Modeling policy development: examining national governance of stem cell-based embryo models

Advances in in vitro culture conditions have enabled researchers to direct human pluripotent stem cells (hPSCs) to differentiate into sophisticated and increasingly accurate models of in vivo processes [1], including aspects of the developing human embryo [2]. These stem cell-based embryo models (SCB-EMs) have emerged as an important tool for studying embryonic development. For instance, ‘non-integrated' SCB-EMs [3], which lack extraembryonic tissue and other features necessary for embryonic implantation and viability, provide snapshots of human gastrulation [4] and neurulation [5]. Early pregnancy loss [6] often occurs during these stages, which occur too early to be observed in vivo, so in vitro research is critical to improve assisted reproductive technology. Furthermore, in recent years, researchers have created 3D models of mouse [7] and human [8] blastocysts, representing integrated development of the entire embryo, including its extraembryonic membranes. In a recent study, mouse stem cells were aggregated to form a synthetic embryo with sustained development beyond the initiation of organogenesis [9]. A model's fidelity to embryogenesis is vital to ensure knowledge gained about the principles and mechanisms of cellular organization is biologically meaningful and clinically relevant [10]. As such, scholars envision that with sustained in vitro culture, human 'integrated' SCB-EMs [3] may consequently approach benchmarks considered morally relevant on the human embryonic developmental timeline [11].

Despite these advances, knowledge of embryonic development is still hampered by technical, regulatory and ethical limitations, such as the widely adopted 14-day regulatory limit on embryo cultivation (so-called 14-day rule) [12–15], thus preventing the validation of SCB-EMs in weeks 3 and 4 of development. SCB-EMs defy easy associations with common moral reference points and regulatory categories defining human reproductive materials: they are not functionally equivalent to embryos but have become increasingly similar through technical advances in stem cell culture [11]. They also raise concerns over the adequacy of current regulatory frameworks and oversight processes governing their creation and use in research. In this article, the authors will address these concerns as they relate to national regulation, highlighting opportunities to deliberate on appropriate policy and governance of SCB-EM research.

The International Society for Stem Cell Research (ISSCR) Guidelines for Stem Cell Research and Clinical Translation (hereafter Guidelines) have gained legitimacy over time by raising awareness of new ethical challenges, guiding scientific practice and aiding in the interpretation and implementation of national policy. Reflecting evolving science, the 2021 update to the Guidelines revises the recommended levels and types of oversight allocated to different forms of SCB-EM research, suggesting new ways to define and standardize SCB-EMs. However, the Guidelines also suggest relaxing the long-preserved 14-day rule, reflecting optimism about the utility of embryo research and faith in institutional oversight. Given the ISSCR's global influence on ethical conduct, it is timely to assess how the Guidelines might influence policy development and oversight mechanisms for SCB-EM research.

Materials & methods

Previous scholarship has demonstrated how diversity in national policy governing embryo and stem cell research reflects unique social, cultural and political histories [16]. Through juxtaposition with national policies in 11 research-intensive countries (UK, Australia, Israel, Japan, China, Spain, Sweden, Germany, France, USA, Canada), the authors will examine the Guidelines' new categorization of SCB-EM research as well as the ways in which the Guidelines might fill national regulatory gaps and their potential in prompting policy review. The goals of this article are twofold: to articulate national norms that currently govern SCB-EM research by comparing with current best practices (e.g., the Guidelines) and to establish the utility of scheduled policy review so as to respond to scientific developments. A thorough account of the tools available to policymakers (e.g., governments, professional organizations, researchers) can expand imaginations for policy development, facilitating the alignment of SCB-EM governance with societal interests. It also sheds light on areas where further ethical reflection and policy development might be needed in order to foster advancement of the stem cell field.

The authors' study was conducted by employing standard methodology for international comparative policy/law research and analysis, drawing on primary (e.g., laws, statutes, professional guidelines) and secondary (e.g., academic literature) sources identified through standard tools/databases (e.g., Lexis-Nexis, Westlaw, Google Scholar, PubMed). Focus was given to both self-regulation or ‘soft laws’ (e.g., best practices, professional guidelines) and legislative approaches or ‘hard laws' (e.g., laws, statutes, regulations) in the areas of embryo, human biomedical, reproductive and stem cell research. The authors built this methodological approach on previous comparative policy studies and employed similar classification models to categorize policy approaches [17–20]. Following standard legal methodology, the authors did not set a specific time period of inquiry, but rather focused on current national law or policy.

