Democratic Governance of Human Germline Genome Editing

In November 2018, a Chinese researcher, Dr. He Jiankui, announced the birth of two genome edited babies, the so-called “CRISPR babies.” The “He debacle” drew the world’s attention to the urgent need for responsible governance of human germline genome editing (GGE). In response to the “wake up call from Hong Kong,”¹ the National Academies of Sciences, Engineering, and Medicine (NASEM), the Chinese Academies of Science, and the Royal Society of the United Kingdom (henceforth the “Academies”) established a commission “to develop a framework for considering technical, scientific, medical, regulatory, and ethical requirements for germline genome editing, should society conclude such applications are acceptable.”² This move was not surprising. The life-sciences community has grown accustomed to international summits and commissions led by elite scientific and bioethics experts who step in to address governance questions raised by unanticipated biotechnological developments. Many leading genome-editing researchers reacted to the idea of a regulatory commission as the only imaginable next step.³ We offer a different view.

An international regulatory commission offers only one approach to governing genome editing—one that is both premature and incomplete. For the Academies, establishing a framework is the top priority, but just how this framework will be subject to, at best, an emergent societal consensus remains poorly defined. The Academies seem to conceive of societal consensus as distinct from, and developed independently of, the regulatory framework. Yet, societal input that is framed by an agenda already set by experts is an unsustainable model of governance: it not only transgresses fundamental democratic norms, but also spells trouble down the line for both science and society.⁴ Moreover, the relationship between a central regulatory commission and the far-flung international research community needs to be carefully considered.

In the “CRISPR babies” case, a major area of concern was the disconnect between Dr. He’s research team and governance bodies scattered across the globe. One of Dr. He’s multiple failings was that, to our knowledge, he did not actively participate in open, public debate about the governance and ethics of human GGE. As has been widely reported, however, He did not act alone. The conversations he had with multiple American and other scientists were undertaken in confidence and in private.⁵ Indeed, his mistakes included relying upon the judgment of a poorly informed ethical review body that deliberated behind closed doors, and treating the Academies’ guidelines⁶ as a checklist of ethical requirements that he judged himself to have met.⁷ He proceeded as if the question of whether to undertake his clinical experiments was ultimately for him alone to decide, once he had engaged in what he took to be sufficient consultation.

There is no question that Dr. He bears the primary responsibility for the so-called debacle. Yet, we must also recognize that he was, in effect, set up to fail by a system of governance that places ethical authority in a small number of hands, often employs behind-closed-doors negotiation, and prefers scientific-self-regulation to more open and socially inclusive processes of deliberation and judgment. Although the 2017 NASEM guidelines defined strict criteria for GGE, they stopped short of calling for a moratorium or new regulatory arrangements, thus leaving intact the notion that science (and scientists) can self-regulate by judging for themselves whether the criteria are met. This is the protocol Dr. He evidently followed. When he sought advice about the ethical acceptability of his experiment from his postdoctoral mentor at Stanford, his mentor’s advice was simply to “get IRB approval.”⁸

In the wake of this case, there have been calls led by Eric Lander, Francoise Baylis, and colleagues for an explicit declaration of a global moratorium and for mechanisms to enforce it.⁹ Even that proposal has been seen by many scientists as controversial, although it asks merely for a temporary moratorium on making edited children and not on the forms of preclinical research and rule-making that precede and incentivize that intervention. There is strong resistance to limits on research that are not fully controlled by (and therefore also subject to being lifted by) the scientific community. Yet, this kind of reaction against any external supervision of science elevates scientific self-regulation over democratic governance of a matter that rightfully belongs to all of humanity.

Six Concerns with the Academies’ Approach

Given the complex international landscape of human GGE, as well as significant cross-national differences among regulatory cultures,¹⁰ deferring to a single commission to set the agenda for global governance raises troublesome questions of framing and representation. The path to ensuring democratic governance demands active and sustained reflection by scientists on their own practices, in partnership with scholars from other disciplines, as well as publics from varied social, political, and religious backgrounds.^11–14 We need to open up the imagination of governance in this emerging and highly consequential research field to a wider diversity of views and voices. Robust, long-term democratic governance is required for a project that, as a pending resolution in the U.S. Senate¹⁵ rightly notes, “touches on all of humanity” across multiple generations. As such, governance must not be appropriated here and now by the self-appointed authors of a framework for bringing that project into rapid clinical use.

