Anticipating the Ethical, Legal, and Social Implications of Human Genome Research: An Ongoing Experiment

Abstract

Dr. Victor McKusick was a founding member of the joint NIH-DOE working group that designed the federal effort to address the ethical, legal, and social implications of the U.S. Human Genome Project in 1989. A key feature of this effort was its commitment to anticipating genomics-driven questions before they became urgent practical dilemmas, by complementing the scientific effort to map and sequence the human genome with projects by a wide range of social scientists, humanities scholars, legal experts, and public educators designed to equip society with the foresight required to optimize the public welfare benefits of new genomic information. This essay describes the origins of that experiment and the model of anticipatory science policy that it produced, as one piece of Dr. McKusick’s extraordinary intellectual legacy.

Introduction

One of the most unusual experiments within the U.S. NIH-DOE Human Genome Project (HGP) was launched during the Project’s initial press conference on Oct 1, 1988, when the newly appointed Director of the HGP’s NIH arm, Dr. James Watson, responded to a reporter’s question. The reporter asked about the social implications of decoding the human genome, and Dr. Watson responded by announcing that NIH would be dedicating 3–5% of its HGP funding to studies dedicated to anticipating and addressing those very issues (Schmeck, 1988). The reporter’s question was not unanticipated, given the checkered history of the U.S. Eugenics Movement in the first half of the 20^th Century and the institutionalization of “bioethical” discussions of new genetic technologies and science (such as prenatal diagnosis, population genetic screening, “sociobiology,” predictive genetic testing, and gene therapy) as they emerged in that Century’s second half. As I explain below, these precedents were powerful motivators not to allow the Human Genome Project to ignore its ethical, legal and social implications, and those implications had been flagged as important for attention by both of the HGP’s feasibility and planning reports by the National Academy of Sciences (NRC, 1988)and the Congressional Office of Technology Assessment (OTA, 1988). But Dr. Watson’s announcement effectively ratified those recommendations and inaugurated a new chapter for NIH research funding, by pairing a path-breaking biomedical research effort with concurrent science policy and biomedical ethics research on where its new paths might lead. The next step was to design this unusual experiment. In 1989 an ad hoc committee of the newly formed National Advisory Council on Human Genome Research was created to accomplish that task on behalf of NIH and the DOE: the “Joint Working Group on Ethical, Legal, and Social Issues (ELSI) related to mapping and sequencing the human genome,” or, as it quickly became known, the “ELSI Working Group” (ELSI WG). Dr. Victor McKusick, who had just become the founding President of the new international Human Genome Organization was invited to join this committee, and was instrumental in helping to design the unprecedented plan they developed for realizing the HGP’s new commitments to considering the social impacts of its scientific work.

The original ELSI WG was chaired by Nancy Wexler, Ph.D., who had helped orchestrate the international mapping of the genomic variants responsible for Huntington’s Disease in the 1980’s. In addition to Dr. McKusick, the group included Jonathan Beckwith, Ph.D. (molecular genetics), Robert Cook-Deegan, M.D.(science policy), Patricia King, J.D. (health law), Robert Murray, M.D (medical genetics), and Thomas Murray, Ph.D. (bioethics) (Fink, 1990). The basic charge to this multidisciplinary group in the first five-year plan for the U.S. Human Genome Project was two-fold: to “[d]evelop programs addressed at understanding the ethical, legal and social implications of the human genome project,” and to “[i]dentify and define the major issues and develop initial policy options to address them.” (US DHHS/DOE, 1989). After its first formal meeting in November 1989, the group elaborated these goals into four aims:

1. Anticipate and address the implications for individuals and society of mapping and sequencing the human genome;

2. Examine the ethical, legal, and social consequences of mapping and sequencing the human genome;

3. Stimulate public discussion of these issues; and

4. Develop policy options to assure that genetic information is used for the benefit of individuals and society (Fink, 1990).