What is in a name?

Central to the SCB-EM discourse is whether (or not) existing research policies for human reproductive materials (e.g., gametes, embryos) and stem cells are appropriate to guide SCB-EM research. Whether embedded in hard or soft laws, concepts describing the nature of an entity (e.g., embryo, SCB-EM, gamete) are important, as they impact the governance pathway and also convey moral or social judgment about the said entity. Definitions are the source of an entity's legal status and of moral justifications for limiting the purposes for which it can be studied, created or used in research. This is why socioethical considerations have acquired substantial importance as a tool for policymaking.

Recent calls for policy review have focused on how definitions taken ad litteram (e.g., the text of the norm) influence the permissibility and oversight of SCB-EM research [21]. Human embryo definitions are useful starting points to help determine which regulations may apply to SCB-EMs in lieu of explicit guidance, but policy definitions vary in scope. In some countries, they refer either to the embryo's potential to become a human individual (e.g., Germany [22], Japan [23]) or to a point in time, such as when they reach a morally relevant developmental stage (Australia [24]). Definitions also establish governance pathways. For example, recently, Australian regulators determined that the country's expansive statutory embryo definition encompassed so-called iBlastoids, an integrated SCB-EM formed from reprogrammed human fibroblasts [25], and thus these models required regulation and oversight from Australia's national embryo research licensing committee [26]. Although Australia's statutory embryo definition was last revised in 2006, before the advent of SCB-EMs, its breadth indicates the policymakers’ intent for research on embryos and embryo-like entities to be subject to similar ethical review processes. However, this situation is unique, as in most national policies it is not evident whether the intent was to also encompass SCB-EMs or similar entities and therefore subject them to extant regulation and oversight.

The ISSCR's approach to SCB-EMs has evolved over time, reflecting both scientific advances and ethical reflection. For instance, the 2016 version of the Guidelines introduced the term ‘embryo-like structures' to guide oversight of “the assembly, differentiation, aggregation, or re-association of cell populations in a manner that models or recapitulates key stages of embryonic development” [27]. This version tethered increased scrutiny to these entities’ capacity “through engineering or self-organization” to manifest “human organismal potential” if maintained in culture. According to the 2016 version, research on embryo-like structures with “human organismal potential”, such as embryo research, should be subject to a “specialized” oversight process that would account for the unique ethical concerns that arise when an in vitro research object itself has been attributed certain moral status. However, although the organismal potential criterion has a sound theoretical basis, it cannot be measured or validated for SCB-EMs because of ethical concerns and gaps in knowledge about embryonic development, thus rendering it a useless regulatory tool. For this reason, the updated 2021 Guidelines [3] replace the nebulous 'embryo-like structures' terminology with a new term – SCB-EM, abandoning the organismal potential criterion and adopting integrated versus non-integrated SCB-EMs as criteria. Integrated SCB-EMs are defined as entities containing embryonic and extraembryonic structures necessary to represent development of the entire embryo. Non-integrated SCB-EMs are categorized by their ability to recapitulate some, but not all, aspects of the peri-implantation embryo.

New categories and applications of existing oversight models: the ISSCR paves the way

One overarching goal of the Guidelines is to provide guidance for appropriate levels of ethical review and oversight of in vitro research involving stem cell-based entities that could be deemed ethically or socially controversial. To this end, the Guidelines changed the categorization of permissible types of research and corresponding oversight recommendations (Figure 1). For integrated SCB-EMs, specialized oversight is prescribed by subjecting them to the same oversight process as in vitro embryo research, including the derivation of human embryonic stem cells (hESCs). As with embryos, the creation and study of SCB-EMs merit cautious and transparent monitoring as well as justification for performing experiments “in a human rather than animal model system” [3]. The Guidelines thus extend a premise reflected in policies in most research-intensive countries, “that research on entities with questionable moral status should proceed with caution” [18]. For non-integrated SCB-EMs, review by existing mandates for laboratory research is recommended, thus conceptually distancing SCB-EMs from the embryos they attempt to replicate, reflecting the fact that SCB-EMs can only emulate embryogenesis through sustained and intentional external influences.

