing choices; unequal access to healthy behavior and physiology are merely for medical scientists or clinicians to food, education, work and housing the result of innate, biological po- do. This is, perhaps, the most tragic environments; disparate access to tential, causes affirmative harms in flaw and the most serious threat water and sanitation; and, indeed, perception and prejudice. However, that scientific racism presents to non-genetic transmission of bio- it is the sixth and final critique that the precision of precision medicine. logical differences among the races.

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Importantly, access to all these social White mothers while infants born all-cause Black mortality rate. The determinants of health is affected by to African American mothers die same proxy of area racism was utilized racism. Thus, understanding racism at twice the rate,44 notwithstanding to measure the relationship between as both a direct and indirect mecha- higher incomes and educational at- area racism and birth outcomes. nism producing disparate health tainment than their White counter- After adjustment for maternal age, outcomes in minority groups is cru- parts. Research suggests that African Census region, county-level mea- cial to developing an individualized American women’s lifetime exposure sures of urbanicity, percent of Black understanding and clinical treat- to interpersonal racial discrimina- population, education, and poverty, ment of these patient populations. tion is associated with pregnancy researchers found that each standard Dr. Camara Jones59 has defined outcomes.63 Continuous exposure deviation increase in area racism was three levels of racism that adversely to racial discrimination is associated associated with relative increases of affect health: internalized, inter- with cardiovascular responses that 5% in the prevalence of preterm personal and systemic. Internalized could harm pregnancy outcomes. birth and 5% in the prevalence racism is the incorporation of rac- An association has also been found of low birthweight among Blacks. ist ideologies, beliefs or attitudes between low-income, urban Afri- Genomic research must address within a person’s worldview.60 Inter- can American mothers’ perception racial inequality before biomarkers personal racism refers to racist in- of exposure to unfair treatment and and stochastic modeling can be ef- teractions among people. Systemic infant birthweight. The association fective in producing and informing racism, also known as structural, between exposure to racism and very the promising therapeutic prospects cultural, societal, civilizational and low birthweight is strongest among of precision medicine and translat- institutionalized racism, refers to mothers who engage in high-risk ing these breakthroughs into the prejudiced institutions controlling behaviors, which may reflect the clinical setting. Fortunately, preci- access to material, informational and impact of institutional racism on sion medicine scientists have dem- symbolic resources. The effects of health such as the disproportion- onstrated cognizance of the historic each must be recognized and includ- ate targeting of African Americans discrimination by the scientific com- ed in quality precision medicine. for alcohol and tobacco products. munity and its threat to reliable and A body of emerging literature has Other emerging literature links valid research. For instance, Gior- considered the aggregate impacts of structural racism to disproportion- gio Sirugo reported that by 2018, racism on individual health. African ately adverse health outcomes for 78% of the individuals included in Americans have disproportionately minority populations. Researchers genome-wide association studies been exposed to environmental stim- have found that residential segrega- (GWAS) were of European ancestry, uli that may be sources of chronic tion highly correlates to poor health despite this demographic constitut- and acute stress including perceived outcomes.54 Several studies utilized ing only 15% of