Ethical Oversight of GWAS Studies: Are We Doing Enough to Protect Communities?
Authors: Heather Shattuck-Heidorn, Marion Boulicault, and Maayan Sudai
Does human sexuality have a genetic component? In an era of genomics that allows parents to select for traits such as the skin color or eye color of their baby, and of continued discrimination, imprisonment, and even death penalties for LGBTQ+ people globally, questions around the genetic determinacy of sexuality require close ethical consideration. Yet in late August 2019, a new study on just this topic published in Science[i] was exempt from standard bioethical mandates concerning human subjects research. In this post, we’ll learn why, as we explore a little of the complex terrain of ethics in the age of big data genomics.
The research group - Ganna et al., based at the Broad Institute at MIT - was certainly aware of the ethical dimensions of their work, acknowledging within the paper that ”the topic explored in this study is complex and intersects with sexuality, identity, and attraction and potentially has civil and political implications for sexual minority groups.” Additionally, the researchers reached out to LGBTQ+ advocacy groups nationally and spoke to groups within their local institutions - one of the authors even wrote about how engaging the community helped him “strengthen science”. And yet, the group has come under fire within the LGBTQ+ and genomics community for concerns that this work will be used to harm LGBTQ+ communities and that it fails to meet accepted ethical standards.
What ethical principles are expected to be taken into consideration in scientific research? Biomedical research ethics in the United States is primarily guided by the Belmont Report. Written under Congressional mandate in response to the egregious ethical breaches of the 20th century (such as medical experimentation without consent and on vulnerable populations, including the Tuskegee Study and at prisons and mental institute wards throughout the country), the Belmont Report identifies three ethical core principles: (1) respect for persons, (2) beneficence, and (3) justice. Today in the US, any research that uses human subjects must show (usually via an institutional review board, commonly referred to as IRB, approval process) that it upholds these three principles.
“What does it mean that Ganna et al.’s research... is considered in compliance with ethical standards?”
The Belmont Report, however, is specifically aimed at research that involves identifiable human subjects. Here is where it gets tricky. What counts as “human subjects research” is determined by the Federal Policy for the Protection of Human Subjects, 45 CFR part 46, colloquially known as the “Common Rule”. In practice, the secondary use of de-identified data is exempted from the regulation. De-identified data is defined as data from which the identity of the individuals involved cannot be extrapolated. Like most research in genomics, Ganna et al.’s genome-wide association (GWAS) study of same-sex sexuality only involved genetic and survey data stripped of all personal identifiers (such as name or address). Despite arguments that re-identification of genomic data is possible using even relatively short sequences, currently, genetic data stripped of personal identifiers is considered de-identified. As such, the Belmont Report does not legally apply, and therefore researchers have no obligation to justify how the research upholds the three principles.
Nonetheless, one of the primary ethical criticisms aimed at the study thus far is that it fails to uphold the principle of beneficence. In the Belmont Report, beneficence is defined as follows: “two general rules have been formulated as complementary expressions of beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits and minimize possible harms” (Part B.2). Although not legally required, what would happen if we held this GWAS study accountable to the principle of beneficence?
Critics of the GWAS have suggested that the benefits of the study are unclear, and further, that the study might in fact harm members of marginalized groups. For example, companies are already using results from this study to offer a “How gay are you?” test. Despite the study’s authors’ claims that there is no ‘gay gene,’ and despite repeated disclaimers from the company (indeed, the app is “currently unavailable” due to online pressure), we worry that this app and others like it will prompt many to interpret the study as demonstrating that human sexuality is predominantly genetic, which might have significant ethical repercussions (e.g. might this lead to a push for prenatal tests for homosexuality?).
If this GWAS were subject to IRB review, questions of beneficence might have been more carefully considered. Perhaps studies with clear ethical and political significance, like this GWAS study, should be subject to the Belmont Report, despite the fact that the data is de-identified (others have made similar suggestions).[ii] It’s unclear, though, whether standard ethical paradigms, like Belmont, would be sufficient for grappling with the ethical consequences of GWAS studies. Current bioethics paradigms are highly individualistic: they focus on risks and benefits to individual participants. However, the risks and benefits arising from GWAS studies concern not only individual research subjects but also groups and communities. Thus perhaps this study should not only be subject to current bioethical standards but should also be subject to further ethical standards that go beyond the individualistic Belmont approach.
