A Vision for Empirical ELSI along the R&D Pipeline

In the 30 years since its inception under the auspices of the National Human Genome Research Institute (NHGRI), the field devoted to examining the ethical, legal and social implications (ELSI) of genetics and genomics in the United States (US) has proven a fruitful space for multi-disciplinary, multi-method and multi-level research at the cutting edge of biomedicine and society. Initially serving as a disciplinary home for normative and conceptual studies of the unintended consequences of the Human Genome Project and related life sciences research and development (R&D) (McEwen et al. 2014; Parker et al. 2019; Dolan, Lee, and Cho 2022), ELSI research in the early 2000s became increasingly investigational and observational. This came about following an “Empirical Turn” which brought social science methods into conversation with modern medicine’s evidence-based approaches, applying both to questions in bioethics (Borry, Schotsmans, and Dierickx 2005; Halpern 2005). Empirical ELSI investigators have since articulated a research agenda that expands the field’s focus beyond the expertise of professional ethicists, engaging the perspectives and voices of those directly or indirectly impacted by these technologies including patients, publics, and practitioner communities (Walker and Morrissey 2012; Dolan, Lee, and Cho 2022).

Available evidence suggests that engaging publics and end-user communities in life sciences innovation research is important for enhancing public trust in science and disrupting the legacies of injustice that reinforce health equity gaps and disparities in research and clinical care (Fohner, Volk, and Woodahl 2019; Blanchard et al. 2020; Dolan, Cho, and Lee 2023; Hull, Brody, and Sterling 2023; Reardon et al. 2023). Nevertheless, prevailing models for the design and conduct of ELSI-informed research and governance remain overwhelmingly retrospective. This may be due in part to the structure of public science funding in the US, which allocates the vast majority of federal grant support to basic science, engineering, and technology development. ELSI-based inquiry is typically funded “downstream” in the R&D pipeline (Walker and Morrissey 2012), often occurring in parallel with first-in-human studies of technology, too belated to meaningfully inform research strategy, technology design, or implementation. Relegating studies of technology’s human dimensions and social consequences to the latter phases of R&D limits the ability of patients, publics, and practitioner communities to contribute important inputs and feedback to the research and design process. Moreover, because ELSI-informed findings can support more effective alignment of technology design with community needs and values at the outset, this structure also undercuts ELSI’s potential to shape and improve emerging technology in the eye of publics and as such, enhance public acceptance and uptake (Schairer et al. 2019).

There have been efforts to expand federally funded research that aims to promote collaborative, early-stage studies led by technologists alongside those led by social scientists and bioethicists, such as the ethics cores of the NIH’s Bridge2AI program, or the ‘LEEDR’ (legal, ethical, environmental, and dual use research) component of the DARPA Safe Genes program. However, in general, technologists tend to pursue and occupy lead roles in these types of projects, while social scientists and bioethicists tend to be recruited to already-initiated proposals and projects and then “embedded” in ways that may limit the scope of their contributions to overall research design and direction (Viseu 2015; Conley et al. 2020). This re-invigorates long-standing debates about the scholarly independence of ELSI as a field that seeks to critically scrutinize the very science to which it is inextricably financially tied (Juengst 1996; Meirom et al. 2016).

It is these tensions and missed opportunities that prompt us to advance an alternative vision for the future of empirical ELSI: insofar as empirical ELSI approaches are strongly positioned to empower community input, identify and address inequities, and minimize harms for diverse sectors of society, they should be considered a necessary corollary of federally-funded technology R&D across the entire pipeline, including at early and upstream phases, for example accompanying research at the R21 or R03 stage in NIH parlance. This vision endorses reconceptualizing empirical ELSI as valuable to every stage of R&D and promoting its role within science and innovation beyond genomics, fostering critical reflection on the limitations of existing norms around funding and interdisciplinary power-sharing in collaborative research practices.

Upstream ELSI: integrating community value(s) within technology design and development