The stories of how each of these aims has played out over the subsequent thirty years merit their own historical essays, because each raised basic epistemic, methodological, and political questions that have continued to be debated for what has become known as “the ELSI research community.” After all, how does one go about anticipating the implications of new science before they happen? Which potential consequences should be given the highest priority for attention? How does one productively engage the public on such issues? And how should practical policy solutions be developed, if they are to “future proof” our expected new knowledge? But all of these debates have been animated by the challenge posed the first question: the challenge of developing ways to anticipate ethical, legal, and social implications before science provokes them as practical policy issues. The purpose of this essay is to contribute to the story of that challenge, by describing the approach that Wexler, McKusick, and the ELSI WG took to it in designing the HGP’s ELSI experiment and the model for anticipatory ELSI research that has grown out of their work.

The ELSI “Un-Commission”

Before the ELSI WG, U.S. federal efforts to address important ethical issues in biomedical research had typically proceeded through the formation of independent blue-ribbon commissions or agency-based expert advisory panels (or by contracting with organizations like the National Academy of Sciences to do the same) and funding the studies these committees recommended through targeted contracts and grants (Bulger et. al., 1995). The ELSI WG’s disruptive leap was to forego this route in favor of creating an “un-commission,” by embracing NIH’s commitment to the power of investigator-initiated research and opening up competitive funding to the whole world of scientists, scholars, and professionals with perspectives to offer on human genome research and its implications ( Cook-Deegan, 1994; Juengst, 1996). As McKusick would later write with Francis Collins,

Perhaps the most unusual feature for a basic science enterprise, 3% to 5% of the budget [for the HGP] was set aside from the outset for research on the ethical, legal and social implications of this expected acceleration in obtaining genetic information about our species. In the past, ethical, legal, and social analysis of the consequences of a scientific revolution often were relegated to other groups outside the scientific mainstream or lay dormant until a crisis developed. This time, the intention was to inspire a cohort of ethicists, social scientists, legal scholars, theologians, and others to address the coming dilemmas associated with increased knowledge about the genome, from social and legal discrimination on the basis of genetics to more philosophical issues such as genetic determinism. (Collins and McKusick, p. 541)

Three assumptions in this quote are important to notice. First, the vision is explicitly anticipatory – aimed at “addressing coming dilemmas” created by “the consequences of a scientific revolution” rather than allowing them to “lay dormant until a crisis developed.” Second, it was important to the design of the ELSI experiment that this anticipatory effort was not framed as something being “relegated to other groups outside the scientific mainstream,” but as an integral feature of a basic science enterprise. For the ELSI WG, the anticipation of consequences was counted alongside genetic mapping and the development of sequencing technologies as part and parcel of the Human Genome Project. At the same time, however, this effort could not be limited to genome scientists. To gain foresight on the possible consequences of the genomic revolution the effort’s forecasts required the scope that could only be achieved by combining as wide a range of perspectives as possible. This meant partnering with a “cohort” of scholars and professionals from a range of other disciplines equipped to help ‘cover all the angles’ in their horizon scanning, including qualitative fields like philosophy, sociology, history, religious studies and law (Murray, 1992; Parker et. al., 2019). Multiplying the perspectives involved in the HGP’s horizon scanning efforts meant expanding the range of voices at the genomics community’s table as well, which would have important implications for both genome research and the ELSI program’s agenda in the years that followed, as I suggest below.

To inspire this variegated cohort to collaborate with the genomics community as partners in the Human Genome Project’s horizon scanning efforts, the ELSI WG did what came naturally within their institutional contexts: rather than distancing them from genome science by recommending some extraordinary mechanism like a special commission, they invited these scholars and professionals to consider themselves fellow members of the genome research community, by making their “science” eligible for the same kinds of support open to their genetic mapping and sequencing colleagues. They encouraged the NIH and DOE to establish an extramural grant-making program to support ELSI research, alongside its funding programs for mapping and sequencing research, and to solicit applications for competitive peer-reviewed awards under the regular NIH grant categories, including R01 research grants, R25 education grants, and F31 and 32 individual fellowships. To make the program as inclusive and “crowdsourced” as possible, the ELSI WG drafted a very broad menu for the new NCHGR ELSI Program’s initial call for applications, ranging over nine topical domains, as listed in Box 1.