the global popu- racism.61 Experiences of racial dis- internet search-based proxy of area lation. Asians represented another crimination and mental health out- racism by measuring area racism as 10% of the individuals included in comes are often affected by stress.62 a proportion of Google searches or GWAS, while African and Hispanic The biomarker measure, allostatic tweets containing the “n-word.” 64 populations comprised only 2% load, calculates the “wear and tear on One study found that areas charac- and 1%, respectively. Further still, the body” that accrues after repeated terized by a one standard deviation nearly three-quarters of GWAS have or chronic stress. Several studies have greater level of area racism were as- been conducted in either European found evidence of the association be- sociated with an 8.2% or 30,000 in- (52%) or Asian (21%) populations.65 tween individually mediated racism crease in the all-cause Black mortality Landry et al explained the striking and poor health. For example, Afri- rate annually; even after controlling difference between the prevalence of can American mothers die at three to for White mortality rate, area racism diseases in underrepresented com- four times the rate of non-Hispanic was still significantly associated with munities and the lack of studies be-

636 Ethnicity & Disease, Volume 29, Supplement 3, 2019 Commentary: Precision Medicine Equity - Matthew ing conducted to better understand erating Research (CSER2) Consor- crucial to developing an individual- these diseases. For example, Landry tium. While these efforts to diversify ized understanding and clinical treat- found no studies whatsoever in un- the database and scientific workforce ment of these patient populations. derrepresented groups for colorectal are important, they are not enough. cancer and fewer than 5% of studies 3. Increase Funding for for breast cancer included patients Ecologic Development of Data from underrepresented groups.66 Recommendations Science Focusing on Epigenetic Clearly this can mean that underrep- Heritability resented groups are less likely to be Precision medicine presents a Epigenomes are chemical com- able to find the causes of their dis- promising opportunity for the fu- pounds and proteins that influence eases and reap the benefits of being ture of health care; but if we are to gene expression without modifying able to detect and understand dis- truly advance the interests of health the underlying DNA. Epigenetic ease. Researchers will need to make and health equity, we must ensure change is heritable and may occur concerted efforts to include minority that precision medicine is precise rapidly in response to environmen- populations in genomic studies as and considers the environmental, tal conditions and the experiences of racial minorities are often reluctant as well as genetic, determinants parents. A greater understanding of to participate for multiple and com- of disease. In furtherance of this epigenetic inheritance will enhance plex reasons. Some of these relate to goal, policymakers should adopt our knowledge of ways that the envi- historic research abuses such as the the following recommendations: ronment, including the social deter- Tuskegee syphilis experiment, now minants of health, influence genetic familiar to most.67 But other reasons 1. First and Foremost, expression and inform our decision include lack of information68 and Unequivocally and to promote better health outcomes. lack of diversity among researchers Resoundingly Reject All who can engender trust in minor- Attempts to Biologize Race 4. Recognize and Address ity communities.69 Efforts to address The scientific community must Disparities in Genomic these disparities are hopeful. For engage in a concerted and con- Medicine example, the National Institutes of sistent condemnation of all ef- Gross racial inequality in genom- Health (NIH) has launched the “All forts and expressions that biolo- ic research will continue to frustrate of Us” program to collect health, ge- gize the social construct of race. the efficacy and