Bridging between societal concerns and the regulatory governance of emerging biotechnology, the core of ELSI’s mission remains the generation of insights that can enhance research processes, clinical practices, and policy-making oriented to enhancing patient and community experiences and the health benefits of genomics, precision medicine, and the life sciences (Kaye et al. 2012; Burke et al. 2015; Dolan, Lee, and Cho 2022). Just as precision medicine approaches have sought to deliver more tailored care to individuals by replacing traditional “one-size-fits-all” models of clinical decision-making, so too has empirical ELSI been instrumental in building recognition that successful implementation of life science technologies requires adaptation to the specific features of each setting. Contextual factors, such as neighborhood, perspectives and beliefs of communities, families, and individuals, sociocultural traditions, and linguistic practices frequently vary across local settings, and communities may encompass differing values and orientations to technology (Musschenga 2005), all of which can significantly impact the real-world uptake and success of genomic research and tools. Empirical ELSI projects have sought public input on cherished values that may underlie a community’s stakes in the genomics enterprise, on the perceived value genomics products and services might deliver toward advancing communities’ health goals, and on the ethics of defining “value” itself. Such engagements can promote more equitable distribution of technology’s benefits (Tindana et al. 2017; Claw et al. 2018; Kraft et al. 2018; Lemke et al. 2022). Conversely, empirical ELSI has demonstrated that failure to consider these factors can reinforce problems of inequity, whereby certain communities are excluded from access to benefits or research representation (Lee et al. 2019; Sabatello 2019; Dolan, Cho, and Lee 2023). In recognizing that one-size will not fit all, empirical ELSI raises new stakes for the field as a whole, with an implicit call to implement research that is locally-sensitive while also informing policy and practice at a national and global level.

Applying empirical ELSI’s tools “upstream,” or at earlier stages in technology R&D pipelines, has been a topic of discussion and debate within certain areas of genomics research, such as genetic engineering and gene drive science (Schairer et al. 2019), but remains under-utilized in our view. Upstream approaches have been supported by public funders in Canada, Europe, and the US to advance responsible research and innovation, and have been tested under various frameworks such as deliberative design and public engagements around genomics (Burgess, O’Doherty, and Secko 2008), real-time-technology assessment in nanotechnology (Guston and Sarewitz 2002; Fisher, Mahajan, and Mitcham 2006; Fisher 2019), interdisciplinary collaborations in synthetic biology (Balmer et al. 2016), and ELSI co-design in information communication technology (Liegl et al. 2016). Upstream approaches go by different names, but each advocates for a more prominent role for stakeholder engagement within the innovation ecosystem. As such, these approaches echo philosophical and practical similarities with the principles of participatory action research (PAR) and community-based participatory research (CBPR) (Holkup et al. 2004; Duke 2020; Duran 2023), approaches which have gained traction across public health and healthcare research. As recent ELSI studies have demonstrated, including in this special issue, publics, including research participants and impacted communities, are interested in being active participants in science and technology, staying apprised of scientific developments and new findings, and understanding what researchers are doing or have found with their data and samples (Wolf and Green 2023). Importantly, upstream empirical ELSI could facilitate a needed shift in perspective from understanding publics as research partners by virtue of participation as subjects and donors, to involving publics as partners with more active involvement in the research process (Blasimme and Vayena 2016; Blanchard et al. 2020; Hudson et al. 2020), from problem identification and definition, to study design, to shared decision-making along the entire R&D continuum.

We propose that initiating empirical ELSI research upstream in the R&D pipelines for emerging technologies, as early as the conceptual and design phases and proceeding synchronously throughout the entire continuum of the translational science spectrum, would generate significant benefits for all. If conducted in real-time along the entire innovation pipeline, upstream empirical ELSI could facilitate the design of frontier technologies that at their outset are keenly self-reflexive, prospectively attuned to and aligned with social and ethical considerations and public values, and thus better situated to equitably advance health policy and public health. From a research perspective, upstream ELSI can prospectively inform on community values, objectives, and the most relevant measurable outcomes, in order to better align technology R&D with context-driven measures of “success” within a local or community implementation effort. This would more effectively support the desirability, acceptability and accessibility of research processes and products within communities, resulting in products and services that are more likely to be welcomed or adopted (Munung, de Vries, and Pratt 2021).

Looking forward: enabling upstream empirical ELSI across the technology landscape

ELSI’s history and funding ties to NHGRI have confined much of its work to genome-associated technologies, and over the years ELSI has been instrumental in improving the informed consent process for largescale genomics research, securing data privacy and data sharing protections for participants, advancing ethical return of individual genetic research results and incidental findings, and advocating for legislation to protect against genetic discrimination (Clayton et al. 2010; Callier et al. 2016; Bledsoe 2017). However, other emerging technologies offer exciting opportunities for broadening ELSI’s impact and reach and may warrant more formally incorporating support for ELSI beyond NHGRI. One example may be generative artificial intelligence (AI), which is being developed into chatbots and other human-machine communication interfaces that portend significant transformations in clinical practice, biomedical research, and the patient experience of health care (Ahmed, Zeeshan, and Lee 2023). In part due to the technology’s rapid emergence, data for informing ethical and equitable policy and governance around AI, including in medicine, remains lacking. Empirical ELSI approaches are well suited to generating findings to guide the responsible development of AI across domains. Within health-allied contexts, they could enhance the prioritization of equitable implementation and decision-making by robustly addressing the now-familiar issues of privacy, consent, and autonomy that attend data-driven and digitally-networked innovations and facilitating ethical design by embedding community values within R&D processes. Had empirical ELSI-style approaches been recognized for the tools they could offer toward specifying and addressing such concerns and been featured more prominently within the research innovation ecosystem of the early 2000s, major concerns around generative AI may have been more democratically and preemptively addressed during initial stages of design and development. Moreover, this might have better informed anticipatory policy and governance, rather than the regulatory scramble that is shaping up in the aftermath of product release to the public (White House 2023).