Box 1.

1. Fairness in insurance, employment, the criminal justice system, education, adoption, the military, and other areas;

2. Psychological and societal responses to individual genetic information;

3. Privacy and confidentiality (including ownership, control, and consent);

4. Genetic counseling, including prenatal and presymptomatic testing, testing in the absence of therapeutic options, and population screening versus testing;

5. Issues of reproductive choice;

6. Medical practice, including standards of care, training, and education of patients and the general public;

7. Historical misuses of genetics, especially eugenics, and relevance to the present;

8. Commercialization, including property and intellectual property rights, and accessibility of data and materials;

9. Philosophical issues such as definitions of health and disease and questions of determinism and reductionism (Wolfe, 2002).

Over the last thirty years, this menu has been prioritized, tailored, and supplemented through numerous iterations of that original Program Announcement and the special Requests for Applications that have been issued to underscore particular topics for attention or add new ones. But the basic Un-commission model for ELSI research – the idea of integrating multiple perspectives into genomic research in an ongoing way to continuously triangulate on the implications of new advances in the science as they come to emerge-- has proven durable.

Indeed, ELSI research has been embraced as a normal part of human genome science, and institutionalized in its professional organizations (such as the international Human Genome Organization and the Global Alliance for Genomic Research) and, even more significantly, by its central funding hub at NIH and the sponsor of the ELSI experiment, the National Human Genome Research Institute. The NHGRI not only continues to offer extramural research funding for ELSI research, but has established a Division of Genomics of Society that coordinates that program with intramural ELSI research efforts, appointed ELSI Scholars to the National Advisory Council for Human Genome Research, and built ELSI research into its major genome science initiatives, such as the Clinical Sequencing Exploratory Research consortium, the Human Microbiome Project, the eMERGE and IGNITE consortia examining the clinical integration of genomic tools, and the NSIGHT initiative to study the risks and benefits of newborn sequencing (cf. www.genome.gov).

As a result of these synergies, today the ELSI WG’s legacy is a whole field of “ELSI research” with its own academic infrastructure of institutional centers, training programs, consortia, conferences, and international networks (Kaye, et. al., 2012). If imitation is sincere flattery, the model’s adoption within genome research efforts around the globe (cf. Yoshizawa, et al., 2014). and by new initiatives in other scientific fields (cf. Fisher, 2005) attest to its success. Moreover, as I’ll discuss in more detail below, ELSI research has had a remarkable – and initially unexpected—reflexive impact on the conduct of scientific human genome research itself.

Both the institutionalization of this field and its influence suggest that the challenge of the ELSI WG’s anticipatory aspirations has been met. But has it? And if so, how? As a philosopher (and one with a 30-year conflict of interest on this question as the first NIH program officer charged with implementing the ELSI WG’s vision), I should leave the objective assessment of those questions to professional historians. But I think that even an insider’s review of the history of ELSI research can generate some hypotheses for these historians to explore, suggesting the ELSI WG’s model provided remedies and resources for meeting the challenges its anticipatory ambitions faced.

The challenge of anticipatory technology assessment

“Anticipatory governance” has become a term of art in some corners of science policy over the last several decades, driven (interestingly enough) by the explicit adoption of the ELSI Program’s model by the National Science Foundation’s effort to launch a national research effort on nanotechnology (Guston, 2013). In those contexts, anticipatory governance is defined as “a broad-based capacity extended through society that can act on a variety of inputs to manage emerging knowledge-based technologies while such management is still possible” (Guston, 2013, p. 219). As an approach to scientific planning and priority-setting, anticipatory governance has roots in the wave of interest in “technology assessment” that created the U.S. Congress’s influential Office of Technology Assessment in the 1970s (Bimber, 1996) and the preceding enthusiasm for “futurism” in the 1960s (Toffler, 1975). But attempts to extrapolate ethical and social policy questions from new scientific ideas have also been hallmarks of the field of bioethics throughout its history over the same period (Gaines & Juengst, 2008). The ELSI program’s vision is the 1990’s offspring of both these intellectual movements and inherited a double-dose of a recessive trait that each brought to their union: the problem of prediction.