equity of precision nomic, and behavior data from one medicine unless the scientific com- million Americans and to specifi- 2. Create Policies Ensuring munity makes concerted efforts to cally oversample and build trust with the Inclusion of Social include currently underrepresented communities that have been histori- Determinants of Health in populations into future studies. This cally underrepresented in research.2 Research Funding process necessarily requires establish- At last report more than 100,000 Racial disparities and health sta- ing trust among underrepresented participants have been enrolled. tus and outcome are largely driven groups that have historically been ex- NIH has also awarded $18.9 million by social and environmental concluded from and exploited by medi- toward research that aims to acceler- texts such as economic opportunity, cal research and the recruitment of a ate the use of genome sequencing in access to healthy food, education, diverse scientific workforce that can clinical care, including efforts to en- and housing, structural barriers to engender trust in these communities. sure that the effectiveness of genomic healthy life choices, and non-genetic medicine can be applied to all indi- transmission of biological differenc- 5. Increase Access to Precision viduals and groups, including un- es. Understanding the role these de- Medicine Services derserved populations, through the terminants play in producing dispa- The opportunities and benefits Clinical Sequencing Evidence-Gen- rate health outcomes for minorities is provided by precision medicine

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14. NPR. Troubling History in Medical Research will be limited unless patients of all prove and indeed transform health Still Fresh for Black Americans. October 25, backgrounds have access to these care delivery for all patients, regard- 2017 Available at: https://www.npr.org/sec- tions/health-shots/2017/10/25/556673640/ services. Ensuring equitable access less of race, color, or national origin. scientists-work-to-overcome-legacy-of-tuske- begins with the elimination of bar- gee-study-henrietta-lacks riers to services such as a lack of in- Conflict of Interest 15. Weinberger DR. The Promise of Precision No conflicts of interest to report. Medicine Is not for Everyone. August 13, surance coverage and the inability to 2018. The Conversation, Available at: http:// see relevant health professionals that theconversation.com/the-promise-of-person- References alized-medicine-is-not-for-everyone-100997. produce existing health disparities. 1. National Institutes of Medicine U.S. 16. Dobratz BA, Shanks-Meile SL. The White National Library of Medicine, “What is the Separatist Movement in the United States:” 6. Increase Education of Precision Medicine Initiative?” Available at: White Power, White Pride! Baltimore, MD: https://ghr.nlm.nih.gov/primer/precision- JHU Press; 2000. Scientists and Communities medicine/initiative. 17. Belew K. Bring the War Home: The 2. National Institutes of Health, All of Us Re- Scientists and clinicians must be White Power Movement and Para- search Program Backgrounder. Available at: military America. Boston, MA: Harvard trained to include social determi- https://allofus.nih.gov/news-events-media/ University Press; 2018. https://doi. nants, including individual, cultural, media-toolkit/all-us-research-program-back- org/10.4159/9780674984943 grounder and structural racism measures in 18. Holtzman NA, Rothstein MA. Eugenics and 3. Bolling v. Sharpe, 347 U.S. 497 (1954) genetic discrimination. Am J Hum Genet. research funding. Enhanced fund- Amendments V and XIV, United States 1992;50(3):457-459. PMID:1531726 Constitution. ing for ecologic development of data 19. Cohn EG, Henderson GE, Appelbaum PS. 4. Duster T. Backdoor to Eugenics. New Distributive justice, diversity, and inclusion science focusing on environmen- York, NY: Routledge; 2004. https://doi. in precision medicine: what will success look tal as well as epigenetic heritability. org/10.4324/9780203426951 like? Genetics in Medicine. 