Grounded in Reality: Integrating community values and priorities of end users in human gene editing

An Argument in Search of an Application

The target article “Reasons and Reproduction: Gene Editing and Genetic Selection” by McMahan and Savulescu (2024) makes several key assumptions we contest. Despite acknowledging the existence of a strong counter argument, the article remains fixed on the assumption that an “able-bodied state” (including being neurotypical) is a priori a preferable state of being. Building on Savulescu’s prior work on procreative beneficence, it tries to infer a moral obligation to choose this better outcome. And it implies a parental obligation toward such choices, which the authors extend to both embryo selection and gene editing. Several of the examples the target article uses to support an obligation toward gene editing address conditions for which there are already established therapies (e.g., Trikafta for cystic fibrosis) or ongoing clinical trials (some genetic forms of deafness). While espousing empirical support, it ignores the existing empiric data (Jaffé et al. 2006 and Donnelley et al. 2023 regarding CF and Freeman et al. 2022 for deafness)) in favor of hypothetical thought experiments.

The authors do well to challenge us to tease out the comparative moral and ethical acceptability of germline gene editing, preimplantation genetic testing, and embryo selection. Unfortunately, decontextualized analyses have limited utility and conceptual arguments divorced from real-world empirical data pose their own ethical problems. The authors rely on analytic metaethics to develop normative claims that stand in stark contrast to empiric and narrative research in patient experience, disability studies, patient decision-making, and ethics literature. As ethicists and social science researchers currently conducting a large study engaging patient communities and policymakers on prenatal gene editing – and who have previously led qualitative stakeholder research about prenatal diagnosis, somatic and germline gene editing – we suggest an alternate discourse based in empirical reality and which centers discussions of gene editing and genetic testing and embryo selection where they belong: with individuals and families who understand what it means to live with a genetic condition.

Prioritizing and Harmonizing the Voices of Diverse End-Users

We have argued that any discussion of implementing novel interventions, including gene editing, should be situated within a translational justice framework (Allyse et al. 2023). This approach encourages incorporating the community values, goals, priorities of end users - primarily patients, families, and communities – beginning at the bench and continuing through all stages of the translational process. This requires bringing together multidisciplinary teams that can engage with the possible applications of a technology on person-centered, practice-centered, and system levels.

Those best situated to examine the normative questions that underlie gene editing are those with lived experiences of the relevant genetic conditions. These communities are profoundly aware of the complex realities of genetic conditions and, more importantly, the health care environments within which families must make tough, even impossible, choices. There is a significant body of historical literature documenting that people with lived experience of a genetic condition have subjectively different interpretation of their own quality of life (Boardman and Clark 2022). It is within this context that they carefully evaluate the socio-ethical nuances of potential reproductive technologies such as embryo selection (e.g., Cheng et al. 2022) and genetic therapies (gene therapy or editing). Importantly, these families are keenly aware of broader societal inequities and stigmas that may influence perceived responsibility towards future generations and reproductive decision-making.

The target article is based on a fallacy of incomplete evidence; it selectively disregards existing data about how individuals and families actually feel about genetic conditions. The authors repeat the mistakes of the past, namely marginalizing the voices of those with lived experience in favor of those with positions of power within medicine, science, and philosophy. This has resulted in many deleterious effects, including a “medicalized” framework which centers on preventing or “curing” impairment through technological advancement and seeks to limit the diversity of the human condition, while ignoring the multitude of social barriers and biases faced by those affected by a genetic condition. Setting aside the misguided elitism of “procreative beneficence” which this work expands upon, it is by no means certain that attempts to promote “better” lives or outcomes will have this intended effect. This is especially the case when individuals and families are presented as passive recipients with the moral obligation to select certain embryos or genetically alter their future offspring, rather than as central decision-makers with the autonomy to make choices they perceive to be most congruent with their values and priorities. Particularly since empiric data already exists to inform this debate, the relevant voices should not be imagined nor should the values of affected individuals or their offspring be projected upon them - an approach which risks being both offensive and wrong. Real communities stand to be the most affected by genetic technologies and should be at the forefront of these conversations.

Multilateral Policy Generation

Other important voices should be incorporated, including clinicians and scientists who can ground the conversation in what is possible, rather than science fiction, and provide a nuanced understanding of the costs and benefits patients will need to weigh when considering gene editing or embryo selection. Policymakers (i.e., governmental or professional actors) and interest groups also bear an important role in these conversations, given their role in establishing governance frameworks for gene editing technologies, and determining how to best implement them to maximize fairness and minimize harms to individuals and communities. Researchers and scientists must be willing to re-think their endpoints in light of community input that reflects lived experiences of genetic conditions, to ensure they are engaged in research that addresses genuine needs. Recent history has shown that, in the absence of community input, the first attempts at human germline gene editing focused on HIV infection and hypercholesterolemia, conditions for which numerous pharmacological therapies already exist and for which no compelling unmet medical need warrants prenatal intervention.

Fostering strong connections between theory and practice reduces biases, engenders community trust, and ensures meaningful impact on improving patient care. It also considers human dignity and respect for persons when formulating policy (Wilkinson et al. 2023). We - along with many of our bioethics colleagues - have utilized partnership-oriented research strategies such as community-based participatory research to ensure that individual and community-level perspectives are prioritized, rather than excluded from bioethical discourse (Shore et al, 2008). Individuals involved in shaping the translational pathway of a technology have many choices: they can choose to further ableist dialogue and isolate those most impacted by a technology or recognize the value of community expertise. Community expertise can only be gained by making a place for people with genetic conditions at the table. Their views must be elicited without preconceived bias and the conversation must continue over time as technology and the policies that shape its use continue to advance. These conversations will not be simple or straightforward, but they are necessary to avoid repeating the injustices of the past.

Finally, individuals with genetic conditions and their families, a diverse array of community groups, scientists developing technological solutions, and policymaker/regulatory groups overseeing their implementation, should collaboratively shape real-world policy. Policies can serve as an important tool to influence the social context, fostering change in prejudicial and potentially ableist societal attitudes, re-defining dominant ideologies regarding normalcy and genetic diversity, and prioritizing the socio-moral values of equity and inclusion. We must create governance systems which ensure that the priorities and goals of end users are safeguarded and accountability and trustworthiness are fostered.

Conclusion

When done well, normative and empirical approaches to bioethics complement and enhance each other and are critical to improving our understanding of real-world moral issues, including the appropriate use of gene editing and embryo selection. These benefits can only be realized when end user values, priorities, and experiences are permitted to guide and shape bioethics discourse in a multidisciplinary context. Failure to do so limits and distorts its relevance and applicability at best and commits expressivist harms at worst.