The impact of the three major human genome editing reports on the governance landscape

Abstract

In 2018, the scientific community was shocked by news that a rogue scientist’s genome editing of embryos had resulted in the birth of twin girls in China. Three major international reports offering ethical and governance guidance on human genome editing (HGE) (by the National Academies’ and Royal Society’s International Commission, the WHO, and the European Group on Ethics) followed in 2020 and 2021. This paper examines whether and how the publication of these reports has had any discernible impact on the global governance landscape. We compare global laws and regulations before and after the reports’ issuance as well as the evolution of softer forms of governance, including funding standards and scientific norms. Data includes the three reports and interviews with people who participated in drafting them. Our analysis indicates that it is impossible to draw direct causal connections between the reports and subsequent legal reforms. In fact, very little has changed in the global legal landscape since they were issued. However, the reports, as well as the broader governance environment (both hard and soft law) reflect a widely shared set of scientific and moral values that have been evolving over the last decade. In that sense, the reports have played an important role in refining, ratifying, and publicizing those values. The weight accorded to the reports will make it near impossible for the scientific community and its governmental overseers to repudiate those values and will help to ensure that future scientific developments will be evaluated in their light.

Introduction

The years 2020-21 saw the publication of three major international reports on the ethics and governance of human genome editing (HGE): the International Commission on the Clinical Use of Human Germline Genome Editing (IC), Heritable Human Gene Editing (HHGE) (NAM 2020); the World Health Organization Expert Advisory Committee (WHO), Framework for Governance and Recommendations (WHO 2021), and the European Group on Ethics in Science and New Technologies (EGE), Opinion on Ethics of Genome Editing (European Commission 2021). The triggering event for this surge in governance-related activity occurred at the Second International Summit on Human Gene Editing (HGE) in Hong Kong on November 27–29, 2018, which our team attended. The summit was sponsored by The Academy of Sciences of Hong Kong, the British Royal Society, and the U.S. National Academies of Sciences, Engineering, and Medicine. Topics included social and philosophical reflections on manipulating genetic variation, governmental actions regarding human genome editing, basic and translational research, and human embryo editing. During a presentation on the last topic, Professor He Jiankui of China’s Southern University of Science and Technology announced the birth of twins whose genomes had been edited as embryos. He’s presentation, “Developing a CCR5-targeted Gene Editing Strategy for Embryos Using CRISPR/Cas-9,” set off a critical firestorm (Saey 2019; Stein et al. 2018; Regalado 2019). In 2019, a Chinese court found He and his collaborators guilty of forging ethical review documents and misleading doctors into implanting gene-edited embryos into two women, in deliberate violation of national research and medical ethical regulations. He was sentenced to three years in prison.

The important longer-term implications of this event include the three major international reports and the extensive research, consultations, and deliberations that preceded them. In light of the vast amount of time, money, and expertise that they consumed, and the exceptional publicity that they generated, we ask the question: What difference have these reports made? More specifically, have they inspired governance reforms at the international or national levels? If not, have they contributed to the governance and practice of HGE in other important ways? We have conducted a multi-year, multidisciplinary study of the emerging governance of HGE, with interviews of significant stakeholders, including many of those who wrote the three reports, analysis of the reports themselves, and participant observation of relevant conferences. We find that the reports have had little direct impact on laws and regulations, but significant impact on the norm-setting activities of a broad network of other stakeholders. The overall result has been the definition and reinforcement of a set of shared norms about HGE that may be of greater practical importance than laws and regulations.

It is important at the outset to define governance and distinguish it from government. Governance includes binding treaties, laws, regulations, and decisions issued and enforced by governments, which are sometimes called hard law. But governance is a far broader concept. As stated in the WHO’s A Framework for Governance, which is a focus of this paper:

[Governance] includes but is not limited to government, in the sense of formal, “hard” legislation or regulation that can be enforced by government authorities. But scientific governance also takes “soft” forms, like professional rules, norms, and practices; aspirational standard-setting by expert bodies and organizations; rules and practices of funding agencies; principles and practices of journal editors; and, in the standards followed by universities in hiring, promotion, and tenure. Some forms of governance are imposed from the top down, whereas others emerge from everyday practice (10).