2015; 19(2), 157– 5. Collins FS. Shattuck lecture—medical 159. https://doi.org/10.1038/gim.2016.92 and societal consequences of the Hu- 20. Smedley BD, Stith AY, Nelson AR. Unequal man Genome Project. N Engl J Med. Treatment: Confronting Racial and Ethnic Conclusion 1999;341(1):28-37. https://doi.org/10.1056/ Disparities in Health Care. Washington, DC: NEJM199907013410106 PMID:10387940 National Academies Press. 2003. 6. Kahn J. Revisiting Racial Patients in an Era 21. Fine MJ, Ibrahim SA, Thomas SB. The Without question, the Precision of Precision Medicine. 67 Case W.Res.L. Rev. role of race and genetics in health dis- 1153; 2017. Available at: https://scholarly- Medicine Initiative has enormous parities research. Am J Public Health. commons.law.case.edu/caselrev/vol67/iss4/15 2005;95(12):2125-2128. https://doi. potential to advance the quality of 7. Snyderman R. Personalized health care: org/10.2105/AJPH.2005.076588 from theory to practice. Biotechnol J. health care and improve health out- PMID:16257933 2012;7(8):973-979. https://doi.org/10.1002/ 22. Risch N, Burchard E, Ziv E, Tang H. comes for all. However, the two most biot.201100297 PMID:22180345 Categorization of humans in biomedical important and influential steps that 8. Kevles DJ. In the Name of Eugenics: Genetics research: genes, race and disease. Genome and the Uses of Human Heredity (No. 95). precision medicine scientists can Biol. 2002;3(7):Epub 2002 Jul 1. Available at Boston, MA: Harvard University Press. https://10.1186/gb-2002-3-7-comment2007 and should take to protect precision 1995. 23. Klick J, Satel S. The Health Disparities Myth. 9. Dorr GM. Segregation’s Science: Eugenics medicine equity are first to denounce Washington, DC: American Enterprise and Society in Virginia. Charlottesville, VA: Institute for Public Policy Research; 2006. and distinguish this movement from University of Virginia Press; 2008. 24. Hoffman KM, Trawalter S, Axt JR, Oliver the pseudo-science of eugenics, and 10. Roberts DE. Killing the Black Body: Race, MN. Racial bias in pain assessment and Reproduction, and the Meaning of Liberty. second to incorporate a comprehen- treatment recommendations, and false New York City, NY: Vintage Books; 1999. beliefs about biological differences between sive, ecological understanding of the 11. Caplan AL. When Medicine Went Mad: Bio- blacks and whites. Proc Natl Acad Sci ethics and the Holocaust. Totowa, New Jersey: fundamental social and environmen- USA. 2016;113(16):4296-4301. https:// Humana; 2012. doi.org/10.1073/pnas.1516047113; tal determinants of health outcomes 12. The Racial Integrity Act, Virgnia Senate PMID:27044069 in all research. These steps will help Bill No. 219. 1924. Available at: https:// 25. Tsai J. What role should race play in medi- s3.amazonaws.com/omeka-net/3933/archive/ to clear the way for scientists to accu- cine? Scientific American – Voices. Sept. 12, files/a21dd53f2a098fca5199e481433b4eb2. 2018. Available at https://blogs.scientificam- rately and equitably translate the sci- pdf?AWSAccessKeyId=AKIAI3ATG3OSQL erican.com/voices/what-role-should-race- O5HGKA&Expires=1571270400&Signatur ence of genomic and precision medi- play-in-medicine/. e=O9910pY3H3J%2BPysPwaOZFrOglA0% 26. Smedley A, Smedley BD. Race as biology cine into the clinical setting. Only 3D is fiction, racism as a social problem is real: then will the Precision Medicine Ini- 13. Buck v. Bell (No 292). 1927. Information Anthropological and historical perspec- available at https://www.law.cornell.edu/ tiative live up to its potential to im- tives on the social construction of race. AM supremecourt/text/274/200 Psychol. 2005;60(1):16-26. https://doi.