At one level, the problem of prediction behind anticipatory ELSI work is the universal one exemplified by the Dan Quayle quote above: i.e., unavoidable uncertainty about the course the future will take, and the irreducible risk that our predictions will be wrong. This challenge is common to every human planning exercise. In its “homozygous” state in the ELSI effort, the problem of prediction is even triply compounded, since the ELSI research aspires to anticipate the future social consequences of anticipated future scientific advances in our abilities to anticipate future health risks and phenotypic expression through genomic analysis (Juengst, 1995).

But the basic problem of prediction also poses two other threats to the health of the ELSI enterprise that are potentially more serious. The first is the worry that ELSI forecasts will not just be wrong, but will be too far divorced from scientific reality to do anything but generate unnecessary public alarm about the genomic research enterprise (Caulfield, et. al., 2013; Moreno & Guyer, 2004). One colorful expression of this concern was offered by an ELSI researcher in the context of the Human Microbiome Project:

“Chicken Little bioethics – we’ve seen it all before. To engage in it is to list every conceivable ethical, legal or social implication -- always negative– of a given program, procedure or line of inquiry. It is the Dr. Jekyll to the Mr. Hype that inevitably accompanies paradigm shifts in medicine. Appropriately scaling our level of concern requires, where possible, replacing the inventory of potential, conceivable risks and benefits by an assessment of empirically grounded, quantifiable, and actual risks and benefits. “ (Huss, 2017, p.48)

Others have echoed this caution, arguing that the antidote to “science fiction” scenarios in ELSI research is to stay as close as possible to the actual scientific horizon in anticipatory ELSI work, by working closely with practicing scientists:

“Bioethicists must work harder to understand the fast-changing truths and limits of basic science, and they must incorporate only appropriate and authentic science into their discourse, just as they did in the past when addressing the quandries of clinical medicine…They can best do this by ensuring that decision-making and public policy are grounded in facts, not fictions and fantasies.” (Guyer and Moreno, 2004)

The second danger is that ELSI forecasts will not just be fallible, but that they will divert attention from other more important issues. It is often pointed out, for example, that missing from the ELSI Program’s original menu of topics are questions about whether the Human Genome Project should be undertaken in the first place and, if so, how its research should be conducted. By taking an anticipatory posture that focuses on the downstream implications and applications of new genomic information, critics argue, the ELSI WG’s vision assumes the current trajectory of genome research and ignores any ethical challenges that might come up along the way (Schick, 2016). More recently, a variant of this concern has been that, even when ELSI research is prescient about the trajectory of genomic science, the ELSI effort is too focused on a technological future that will only affect a privileged subset of society, at the expense of other fundamental social justice issues that are in more urgent need of public attention, like implicit racism and sexism in science and inequitable access to health care (Fabi and Goldberg, 2021).

Both of these concerns –either being too disconnected from the science or being too fixated on it -- have challenged ELSI research since its inception under the ELSI WG’s vision, and continue to shape its content and trajectory. But two (very McKusickian!) features of that original vision have been critical in blunting the force of both worries in practice as they have been interpreted and pursued over the efforts last three decades: the ELSI WG’s idea that ELSI research should be considered part of “normal science” in genomics and their impulse to draw from history in crafting their agenda for the program.