These two categories of governance are often described as hard law and soft law.

In our team’s prior work, we interviewed 92 international scientists and governance professionals and assessed their views on the permissibility and appropriate governance of HHGE. We found widely divergent views on both topics, concluding that “the overall lack of consensus among our respondents … highlights the conflicting value systems that complicate the development of governance mechanisms” (Cadigan et al. 2024).

In this paper we examine each of three reports individually, reporting the views expressed in interviews by those who drafted it and analyzing its text. We then present a summary of hard law developments in the countries and regions that are the leaders in HGE research. We discuss our findings on the cumulative effects of the reports on both government and governance more broadly, followed by a discussion of what those findings say about the value of the reports themselves and the report-drafting process.

The state of governance before the reports

In 2020, Baylis and colleagues published a comprehensive survey of global policy concerning heritable human genome editing and germline genome editing Baylis et al. 2020). They defined the former as “the transfer of genetically modified embryos to a uterus to initiate a pregnancy that would result in the birth of a child with a modified genome.” The latter uses similar methods, but any resulting genetically modified embryos are used for research, not reproduction. (p. 367) The authors considered 125 “policy documents” from 96 countries, including domestic laws, regulations, and ministerial statements that have the force of law; as well as the 1999 (and thus pre-genome editing) Oviedo Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine, which is legally binding in the 29 European countries that have ratified it. They concluded that 75 of the 96 countries prohibited heritable human genome editing (for reproduction) either absolutely (70) or with exceptions (5), with none clearly permitting it, while 23 of the 96 prohibited germline genome editing (not for reproduction) either absolutely (19) or with exceptions (4), with 11 clearly permitting it. The authors’ described “the extent of this policy concurrence [as] striking,” especially against the background of the vague findings of prior surveys, and argued that it should inform future deliberations by “those proposing international recommendations, guidelines, or agreements” (pp. 374 − 75). We next consider the three reports in the context of this legal background.

The three reports

International commission on the clinical use of human germline genome editing (NAM 2020)

The IC report, commissioned and sponsored by the U.S. National Academy of Medicine and National Academy of Sciences and the UK Royal Society, was first among the three. According to its Foreword, the IC report was commissioned “at a time when the reported birth of the ‘CRISPR babies’ in China was fresh in many minds” (ix). The IC’s mandate was limited to HHGE. The IC’s charge from its sponsors was not to evaluate the desirability of pursuing HHGE, and its report consequently “does not make judgments about whether any clinical uses of a safe and effective HHGE methodology, if established by preclinical research, should at some point be permitted” (2). Rather, the IC “was specifically tasked with defining a responsible pathway for clinical use of HHGE, should a decision be made by any nation to permit its use” (xi). Governance was not part of the original charge. The word “governance” does not appear in the IC’s Statement of Task (30), but the topic became an entire chapter in the report. As noted below, the report acknowledges—and preemptively defers to—the work of the WHO, which had begun at the end of 2018 (ix).

Interviews of IC members

The seven members of the IC whom we interviewed told the story of how governance emerged as a major focus of their work. All seven emphasized that governance was outside of the original mandate of the IC, stating, for example:

“Our brief was to look at clinical implementation.”

“The commission was not tasked with the governance. We did make some recommendations on governance [at the end], but that was not the main focus of the commission.”

Six of the seven interviewees made direct comparisons with the WHO Framework, acknowledging both the Framework’s broader scope in addressing somatic and heritable genome editing and the WHO’s relatively greater position of global authority. For example:

“The WHO … has a little bit more authority. Although, it still really cannot enforce many things, but at least it’s an organization that has a more broad impact. And they have published reports which are more broad.”

“So, that question [governance] was supposed to be the one that the WHO commission was to opine on. But we were supposed to … focus on what I would call the translational pathway.”