Just as the updated Guidelines expand research frameworks to encompass integrated SCB-EMs, they also address potential incompatibilities with national policy. By replacing a 14-day limit on integrated SCB-EM culture with the suggestion that SCB-EMs be cultivated “for the minimum time necessary to achieve the scientific objective” [3], the Guidelines exempt SCB-EM oversight from bright-line prohibitions common to national embryo research policy (Table 1). The recommendation is grounded in an ethical and practical rationale: SCB-EMs are (currently) incapable of full human development (and thus ethically distinct from human embryos), and a discrete temporal limit may not be appropriate, as they may develop at different rates than human embryos and spend extended time in culture as stem cells [28]. However, opponents of the relaxation of the 14-day rule argue that discrete barriers on embryo research “remind us to maintain a sense of reverence as we try to understand life's mysteries and to promote the flowering of human wellbeing” [29].

Although the ISSCR represents global professional consensus, national embryo and stem cell research policy is heterogeneous. To forecast how the Guidelines might complement or conflict with these policies, it is necessary to consider how existing norms may inform SCB-EM governance. In the countries surveyed, stewardship is often exercised through statutorily established licensing and oversight requirements. Based on the premise that standard oversight procedures may not provide sufficient scrutiny for what could be considered morally contentious research, countries often require additional approval from a specialized deliberative body equipped to critically examine these projects. In the majority of countries surveyed, a central governing body is charged with specialized review of embryo research. However, in countries such as Sweden [30], China [31] and the USA [32], embryo research is reviewed entirely at the regional or institutional level. Most countries surveyed process embryo research proposals through both standard and specialized processes of research oversight (except Sweden, which does not require specialized review of embryo research [33], and Germany, which forbids human embryo research). However, despite sharing common goals, reflected in dual review, considerable heterogeneity exists in the remits attributed to review committees.

The Guidelines further offer guidance about the composition and remit of specialized committees, which is generally followed by national embryo/stem cell oversight committees (typically multidisciplinary, featuring experts in law, ethics and stem cell/embryo research as well as lay public representatives). In terms of competency, the Guidelines recommend that these bodies review, approve and conduct ongoing monitoring by rigorously evaluating the scientific, ethical and legal aspects of research involving both embryos and integrated SCB-EMs [3]. Although central embryo research licensing authorities in the UK and Australia actively monitor research, national policies, such as those in Israel [34], Spain [35], Canada [36] and Japan [37], entrust direct supervision of ongoing research to local research teams and institutions. In these countries, specialized review bodies monitor embryo research from a distance, mainly receiving reports on major protocol changes and project termination.

As the ISSCR has become a transparent, globally respected source of ethical standards and best scientific practices in the field, the impact of the Guidelines cannot be underestimated. Their uptake is exemplified by ethics statement sections in contemporary SCB-EM research articles, which, in addition to describing standard review and approval processes, either claim compliance with [8] or use verbiage from the Guidelines [4]. However, the Guidelines classify embryo and stem cell research in ways that fundamentally differ with some national policies, indicating that their approach to SCB-EMs may also be in conflict with these norms.

Sanctions are common to embryo research governance, but are they useful for SCB-EMs?

Across the globe, policies often buttress restrictions on embryo research with criminal sanctions, reflecting forceful societal views regarding the potential for commodification. The imposition of criminal sanctions for misconduct is commonplace, yet countries vary significantly in their approach to misconduct with regard to in vitro embryo research. In relatively lenient examples, Japan [23] and Sweden [30] levy mild (imprisonment for 1 year or less) sanctions, whereas China and Israel [38] do not criminally punish any specific in vitro research techniques. Other countries impose longer prison sentences for performing prohibited techniques. For instance, France [39], Canada [40] and Germany [22] threaten harsh (imprisonment for 3 years or more) penalties for creating an embryo for research purposes. Punishments for regulatory noncompliance also vary: avoiding embryo research licensure requirements in the UK [41] and Australia [24] can be met with a prison sentence, whereas Spanish law punishes regulatory noncompliance with fines and administrative penalties [35].

Advances in SCB-EM research should prompt policymakers to consider not only whether and to what extent punishments for embryo creation and culture beyond 14 days should apply to SCB-EMs but also the criminalization of such misconduct. The threat of severe punishment may deter SCB-EM researchers from acknowledging the ethical ramifications of their own work, incentivizing them to emphasize the ways in which SCB-EMs are not equivalent to embryos. Although box-checking with reference to decades-old legal definitions may suffice for legal compliance, it may also undermine the more nuanced (and needed) ethical assessments and public debate essential to responsive regulation.

