L26/O-235 Governing proportionally to developmental probabilities: Potential problems for human embryos and human stem cell-based embryo models (SCBEMs)

Human Reproduction, vol. 41

Abstract

Abstract Study question Under what conditions— if any —can it be legitimate to govern research with (clusters of) human cells proportionally to their developmental probabilities? Summary answer Governing research proportionally to the developmental probabilities of human cells can only be legitimate if such probabilities are grounded in empirical data and normative standards. What is known already The question of whether (clusters of) human cells can develop into human beings remains central to ethical and regulatory debates about their use in research. This is also reflected in recent position statements on the governance of SCBEMs, aggregates of pluripotent stem cells (PSCs) made to resemble early embryos but whose developmental potential remains uncertain. To address this uncertainty, some scholars suggest that governance should treat the developmental potential of SCBEMs as a matter of degree, and regulate their use in research proportionally to that degree— an approach that is reminiscent of interpretations of potentiality as probability in ethics literature. Study design, size, duration This study reviews, analyzes, and discusses approaches that propose governing SCBEMs proportionally to their developmental probabilities— that is, the degree to which they are likely capable of developing into human beings. Participants/materials, setting, methods This study draws on academic and grey literature that discuss governing research with human SCBEMs proportionally to their developmental probabilities. Materials include guidelines, position statements, original research articles, and reviews found through PubMed and bioRxiv. Additional sources are identified through snowballing. Search terms include embryo models, embryo-like structures, developmental potential, potentiality, complexity, guidelines, governance, and associated terms. The study uses conceptual and normative analysis to identify tensions and outstanding questions for legitimacy. Main results and the role of chance The analysis shows that governing human SCBEMs proportionally to their developmental probabilities can be justified in principle, but only if applied with caution. Translating the developmental potential of human cells into measurable probabilities raises technical and normative questions that must first be addressed. A first question concerns how to avoid overlooking individual cases. Governance based on probabilities must rely on statistical data from groups or cohorts that may be presently lacking and inaccurately reflect the developmental capacities of individual (clusters of) human cells. As a result, cases that fall outside statistical averages risk being misclassified or treated unfairly unless governance frameworks can adequately account for such variation. A second question concerns how to prevent regulatory arbitrariness. What counts as a “probable” or “normal” course of development is ultimately dependent on contextual factors such as technological advancements, available resources, and regulatory environments, all of which can change and differ across jurisdictions. Moreover, translating developmental probabilities into discrete normative categories requires drawing epistemic thresholds that become difficult to defend without empirical data or shared normative standards to support them. In this respect, proposals to govern SCBEMs proportionally to their developmental probabilities must confront the problem commonly described as the sorites paradox. Limitations, reasons for caution This study cannot provide empirical data on how likely SCBEMs are to develop further and is constrained by the scope and interpretation of existing literature. The study also cannot address jurisdiction-specific factors in detail or foresee future technological advancements. Accordingly, its conclusions are intended to be analytical rather than prescriptive. Wider implications of the findings These findings suggest that governing SCBEMs proportionally to their probability of developing into human beings can be defensible. However, this requires (more) empirical and normative grounding, thereby highlighting areas in need of further reflection and implications for other fields of research with (clusters of) human cells, including research with embryos. Trial registration number No

Authors 2

1. A Pereira Daoud Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leids University Medical Center, Ethics & Law , Leiden,

2. N. De Graeff Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leids University Medical Center, Ethics & Law , Leiden,