However, despite their limited mandate, several interviewees expressed a belief that governance could not be completely absent from the IC report, including these comments:

“I said, well, I understand that you don’t want there to be a conversation about the ethics of whether or not, but it’s like saying there’s not ethics issues in clinical research. Of course there is and are. So, they relented about that.”

“We had a whole section on governance … that wasn’t specifically what we were asked to do. We realized that was more the purview of the WHO document. But we felt that we needed to say something, that we couldn’t be silent on it.”

Some participants identified this as an opportunity for collaboration with the WHO, while others identified this as a source of conflict with the WHO; for example:

“We also had a couple of meetings with the WHO as we went along so that we could keep them informed of our thinking and they could tell us a little bit about their thinking, because we didn’t want two reports that said something completely different.”

“Some of the people on the WHO commission thought that we had overstepped our charge and waded into theirs in an unhealthy way. So, even though we felt really constrained, they thought we had not been sufficiently constrained.”

Nonetheless, many participants did share opinions on the role of governments and other authorities in governance.

“I think in the end, it [governance] will have to fall on the individual governments, and they have to be responsible.”

“There can be some impact from professional organizations saying, you know, we don’t condone it [HHGE], we think it’s not ready.”

“Sometimes these kinds of guidelines, rather like the commission’s report, are most useful in those countries that lack regulation.”

“We recommended to have a scientific board, right. You have to have really good people to help you decide. But the final say, it has to be the (local) government.”

The IC report

The relevant chapter of the IC’s report on HHGE is Chap. 5, Governance. As suggested by the interviewees quoted above, governance was outside the original scope of the report and this final chapter was added as an apparent concession to the commission members who insisted on some discussion of the topic. In any event, the chapter makes clear that the IC’s intent is to state governance principles, leaving the specific mechanisms to other authorities:

The chapter does not delve into detail on how national and international governance systems for HHGE would ultimately be implemented by countries and by the international community—ongoing dialogues including the work of the WHO’s Expert Advisory Committee are exploring this area in greater depth. However, this chapter concludes with recommendations for core components of these efforts (145).

In terms of general principles, any such governance system “would need to include the ability to oversee all stages of the translational pathway” (145). Before clinical use in any country, there should be “public engagement on whether it would be acceptable to use HHGE in that country” (146). Any country allowing HHGE would need “regulatory mechanisms to oversee use of HHGE and impose sanctions where appropriate” (153).

While it stops short of laying out specific legal reforms, the IC’s report does delve into significant detail about the principles that such regulatory mechanisms should embody, at both national and international levels. At the national level, it recommends that regulatory systems address a number of issues, including:

1. “[G]iving clear and unambiguous direction to researchers and clinicians”;

2. “ensuring that researchers and clinicians adhere to norms of responsible science”;

3. “providing transparency to the world community”; and.

4. “being responsive to international scientific consensus regarding the current state of HHGE technologies” (154 − 56).

At the international level, it recommends that:

any proposed mechanism for international governance of HHGE will need to provide at least three functions:

1. “[a]n international scientific advisory panel”;

2. “[a]n international body for evaluating and making recommendations on crossing major thresholds associated with the clinical use of HHGE”; and.

3. “[a]n international mechanism by which individuals or organizations in one country can bring forward technical or ethical concerns arising from HHGE work conducted in their own country or in another country” (157).

WHO (WHO 2021)

In contrast to the IC report, the two WHO reports—the brief Human Genome Editing: Recommendations (Recommendations) and the much longer Human Genome Editing: A Framework for Governance (Framework)—are both concerned entirely with governance. The drafting committee’s charge was “to advise and make recommendations on appropriate institutional, national, regional and global governance mechanisms for human genome editing” (Framework: ix). The committee worked for two years. In pursuit of its governance mandate, it reviewed literature; consulted widely with experts, other interested individuals, international organizations, and civil society groups; conducted online consultations; and circulated drafts (Framework: ix-x).

