Futureproofing ethical SCBEM innovation

The Nuffield Council on Bioethics (NCOB) has released a report outlining a proposed framework for governing stem cell-based embryo model (SCBEM) research. Central to our recommendations is the call for clear legislative action to differentiate SCBEMs from embryos and to safeguard against ethical breaches. This includes measures to prevent a SCBEM from being transferred into the reproductive tract of a human or other animal, and to ensure that SCBEMs are not developed that are capable of feeling pain or awareness, if that becomes possible in the future.

Understanding SCBEMs in research

The term 'SCBEM' refers to an array of structures derived from pluripotent stem cells, designed to mimic or replicate characteristics of natural embryos. These innovative structures hold immense potential as research tools, offering new insights into early human development. In time, the research could also lead to applications to improve IVF and test drugs used in pregnancy.

A balanced approach to regulation

Since March, NCOB has been conducting an ethical and governance review of SCBEM research, guided by an expert working group which I was privileged to chair. Our report, published on 27 November, advocates for a phased regulatory strategy. In the short term, we recommend 'soft' governance while envisioning the introduction of 'hard' legislation as research progresses. This dual approach is designed to foster innovation while maintaining a strong ethical framework and ensuring tangible public benefits.

Ethical concerns and recommendations

Throughout our review we were fortunate to hear from individuals and organisations directly involved in the development and oversight of SCBEMs, as well as in the wider discourse around the ethical and governance issues SCBEMs raise. We have also been influenced by a handful of initiatives involving members of the public in discussion about SCBEMs and how their use might be governed. We recognise the need for ongoing ethical discussion as the field develops, including through wider public and stakeholder engagement, and this is made clear in our recommendations.

Although there is uncertainty about the potential of SCBEM research and what features or characteristics of models might be considered ethically significant, we heard in our evidence an emerging consensus on the critical ethical issues.

Among the 'red lines' that we identified are research projects aiming to develop SCBEMs for reproductive purposes and SCBEMs that have capacity for pain or awareness. Both issues were raised in a 2023 UK public dialogue, run by Hopkins Van Mil on behalf of Cambridge Reproduction and PET (see BioNews 1234).

The role of the UK SCBEM code of practice

That public dialogue fed into a new Code of Practice for the Generation and Use of Human Stem Cell-Based Embryo Models (SCBEM Code of Practice), published jointly by PET and Cambridge Reproduction in July (see BioNews 1246a and 1246b).

In our report we welcome the SCBEM Code of Practice as a timely and proportional guide for researchers. We call on institutions, regulators and funders to help embed and enforce it, in particular by setting up the proposed register and oversight committee in a timely way. The SCBEM Code of Practice applies a case-by-case limit to culture time that will be set by the oversight committee, based on the particular objectives of the research project.

We advise that the oversight committee should work towards a clear upper limit for SCBEM culture, and we suggest an interim upper threshold as a first step in that process. The threshold should make clear that no complex or complete SCBEM will be allowed to develop to the point that it can experience consciousness or pain, and that exploration of reproductive potential, including through forms of ectogenesis, should have a clear upper limit.

Limitations of soft governance

While soft governance serves as a good starting point, it alone cannot address the risks associated with advancements in SCBEM research. Although there is broad agreement that SCBEMs are not currently equivalent to embryos, there may come a point where a more complex SCBEM is considered, as a matter of scientific consensus, to be functionally very similar to one.

At this point it could be legally considered to be an embryo because:

• The Human Fertilisation and Embryology Authority could adopt a broader definition of 'embryo'.
• Or a court could decide that it fits in the ordinary definition of 'embryo'.
• Or the definitional change could be made through statutory regulations.

Because the point at which this happens will be contentious, there is potential for this shift to happen either too late to prevent unethical research, or too early to foster ethical research that has potential to benefit society. Our call for a proactive response to the next stage of regulation, is made to pre-empt the potential for untimely or ill-fitting regulation of SCBEMs as embryos.

Introducing the 'regulatory sandbox'

To address these challenges, the report proposes an amendment to the Human Fertilisation and Embryology Act 1990 that explicitly excludes SCBEMs from the legal definition of embryos and makes provision for their bespoke and targeted regulation. This amendment would pave the way for the creation of a flexible regulatory framework known as a 'regulatory sandbox.'

This model would serve as a controlled environment for innovation, allowing researchers to explore new developments under regulatory oversight. By acting as a testbed for research, the sandbox would enable regulators to determine which types of SCBEM require regulation and on what basis, while also providing researchers with access to guidance and oversight.

A call for legal safeguards

To solidify ethical boundaries, we are recommending a statutory ban on the transfer of SCBEMs into the reproductive tract of a human or other animal. This legal measure would carry penalties for violations, adding to current disincentives including the prohibition in the SCBEM Code of Practice and possible legal sanctions such as disciplinary action.

A governance framework for the future

Taken together, these recommendations form a robust and adaptive governance framework for SCBEM research. The key components of this framework are:

• Clear legal definitions – Establishing a distinct legal status for SCBEMs to avoid regulatory ambiguities.
• Reinforced ethical boundaries – Ensuring that ethical red lines are upheld, safeguarding against harmful or controversial research outcomes.
• Flexible regulation – Implementing dynamic structures, such as the regulatory sandbox, to allow regulation to evolve alongside scientific advancements.

Striking the right balance

This governance approach underscores the importance of adaptability, collaboration, and foresight. By proactively addressing ethical concerns and creating a flexible regulatory framework, NCOB is setting the stage for a future where SCBEM research can thrive responsibly. As scientific advancements continue to push boundaries, this framework will serve as a guide to navigating the complex intersection of innovation and ethics.

Professor Emma Cave will present this work at the 2024 PET Annual Conference – 40 Years after the Warnock Report: What Is the Embryo's Special Status? – in central London this coming Wednesday (4 December 2024).

Conference registration will close shortly. Find out more, and register to attend, here.