What Is the Embryo's Special Status in the Lab?

The second session of the 2024 PET (Progress Educational Trust) Annual Conference – '40 Years after the Warnock Report: What Is the Embryo's Special Status?' – was chaired by Fiona Fox, chief executive of the Science Media Centre and former chair of trustees at PET. This session – 'What Is the Embryo's Special Status in the Lab?' – focused on the opportunities and challenges presented by the use of human embryos in research.

Fittingly, the Anne McLaren Memorial Trust Fund was sponsor of this session. The late Professor Dame Anne McLaren was a leading developmental biologist and a key member of the Committee of Inquiry into Human Fertilisation and Embryology, the findings of which are widely known as the Warnock Report.

No less fittingly, the first presentation was given by a developmental biologist – Professor Shankar Srinivas, from the Institute of Developmental and Regenerative Medicine at the University of Oxford. His presentation – 'How Human Embryos Help Answer Questions that Other Model Systems Do Not' – explained why, despite the value of animal models and stem-cell-based systems such as organoids and stem-cell-based embryo models (SCBEMs), there is sometimes no substitute for what can be learned by studying actual human embryos.

Professor Srinivas gave the example of how researchers are trying to unravel the chemical processes that drive development from fertilised egg to a multi-cell blastocyst (the stage at which implantation can occur). Even at these earliest stages of life, there are fundamental differences between how mouse embryos and human embryos develop in terms of their size, geometry, topology and timing. There are also significant differences in cell migration to form progenitors of different tissues and organs, even before the appearance of the primitive streak, which occurs around 14 days after fertilisation in human embryos.

The second presentation – 'The Special Status of Research Embryos: How Do Researchers Obtain Them?' – was given by Professor Geraldine Hartshorne, scientific director of the Coventry Centre for Reproductive Medicine.

Professor Hartshorne outlined how the number of embryos available to researchers has fallen substantially, from almost 18,000 in 2004 to under 700 in 2019, despite the number of IVF cycles each year having risen dramatically in that timeframe (see BioNews 1220). She suggested that this was not due to reluctance on the pert of IVF patients to donate surplus embryos for use in research, and cited HFEA data suggesting that 58 percent of patients would prefer unused embryos to be used this way, versus only six percent who would prefer their unused embryos to be allowed to perish.

The two main difficulties, she suggested, are that only a small proportion or IVF clinics have links to research projects, and that there are large administrative and regulatory burdens involved in donating embryos to research. Specifically, the HFEA interprets the Human Fertilisation and Embryology Act as stipulating that embryos can only be donated to a specific research project, as well as further bureaucracy resulting from the UK's research governance framework for health and social care. She compared the consequences to a game of 'snakes and ladders', in which it can take 18-24 months to obtain funding for research projects, if they are successful.

Professor Hartshorne concluded by reiterating her call for a national research embryo bank to be established as an intermediary between clinics, patients and research projects (see BioNews 1243). A case for such a national embryo bank had also been made by Dr Valerie Shaikly during the previous session (see BioNews 1268), and by others at the previous year's PET Annual Conference (see BioNews 1219). Professor Hartshorne argued that such a facility would allow more research to drive evidence-based improvements to IVF, as well as promoting advances in basic science.

In addition to her presentation, Professor Hartshorne also created an artwork entitled 'Breaking Free' that was exhibited at the conference, alongside other artworks that had been created as part of the 'New Horizons in Fertility Research' project. These artworks involve artists collaborating with researchers who study human embryos and gametes, and were previously the focus of the PET event: 'Where Art Meets ART: Creative Exploration of Fertility Research and Treatment' (see BioNews 1244 and 1250).

The third presentation – 'Human Embryo Research in the Lab: Insights, Opportunities and Challenges' – was given by Dr Norah Fogarty, who is group leader at the Centre for Gene Therapy and Regenerative Medicine at King's College London.

Dr Fogarty was previously part of the team that received the first HFEA licence to use CRISPR-based genome editing on human embryos (see BioNews 837 and 919). She now runs her own lab, which focuses on studying early placenta development by looking at signalling factors and transcription factors that may be implicated in early miscarriage or failure to implant. Her group is currently refining its techniques using stem cells, organoids and SCBEMs, before proceeding to work on embryos.

Dr Fogarty spoke about the technical advances that are driving embryo and human developmental research. Approaches such as single-cell RNA analysis, genome editing, extended embryo culture techniques and stem-cell based embryo models are opening up new avenues to address longstanding questions. Dr Fogarty also emphasised the importance of collaboration, in terms of different teams working together to get the most information and value from each precious embryo, and also in terms of the UK regulatory landscape enabling researchers to collaborate.

The final presentation offered a perspective from outside the UK. 'Embryo Research in Belgium: Pros and Cons of the 2003 Law' was presented by Professor Karen Sermon, who is chair of the European Society of Human Reproduction and Embryology (which was another of the conference sponsors), as well as being professor of genetics and embryology at the Free University of Brussels.

In Belgium, embryo research is governed by a law passed in 2003 that incorporates elements – such as the 14-day rule – that originated in the Warnock Report, but have been adopted more widely in the intervening years. This law allows embryo research to take place with permissions from local and federal ethical committees who consider factors such as the goals of the research, potential scientific and medical benefits, and whether the aims could be met using alternative models. The law bans research using embryos from pursuing eugenic or cloning goals, and also prohibits the commercialisation or patenting of findings.

After the presentations, all four speakers returned to the stage to answer questions from the audience. A good-natured disagreement emerged between Professor Hartshorne and audience member Professor Peter Braude, emeritus professor of obstetrics and gynaecology at King's College London, about how many researchers are actually engaged in (or attempting to engage in) embryo research in the UK at the moment.

This discussion led to widespread agreement among the panel that it can be hard to be certain of the exact number, as HFEA licences only reflect successful applications that have obtained funding, and administrative burdens can discourage researchers. Professor Hartshorne added that arguing for funding was made more difficult because the NHS does not view fertility treatment as a priority, and Professor Srinivas commented on the amount of paperwork involved in human embryo research being considerably more than that for working with animal subjects.

The need for a centralised embryo bank to manage storage and paperwork was discussed, with widespread support among the panel and the audience. However, statutory change – or in the shorter term, a change to the HFEA's interpretation of existing legislation – would be required, in order for this to become a reality.

PET would like to thank the sponsor of this session (the Anne McLaren Memorial Trust Fund) and the other sponsors of its conference (the British Fertility Society, Burgess Mee, the European Society of Human Reproduction and Embryology, Born Donor Bank, Merck, Ovoria Egg Bank, Theramex, TMRW Life Sciences and the Institute of Medical Ethics).