WHO interviews

The six members of the committee whom we interviewed reflected on both their charge and its challenges. Many participants shared opinions on the usefulness of the WHO Framework for governments and other stakeholders; for example:

“The idea was that WHO was going to … help governments organize themselves to regulate however they wish.”

“We … give those people charged with developing regulations or a governance framework in their countries enough food for thought to test their framework against … use-case scenarios.”

“The hope was to empower civil society organizations … that they can do important work, and that government could do important work by at least understanding that there are multiple ways of governing.”

“We think of the whole governance framework as about providing and listing tools. The same thing with the scenarios, it ’s about tools … And about the ethics and values principles, they ’re thought of as tools.”

However, some participants expressed reservations, ranging from pragmatism to pessimism, about the impact of the WHO Framework, including:

“There is a real pragmatism to this: ‘Look, there are things that we might want, but the best we can actually hope for is themes under the banner of ‘moral suasion.”

“It will probably will not work … they only work to the extent that local authorities are interested in enforcing anything.”

WHO reports

The Recommendations are succinct, addressing such topics as leadership by the WHO, international collaboration, and ethical values and principles. Each Recommendation is accompanied by statements of Purpose, Relevant Values and Principles, Actions (very general processes), and Practical Considerations. The committee summarizes its overall approach as follows:

“Effective governance and oversight of human genome editing will require laws, policies and practices at institutional, national, regional and international levels across the world. While the Committee’s governance framework details a number of approaches and resources that might be helpful, the practical implementation of governance for human genome editing will require working with many different groups, peoples and institutions who will each bring their experiences, strengths and resources to this collective effort. WHO can, and should, play a leadership role in providing technical, legal, ethical and regulatory expertise and helping to sustain efforts to regulate or govern human genome editing in all its Member States” (Recommendations: 4).

The title of the Framework is apt: it is indeed a framework, in the sense of a structured outline of things to consider rather than a set of specific solutions. Throughout—and explicitly in Part 3 (Governance of Human Genome Editing)—it sets out values, principles and processes rather than specific legal recommendations. Part 4 (Tools, Institutions and Processes for Governance of Human Genome Editing) covers the entire range of governance processes that are available, from formal laws and regulations to the whole range of soft law options (it uses the term) that we discuss throughout this paper.

Part 5 (Scenarios) lays out a set of hypothetical scenarios. Each scenario explores a different aspect of good governance. It begins with a short description of a possible future event; the examples include clinical trials for sickle-cell and Huntington diseases, unscrupulous entrepreneurs and clinics offering HGE for various purposes, and the use of HGE for enhancing athletic ability. For each case, the report identifies relevant values, principles and questions to be considered when developing oversight measures (from Part 3) and potentially useful tools, institutions and processes of governance (from Part 4). The analyses are not intended to be prescriptive:

"These scenarios are intended to show how the various elements discussed in this governance framework come together in practice. They illustrate the types of practical challenges that might be encountered in the future when implementing good governance for human genome editing research. Many of the issues raised in the scenarios are cross-cutting; that is they could also apply to other scenarios" (Framework: 40).

Notwithstanding the IC’s express deference to the WHO process, it is striking how similar the WHO’s values, principles, and possible governance approaches are to those described in the IC report. The obvious inference is that these two groups of high-profile, well-connected experts, some of whom consulted with each other, were expressing pre-existing and widely accepted norms and understandings.

EGE (European commission 2021)

The EGE is a fundamentally different group in that its target audience is the European Commission, the executive branch of the European Union, and not the world at large. In preparing its report, the EGE drew on “an already wide range of opinions and statements of national ethics councils, scientific academies, professional societies and other organisations, as well as on scientific literature”; they organized an international roundtable in Brussels; and “liaised with the WHO Expert Advisory Committee” (p 11).