Remedies and Resources

It is true that ethical issues in the conduct of human genome research are conspicuously absent from the ELSI WG’s original agenda for ELSI research (cf. Box 1). But the incorporation of this effort into the infrastructure of the Human Genome Project and its institutionalization at NIH and DOE had the effect of ensuring this omission would not last long. As I have detailed elsewhere (Juengst, 1996), just two years into the HGP the call for a follow-up effort to study human genomic diversity in “vanishing populations” across the globe immediately raised a raft of ethical questions: How should such populations be defined and how should their interests be best protected? What role should notions of “group harms,” “community engagement,” and “reciprocity” play in the process of research recruitment for such efforts – or in their review by institutional research approval committees and funding bodies? How should our traditional commitments to the voluntariness, confidentiality, and revocability of research participation play out in these contexts? To what extent and in what ways should research results be “returned” to participants? What should genome scientists learn from the ways that genetic research with families –like Dr. McKusick’s work with the Amish— has been conducted and what should genetic family studies learn from these genomic debates? With the ELSI infrastructure in place, these questions quickly engendered interdisciplinary conversations that brought together ELSI perspectives and basic science planning in ways that enabled the ELSI effort to stay rooted in the unfolding science and address “upstream” questions of research design in influential ways (Hilgartner 2016). By 1998, the program’s highest priority was to “examine the issues surrounding the completion of the human DNA sequence and the study of human genetic variation.”(Collins, 1998), and over the subsequent decades, it has become standard for new NIH genome research initiatives, like the Human Microbiome Project, the All of US Cohort/Precision Medicine Initiative, the coordinated CSER effort to assess clinical sequencing protocols, and the multinational H3 Africa initiative to incorporate dedicated ELSI research components designed to anticipate and implement these considerations from the start. Today the NHGRI ELSI Program still prioritizes studies of “issues that arise in connection with the design and conduct of genetic and genomic research” on its program menu (NIH, 2020).

Just as importantly, the emergence of human genome variation research as fundamental to the HGP’s most beneficial applications -- precision medicine, pharmacogenomics, vaccinomics, and genomic epidemiology-- and the ELSI community’s engagement with its challenges has also guaranteed that its responsiveness to worries that its attention might be distracted from social justice issues. Just as the gaze of the ELSI effort has been led upstream into genomic research design by these challenges it has also been led beyond the lab to grapple with the larger social determinants of its issues. At the very beginning, the ELSI WG itself took on the issue of health care access in the context of the U.S. health care system, by creating its Task Force on Genetic Information and Insurance, to jump-start the lineage of research and policy work that would eventually lead to the passage of the Genetic Information Non-Discrimination Act (GINA) in 2008 (NIH-DOE Task Force, 1993; Suter, 2019). Meanwhile, special NHGRI ELSI Program funding initiatives have targeted issues of racial classification in genomics and the impacts of genomics on population health disparities, cultivating the rich literature that supports the ongoing science-policy debates on those topics. Almost all of the eleven “Centers of Excellence in ELSI Research” established since 2005 have been dedicated to work aimed at bringing the interests of different marginalized communities to the fore in the planning and dissemination of genomic research, and they have created some of the most robust pipelines for diversifying genomics’ scientific workforce as well as bringing new voices to the ELSI conversation (https://www.genome.gov/Funded-Programs-Projects/ELSI-Research-Program/Centers-of-Excellence). All these efforts speak to a distinctive lack of the kind of technological myopia that some critics fear, and reflect two important dimensions of ELSI’s “Un-commission” approach: the flexibility and freedom built into the NIH extramural grant-making process to refresh its menu as the needs of science and society evolve, and the ability of NIH’s investigator-initiated “crowdsourced” approach to soliciting an expanding range of voices to address those needs.

Moreover, it is not a mystery why the ELSI research community was poised to look both upstream and beyond the lab in its inquiries. The other important feature to note about the ELSI WG’s approach to anticipatory ethics is the way it leverages the past. As ELSI WG member Patricia King wrote, “the past is prologue” for any consideration of the social context of new genetic information, because the historical interactions of genetics and society are what will structure the ways in which any new knowledge is generated, delivered and received by the public (King, 1992). In fact, the original nine topics the ELSI solicitation all echo particular episodes from genetics interactions with society in the past.

