Global governance of human germline genome editing: An advocacy coalition framework analysis

Abstract

This article examines the global governance of human germline genome editing (HGGE) using the Advocacy Coalition Framework (ACF). Based on reports and documents from international organisations, professional groups, and national governments (2015–2025), the study identifies three advocacy coalitions, precautionary, scientific innovation, and moderate, that shape the international regulatory landscape. The findings show that the precautionary coalition, using the 2018 ‘He Jiankui incident’ as an internal shock, has strengthened its position, leading to widespread restrictive national legislation on clinical HGGE. However, the lack of a unified international framework has caused regulatory fragmentation and ongoing tensions among safety, ethics, and innovation. The article concludes that coalition dynamics remain fluid, and future governance will likely change in response to technological advances and further policy shocks. This research improves understanding of coalition-level interactions in the global governance of emerging biotechnologies.

Introduction

Genome editing, one of the fastest-evolving technologies in recent years, aims to modify the genes of living organisms to improve understanding of gene function and support potential therapeutic applications for correcting genetic abnormalities (Xue and Shang, 2022). The technology was initially limited to specific organisms, such as mice or yeast, but later advanced to make human genome editing a realistic possibility. Early biomedical research and applications were limited by the high cost and time required for techniques such as zinc finger nucleases and transcription activator-like effector nucleases. The introduction of the clustered regularly interspaced palindromic repeats (CRISPR/Cas9) gene editing tool in 2012 transformed the field. ¹ CRISPR/Cas9 allows cost-effective and precise DNA modifications, which has led to its widespread use in biomedical research worldwide.

Among the various applications of the CRISPR/Cas9 tool, including somatic (non-heritable) genome editing, significant attention and concern focus on human germline genome editing (HGGE). Germline, or heritable, gene editing could change genes that cause inherited diseases from one or both parents. Genes may be altered to protect against diseases, such as by modifying those involved in heart disease, or to address genetic variants that cause infertility. In addition, HGGE could be used to enhance human characteristics if specific genes linked to desired attributes are identified and modified. The consequences of HGGE could result in permanent and substantial changes to the human gene pool, with the potential for unforeseen individual and societal effects. Social scientists and ethicists have also expressed concerns that altering human genomes may increase inequality and discrimination by enabling wealthy individuals to select traits such as skin colour for their children. The ethical issues related to genome editing go beyond technology and ethics, raising fundamental questions about humanity, as Kant asked: ‘what is it to be human?’ (Ebeling and Gebhard, 2022).

UNESCO has recognised the genome as the common heritage of humankind. Whether and how to alter the human genome is a matter of global significance, requiring international discussion and regulation. Despite extensive debate among various stakeholders, an international agreement on the regulation of HGGE remains elusive (Conley et al., 2020). A pivotal moment in the global regulatory landscape of HGGE technology occurred in 2018, when Chinese scientist He Jiankui announced the birth of twin girls whose CCR5 gene, linked to HIV susceptibility, had been edited using CRISPR/Cas9. This event was the first known case of CRISPR-edited babies in human history. He’s experiment was widely condemned for violating ethical norms and safety protocols, and for disregarding established international guidelines and national legal frameworks. In response, an international group of ethicists and researchers, including some original developers of CRISPR/Cas9, called for a temporary 5-year global moratorium on the clinical use of HGGE to allow time for further investigation into the technology’s safety and for global agreement on acceptable applications (Lander et al., 2019).

While existing literature published after the 2018 incident focuses on the detailed account of the 2018 incident (Greely, 2019), the Chinese responses following the incident (Gang and Peng, 2023; Peng et al., 2022), ethical considerations of the use of HGGE technology (Gostimskaya, 2022), future directions of global governance and regulations on HGGE (Rueda et al., 2025), positions of WHO (Thaldar and Shozi, 2023) and UNESCO (Gaydarska et al., 2024) on HGGE, opinions of scientists and professionals (Cadigan et al., 2024), and public opinion on HGGE (Houtman et al., 2023), there is a lack of detailed analysis on the interactions of actors shaping the current global regulatory landscape of the technology in the aftermath of the incident. This article addresses this gap by applying the Advocacy Coalition Framework (ACF), based in public policy theory, to examine how actors interact to shape international regulation of HGGE. By systematically analysing coalition-level interactions, this study offers a novel contribution to understanding the dynamics underpinning global governance of emerging biotechnologies.

An inductive approach is used to identify coalitions within this policy subsystem by collecting and analysing reports and documents from relevant international organisations (e.g. WHO, UNESCO/IBC, the EU), professional groups (e.g. WMA, ISSCR), and national governments (e.g. the United States and China) related to ‘human germline genome editing’ published between 2015 and 2025. Using the ACF, the article shows the configuration of advocacy coalitions within the international policy subsystem of HGGE technology. It argues that the current global regulatory landscape is shaped by a precautionary coalition, which used the 2018 internal shocks to reinforce its policy core beliefs and secondary aspects. This article contributes to the literature on International Relations (IR) and global governance by examining coalition-level interactions that shape the governance of emerging technologies.