Although its audience may be narrower than the other two groups, the EGE—at least as stated in the Introduction to its report—perceived its task to be broad. First, it takes on all aspects of genome editing, both somatic and germline, in humans, animals, and plants. While the Introduction disclaims “a comprehensive ethical analysis across all domains,” it does promise to highlight “key ethical concerns because they are deemed particularly ethically problematic, they are new and distinctive to this technology, or they have particular salience at the EU level” (p 11). Moreover, the Introduction also states the EGE’s intent “to examine how specifically the EU can and should shape governance and policies for genome editing.” As will be seen below, this latter objective is somewhat at odds with comments made by EGE members in interviews, as well as the body of the report.

The Introduction also makes a fascinating comment about the relationship between language and reality: “It is well established that the language that we use to frame reality does not merely represent reality but also shape it” (p 15). As we will discuss, the three reports’ capacity both to represent and shape reality is at the core of their influence and value.

EGE interviews

Interviewees from EGE were explicit in their audience being the European Commission. Therefore, EGE interviewees did not mention the role of national governments in governance. As one said:

“Our goal is to advise or to give recommendations to the European Commission, [on] what they can do in policy making, research funding, observatories, platforms for participatory discussion.”

In contrast to the IC, interviewees from EGE included ethics in the scope of their mandate:

“Our scope is much broader and mainly about ethics. As I read some of these [other] reports, they say, well, let’s first clarify the scientific issues, then we’ll think about ethics.”

However, similar to the IC, interviewees from EGE also mentioned the WHO as the ultimate authority to address questions of global governance:

“We were not very specific about [governance] because we said that’s the issue of the WHO. We just wanted to underline that we find global governance a very important issue.”

There is an obvious tension between this disclaimer of specific interest in governance and the role of ethics in governance as we, following a broad consensus, have defined it. In its softer but still significant forms, governance includes ethical and other norms. The fact that EGE members drew a boundary between ethics and governance is thus striking.

EGE opinion

Consistent with the interviews just quoted, the EGE report is modest in making specific governance recommendations. In a brief (four paragraphs) section entitled “Governance and ‘who should decide’” (p 20–21), the overarching observation is “the lack of robust structures of global governance.” Looking forward, the report notes that even though human-related uses “require a global governance approach... it is difficult to take regulatory measures of worldwide scope that are efficient and respected by all States.” The section concludes with two paragraphs that state broad principles for governance and posit three key questions: “How are decisions to be made? Who decides and who ought to decide?”

The EGE’s more specific recommendations are fundamentally similar to those of the IC and WHO. Echoing the other two reports, the EGE recommends that the Commission:

• “Foster broad and inclusive societal deliberation on genome editing” (p 84);

• Seek “a general agreement resulting from informed global dialogue” before the application of genome editing” (p 84);

• “Develop international guidelines and strengthen national, regional and global governance tools,” working in concert with other international bodies (p 85);

• Create a “European Platform” for HGE information-sharing... (p 86);

• “Protect social justice, diversity and equality” (p 87); and

• “[P]roactively safeguard against enhancement or deenhancement of traits and to ensure that investments in research on germline genome editing have the purpose of protecting health” (p 87).

Status of governance law in the six major genomics editing research jurisdictions

The status of governance in the six jurisdictions that dominate genomics editing research (United States, Canada, European Union, United Kingdom, China, and Japan) (the “Big Six”) is summarized here and presented in more detail in Fig. 1.

Fig. 1.

Gene editing regulation in the “Big Six”

The Big Six jurisdictions are shown with the level of regulation for therapeutic and germline editing programs according to the Global Gene Editing Regulation Tracker (GGERT). The GGERT is a public resource compiled by the Genetic Literacy Project that monitors the status of regulation for gene editing methods worldwide. The regulation of gene editing methods in humans is subdivided as either therapeutic (methods of editing adult human cells to treat disease, including gene therapy and stem cell therapy) or germline (methods of editing human embryos or germ cells that alters heritable genetic material). Within each category, countries are rated as having no unique regulations for gene editing beyond standard pharmaceutical regulations, being lightly regulated with minimal restrictions or requirements (“light”), having proposed regulation that would not impose unique regulations beyond that which is required for pharmaceuticals, having regulations in development, being highly regulated (“strict”), mostly prohibited, limited for research purposes with no clear regulations, or prohibited (“prohibited”). Germline editing for Canada is the strictest of the Big Six, where germline editing is prohibited even for research purposes. In the U.S., germline editing research is prohibited with federal funds.