In their 2018 statement prior to the formation of the International Commission, the organizing committee of the Second International Summit on Human Genome Editing in Hong Kong invoked the He case as a justification for charting a “translational pathway” and standards for pushing forward into precisely the territory that Dr. He had illicitly entered.¹⁶ Thus, even though Dr. He’s experiment was criticized as irresponsible and “premature,” the Academies moved forward with a new urgency to legitimate just such research. The Academies’ approach treats it as a forgone conclusion that germline editing will be done, and thus should be done according to a framework their appointees will designate. Although He was widely called a “rogue,” including by Summit leaders,^17,18 this path will have the effect of positioning Dr. He as a pioneer who was fundamentally on the right track but rushed ahead too carelessly. Proceeding on this course does a disservice to the long-term democratic governance of science. Moreover, it may well harm the future of biomedicine, even if it produces short-term windfalls for some well-placed and well-resourced research and medical communities.

The leaders of the genome-editing research community cannot shelter behind claims of disinterestedness. The community promises cures as the main justification for gaining resources for their work, but high commercial interest as well as prestige are at stake in rapidly advancing toward genome-editing cures. Even within science, multiple interests are in play. With the chilling effects of the Jesse Gelsinger gene therapy tragedy 20 years ago in mind,¹⁹ the somatic editing community recognizes that problems with GGE may quickly spill over into somatic research. For this community, blocking or delaying GGE may reduce the risk of disrupting the growing market for somatic editing. For those in GGE, however, a green light now gives more leverage to those who can move quickest within newly established rules. Standard conflict of interest rules cannot neutralize the cross-cutting interests of scientists who have a lot at stake in establishing rules that are friendly to their own lines of work.

Against this backdrop, both Dr. He’s experiment and the Academies’ response reflect systemic problems in existing governance thinking by leaders within the scientific community. The numbered list here demonstrates six recommendations to generate broader public engagement with the governance of genome editing and related technologies—none of which the Academies’ approach has grappled with to date.

1. Make room for greater diversity in posing and framing key questions

National science academies tend to view the world through narrow lenses. They are in their nature interested parties, committed first and foremost to the advancement of research and associated benefits from rapid commercialization. Consequently, they are not best positioned to frame the right questions for ethical deliberation or to decide who should be at the table to discuss them. This has been demonstrated repeatedly. For example, social sciences, democracy experts, and even religious groups figured in only a minority of summit sessions. Religion was not even mentioned until the final session of the 2015 International Summit on Human Gene Editing, and then only by a member of the audience who pointed out that it had been completely absent from the official proceedings, despite the fact that billions of people around the globe turn to religion as an important source of moral insight.

International perspectives on the challenges of governance posed by the global circulation of tools, knowledge, and now even genome-edited people were likewise hardly broached. The discussions driven by the Academies mostly failed to recognize how deep traditions in the law, political theory, and humanities may offer insights about the right modes of deliberation, and how some voices and values come to matter and gain power in society while others get sidelined or excluded.²⁰ Further, legal scholars, science, technology, and society (STS) analysts, novelists, filmmakers, not to mention a cross-section of patients, affected communities, and the “general public” were strikingly absent in most of the Academies’ efforts. The summits failed to convene a group of leading thinkers about ethical, legal, and social dimensions of biomedicine commensurate in size and stature that of the convening scientists. Thus, it is not surprising that the range of alternative ideas about what is at stake and what alternative paths exist was limited.

One example is instructive. The International Commission created in response to He’s experiment includes numerous technical experts but not a single representative from the disease or disabilities communities that are supposed to be the immediate beneficiaries of germline editing. Yet, it is well understood by scholars and by disease and disability advocates that the ways experts characterize problems of disease and disability and define research agendas in the name of “fixing” them often reflect false assumptions about affected people and ignore crucial dimensions of social context.^21–23

Such deficiencies are evident even in the domain of editing out ostensibly straightforward genetic causes of disease and disability.²⁴ GGE, which extends well beyond that limited domain, could bring added problems. Given the species-wide effects of genome editing, robust deliberation requires a much wider spectrum of perspectives than those of communities whose diseases have been the initial focus of the technology. The fact that even the most immediately affected groups were left out illustrates just how far short of the mark current efforts are falling. In the face of the Academies’ runaway efforts to produce quick answers, they have left the most important questions unasked. Who should be framing the questions of governance? By what process? In accordance with whose theories of good politics?

2. Ask about the purposes of research before new steps are taken

Just because one person has crossed a line, it has not suddenly become necessary to “reach international agreement”¹ on how to cross that line the next time. Despite the fact that one scientist took it upon himself to ignore an important line, the right questions still remain whether such a line should be crossed at all, if so under what conditions, and who has the authority to make that call anyway.