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org/10.1037/0003-066X.60.1.16 white mortality gap in 1960 and 2000. 52. Dar-Nimrod I, Heine SJ. Genetic essential- 27. Collins FS. What we do and don’t know Health Aff (Millwood). 2005;24(2):459-464. ism: on the deceptive determinism of DNA. about ‘race’, ‘ethnicity’, genetics and health https://doi.org/10.1377/hlthaff.24.2.459 Psychol Bull. 2011;137(5):800-818. https:// at the dawn of the genome era. Nat Genet. PMID:15757931 doi.org/10.1037/a0021860 PMID:21142350 2004;36(11)(suppl):S13-S15. suggesting 39. Sarich V. Holloway’s advance praise for race. 53. Satel S, Klick J. Don’t despair over dispari- a focus on the more proximate causes of In Ralph L, ed.: Race: The Reality of Human ties. Wkly Stand. 2004; https://sallysatelmd. health disparities than genetics. https://doi. Differences. New York, NY: Routledge; 2018. com/articles/2004/dont-despair-over-dispari- org/10.1038/ng1436 PMID:15507997 40. Grumbach K, Mendoza R. Disparities in ties/ 28. Foster MW. Book review of Race: the human resources: addressing the lack of 54. Williams DR, Lawrence JA, Da- reality of human differences.J Clin Invest. diversity in the health professions. Health vis BA. Racism and health: evidence 2004;113(12):1663. https://www.ncbi.nlm. Aff (Millwood). 2008;27(2):413-422. and needed research. Annu Rev Public nih.gov/pmc/articles/PMC420514/; https:// https://doi.org/10.1377/hlthaff.27.2.413 Health. 2019;40(1):105-125. https:// doi.org/10.1172/JCI22151 PMID:18332497 doi.org/10.1146/annurev-publ- 29. U.S. Census, Overview of Race and Hispanic 41. Robison J. The devil and the demographic health-040218-043750 PMID:30601726 Origin: 2010. Available at https://www. details, Gallup. February 25, 2003. Available 55. Berkman LF, Kawachi I. A historical frame- census.gov/prod/cen2010/briefs/c2010br-02. at: https://news.gallup.com/poll/7858/devil- work for social epidemiology. In: Berkman pdf/ demographic-details.aspx LF, Kawachi I, eds. Social epidemiology. New 30. Burchard EG, Ziv E, Coyle N, et al. The 42. Zuckerman P. The Devil? Seriously?Psychol York: Oxford University Press; 2000:3. importance of race and ethnic background Today. September 28, 2015 https://www. 56. Williams DR, Jackson PB. Social sources in biomedical research and clinical practice. psychologytoday.com/us/blog/the-secular- of racial disparities in health. Health N Engl J Med. 2003;348(12):1170-1175. life/201509/the-devil-seriously Aff (Millwood). 2005;24(2):325-334. https://doi.org/10.1056/NEJMsb025007 43. Sarich V, Miele F. Race: The Reality of Hu- https://doi.org/10.1377/hlthaff.24.2.325 PMID:12646676 man Differences. New York, NY: Westview PMID:15757915 31. Satel S. I am a racially profiling doctor. New Press; 2004. 57. Daniels N, Kennedy BP, Kawachi I. Why York Times, 2002;5:56-58. 44. National Center for Health Statistics. Health, justice is good for our health: the social 32. Gelernter J, Kranzler HR, Satel SL, Rao United States, 2016, With Chartbook on determinants of health inequalities. Daedalus. PA. Genetic association between do- Long-term Trends in Health (No. 2017). 1999;128(4):215-251. PMID:11645876 pamine transporter protein alleles and Washington, DC: Government Printing Of- 58. Mensah GA, Mokdad AH, Ford ES, cocaine-induced paranoia. Neuropsy- fice; 2017. Greenlund KJ, Croft JB. State of chopharmacology. 1994;11(3):195-200. 45. Kuzawa CW, Sweet E. Epigenetics and the disparities in cardiovascular health https://doi.org/10.1038/sj.npp.1380106 embodiment of race: developmental origins in the United States. Circulation. PMID:7865100 of US racial disparities in cardiovascular 2005;111(10):1233-1241. https://doi. 33. Gelernter J, Kranzler H, Satel SL. No as- health. Am J Hum Biol. 2009;21(1):2- org/10.1161/01.CIR.0000158136.76824.04 sociation between D2 dopamine receptor 15. https://doi.org/10.1002/ajhb.20822 PMID:15769763 (DRD2) alleles or haplotypes and cocaine PMID:18925573 59. Jones CP. Levels of racism: a theoretic dependence or severity of cocaine depen- 46. Kistka ZA, Palomar L, Lee K, et al. Racial framework and a gardener’s tale. Am J dence in European- and African-Americans. disparity in the frequency of recurrence of Public Health. 2000;90(8):1212-1215. Biol Psychiatry. 1999;45(3):340-345. https:// preterm birth. Am J Obstetrics & Gynecol- https://doi.org/10.2105/AJPH.90.8.1212 doi.org/10.1016/S0006-3223(97)00537-4 ogy. 2007;196:131.e1-131.E6. https://doi. PMID:10936998 PMID:10023512 org/10.1016/j.ajog.2006.06.093 60. Paradies YC. Defining, conceptualizing and 34. Satel S. Race and medical bias. The Atlantic 47. Weinhold B. Epigenetics: the science characterizing racism in health research. Crit Online Digital Edition (January 2001). Avail- of change. Environ Health Perspect. Public Health. 