In the years since the reports, there have been no international treaties or major changes in hard law at the national or international level within the Big Six. The most significant change occurred in China in the form of ethical review measures promulgated in 2024 that combine hard and soft law elements. The Measures for the Ethical Review of Life Science and Medical Research Involving Humans expanded existing ethical review of gene editing research to include a broader range of activities (e.g., human cells, tissues, organs, embryos, and fetuses), to ensure that studies undergo rigorous ethical scrutiny, and to require enhanced informed consent for clinical studies. Reported reactions in China are mixed, with specific concerns that the Measures are limited to publicly funded research (Interesse 2024).

Governance in the Big Six varies by jurisdiction and may (or may not) distinguish between somatic therapeutic gene editing and heritable germline editing (Fig. 1). In all of the jurisdictions, gene editing is permitted for therapeutic purposes with varying levels of hard and soft governance. Therapeutic gene editing remains strictly regulated in the U.S., Canada, the U.K., and the EU, while it is lightly regulated in China and Japan. Germline gene editing is prohibited in Canada, the U.S., and the EU, is strictly regulated in the U.K. and China, and is lightly regulated in Japan. The U.S., for example, prohibits germline gene editing using federal funds and also uses hard governance to require somatic gene editing therapies to undergo traditional FDA approval. Recently, the FDA released soft governance guidelines (“Nonbinding Recommendations”) to better inform the development process for gene editing therapies (FDA 2024). By contrast, lighter regulations in Japan permit gene therapy programs to be approved through an expedited showing of safety and clinical efficacy (Teijin 2023). Interestingly, violations of regulations related to germline editing are not punishable by law in Japan (Aikyo et al. 2023).

Discussion

Very little has changed in the global legal and regulatory landscape since the reports were issued. Consequently, it is impossible to draw any direct causal connections between the reports and any significant subsequent government reforms. Specifically, there have been no new HGE-specific treaties or international or national laws or regulations, with the exception of China. Instead, the application of existing legal and regulatory frameworks at the national and EU levels is evolving to adapt to the special demands of somatic HGE, as illustrated by drug and therapy approvals and the allocation of government funding. In addition, non-governmental standard-setting—the realm of soft law—has also evolved quickly.

There are several examples of such regulatory evolution. In late 2023 the USFDA approved Casgevy^®, a sickle cell gene therapy that uses CRISPR gene editing technology (FDA 2023). A month later, the FDA issued final guidance intended to assist sponsors in seeking approval for gene therapy products that incorporate somatic HGE; the guidance supports the use of an accelerated approval pathway (FDA 2024; Eglovich 2024). Parallel developments are underway at the European Medicines Authority, which has also approved Casgevy^® and is developing general standards (Tavridou et al. 2024). In the funding realm, the WHO Framework (86) describes the IC guidelines as “a powerful influence on the legal conditions later developed for federal funding of this research in the United States.” In the soft law category, the Framework (86) provides a list of professional societies and organizations that have developed guidelines on human genome editing, including the American Society of Human Genetics, the American Society for Reproductive Medicine, the European Society of Human Genetics, the European Society of Human Reproduction and Embryology, the International Society for Stem Cell Research, and the Japan Society of Human Genetics.

With respect to HHGE, the near-universal prohibition for reproductive purposes reported by Baylis and colleagues in 2020 (Baylis et al. 2020) remains in place. In March2023, the U.S. National Academies, the U.K. Royal Society, the U.K. Academy of Medical Sciences, and the World Academy of Sciences conducted a Third International Summit on Human Genome Editing, which our team attended and observed. The Summit considered both somatic genome editing and HHGE. In its concluding statement, the Organising Committee reported that “numerous clinical trials using somatic human genome editing are in progress or soon to be initiated, with preliminary but encouraging results that point to future therapies,” and urged attention to the problem of equitable access (Royal Society 2023). In a brief paragraph on HHGE, the Committee opined that it “should not be used unless, at a minimum, it meets reasonable standards for safety and efficacy, is legally sanctioned, and has been developed and tested under a system of rigorous oversight that is subject to responsible governance”—conditions that had not been met (Royal Society 2023). Reflecting back on the 2020 IC report’s goal of designing a responsible pathway for HHGE, the sponsors of that report seem to have concluded that the implementation of that pathway remained, at most, a remote future possibility.