Intent or inertia? Existing mandates & discrepancies between Guidelines & national policies

Although national policies governing embryo and stem cell research vary (Table 2) [16], there is near consensus that this research should only proceed following specialized review, albeit using different oversight approaches. For example, in the UK [42], Australia [43], Israel [34] and Sweden [33], research on anonymized hESC lines may proceed without ethics review because it is deemed to pose minimal risk of harm to participants (i.e., embryo donors who consent to hESC derivation), whereas policies in the US [32] and France [44] require research teams to notify specialized review bodies of new hESC research projects. In China [31], Japan [45], Spain [35], Canada [36] and Germany [46], specialized review committees must verify the ethical provenance of cells prior to approval (Figure 2). By contrast, the Guidelines posit that in vitro hESC research should be exempt from specialized reporting and review requirements, imposing a less stringent standard than that present in most countries surveyed. Furthermore, the Guidelines view the creation of human embryos for research purposes as permissible with appropriate oversight, whereas nearly half of countries surveyed either discourage (Israel [34]) or prohibit (Australia [47], Spain [35], Germany [22], Canada [40]) research embryo creation. Considering that human induced pluripotent stem cell research apparently “avoids the ethical problems specific to embryonic stem cells” [48], most national policies place this type of research outside the purview of specialized review bodies, categorizing projects according to standard protocols for research with human participants. Because stem cells are widely regarded as research artifacts with negligible moral worth [49], their study has been encouraged to answer research questions related to embryogenesis without using human embryos, and this regulatory approach has likely stimulated growth in the field. Thus, the question emerges: how should these criteria be extrapolated to SCB-EMs?

The Guidelines advance a policy of equivalence between human embryos and integrated SCB-EMs by recommending they undergo the same process of specialized review. The ISSCR recognizes that it may not be within the competence or responsibility of laboratory research review bodies to consider the moral, scientific and societal implications of integrated SCB-EMs when evaluating the acceptability of proposed research. However, the Guidelines entrust “existing mandates and committees for laboratory research” [3] with review and monitoring of non-integrated SCB-EMs, implying that their research does not generate similar ethical concerns. They further suggest that non-integrated SCB-EMs should be “reportable but not typically reviewed” by a specialized review process, echoing a common national approach to hESC research governance. Essentially, this categorization allows specialized review bodies to monitor and guide research on non-integrated models “from a distance”, entrusting research teams with primary oversight responsibilities.

Although the Guidelines' proposed oversight pathways mirror existing national processes, discrepancies between the Guidelines and national policies demonstrate different evaluations of the ethical concerns and likely benefits of stem cell research. For example, the suggestion that countries should consider relaxing the widespread 14-day limit on human embryo culture following ‘broad public support’ [3] would overturn a standard upheld in every country surveyed (except Germany, which prohibits embryo research entirely) (Table 1). However, although divergent ethical evaluations are reflected in national embryo research policies (Table 2), with the recent exception of France (discussed in more detail later), most countries have not contemplated how to categorize SCB-EMs. Because SCB-EMs are not currently viable and may be formed without using human reproductive materials, they are likely exempt from the stringent justificatory burdens and technical restrictions on embryo creation and use as imposed by national statutes. Remaining oversight requirements will pertain to the cells that comprise SCB-EMs, with scant normative guidance on how they should be used in vitro.

Furthermore, in contrast to the Guidelines, national policies governing in vitro embryo and stem cell research have scarcely been revisited over the past decade. Periodic review ensures that policy remains relevant. Without it, it is unclear whether the status quo reflects a satisfaction with the ability of national rules to govern scientific developments (e.g., SCB-EMs) or, rather, a lack of political will to reopen contentious societal dialogues. ISSCR's efforts to continuously update best practices demonstrate reaffirmation of their commitment to balance scientific freedom with cautious regulation.

Revisiting embryo & stem cell research governance

Legislative change poses a substantial procedural burden, and legislators are accountable to constituencies with a wide range of views, including communities that might oppose embryo and stem cell research. A lack of periodic policy review may reflect a political strategy so as not to reopen contentious public debate that could adversely affect the direction of a scientific field. Countries that have engaged in policy review may provide a blueprint for countries seeking to incorporate governance of SCB-EMs into embryo research governance frameworks.