Taxpayers, through federal funders, have financially supported much of the foundational research leading to this century’s transformative technologies, including blockbuster drugs and vaccines, clean energy, high-performance and networked computing, geoengineering, and self-driving cars, without which these developments simply would not exist (Mazzucato 2015; Mervis 2017; Reif 2017; Fleming et al. 2019; Barenie et al. 2021; Lepori, Jongbloed, and Hicks 2023; Myhrvold 2016). Companies leading R&D in these fields also benefit from government contracts, grants, and incentives that support commercialization (Mazzucato 2015; Block and Keller 2011; Bateyko 2023). Despite the role of public dollars in driving these technologies forward, federal funding agencies typically have not made ELSI research part of the culture of these R&D projects they support, nor, with the exception of NHGRI, explicitly set aside taxpayer dollars to advance such work.

There is a case to be made that research funded by the public should be carried out first and foremost by a guiding and abiding commitment to serving the public interest, not by a priori assuming what that interest is, but through careful, locally situated, and empirical elaboration. This is a mission that upstream, empirical ELSI could help fulfill if sufficiently resourced and enabled through thoughtful reframing of both the culture and infrastructure of science. This would presuppose cultural shifts in how science is done, perhaps identifying ways to encourage and support ELSI researchers to initiate projects as the lead or PI, or funding announcements that call for collaboratively structured project leadership teams in which ELSI researchers are better supported to explicitly articulate the relevance of societal issues to application-specific design (Shumpert et al. 2014). The NIH has experimented with the latter, but more could be done to re-imagine the coordination of work across research teams and consortia to better balance leadership and share power across disciplines and avoid the political and logistical challenges that can impede embedded or interdisciplinary work (Hilgartner, Prainsack, and Hurlbut 2017). Innovation goals and processes would also need to be reframed to prioritize public deliberation and participation. Robust mechanisms and pathways for incorporating feedback would need to be developed to ensure that empirical findings and community input can meaningfully inform research and design processes. It is also critical to continue to strengthen efforts to diversify the ELSI and STEM workforces by expanding pathways for attracting and retaining diverse expertise, including from impacted communities, within the work (Claw et al. 2018; Fletcher 2023). Finally, incorporating upstream, empirical ELSI more widely within the publicly-funded R&D ecosystem would advance responsible innovation across technology sectors. The long-term gains of such an expansion, in terms of identifying ethical, legal, and social barriers earlier in the process, and fostering research outcomes that scale more efficiently and effectively to the entire population, are likely to make such restructuring and investments worthwhile.

The quickening pace of transformative changes in our societies, catalyzed by technology’s impact on our world, render this a critical juncture at which to reflect on how publics and communities have traditionally been positioned in relation to science and technology, and how we can redress inequities moving forward. We sit at a crossroads in which cutting-edge science and industry drive a research ecosystem fueled by public investments but are insufficiently accompanied by ethical oversight or public input. The pervasiveness of AI, technology’s acceleration of climate change, and the lack of a just and affordable healthcare system in the US are evidence that collaboration, partnership, trust, accessibility, ownership, accountability, and transparency need to be better integrated into our technology R&D. Empirical ELSI is well positioned to help facilitate these objectives and to serve as a bridge for building long-lasting partnerships with communities that incorporate, in rich and robust ways, the perspectives and expertise of patients, physicians and publics into the technology enterprise. Empirical ELSI’s participatory methods and its history as an active site for catalyzing scientific, social, and research innovation hold promise for its ability to lead the next chapter of research at the interface of technology and society in ways that honor human dignity, acknowledge and redress histories of marginalization, and provide ongoing, data-driven assessment and evaluation of interventions to maximize their potential for successfully advancing equitable health for all.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the Center for Empathy and Technology within the T. Denny Sanford Institute for Empathy and Compassion at the University of California San Diego and funding from the National Center for Advancing Translational Sciences (1R01TR003514; PI: Bloss).