UK Code of Practice for human embryo models: A view from America

There comes a time in the affairs of science and technology when groundbreaking advances need oversight.

That moment arrived when American scientists agreed on a moratorium for recombinant DNA technology in the 1970s. A decade later, a Voluntary Licensing Authority provided oversight of IVF and embryo research before the UK government passed legislation. There are now calls to weigh the risks and benefits of artificial intelligence.

This month a partnership between Cambridge Reproduction and PET (the Progress Educational Trust) published a Code of Practice for on the Generation and Use of Human Stem Cell-Based Embryo Models (the SCBEM Code of Practice), compiled by a Working Group of scientists, lawyers and ethicists (see BioNews 1246a and 1246b) with international input and an accompanying public dialogue (see BioNews 1234).

Stem-cell-based embryo models (SCBEMs) promise to throw light inside the 'black box' of human embryology at early post-implantation stages of pregnancy (see BioNews 1200, 1206, 1221 and 1229). Mouse embryology is much better understood but it imperfectly mirrors human gastrulation, a pivotal event leading to the formation of the anterior-posterior axis and germ layers that become foundations for morphogenesis. Practical and ethical problems have encouraged the creation of in vitro models that represent development in situ and avoid using human embryos.

Assisted reproductive technologies have revealed that embryos often fail to survive or thrive after intrauterine transfer, leaving only a biochemical signature to show that they existed. Although endometrial receptivity is suspected as the main cause, embryonic factors are potential contributors that can now be investigated with SCBEMs.

These embryo models also provide new opportunities for studying environmental conditions after implantation, and screening drugs at a critical period when morphogenetic movements make embryos vulnerable to teratogenesis. Genome editing and transfection will advance fundamental knowledge of cell lineage determination, with potential benefits for clinical practice we can yet hardly imagine.

The pace of progress has been extraordinary since the first animal SCBEMs were announced, and is bound to accelerate as more research groups join the field. Several models have been created from almost unlimited sources of embryonic stem cells or induced pluripotent stem cells.

'Blastoids' self-assemble under precise culture conditions to closely resemble embryos at the blastocyst stage (see BioNews 1020, 1088, 1091, 1124, 1204). Their development generates epiblast and trophoblast cells with breathtaking potential that has yet to be explored.

'Gastruloids' formed by aggregating embryonic lineages with extraembryonic cells develop beyond the gastrulation stage, to begin neurulation and formation of rudimentary organs and vasculature. They don't precisely recapitulate the time course and milestones of embryogenesis, but convergence is expected in the future.

These advances have occurred with limited governance, other than the watch of local medical ethics committees. Scientists in the UK are bound by the Human Tissue Act 2004 to seek consent from cell donors. Courts within the UK are unlikely to regard embryo models as legitimate embryos unless Parliament imposes updated guardrails for research. The study of human embryos is already governed by the Human Fertilisation and Embryology Act 1990 for the first 14 days or up to the primitive streak stage, which leaves the prolonged culture of embryo models in governance limbo.

The SCBEM Code of Practice fills a gap with a uniform ethical standard, building on the 2021 guidelines from the International Society for Stem Cell Research (ISSCR). Although neither document has legal force, they carry the weight of panels of distinguished drafters. Compliance is voluntary but peer pressure will prevail, and grant funders are expected to insist.

An Oversight Committee with broad representation will review applications, and publish a list of approved projects on a publicly accessible register. A non-governmental code can respond more nimbly to unanticipated paths of discovery than statutory law, that tends to plod behind science.

The transfer of human or animal SCBEMs to a human uterus is strictly forbidden as a core principle, and, likewise, the reciprocal transfer of human to animal. This precaution is necessary, to stop a maverick from putting women at risk with an entity that has little (and probably no) pregnancy potential at present.

The policy constrains research to valid scientific goals; it won't sanction unleashed curiosity, such as testing the limits of growth. The Code avoids a rigid distinction between 'non-integrated' and 'integrated' models with extraembryonic components, and will decide termination dates for each experiment on merit. These policies depart from current ISSCR guidelines, but are understandable given the variety of models and timetables in new technology.

The goal is to support high-quality and transparent research to maintain public trust. Reports of SCBEMs with primordial hearts that can beat and nerves that conduct impulses may create unease in the lay public (especially in the USA). People will question whether the creation of such embryo models should be allowed, and whether the models feel pain. Hopefully, the media will restrain the temptation to create sensation and the kind of fear engendered by IVF before the birth of Louise Brown. The Oversight Committee and the scientists themselves will need to be effective advocates.

I will close with a quibble, not about the Code but about the name chosen by the ISSCR for these embryoids. 'Stem-cell-based embryo model' is rather a ponderous label for digestion in public spaces, more so after translation into foreign languages. And SCBEM is a bulky outlier in the family of acronyms in reproduction and embryology (IVF, ART, IUI, etc). I prefer a simpler, more memorable name and sufficiently generic to capture variety without sacrificing precision – something like, ahem, a HEM for Human Embryonic Model. By whatever name these models are known, the recent flurry of news is only the first page of an unfolding story.

The author publishes personal perspectives on embryology and reproduction on Substack at What's Hot in Fertility?