France's recent legislative review provides us with an interesting example. France has continuously revised its laws on bioethics in response to evolving ethical standards and scientific developments. It has relaxed its oversight requirements for hESC research, changing the remit of the federally appointed specialized review body, the Biomedicine Agency, for instance. Following a statutorily required “public debate in the form of general statements” and reports from several deliberative bodies evaluating the impact of the 2011 bioethics law [50], the 2021 law on bioethics imposed a statutory 14-day limit on embryo cultivation where there previously was none, removed regulatory barriers to in vitro hESC research and required researchers to declare projects that use hPSCs to model embryos to the Biomedicine Agency. Interestingly, a February 2020 version of the proposed new bill by the French Senate would have allowed in vitro embryos to be developed for up to 21 days for the purpose of studying gastrulation [51], but the National Assembly ultimately chose to mirror the prevailing international consensus. The review process also addressed the potential for litigation over the acceptability of contentious hPSC research which was left entirely to the discretion of the Biomedicine Agency [50]. Based on the understanding that hESCs, like human induced pluripotent stem cells, should not be legally equivalent to embryos but can be used to generate “ethically sensitive cells”, the new law is also the first to threaten criminal sanctions for regulatory noncompliance specific to SCB-EMs. It is worth noting that although France's legal and regulatory framework continues to evolve, statutory prohibitions on human cloning and research embryo creation have remained in place.

Israel's legal framework is less comprehensive than France's – limited to a moratorium on human reproductive cloning and reproduction using genetically modified reproductive cells subject to periodic review [52]. Here the use of legislative review helps clarify legislative intent. With this review process, Israel renewed its decision to eschew legal sanctions and prescriptions, thereby reflecting its trust that researchers and institutions will remain scrupulous in evaluating evolving international standards. It remains to be seen whether this approach can be extrapolated to the governance of SCB-EMs.

Identifying likely sites of policy adaptation and the factors that facilitate or block their activity is crucial to forecasting responses to the Guidelines. Although Israel and France and Australia, which scheduled parliamentary review of a recently passed law approving mitochondrial donation [53], are the only countries surveyed that regularly schedule review of legislation related to embryo research, other national policies also contain built-in avenues for revision. In the UK [41], Australia [24], Spain [35], Germany [46], Sweden [30] and France [44], a combination of federal laws, regulations and ministerial ordinances outline the powers, remits and compositions of bodies that review embryo research (or, in Germany's case, hESC research, as all embryo research is prohibited). Government officials are empowered to issue regulations to further the effects of the overarching legislative framework, but significant modifications require broader input; for example, the 2015 UK regulations that permitted mitochondrial donation in human reproduction required approval from both Houses of Parliament [54]. Japan [23], Israel [52] and Canada [40] also use legislation to prohibit certain research techniques, but ethics oversight is described in guidelines designed by committees within or adjacent to federal ministries of health and/or education. For instance, Japan's permissive legal framework has enabled the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to streamline hESC research ethics review, facilitating the use of hESCs in regenerative medicine [55], without renewing parliamentary deliberation [56]. In the US, federal in vitro embryo research policy is limited to an annually renewed prohibition on funding for embryo research [57], so privately funded embryo research is governed by state laws and, commonly, through institutional adoption of professional guidelines [32]. In China, prohibitions and governance structures stem almost entirely from guidelines [31] developed and “enforced by the ministries with binding effect” [58], without a clear blueprint for revision.

In other countries, Japan for instance, a technocratic approach to policy development reflects legislative intent. The Japanese Act on Regulation of Human Cloning Techniques [23] called for a one-time report 3 years after its passage that would review how human fertilized embryos should be handled “as the emerging potential of human life”. The ensuing report [59] advanced their ethical assessments – that human fertilized embryos should not be created for the purpose of harvesting stem cells, that cloned embryos are “ethically similar” to human fertilized embryos and that primitive streak formation marks the beginning of the human individual – that continue to guide Japanese policy. The MEXT minister organizes ethical review of research according to these basic principles. The Specified Embryo Research Committee, a subcommittee of MEXT staffed by medical professors, law and social science experts and embryologists [60], meets roughly five times annually to review guidelines within its purview, reviewing new articles and technological developments [56]. Through iterative review in tandem with an exhaustive list of conceptual definitions contained in foundational legislation, Japanese ministers actively apply a permissive approach with regard to in vitro embryo research to incorporate evolving science into existing guidelines. Although the MEXT minister has not yet issued specific guidelines for SCB-EMs, the litany of recently updated guidance contains ethical hierarchies and oversight models into which SCB-EMs can fit.