The remaining sections of the article are organised as follows. The first section examines the application of the ACF to understanding global governance of HGGE. The second section describes the development of HGGE technology as a nascent international policy subsystem, detailing the actors, policy core beliefs, secondary aspects within the coalitions, and the strategies used by the precautionary coalition that enabled its dominance. The third section analyses the potential development of coalitions within the nascent HGGE policy subsystem.

Theoretical framework: ACF and its application to HGGE

The main contribution of this article is the application of the ACF to demonstrate how actors interact to shape the current global regulatory landscape of HGGE technology after the 2018 incident. Developed by Sabatier and Jenkins-Smith in the mid-1980s, the ACF is a theoretical framework that explains how individuals collaborate to make collective decisions in public policymaking. The framework highlights the importance of coalitions, which are formed based on shared beliefs within a specific policy subsystem (in this case, HGGE technology). The ACF recognises that significant policy changes often result from external or internal shocks (Cairney, 2020). External shocks may include increased ethical concerns about technology use, while internal shocks may involve failures in international regulatory mechanisms. By considering these factors, the ACF provides a comprehensive perspective for understanding both the policymaking process and the development of governance structures in global technological fields, including HGGE (see Introduction to the Symposium).

Furthermore, integrating insights from IR, especially its emphasis on global interactions and power dynamics, strengthens the empirical use of the ACF at the international level. Although the ACF was originally developed to explain policy change at national and sub-national levels, the parallels between international and national policy dynamics indicate that the ACF is suitable for analysing policymaking processes internationally. An international policy subsystem aims to support cooperation within a specific international regime, while national policy subsystems create policies to enable such cooperation. Therefore, this article uses the international policy subsystem of HGGE technology as its unit of analysis. Actors in this subsystem, similar to those at the national level, are expected to join advocacy coalitions at the transnational level (see Introduction to the Symposium).

Studying the governance of HGGE technology using the ACF adds to empirical research on nascent policy subsystems within ACF scholarship. HGGE technology is a recent example of such a subsystem, having only recently appeared on the public agenda. It has a short history of policy outputs, limited attention in public decision-making, and only recently have advocates for its regulation become active (Stritch, 2015: 438). ACF literature states that actors in nascent policy subsystems often have loosely defined beliefs or fragmented positions, even if they have previously developed policy positions on related issues (Beverwijk et al., 2008). The international policy subsystem for HGGE technology reflects this pattern, which will be discussed in the following sections.

HGGE as a nascent international policy subsystem

Regarding the development of the international policy subsystem for HGGE technology, one of the earliest regulatory efforts took place at a conference in California in January 2015. The conference outcomes, published in Science, included recommendations against introducing heritable changes in human embryonic cells (Baltimore et al., 2015). To guide genetic research involving rDNA technology, the ‘precautionary principle’ first proposed by David Baltimore and Paul Berg at the second Asilomar conference in 1975 was reintroduced at the 2015 conference (Berg et al., 1975). ² In the same year, UNESCO updated its guidance in the 2015 International Bioethics Committee (IBC) report, incorporating advances in genome editing and building on its previous declarations on bioethics and human rights in the human genome from 1997, 2003, and 2005. ³ Further discussions occurred at the first International Summit on Human Genome Editing in December 2015. However, these 2015 initiatives did not result in a unified global regulatory framework for HGGE. One main reason for this lack of cohesive regulation was the absence of a major exogenous shock before 2018 – an event or crisis significant enough to disrupt the existing policy equilibrium. At that time, stakeholders generally viewed the prevailing regulatory approach, which depended on self-regulation and national laws, as sufficient for overseeing the clinical use of HGGE. ⁴ Consequently, there was little motivation for stronger international coordination or legally binding agreements.

Advocacy coalitions in the global governance of HGGE

Within this nascent international policy subsystem of HGGE, three advocacy coalitions have been identified: the precautionary coalition, the scientific innovation coalition, and the moderate coalition. These coalitions differ in their policy core beliefs regarding HGGE technology regulation, with each coalition also displaying nuanced differences in secondary aspects. The composition of each coalition, their policy core beliefs, secondary aspects related to HGGE technology, and the strategies used by the precautionary coalition that led to policy changes after the 2018 incident are described below.

