Embryo models and governance – the honest measurement of elastic

Professor Søren Holm, writing in BioNews (see BioNews 1253), challenges proposals for the governance of research involving stem-cell-based embryo models (SCBEMs). These proposals are set out in the new Code of Practice for the Generation and Use of Human Stem Cell-Based Embryo Models (the SCBEM Code of Practice).

The Code endorses the recommendation, in the latest Guidelines for Stem Cell Research and Clinical Translation published by the International Society for Stem Cell Research, that research involving certain SCBEMs should be subject to approval by an oversight committee.

Professor Holm compares the guidance provided to the proposed SCBEM Oversight Committee with the guidance provided to UK research ethics committees (RECs) by the Health Research Authority (HRA). Whereas the HRA guidance includes standard operating procedures, and a framework of questions to which RECs must turn their attention when considering a research proposal, Professor Holm finds the guidance provided to the SCBEM Oversight Committee by the SCBEM Code of Practice distinctly thin.

The Code, says Professor Holm, 'is not clear what a researcher should take into account, or how the Oversight Committee should judge whether relevant ethical considerations have been taken into account, or whether a research project is ethically (as distinct from scientifically) problematic'. The Code also 'provides no clear standards for what might make a research project unethical, except in relation to the implantation of SCBEMs'.

This paucity of ethical standards, Professor Holm contends, undermines the Oversight Committee, which 'despite being eventually established according to the best principles of impartial appointment, and despite therefore containing only members of the highest integrity, will not be able to provide ethically robust oversight, since the Code does not provide sufficient guidance on what ethically robust oversight is, substantively'.

Professor Holm concludes: 'As we say in Danish, "it takes honesty to sell elastic by the metre". But even honesty is not enough, if elastic is being sold by the metre in the absence of a ruler'.

Professor Holm's allusion to regulating the sale of elastic highlights a challenge at the heart of science regulation that is acute in the governance of research involving SCBEMs, and is largely absent in research on human subjects (which, as Professor Holm emphasises, falls under the Declaration of Helsinki). Unsurprisingly, the SCBEM Oversight Committee is not simply a REC.

The empirical nature of research enables us to characterise entities falling within the scope of a regulation, particularly its defined terms, in ever greater detail. Equally, it enables us to distinguish subject matter that is out of scope.

To give a relevant example, if a SCBEM were empirically indistinguishable from a live human embryo it would be regulated as an 'embryo' under the Human Fertilisation and Embryology Act.

However, the much greater number of possible non-embryo SCBEMs not only have poor nomenclature but are unregulated, despite a variety of possible ethical concerns. Some of these concerns resonate with issues in human embryo research, some with questions that are shared with the equally unregulated field of neural organoid research, and some with other contexts entirely.

While science keeps generating such out-of-scope subject matter, regulators are forbidden by the rule of law from construing statutory terms to capture subject matter falling beyond the legislator's intention. Further, demand for Parliamentary time leads to years of delay in passing new or amending legislation, during which period further scientific knowledge has emerged and public benefit deriving from it has been stifled.

In seeking to resolve this dilemma, legislators face two main options. The first is to draft highly detailed definitions, or to explicitly exclude certain entities which may themselves be defined. This brings certainty to the regulation of known subject matter, while making it more likely that novel entities will fall outside its scope.

The second option is to draft definitions to capture a wide class of possible entities, existing and unconceived, subjecting them all to the same regulation irrespective of their differing impacts. This inevitably leads to disproportionate regulation of low-impact entities, which would be both high-handed and obstructive to the conduct of responsible science.

The regulation of possible SCBEMs is especially problematic, because of the wide variety of subject matter and the differing and sometimes combined ethical issues invoked. On the one hand, providing detailed rules applicable to specific, highly defined objects would not capture entities outside the definition. On the other hand, a 'one-size-fits-all' SCBEM rule would be disproportionately burdensome on most SCBEMs. In addressing the dilemma of governing unforeseen subject matter (Professor Holm's elastic), the SCBEM Code of Practice adopts a new approach, and it is this that concerns Profesor Holm.

Drafting rules to cover the multiplicity of possible SCBEMs, each with differing ethical implications and weight, was beyond the scope of a project focused on devising a governance architecture, for which the bigger issue was how to regulate ethically consequential change in a proportionate way (see BioNews 1246).

The best approach, in our view, was to empower an Oversight Committee (unlike a REC) to make decisions informed by – for example – the recommendations of the rapid review project on SCBEMs currently being conducted by the Nuffield Council on Bioethics. We might anticipate that researchers would be required to show that they had turned their minds to a series of ethical questions about their research project that require more than merely ticking a box, and that decisions would be made on a case-by-case basis.

Rather than calculating the applicable research restriction by measuring the relevant strip of SCBEM elastic beside an already dated SCBEM ethics ruler, the proposed architecture recognises that rules are not a substitute for ethical behaviour, and that it is preferable to require those proposing ethically consequential research to engage directly with ethical questions themselves. This is not to say that a SCBEM ethics ruler is impossible. Far from it.

As the SCBEM Oversight Committee cuts through the applications and develops its jurisprudence, its published precedents should make future applications more straightforward, with the opportunity to revise or introduce new guidelines as issues emerge. In this manner, Professor Holm's ethics ruler is not imposed from above (with the exception of the implantation prohibitions), but derived from ethical behaviour itself, evolving applicable rules in step with developing science in a transparent manner.

Julian Hitchcock was a member of the SCBEM Code of Practice Working Group.

Julian will be speaking at the 2024 PET Annual Conference – 40 Years after the Warnock Report: What Is the Embryo's Special Status? – in central London on Wednesday 4 December 2024.

Julian is speaking at the session 'What Is the Embryo's Special Status in Law?', where his presentation is entitled 'Defining the Embryo: Do We Need a More Meaningful Legal Definition?'.

Find out more about the conference, and register to attend, here.