Section 3.4: Genetics Research, Precision Medicine, Race and Ancestry

Research in genetics, ancestry, and precision medicine has grown exponentially due to the Human Genome Project and advances of CRISPR technology. Precision medicine is the use of advanced computing tools to integrate data from a diverse range of health and research settings. The Human Genome Project catalogued and identified the more than three billion genes in the human genome to create a baseline “reference map” of the human genome. CRISPR refers to both the gene-editing tool (an enzyme called Cas9) and its targets (clustered regularly interspaced short palindromic repeats, pronounced “crisper”). This tool has the promise to target and edit specific portions of genes (identified by the Human Genome Project) within an organism at a level of precision unseen before, which has led to many exciting developments in biological research, biotechnology, and possible treatment for certain diseases. However, advancements in these fields have concerned many scholars, ethicists, and activists, as this research and its technologies have the potential to reinforce and expand upon flawed biological notions of race.

By seeking to identify genes that could be “cured” via CRISPR, such research runs the risk of repeating eugenicist history and simplifying the complicated role that social and structural inequalities play in perpetuating racial health disparities to a gene or set of genes.

Understanding links between genetics and disease is a major component of modern health care. However, linking race with genetics is a fundamental intellectual flaw with consequences for patient diagnosis, care, and treatment. Within medicine’s history of oppression and racism, using “race” in the field of genetics and precision medicine is inherently political with complex sociopolitical origins. Without a critical analysis of this history and the categories used to define “ancestry markers,” such research in genetics and precision medicine hold the possibility and danger of reifying biological racial difference again in a newer, shinier package.

Current research in genetics, ancestry, and precision medicine falls into this trap of continuing to biologize race by several flawed methods that are simply bad science. These include, but are not limited to, (1) using predetermined racial categories to group ancestral markers (i.e., confirmation bias of racial categories) and (2) ascribing health disparities to genetic differences rather than accounting for the complex role of social, environmental, and structural factors on epigenetics and the body.

First, using predetermined racial categories to match to group ancestral markers elides the history of the creation of race as a social construct. Furthermore, the research seeking to match genetic markers to these groups shows that ancestral markers exist, but they are not consistent across the social groups of race. Early and ongoing work in genetics has shown consistently higher in-group variability than across-group variability, thus showing no genetic loci to differentiate between racial categories.[1] Thus the use of “race” in genetics and precision medicine usually relies on scientists creating arbitrary categories for groups of ancestry markers that incorrectly substantiate racial categories rather than challenge the social construct of race.

One example shows the difficulty of applying precision medicine within the existing racist history of medicine. In July 2010, the New England Journal of Medicine published “Genetic Ancestry in Lung-Function Predictions” by Rajesh Kumar et al. In this article, the authors sought to improve upon the racial classifications used in lung function tests. Existing methods utilize patients’ self-identified race (or physician-identified race) to define the normal lung function range for spirometry, so the researchers sought to identify alternative, genetically derived “normal” values. The aim was to use genetics to provide a more “objective” set of normal values. The authors argued that the self-identified racial categories were problematic because individuals are racially admixed, and limited racial categories are “crude descriptors of individual genetic ancestry.”[2] That is, racial mixing is so frequent, and individuals have such complex racial backgrounds, that the self-identified racial categories establish inaccurate baselines for the lung function measurement.

Unfortunately, the research by Kumar et al. ultimately still seeks to confirm what genetic markers might show as “truer” racial categories. This work uses genetics to make a biological argument about social constructs. Although this is a step forward from crude racist assumptions discussed in the spirometry section, their research still fell into the trap of trying to match “ancestry informative markers” (single-nucleotide polymorphisms posited to represent statistically significant genetic differences among those of different ancestries) to socially constructed racial identities (individual self-identified race).

Rather than using genetics to identify markers that may predispose anyone to lower lung function, their study sought to solidify which markers could best predict lowered function for African Americans only. Without addressing the complex factors that mark lived experience (e.g., racism, structural, and societal factors) nor the racist history of the spirometer, this research begins with the assumption of difference for African Americans (again, using the social construct as the starting point for their supposedly more objective scientific approach). Therefore, the study only confirms racial biases by using genetics to try to prove some sort of inferiority in lung function (specifically in “forced expiratory volume”) in African Americans.

Other scientists have similarly sought to more precisely measure differences in lung function between racial and ethnic groups, though definitions and conclusions regarding the influence of racial categories has varied widely.[3] Some researchers accept without question the outdated, yet popularized, notions that African Americans have lower lung function than European Americans.[4] One study, examining the utility of multiethnic adjustment for spirometry, posits that adjustment works for some, but not all, racial groups.[5] This study concluded that ancestry markers would be helpful to better explain observed lung function differences.

Kumar et al.’s research is different because it fits within a larger body of genetics work that seeks to better understand racial disparities in health.[6] This is in contrast with other genetics research that excludes nonwhite participants as a means of “controlling” for race.[7] Yet even research with a progressive, disparities-oriented health research goal can fall into these “traps” of genetics research.