Even the first question is anything but resolved, and yet the Academies’ leadership is proceeding as if public assent either already exists or can be dealt with later, reducing the role of the society to commenting on regulatory initiatives already in motion. This reverses the core principle of democracy—that society’s purposes come from the people. One person who strayed into deeply contested territory, acting with tacit support from his elders in the field, cannot force the rest of humanity to accept a future in which such transgression becomes normal and permissible.²⁵ Nor do we have to accept that because a single scientist crossed this particular Rubicon, it is now up to the scientific community to decide what comes next.

Public permission is a prerequisite to disrupting fundamental elements of social order. What is at stake in rendering the human germline editable is the future of human integrity and autonomy as we have long understood these concepts. How to guide and govern that future is not a question exclusively for researchers eager to extract quick credit and profits from their discoveries.

3. Do not champion self-governance by scientists

No institution in a democratic society governs itself, and science should not be the exception. The Academies’ leaders cite Asilomar as an inspiring model for ensuring scientific responsibility.¹ Yet, history shows that Asilomar was an imperfect mechanism for engendering public trust in the integrity of emerging science. The Asilomar guidelines were a success only inasmuch as they allowed research to go forward after a voluntary moratorium, with minimal public supervision on many fronts. In 1976, amidst the significant public controversy that erupted after Asilomar, Senator Ted Kennedy put the problem succinctly: “They were making public policy, and they were making it in private.”²⁶

If one looks only at the case of agricultural biotechnology, the result of those closed-door deliberations was a political fiasco, even a disaster for the field. Its effects have played out for decades in controversies surrounding genetically modified organisms (GMOs) and beyond. As Monsanto’s fate attests, Asilomar was anything but an unambiguous success story for its approach to product development and marketing. To represent Asilomar as an idealized model of self-governance, a victory lap to be savored over and over again, misrepresents history, ignores relevant scholarship,^4,27,28 and overlooks all evidence to the contrary. Holding up this example as a touchstone for governance is not good science or good policy. It is propaganda. It propagates a faulty vision of good governance and excuses those who still celebrate it from learning from its deficiencies.

4. Reflect the global nature of human values, especially as regards human integrity

The Academies intend to establish a benchmark for global governance, but their approach reflects ideas of progress and human development that are not universal. To take just one example, the Oviedo Convention on biomedical research, which prohibits germline editing and the creation of human embryos for research, is settled law in 29 counties.²⁹ No less importantly, because it is grounded in the legal and normative framework of human rights, the Convention takes a radically different approach to questions of governance from the framework adopted by the Academies’ guidelines. The Oviedo agreement rests on notions about the limits of intervening in human heritability that were not properly aired during the development of the U.S. National Academies guidelines,⁶ though their meaning and scope remain live subjects of debate in Europe.³⁰ For a workable global consensus to develop, it is necessary to bring existing disparities in international scientific and ethical thinking into full view and engage them in meaningful conversation.

5. Rein in the language of “running ahead” to make room for broader perspectives

Dr. He conducted his research on CRISPR-edited babies in about the time it took to gestate a conference. Yet, it took less than three days after the shocking revelation of He’s “rogue” science for the summit leadership to sweep aside the weighty questions raised at its own earlier summit and to declare that because a fundamental line had been crossed, it was time to prepare the regulatory framework for human germline editing.² Otherwise, it is claimed, science will run ahead without proper regulatory guard rails. Consensus can wait. Researchers need permission now.

Thus, the “bombshell” of what has been widely labeled a rogue event is being used to shield what could be seen as a power grab by the scientific community. Unfortunately, there is not enough transparency in the world of translational science, with its agendas set by billion-dollar investments, for the world to see the forces that are at work behind calls for urgency. And yet the public drama that erupted in the wake of Dr. He’s experiment has the hallmarks of that market-driven world, with its hunger for headlines, its ethos of risk-taking, and its relentless pursuit of prestige and profit. Lack of transparency notwithstanding, what is undeniable is that events are following the too familiar script in which calls for scientific self-regulation are redoubled in the name of keeping up with events, and science is reaching into political and moral domains that are beyond its remit and capacity.³¹

The scientific community is worried that Dr. He’s recklessness will create a “public backlash” against genome editing unless regulatory controls are set in place quickly. This is a deeply misguided concern. Public distrust does not come from seeing one expert take one wrong step with a new technology. The fact that chemical, biological, and nuclear weapons have been used in war has not kept society from debating which if any uses are permissible and thus building a culture of restraint. Any powerful technology can be misused, and collective vigilance is needed to make sure that scientists and others understand and respect important social norms. Public distrust becomes significantly more probable when people are shut out of the conversation by an impatient scientific community that unilaterally declares what is moral and decides without debate how far research should go.