The precautionary coalition

Regarding policy core beliefs, the precautionary coalition considers HGGE technology a significant threat to humanity and supports a complete ban on HGGE for all clinical purposes (therapeutic, reproductive, and human enhancement) for a defined period. However, this ban does not extend to germline editing for research, provided these studies do not involve transferring an embryo to a person’s uterus (Lander et al., 2019). The coalition emphasises that safety and ethical considerations should take precedence over scientific innovation in applying HGGE technology. Members include institutions and individuals who support human rights, medical ethics, and international regulatory frameworks related to HGGE. For instance, the European Group on Ethics in Science and New Technologies recommended a broad prohibition on gene editing of human embryos resulting in genome modification in its 2021 guideline (European Commission, 2021). Similarly, UNESCO/IBC called for a moratorium on HGGE technology to prevent unethical changes to hereditary characteristics, even before the 2018 incident (UNESCO, 2015). On secondary aspects, prominent figures such as Eric Lander, Jennifer Doudna, Emmanuelle Charpentier, Paul Berg, David Baltimore, Feng Zhang, and Henry T Greely have called for a temporary five-year global moratorium on the clinical use of HGGE to allow time for developing international guidelines (Lander et al., 2019). The Alliance for Regenerative Medicine, International Society for Cell & Gene Therapy, and the American Society of Gene & Cell Therapy have proposed an extended international moratorium on all clinical applications of HGGE until 2035 (Barrett et al., 2025). The coalition also supports establishing a unified global treaty or governing body to oversee HGGE technology regulation.

The scientific innovation coalition

In contrast, regarding the policy core beliefs of the scientific innovation coalition, its members argue that a total ban on HGGE is unjustified because of the potential medical benefits for humanity. The coalition specifically supports the therapeutic use of HGGE. It mainly includes institutions, individual scientists, lawyers, health biotech companies, patient organisations, and industry representatives. They highlight the negative economic effects and the risk that strict regulations could hinder scientific and economic competitiveness. For example, the American National Academies of Science, Engineering, and Medicine (NSEM) state in their report Human Genome Editing: Science, Ethics, and Governance that clinical research involving HGGE should be allowed (National Academies of Sciences Engineering, and Medicine, 2017). Individual researchers such as Kerry Lynn Macintosh and Bartha Maria Knoppers argue that a total ban could restrict scientific research and delay life-saving technologies for patients, especially children, in urgent need (Knoppers and Kleiderman, 2019; Macintosh, 2019). On secondary aspects, the coalition opposes an international treaty banning all clinical uses of HGGE and suggests lifting the ban on HGGE for therapeutic purposes.

The moderate coalition

The moderate coalition positions itself between the precautionary and scientific innovation coalitions. Regarding policy core beliefs, it supports balancing safety, ethics, and medical innovation. The coalition recognises the need for comprehensive regulations but is concerned that strict regulatory frameworks may discourage or limit research and clinical applications of HGGE (Kaan et al., 2021). Because biomedical research advances rapidly compared to legal and regulatory developments, members suggest that, for secondary aspects, self-regulation and consensus among scientists can help prevent dangerous developments in areas such as human genetic modification. The WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing supports this approach, highlighting the responsibility of individual researchers and warning against irresponsible practices in HGGE (WHO, 2021).

Policy change dynamics: The 2018 internal shock and its aftermath

The ACF states that a major shock, either internal or external to the subsystem, is a key pathway for policy change. However, an event becomes a shock only through the reactions of actors and coalitions within the policy subsystem. These responses may include actors reconsidering their policy core beliefs or coalition members using the event to strengthen their position within the subsystem (Cairney, 2020). In this context, the precautionary coalition used internal shocks as its main strategy to succeed in the policy debate and maintain dominance within the subsystem.

At this point, it is necessary to explain the 2018 incident and its consequences. In November 2018, Chinese scientist He Jiankui announced on YouTube the birth of twin girls whose HIV receptors, CCR5, had been altered using CRISPR/Cas9. This was the first reported case of CRISPR-edited babies in human history. Two days after his announcement, He told the audience at the Second International Summit on Human Genome Editing at the University of Hong Kong that a third genetically modified baby was expected. The experiment received global criticism because it did not follow appropriate safety procedures or ethical guidelines, and it ignored recommendations from international guidelines and legal frameworks. Chinese national law prohibits the implantation of gene-edited human embryos into humans or their development beyond 14 days. He’s announcement revealed deficiencies in both national laws and international guidelines and regulations in preventing the misuse and abuse of HGGE technology.

