Santiago J. Molina: How Scientists Produce Institutions: The Practice and Politics of Genome Editing

On November 16^th, 2022, Dr. Santiago J. Molina, the Mellon Postdoctoral Fellow at Northwestern University, joined an interdisciplinary group at Columbia University to discuss research and dilemmas in the field of genome editing. His talk, titled “How Scientists Produce Institutions: The Practice and Politics of Genome Editing,” was hosted by the Precision Medicine: Ethics, Politics, and Culture working group at Columbia University. Dr. Molina provided an overview of the history of genome editing to orient the audience to how current controversies came to be. He transitioned to talking about the ethical discussions surrounding genome editing, which have been raised by scientists, politicians, and patients.

Dr. Molina centers his discussion on the question of the relationship between the production of knowledge and production of social order. Specifically, the tendency for genetic research (and research as a whole) to categorize participants by race or genetic ancestry, and thereby artificially reproduce racialized social order. Sampling and analytic biases that result in genetic conclusions based on race can be taken advantage of and used to perpetuate inequity, as race inaccurately takes on biological significance. Furthermore, racialized research can be used to influence how practices and systems of classification are legitimated in biomedicine and how bodies of labor and lives are recruited for the purpose of advancing biomedicine. These concepts raise questions of who is benefiting from genome editing, and what groups are carrying a disproportionate burden for this research to advance.

CRISPR-Cas9 has generated extensive controversy. From celebration of the possibility to cure rare diseases to fears of genetically engineering babies based on their appearance and intelligence, it has captured media attention. Dr. Molina investigates the power that this technology possesses to capture public attention and lead to the exercise of control over populations. He provides critical perspective and insight into this field, as he personally interviewed researchers, physicians, and patients to understand their motivations and concerns. He spent time watching them work, listening to their meetings, and synthesizing their key ideas. His talk drew from participant observations, in-depth one-on-one interviews, and archival research. He argued that scientists influence and control the institutionalization of genome editing by ensuring boundaries of self-governance and resisting control from regulatory bodies.

He concluded by describing the model for scientific change. Specifically, he explains that scientists produce a moral order, based on normative claims rooted in visions for the future. Dr. Molina then turned to the audience for questions. The audience brought up dilemmas of corporatization of genome editing and the role of capitalism, which is a point that Dr. Molina had mentioned as a key factor of scientific industrialization and motivation for rapid advancement. He explained that political, economic, and social motivations were all integral to the development and utilization of genome editing technologies, and all had to be considered when interpreting the future of the field.

One audience member made a comment about the global nature of these debates. Specifically of interest, was the story of the “CRISPR babies” and the scientist He Jiankui. Chinese scientist He announced that he used CRISPR technology to edit the genome of human embryos, which were subsequently implanted and resulted in birth of the “CRISPR babies.” He stated that he had edited the embryos to prevent the offspring from contracting HIV. He had largely undertaken this project secretly, and the revelation of this project to the world led to strong emotional responses. The overwhelming global response was ethical outrage.  This controversy raises many important questions about the institutionalization of research and genome editing technology, along with its global nature. For example, who should have control over genome editing technologies, what does informed consent look like, and what types of germline changes should (or shouldn’t) be allowed to be made? While Dr. Molina does not seek to definitively answer these questions, he argues that the current answers are created through the institutionalization of technologies based on a certain moral ideal created by scientists.

The discourse of genome editing

One of Dr. Molina’s main points is that language describing new technologies shapes how it is perceived by the public and incorporated into society. For example, proponents of genome editing have deemed it “DNA as a drug” whereas opponents call it “playing God.” Public perception, scientific and government regulation, and patient education can all be affected by the way CRISPR treatments are described. Language not only affects perspectives of a concept or technology, but in turn changes how these technologies are integrated into societal use. Dr. Molina frames the use of language as a way for scientific institutions to legitimize standardized application of powerful precision medicine techniques, while potentially avoiding extended ethical discussions about using such treatments.

Dr. Molina points out that both sides of this spectrum of language lean into the ideas of hype and hope surrounding gene editing. Phrases such as “playing God” and “cutting edge” emphasize the power of these technologies and are pervasive among news articles and popular media. Due to inconsistent and embellished descriptions of CRIPSR that have filtered from scientific literature to mass media, it is difficult to understand how the public feels about implementing CRISPR more broadly. Dr. Molina discusses the limitation of widespread surveys due to the need to provide education on the topic prior to asking questions such as “Would you support germline genome editing?” Such barriers must be surmounted if public perspectives are to be understood and considered. Indeed, the somatic versus germline debate has long captured researchers’ attention, with calls for moratorium on germline editing that emphasize scientific regulation by the scientific community yet continue autonomy. Still, these discussions remain limited and must start to incorporate the views of the communities these technologies aim to serve.

Role of disability: Who should decide what we edit?

Ruha Benjamin, assistant professor of African American Studies and a faculty associate in the Program on History of Science at Princeton University, provides a disability justice approach to genome editing, with a focus on intersectionality and how social hierarchies are perpetuated through these technologies. In Benjamin’s article (2018) titled “Interrogating Equity: A Disability Justice Approach to Genetic Engineering” she explains that a false distinction is often made between genetic therapy and enhancement. She writes, “The bright line we may wish to draw between laudable and questionable uses of gene editing techniques is more porous than we realize. Many practices that were optional yesterday are medicalized today. Likewise, traits and behaviors that we may regard as ‘enhancement’ today may very well find a therapeutic justification tomorrow.” Dr. Molina incorporates these ideas into his talk to highlight the contingencies of the arguments regarding genetic modification.