There are lessons to be learned here from how populations with a history of community harm stemming from scientific exploitation interact with genomics research. Nearly 20 years ago indigenous communities were already encouraging individuals to consider the short and long term effects, including community effects, of any genetic research they chose to participate in.[iii] In 2004 the Havasupai Tribe filed a lawsuit against Arizona State University, arguing that researchers had misrepresented their interests and were using DNA samples to investigate hypotheses that, despite consent, had not been cleared by the community and carried stigma or harm (such as the basis of mental illness).[iv] We note that the Ganna et al. study also investigated how same-sex sexual behavior related to various mental health issues. Indigenous groups in South Africa have similarly resisted an individualistic model of informed consent for genomics research, arguing that it does not adequately anticipate harm to communities and is insufficient when individual data will represent a larger community.[v] Of course, not all communities will be as well-defined or structured as many indigenous nations and communities, or as available for consultation or consent. Despite this, GWAS researchers would do well to engage with the literature from indigenous communities and scholars exploring similar types of potential harms and effective research strategies.[vi],[vii],[viii]
“This exploration of the genetic architecture of sexuality legitimizes the inquiry into the biological determination of sexuality”
In the end, our question is this: What does it mean that Ganna et al.’s research, exempt from IRB yet extraordinarily capable of impacting LGBTQ+ communities, is considered in compliance with ethical standards? In our Science Letter, and in other posts in this short series, the GenderSci lab investigates the social and historical context of the biobank data used for the Ganna et al. study and explores some of the political implications of their results. The Ganna et al. exploration of the genetic architecture of sexuality, with connections to the prestigious Broad Institute and published in the pages of Science, legitimizes inquiry into the biological determination of sexuality. The reality is, we continue to live in an atmosphere of inequity and discrimination for sexual minorities. As we have written this post, the US Supreme Court is in the process of hearing cases that will decide whether employers can legally discriminate against LGBTQ+ individuals. Given this, it seems more than fair (in fact, it seems ethically essential) to wonder: what community standards should sociogenomicists adopt to ensure compliance with not only with legal mandates but the spirit of ethical scientific research?
Author Statement:
Shattuck-Heidorn led the writing process. Boulicault drew up the initial draft, and Shattuck-Heidorn and Sudai developed it into a full blog post. Shattuck-Heidorn integrated lab member comments and edits during the revision process. All authors provided substantive contributions to the ideas expressed in this blog post and participated in the preparation of the post.
Endnotes:
[i] Ganna, A., Verweij, K. J., Nivard, M. G., Maier, R., Wedow, R., Busch, A. S., ... & Lundström, S. (2019). Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior. Science, 365(6456), eaat7693.https://doi.org/10.1126/science.aat7693
[ii] Parasidis, E., Pike, E., & McGraw, D. (2019). A Belmont Report for Health Data. New England Journal of Medicine, 380(16), 1493–1495. https://doi.org/10.1056/NEJMp1816373
[iii] Harry D., & Malia Kanehe, L. (2005). The BS in access and benefit sharing (ABS): Critical questions for indigenous peoples. In Ed. Burrows, B. The Catch: Perspecitves on Benefit Sharing Edmonds Institute Retrieved from http://www.ipcb.org/publications/other_art/bsinabs.html
[iv] Garrison, N. A. (2013). Genomic justice for Native Americans: impact of the Havasupai case on genetic research. Science, Technology, & Human Values, 38(2), 201-223. https://doi.org/10.1177/0162243912470009
[v] Benjamin, R. (2016). Informed refusal: Toward a justice-based bioethics. Science, Technology, & Human Values, 41(6), 967-990.https://doi.org/10.1177/0162243916656059
[vi] TallBear, K. (2013). Genomic articulations of indigeneity. Social Studies of Science, 43(4), 509-533. https://doi.org/10.1177/0306312713483893
[vii] Reardon, J., & TallBear, K. (2012). “Your DNA Is Our History” Genomics, Anthropology, and the Construction of Whiteness as Property. Current Anthropology, 53(S5), S233-S245. https://doi.org/10.1086/662629
[viii] Friesen, P., Kearns, L., Redman, B., & Caplan, A. L. (2017). Rethinking the Belmont report?. The American Journal of Bioethics, 17(7), 15-21. https://doi.org/10.1080/15265161.2017.1329482