The precautionary coalition, led by prominent figures such as Eric Lander, Emmanuelle Charpentier, and Paul Berg, used their scientific and professional influence to call for a temporary five-year global moratorium on all clinical applications of HGGE. Their positions, grounded in their policy core beliefs and secondary aspects, were published in the leading journal Nature in March 2019. In the article, they explained that a ‘global moratorium’ was not a permanent ban. Rather, they proposed creating an international framework in which countries, while maintaining the autonomy to make their own decisions, would voluntarily agree not to approve any HGGE applications unless certain conditions were met (Lander et al., 2019). ⁵

The call led to a significant policy change within the international policy subsystem of HGGE. By 2019, about 30 countries had enacted legislation that directly or indirectly prohibited all clinical uses of HGGE (Lander et al., 2019). A 2020 global survey found that, among 96 countries surveyed, 75 had imposed restrictions on HGGE use in clinical settings. Only five countries allowed exceptions to these prohibitions, and no country explicitly permitted HGGE (Baylis et al., 2020). These results reflect the policy core beliefs and secondary aspects of the precautionary coalition: although there is no unified international framework, many countries voluntarily chose not to approve any clinical use of HGGE.

Advocacy for a unified international framework, as a secondary aspect of the precautionary coalition, has been reflected in several international reports published between 2000 and 2021. In September 2020, the International Commission on the Clinical Use of Germline Genome Editing released ‘Heritable Human Genome Editing’, which recommended creating an international body to oversee scientific and ethical standards for HGGE. In March 2021, the European Group on Ethics in Science and New Technologies published the ‘Opinion on Ethics of Genome Editing’, calling for a global framework to address the cross-border effects of genome editing technologies. In July 2021, the WHO’s ‘Human Genome Editing: A Framework for Governance’ (WHO, 2021) provided recommendations on governance from institutional to global levels. In December 2021, UNESCO’s ‘Report of the International Bioethics Committee on the Principle of Protecting Future Generations’ endorsed the WHO Framework and called for international law to prohibit HGGE. Together, these reports highlight the need for strong global governance mechanisms; however, a single, globally binding framework for HGGE with enforcement mechanisms has not yet been established. These developments, nonetheless, show increasing momentum towards a unified international regulatory framework for HGGE. Therefore, this article argues that the current global regulatory landscape is shaped by the precautionary coalition, which has used the 2018 internal shock to reinforce its policy core beliefs and secondary aspects.

Discussion: Current landscape and future prospects for global governance of HGGE

This article’s analysis shows that global governance of HGGE is currently dominated by the precautionary coalition, which used the 2018 internal shock to strengthen its policy core beliefs and secondary aspects. Following the He Jiankui incident, many countries adopted restrictive national legislation, reflecting a broad consensus that prioritises safety and ethical concerns over rapid scientific progress. As a result, clinical applications of HGGE are mostly prohibited worldwide, while basic research is allowed only under strict regulatory supervision. The implications of this configuration are considerable. First, the lack of a unified, binding international framework has resulted in a patchwork of national regulations, with most countries voluntarily following the precautionary coalition’s position. This fragmentation may hinder cross-border scientific collaboration and create regulatory loopholes, which could undermine efforts to prevent unethical or unsafe uses of HGGE. Second, the current dominance of the precautionary coalition may limit innovation. The scientific innovation coalition argues that overly restrictive policies could delay the development of life-saving therapies and reduce global scientific competitiveness.

Looking ahead, coalition dynamics within this nascent policy subsystem are unstable and likely to change as the subsystem develops (Sabatier and Brasher, 1993). For example, improvements in genome editing precision and safety could lead members of the precautionary coalition to reconsider their position and possibly join the scientific innovation coalition. Alternatively, the precautionary coalition’s position may become stronger in response to future internal shocks similar to the He Jiankui incident. Besides changes in membership within existing coalitions, new coalitions with distinct policy core beliefs may also form. One possible coalition is the national regulatory coalition, which would support regulatory efforts mainly at the national rather than international level. The World Medical Association and the International Society for Stem Cell Research could be part of this coalition, as both have highlighted the importance of national regulatory frameworks in their 2020 Statement (WMA, 2020) and 2021 Guidelines (ISSCR, 2021). Future developments within the policy subsystem will shape the formation and influence of these coalitions.

In summary, the current global regulatory landscape of HGGE is shaped by the interaction of advocacy coalitions, with the precautionary coalition currently dominant. As the policy subsystem develops, ongoing dialogue among stakeholders and adaptive governance mechanisms will be essential to balance the competing priorities of safety, ethics, and scientific progress. These dynamics highlight the need for continued monitoring and adaptive governance as the field develops.

Conclusion

In conclusion, the ACF supports IR studies in understanding the global governance of HGGE technology. Three coalitions with distinct policy core beliefs exist in the subsystem: the precautionary coalition, which supports a complete ban; the scientific innovation coalition, which opposes a complete ban; and the moderate coalition, which calls for self-regulation by scientists. The 2018 event significantly strengthened the precautionary coalition’s position, resulting in a major policy change within the subsystem. At present, the clinical application of HGGE is prohibited worldwide, while basic research is allowed but subject to strict regulations.

Ongoing technological and governance developments will continue to influence the evolution of this policy subsystem.