Dr. Molina argues that thinking critically about the framework behind scientific ideas and interrogating them from the perspective of equity is part of the process of engaging in what Benjamin describes as “democratizing science.” He explains that the construction and institutionalization of moral imperatives used in scientific practice is currently in vast majority developed by scientists rather than the people they affect. The questioning of practices should include all perspectives, though, and not just represent a narrow segment of the population with the resources to engage in such discussions. Dr. Molina points out that efforts to address these gaps must consider the intersectionality of power, disability, and socioeconomic status. Benjamin provides an example of this intersectionality when she points out that patient advocates often only represent the interests of the middle-class, which neglects many people with disabilities who are impacted by the policies and technologies being discussed. Dr. Molina determines that this exclusion is in-part due to the institutionalization of science. He adds that democratization must include thoughtful efforts to expand conversations about treatments and technologies so that people with disabilities from any background may be heard.

A major issue at the core of disability-related discussions pertaining to genome editing is that the portrayal of gene-editing therapies as miracle cures might then reinforce the social assumption that disability is harmful and needs to be cured or prevented. An important question was raised during a discussion with the PMEPC fellows and Dr. Molina that hits at the heart of ethical debates surrounding genome editing: what kinds of conditions should be treated with genetic material? What is the role of age of onset, life expectancy, disease course, patient population, prevalence, community, culture, and current treatments? If the decisions are made by abled-bodied decision makers who possess incorrect assumptions about the inferior quality of life of people with disabilities, then their policies are sure to entrench stigma and endanger disabled populations.

While there is no single answer to any of these questions, Dr. Molina emphasized the importance of taking the time to ask and consider them. The PMEPC fellows determined that to prevent genome editing from becoming a tool to perpetuate bias and reinforce assumptions about the superiority of some types of bodies over others, it is important to ensure that those making decisions about these technologies truly represent those who will be impacted by them. It is challenging to decide who should make these decisions: should it be patients, doctors, parents, bioethicists, politicians, advocacy groups, industry CEOs, or some other combination? Where is this decision-making taking place? How can scientists, physicians, and policymakers ensure that individuals with disability are, as Benjamin says, “at the table not just on the table?” With complex dynamics at play of economics, capitalism, race, along with disability, it is more important than ever to ensure that patients and impacted communities may provide their perspective.

What does the community think? Perspectives from stakeholders within the sickle cell disease community

Anitra Persaud and colleagues recruited stakeholders within the sickle cell disease community through collaborations with hematologists, community-based organizations, and national conferences to investigate how the community impacted by the diseases feels about the idea of genome editing. In their paper, “A CRISPR focus on attitudes and beliefs toward somatic genome editing from stakeholders within the sickle cell disease community,” researchers held 15 focus groups in the United States and analyzed themes brought up by stakeholders. The four broad themes that emerged from their discussions were: motivations to participate in genome editing for sickle cell disease, information requirements to decide to participate, groups who they would look to for guidance to make the decision to participate, and advice to researchers for how to engage with the community.

Patients, family members, and physicians all expressed hope that genome editing may provide treatment for sickle cell disease, especially since there are few impactful treatments. They were motivated to participate in research by altruism to help family members and friends who might also be suffering from this disease. They were deterred by fear of complications and uncertainty of how CRISPR worked and the permanency of editing genes. They also expressed concern rooted in historic mistrust. This point is very important to consider, especially in the context of historic racial abuses of power by medical professionals. Black patients have had their bodies experimented on, not been given informed consent, and been denied the opportunity to receive life-saving treatments. Once again, a community of Black individuals finds themselves in a position of being the subjects of an experiment that could be used as a proof-of-concept to benefit others, rather than themselves. This fear is clear amongst patient parents, who expressed that they did not want their children to be “guinea pigs.”

During their discussion with Dr. Molina, the PMEPC fellows discussed how this study highlights the complex nature of how to proceed with these types of clinical trials. On one hand, sickle cell disease contributes to tremendous suffering, treatments do little to mitigate the suffering, and a cure provides much needed hope. On the other hand, the medical community may emphasize the importance of rapid advancement without putting due process into understanding the burdens they are placing on a community has historically suffered abuses at the hands of the medical system. This research demonstrates the importance of speaking with communities to understand their concerns and make actionable steps to reduce them. For example, most of those who would participate in research wanted more information about the logistics of the research, type of technology, and its permeance. They also urged researchers to avoid a “one-size-fits-all approach” and note the nuances in different communities and cultural groups. Finally, they advised going out into community spaces to discuss this technology and make educational materials more widely available. All these proposed methods are to support patient empowerment and prevent scientific abuses, so researchers can ethically provide the hope and cure these patients need.

Conclusion

With his thoughtful discussion of the current practices and politics surrounding genome editing, Dr. Molina generated a powerful description of how science has become the institution it is today and what must be considered for an equitable and ethical future of genome editing.