First, the ELSI WG could not ignore the inherited shadow of the ways claims about genetics were used in the U.S. and elsewhere in socially unjust ways under the banner of Eugenics in the first two-thirds of the 20^th Century (Paul,1995; Duster,1990). This deep history flagged the ways in which genetic information can be used to reduce people’s identities to their genotypes and the unfair forms of racism, discrimination, and stigmatization that can occur when such “genetic essentialism” is combined with existing forms of systemic social prejudice (Sabatello & Juengst, 2017). It also put a spotlight on issues of reproductive choice, genetic information control, and the public health applications of genetic information (Rothenberg & Thomson, 1994).

Next, from the living memory of the ELSI WG members, the debates of the 1960s over the relative importance of “nature vs. nurture” and their continuation in the 1970s around “sociobiology” highlighted the need to pay special attention to how new information about the genetic influences on human behavior might be used or misused by different social institutions like the criminal justice system, education, and employment and the consequences of such determinism for individual’s social identities (Lappe, 1979; Rosenberg, 1980). Clinical medicine’s incorporation of new genetic knowledge and tools over the same period, with the emergence of new tools for prenatal and predictive genetic testing and clinical practices like non-directive genetic counseling provided ample evidence of the specific ethical challenges that new abilities to detect and predict genetic health risks would pose to clinicians and families (Hilton et. al, 1973). Similarly, the arrival during these decades of universal newborn genetic screening programs and population-specific carrier testing programs for sickle cell and Tay-Sachs mutations opened up the issues that public health applications of new genomic information would face, especially for the interests of marginalized social groups (Brosco & Paul, 2013). During the 1970’s the extraordinary debate over the advent of recombinant DNA research and its potential risks also produced a new generation of molecular biologists who were alert to the need for wider discussions of their new tools and their implications for society, many of whom would grow into leaders for the Human Genome Project (Jackson & Stich, 1979; Cook-Deegan, 1994).

Finally, the commercial applications of molecular genetics that spurred the biotechnology industrial boom in the 1980s made it clear that the role of the market would need to be on the ELSI agenda, including questions of intellectual property, ownership, and data-sharing (Lappe, 1985) Meanwhile, the HIV epidemic, the voice it gave to the interests of socially marginalized patients, and the movement to recognize the rights of people with disabilities that followed it were powerful motivations to pay special attention to the way new genetic information influences our concepts of health and disease, and the practical issues of fairness that can result (Juengst & Koenig, 1989).

In short, the ELSI WG members did not need to turn to science fiction for direction in establishing its initial agenda: they only had to draw from their own experience in 20^th Cen. human genetics to identify challenges that could be reliably anticipated from the Human Genome Project. Moreover, that history kept the effort’s gaze squarely on issues of social justice, so that when the time came to build off of this historical agenda to address the upstream questions provoked by human genome variation research (and all that followed), each of these topics offered useful starting points for a scientifically grounded, justice-oriented analysis.