A further question is why the three reports have not led to any specific legal reforms. One possibility is that such reforms have been unnecessary: existing legal and regulatory regimes, reinforced by soft law, have been able to adapt to the evolving realities of somatic gene editing, while the prohibitions identified by Baylis and colleagues have adequately constrained HHGE. The regulatory developments discussed above suggest that existing regimes are in fact managing somatic genome editing reasonably well, while HHGE remains controlled, at least on a formal legal level, acknowledging that there is little that can be done on a practical level to control rogue actors and states that tolerate or promote genome-editing tourism.

A second possibility is that the reports—especially the IC’s—took the wrong approach. That is, rather than focusing on scientific pathways and governance toolkits, they should have been more normative and prescriptive, taking clear positions on what uses of genome editing are scientifically and ethically justified, and proposing more specific legal frameworks to advance those positions. The reports themselves, consistent with what we were told by their authors, defended their more modest approaches by arguing that they accurately present the current, albeit transitory state of the scientific evidence and that ethical justification is a culturally relative judgment. Moreover, getting a wide range of countries to give binding effect to any treaty, let alone a controversial one, is a near-impossible task, and it would be at least as difficult to propose specific laws that might be widely adopted at the national level.

In our view, the more modest approach that the three reports took was appropriate, given the inherent limitations that they and their authors recognized. We further believe that their limited direct legal impact has been largely a function of the relative adequacy of the existing legal regime, despite its fractured nature.

Notwithstanding the limited legal impact of the reports, do developments such as these in the broader realm of governance mean that they have been a success? Our answer is an emphatic yes. Recall the stated purposes of all three reports: to promote principles, values, and processes. None offers specific legal prescriptions. Even the most detailed of the three, the WHO’s Framework for Governance, provides a menu of hard and soft options across the governance spectrum. Although not leading to specific hard law changes, the reports have played an important role in publicizing, refining, and ratifying those principles, values, and processes that they were intended to promote. Moreover, the weight accorded to the reports will make it all but impossible for the scientific community and its governmental overseers to repudiate or backtrack from the principles and values they articulate. It will also help to ensure that future scientific developments will be evaluated in their light. The reports and the current governance landscape reflect a widely shared set of scientific and moral values that have been evolving for some time, and the reports will continue to play a vital role in ensuring that the evolution continues.

Conclusion

The reports do not propose specific laws or regulations. Rather, they advocate for values, principles, and processes in developing and applying specific governance mechanisms; and analyze the whole range of available governance mechanisms, both hard and soft, from governmental legal action to funding and editorial standards to norms of responsible science, including adherence to bioethics principles, and transparency in research. In doing so, the reports accomplish two significant things: first, they both reflect and reinforce the values they advocate for in a uniquely public and authoritative way. Second, they make a conclusive case that effective governance of HGE must involve the full range of hard and soft governance options and focus detailed attention on those options. Regardless of whether hard law changes come about, these accomplishments more than justify the time, effort, and expense that went into the three reports.

Author contributions

J.C., G.H., and K.K. contributed to the design and implementation of the research; all authors contributed to the analysis of the results and the writing of the manuscript.

Funding

This work is funded by the National Institutes of Health, National Human Genome Research Institute, 1 R01 HG010661-01A1.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethical approval

This research was approved by the UNC Institutional Review Board, study # 20-1330.

Consent to participate

Verbal informed consent was obtained prior to the interview.

Consent to publish

Participants have consented to submissions to journals.

Competing interests

The authors declare no competing interests.