Even in the UK, a paradigmatic example of centralized embryo research governance and public engagement, explicit policies for SCB-EMs have yet to be developed. UK policy attaches special legal and regulatory provisions to the human embryo via statutory definition. Rather than specifying intrinsic qualities or technical origins that qualify an entity as an embryo, the UK statutory definition is intentionally left vague to encourage continuing discourse on the meaning and value of the embryo [61]. In recent years, absent legislative change, the ethical principles that apply to embryo research have been affirmed and expanded upon through updates to the Human Fertilization and Embryology Authority's Code of Practice, which is subject to approval by both Houses of Parliament [41]. However, if, as was asserted by a recent blog post on the Human Fertilization and Embryology Authority's website [62], SCB-EMs are not encompassed by the statutory definition of an embryo, then they are outside the remit of the UK's embryo research regulations and federal oversight. Under current UK policy, laboratory-based research involving hPSCs does not require approval by a research ethics committee [42]. Because of a dearth of guidance regarding the ethical evaluation of SCB-EM research, it is unclear which precedents UK stakeholders should rely on to develop uniform standards for such research.

The advent of human cloning and, later, gene editing, with the ensuing international debates, prompted ad hoc overhauls of policies. The disruptive potential of SCB-EMs has yet to provoke similar revisions. Scheduled legislative review in Israel and France has offered an opportunity to proactively reflect on whether laws function as intended, providing ethical clarity for researchers, regulators and the public, without removing extant restrictions. Although this tool is seemingly available to policymakers in many contexts, it has seldom been used. Will this change if integrated SCB-EMs continue to push ethical boundaries?

Concluding remarks: modeling SCB-EM policy with public engagement?

As with human embryos, popular conceptions of the moral significance and scientific utility of stem cells, distilled through local, national and international dialogue over the past decades, underlie regulations that define what is deemed ethical research. Although the nature of the human embryo has not changed over time, the capacity of researchers to manipulate stem cells to simulate embryogenesis has developed rapidly.

In tandem with new recommendations for SCB-EM oversight, the Guidelines encourage academic stakeholders and policymakers to “lead public conversations touching on the scientific significance as well as the societal and ethical issues raised” by relaxing the 14-day limit on in vitro human embryo culture, which prevents researchers from validating models of embryonic development beyond formation of the primitive streak [13]. The ISSCR challenges society to evaluate whether the knowledge and therapeutic potential of embryo modeling may generate compelling scientific rationale for permitting parallel advances in embryology. By increasing public familiarity with stem cell research governance and the ethical concerns contained therein, such dialogue may facilitate increased citizen engagement with the stem cell field, further promoting its advancement.

Thus far, there has been little movement toward inclusive, bottom-up public engagement surrounding shifts in embryo research policy [63]. In theory, mandatory legislative review can inspire or promote active public participation in policy debates. Comprehensive review provides an opportunity to address and engage a broad range of stakeholder perspectives. However, even in countries that have engaged in public polling and other dialogues around embryo and stem cell research, questions have persisted regarding the framing of ethical dilemmas [64] and the weight afforded to perspectives outside the technocratic world (e.g., beyond scientists, clinicians and ethicists) [65].

The Guidelines outline a useful conception of the appropriate norms for SCB-EM research governance. They reopen the dialogue on aligning critical scientific innovation with socioethical priorities and concerns together with public trust in science. In the past, this dialogue has elicited strong and diverse responses from societal and governmental institutions alike, particularly when dealing with practices involving early human development. As certain SCB-EMs could be considered morally contentious entities, public engagement in the development of policies and practices governing their creation and use is essential to maintain public trust and support. As a tool for interpreting and developing policy, the Guidelines facilitate public engagement, but the Guidelines alone are not sufficient to connect researchers with the communities they serve. To nourish mutually beneficial growth, researchers and regulators familiar with the nuances of research governance should actively seek dialogue with other stakeholder groups (e.g., governance bodies, scientists and policymakers) to ensure that the categorization and oversight of SCB-EMs respect pluralistic societal values.

Future perspective

Although it may yield long-term societal benefits, the short-term political consequences of reopening potentially controversial or socially sensitive dialogues around human embryo and related research might discourage public dialogue and policy action on this topic. The Guidelines' influence on professional conduct may end up driving the development of policy and the creation of specialized governance infrastructure where none previously existed. Whether bounded by hard (e.g., legislation) or soft (e.g., professional best practices) laws, the collective action of stakeholders, in the form of adherence to robust ethical standards and responsiveness to societal concerns and priorities, will ultimately shape the direction of the stem cell field.