Finally, it is important to note that way in which the design of the ELSI experiment has also prepared the genomics community and society to respond quickly and effectively to emergent new developments, even when they are based on relatively unanticipated scientific and technological innovations. Unlike governance mechanisms that are tied to particular anticipated technologies (like the 1997 National Bioethics Advisory Commission’s report on Cloning Human Beings (NBAC, 1997 ), or scientific methods (like the NIH Recombinant DNA Advisory Committee’s oversight of gene transfer research (Kimmelman, 2009), the broad scope of the ELSI research agenda fostered significant policy-relevant work at levels of abstraction that generated policy resources applicable to multiple new scientific advances. In fact, by legitimizing this kind of scholarship, the ELSI program has encouraged the wider pursuit of such work within the home disciplines of ELSI research like philosophy, women’s studies, and law, even amongst scholars who do not require research grants to pursue their thinking. For example, the whole notion of “designer babies” has drawn significant attention over the years long before the arrival of preimplantation genetic diagnosis, fetal genome sequencing or inheritable human gene editing arrived to give it practical salience, both by ELSI grantees and their colleagues in their home disciplines that become interested in these topics as important issues to pursue. This ripple effect has been a significant consequence of the ELSI grant-making program and has created a deep foundation of basic resources that gives the field a running start once new genomic tools begin to emerge. Thus the rapid consensus over the ethics of the work of He Jiankui’s surprise human gene editing experiment reflects years of work on the ethical and regulatory issues, long before the arrival of the genome editing tools he used.(. Greely, 2020) By the same token, the broader field’s long history of discussion of concepts of genetic determinism and genetic essentialism, while long predating arrival of polygenic risk scores and “sociogenomics”, nevertheless provided resources for anticipating the implications of that emergent science (Lappe, 1979; Bliss, 2018).

Conclusion:

In 2001, Francis Collins and Victor McKusick concluded their anticipatory essay on the promise of human genome research for medicine by emphasizing that

As we cross the threshold of the new millennium, we simultaneously cross the threshold into an era where the human genome sequence is largely known. We must commit ourselves to exploring the application of these powerful tools to the alleviation of human suffering, a mandate that undergirds all medicine. At the same time, we must be mindful of the great potential for misunderstanding in this quickly developing field, and make sure that the advancement of the social agenda of genetics is equally as vigorous as the medical agenda (Collins and McKusick, 2001, p. 451).

The anticipatory ELSI effort that McKusick and his colleagues on the original ELSI WG designed to help ensure that the medical promise of genomic research was complemented with foresight about the societal contexts in which it would be translated into practice has evolved over the decades since their work, but the wisdom in their experimental approach has been enduring.

Some initial concerns– like the possibility raised by early presymptomatic genetic testing for dominant conditions that more probabilistic genomic risk analyses would also have serious negative psychological consequences-- have subsided with the clinical integration of genomics (Parens & Appelbaum, 2019). At the same time, issues, like the challenge of framing genomic information about socially marginalized groups in helpful ways in research, clinical, and public health settings, have only grown more intense as the needs to be both inclusive and respectful have become more acute (Fox, 2020). Moreover, the ELSI experiment far from over. Today the ELSI researchers that are simultaneously the experiment’s participants and its peer reviewers continue to debate a range of questions about its methods, scope, and trajectory. As the applications of genomic tools ramify within and beyond biomedicine, does it still make sense to frame the field (and its grant-making program) in terms of “genome science,” or should it broaden its anticipatory scope to other emerging scientific domains, like stem cell biology or neuroscience? (Scott, 2015). To what extent should the success of ELSI research be tied to its translation to public policy and professional practice (Burke, et. al., 2012)? What structural conflicts of interest might “embedded” ELSI researchers face as “ELSI components” are built into larger scientific initiatives (Selzer et. al, 2011), and how efficacious can their work be in those contexts (Conley, et. al, 2020)?

In the thick of these discussions, it is easy to forget the fundamental merits of the “ELSI hypothesis” with which McKusick, Wexler, and the ELSI WG launched our field. By structuring their experiment in a way that encourages the circulation of new perspectives and expertise through the community of scholars and scientists that constitute the ELSI “un-commission,” the ELSI WG built the same capacity for nimbleness into anticipatory ELSI research that has characterized the history of genome science. By beginning with questions that history taught them could be expected with new genomic knowledge, they insured the broader social determinants of those questions – considerations of justice and health needs-- would drive the ELSI research agenda as well as regulatory considerations and practical policy concerns. And by embracing ELSI research as a prescribed part of human genome research, they made it possible for ELSI research to stay grounded in the actual trajectory of the science by working together with their genomics colleagues on robustly interdisciplinary initiatives.