Kumar et al., for example, seek to provide tools for more efficient and effective care for severe asthma and COPD, which they note African Americans have higher rates of both. Kumar et al. thus represents the good intentions of seeking to improve upon issues of inclusion and to better explain the disparate health outcomes seen across racial lines. But without a critical analysis of what racial categories mean, researchers with good intentions will continue to put forth bad science that uses ancestry markers to (purposefully or not) confirm racialized differences in biology or use genetics to explain away racial health disparities caused by social and structural determinants of health. For example, Parker et al. (2014) pick up on the ancestry-based claims of Kumar et al. to claim that a particular genetic marker can predict lower COPD lung function metrics for African Americans only, again reinforcing a biological “brokenness” in African Americans rather than addressing the role society and other factors may play.[8] This is unlikely to be helpful in addressing health disparities as Kumar et al. intended, instead explaining away the disparities with genetic differences. Addressing health disparities through genetics and precision medicine is therefore very much a slippery slope, which is why we feel this critical analysis of racism and race is crucial to improving the science.

We offer instead two “red flags” for researchers and readers to consider as the field of genetics continues to move forward. We furthermore encourage all researchers and readers to dive more deeply into the field of bioethics, which has been grappling with the implications of this flawed science, to better understand the recommendations for change.

First, categories used to cluster ancestral markers are established by the scientists themselves, rather than by the clustering of the data, and rely on slippery definitions that are, at best, “mired in confusion.”[9] Kumar et al., for example, chose to stratify their data to specifically estimate only “the percent African and European ancestry, assuming two ancestral populations.”[10] This means that the major assumption on which ancestry markers are based is one of confirmation bias (assuming only African and European ancestry in this case), such that scientists’ quests to look for patterns (oftentimes with racial categories as their foundation) will be found. Scholars of race, technology, and health justice have produced significant work for decades, pushing back against the reification of racial categories. Yudell et al. write that “historical racial categories that are treated as natural and infused with notions of superiority and inferiority have no place in biology.” They write furthermore that “using race as a political or social category to study racism and its biological effects, although fraught with challenges, remains necessary” (emphasis added) to “understand how structural inequities and discrimination produce health disparities in socioculturally defined groups.”[11] Other scholars, such as Duana Fulwiley, Dorothy Roberts, and Troy Duster, have argued similarly against the use of a priori categorization in genetic research.[12]

Second, focus on ancestral markers fails to acknowledge the role structural and societal factors play (as Yudell et al. acknowledge) and what role epigenetics thus plays in the development of structural health disparities. As expanded upon in the following section, epigenetics is the modification of gene expression, such that environmental influences can affect to what degree genetic susceptibilities and predispositions are “active” and “inactive.” Given the breadth of public health and medical literature showing how social, structural, and environmental factors affect the expression of genes, research into the genetic foundations of health outcomes must also examine epigenetic influences that factor into differences between phenotype and genotype. Any focus exclusively on genotype with no exploration of how and why certain genes are expressed and influenced by environmental and structural factors is wholly insufficient and should be questioned. The current research landscape of “ancestral identity markers” (single-nucleotide polymorphisms, also called AIMs) runs the risk of ignoring and overlooking this process, attributing focus on racial health disparities to genetic factors rather than social, environmental, and structural influences. The goal is not to practice color-blind medicine, but rather antiracist medicine that addresses all levels of racism.

Why does this matter to us as medical students? We are being taught that the newest, “best” science has the power to individualize our cures, to explain more and more of the mysteries of the human body, and yet it is still steeped in the history and context of racism in medicine. We are often caught unawares by the way educators and clinicians claim genetics as evidence of racialized differences, and this worries us for the future of our practice.

The perpetuation of biological racism in genetics research has important implications for the practice of medicine and health care. Health care is increasingly “evidence-based.” Clinicians rely on researchers to understand physiologic processes, direct innovation, and guide assessments of risk for each patient. Genetics research is, at its most functional, intended to improve health care and is characterized as an “objective” science. However, if such research fails to acknowledge its own biases based on ahistorical and racist foundations, race will continue to be biologized and discussed under the false guise and synonym of “ancestry markers,” and structural issues will continue to be hidden under those same guises.

Furthermore, the issues in genetics research create a dire future for precision medicine, the promising “evidence-based” health care of the future. Precision medicine aims to allow us to tailor treatments and diagnoses to each individual based on their unique genetic footprint. If we continue on this path of misappropriating genetic patterns to biological race, precision medicine will not only fall far short of its goal of treating individuals better, but instead will perpetuate the false notion of biologized race. This hides the social construct of race behind the same false guise of ancestry markers and could harm patients more than individualize and improve their treatment. It allows for and contributes to explicit racial profiling and stereotyping of patients and stands to exacerbate existing disparities in treatment and access to care.

Despite good intentions, such research fails to be innovative at addressing racial health disparities and instead simply “reinvents” conversations about race using the proxy of ancestry and genetics to solidify the social construct of race as falsely “objective science.”

Semantics matter in genetics research and the practice of medicine. The difference between ancestry and falsely biologized race is critical, and it’s our duty as advocates for the health of our patients, as well as creators, disseminators, and users of science, to be careful as the field of precision medicine booms. This will be the field we work in, but we are not trained to engage with it critically. Therefore, we seek to amplify the critical and difficult conversations already existing in the field of genetics in order to ensure clinicians and providers have the tools to practice critically engaged precision medicine.[13]