2006;16(2):143-157. https:// able at: https://www.theatlantic.com/past/ 2006;114(3):A160-A167. https://doi. doi.org/10.1080/09581590600828881 docs/issues/2001/01/satel2.htm) org/10.1289/ehp.114-a160 PMID:16507447 61. Clark R, Anderson NB, Clark VR, Wil- 35. West KM, Blacksher E, Burke W. Genomics, 48. Popejoy AB, Fullerton SM. Genomics is liams DR. Racism as a stressor for African health disparities, and missed opportuni- failing on diversity. Nature News, 538(7624), Americans. A biopsychosocial model. Am ties for the nation’s research agenda. JAMA. 161; Bayer, R., & Galea, S. (2015). Public Psychol. 1999;54(10):805-816. https:// 2017:317(18):1831-1832. health in the precision-medicine era. N Engl doi.org/10.1037/0003-066X.54.10.805 36. Cho MK. Racial and ethnic categories J Med. 2016;373(6):499-501. PMID:10540593 in biomedical research: there is no baby 49. Bayer R, Galea S. Public health in the 62. McEwen BS. Stressed or stressed out: what in the bathwater. J Law Med Ethics. precision-medicine era. N Engl J Med. is the difference?J Psychiatry Neurosci. 2006;34(3):497-499, 479. https://doi. 2015;373(6):499-501. https://www.nejm. 2005;30(5):315-318. PMID:16151535 org/10.1111/j.1748-720X.2006.00061.x org/doi/full/10.1056/NEJMp1506241 63. Collins JW Jr, David RJ, Handler A, Wall PMID:17144171 https://doi.org/10.1056/NEJMp1506241 S, Andes S. Very low birthweight in African 37. Sankar P, Kahn J. BiDil: race medicine or PMID:26244305 American infants: the role of maternal expo- race marketing? Using race to gain a com- 50. Krieger N. Stormy weather: race, gene ex- sure to interpersonal racial discrimination. mercial advantage does not advance the pression, and the science of health disparities. Am J Public Health. 2004;94(12):2132-2138. goal of eliminating racial/ethnic dispari- Am J Public Health. 2005;95(12):2155-2160. https://doi.org/10.2105/AJPH.94.12.2132 ties in health care. Health Aff (Millwood). https://doi.org/10.2105/AJPH.2005.067108 PMID:15569965 2005;24(suppl 1):W5-455-W5-464. https:// PMID:16257941 64. Chae DH, Clouston S, Hatzenbuehler ML, doi.org/10.1377/hlthaff.W5.455 51. Bamshad M. Genetic influences on health: et al. Association between an Internet-Based 38. Satcher D, Fryer GE Jr, McCann J, Trout- does race matter? JAMA. 2005;294(8):937- Measure of Area Racism and Black Mortali- man A, Woolf SH, Rust G. What if we 946. https://doi.org/10.1001/jama.294.8.937 ty. PLoS One. 2015;10(4):e0122963. https:// were equal? A comparison of the black- PMID:16118384 doi.org/10.1371/journal.pone.0122963

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PMID:25909964 65. Sirugo G, Williams SM, Tishkoff SA. The missing diversity in human genetic studies. Cell. 2019;177(1):26-31. https:// doi.org/10.1016/j.cell.2019.02.048 PMID:30901543 66. Landry LG, Ali N, Williams DR, Rehm HL, Bonham VL. Lack of diversity in genomic databases is a barrier to translating precision medicine research into practice. Health Aff (Millwood). 2018;37(5):780-785. https://doi.org/10.1377/hlthaff.2017.1595 PMID:29733732 67. Wendler D, Kington R, Madans J, et al. Are racial and ethnic minorities less willing to participate in health research? PLoS Med. 2006;3(2):e19. https://doi.org/10.1371/journal.pmed.0030019 PMID:16318411 68. Katz RV, Green BL, Kressin NR, Claudio C, Wang MQ, Russell SL. Willingness of minorities to participate in biomedical studies: confirmatory findings from a follow-up study using the Tuskegee Legacy Project Question- naire. J Natl Med Assoc. 2007;99(9):1052- 1060. PMID:17913117 69. Shavers VL, Lynch CF, Burmeister LF. Factors that influence African-Americans’ willingness to participate in medical research studies. Cancer. 2001;91(1)(suppl):233-236. https://doi.org/10.1002/1097- 0142(20010101)91:1+3.0.CO;2-8 PMID:11148585

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