6. Consider researchers’ intentions along with their practices

There is a widespread belief among genome-editing scientists and their advocates that the problem with Dr. He’s experiment was not with his intentions but with their ethically problematic execution. The Academies leadership rightly concluded that He should not have acted on his own, but their proposal clears the way for others to follow along the same path, only with more explicit rules for how to do well what Dr. He did badly. Yet, a far more important reading is that Dr. He was irresponsible not because he acted “prematurely,” without the imprimatur of some of the world’s leading scientific colleagues, but rather because he recklessly prioritized his hunger for scientific reputation over the integrity of our species, including the future of the two new “designer” lives that he helped bring into being.

Concerned with his own scientific advancement, Dr. He took it upon himself to decide for others a basic question that was not his to decide—namely, whether it is appropriate to introduce traits into another human being’s germline. His experiment, moreover, sought to create a genetic fix for a social problem— discrimination against Chinese people who are HIV-positive. Such a pursuit of social ends through biological means is dangerous and irresponsible, regardless how well the designer does the experiment.

A Path of Humility

If leading voices in the international scientific community want to act responsibly and engender public trust, they should adopt a posture of greater humility. How else could have the Academies have proceeded? A defensible response would have unequivocally condemned Dr. He’s experiment, declared that anyone who tries to copy his example will be excommunicated from international science, and followed through on the 2015 summit’s commitment to engendering a “broad societal consensus” on key issues.⁹

Science needs inputs from the wider global community to determine whether human GGE is even a direction that we should pursue. The right to make that call certainly does not belong to an individual scientist such as Dr. He, but just as crucially it does not belong to science. It is not for the Academies’ leadership or their carefully selected representatives to decide how far to go with GGE technologies. This question belongs to all those whose futures will be affected by science’s new powers, and that means quite simply to humanity as a whole.

We must develop the means to see, recognize, facilitate, and affirm a larger ecology of mechanisms of deliberation-for-governance that problematizes (and thereby augments) the approach of the Academies. A global observatory on human genome editing^11–14 would be one mechanism to meet this need. First, it would collect and thus render visible the multiple deliberative and governance activities underway in this field. Second, it would convene and thus catalyze conversations across diverse scholarly communities and publics that are not yet occurring—but should. Third, it would critique ongoing activities by rendering visible the discrepancies across ethical belief systems, as well as the problems of illegitimate appropriation, narrowing down, and exclusion that we have noted above. These three sets of actions would help breed the “cosmopolitan ethics” that needs to be engendered within this field, not only by practicing scientists, specialist bioethicists, or policy makers, but also by citizens around the world reflecting on the future of the species.

Skeptics may respond that a global consensus would not be feasible and that for people to truly understand the stakes involved, science needs to make rapid, unencumbered progress. Such a position, though understandable, should not stand in the way of projects such as the global observatory we have proposed. The enormous powers acquired by CRISPR researchers demand vigorous experiments in democracy to match and, if necessary, curb the full-steam-ahead disposition of high-stakes science. To deny this short-changes the will and intelligence of the citizens of the world. Science, in the words of the philosopher Stephen Toulmin some 45 years ago, cannot function as its own “ecclesiastical court.”³² Scientists should not arrogate to themselves the exclusive authority to chart the path forward. If they truly value a “broad societal consensus,”⁶ they should, at a minimum, agree to a moratorium on research on GGE, while societies and their representatives take up the question of what is at stake and where we should, or should not, go. Such an approach has been proposed by leading voices in science and ethics.⁹

But a moratorium is at best only a starting point for deliberation. Long-term democratic governance of human GGE requires wide public buy-in into asking fundamental questions about human life, its value, its integrity, and its meaning. That process of global self-reflection must begin with greater humility on the part of science, coupled with deeper awareness of questions that science cannot even properly pose, let alone claim the right or capacity to answer on its own.

For references and related items please visit the original The CRISPR Journal article.

The CRISPR Journal, published by Mary Ann Liebert, Inc., delivers cutting-edge multidisciplinary peer-reviewed research, advances, and commentary on CRISPR, the extraordinary technology that gives scientists the power to cure disease and sculpt evolution. The above article was first published in the October, 2019 issue of The CRISPR Journal with the title “Democratic Governance of Human Germline Genome Editing“. The views expressed here are those of the authors and are not necessarily those of The CRISPR Journal, Mary Ann Liebert, Inc., publishers, or their affiliates. No endorsement of any entity or technology is implied.