New Frontiers: Futureproofing Fertility and Embryo Law

The fourth session of the Progress Educational Trust (PET)'s 2021 annual conference – 'New Frontiers: Futureproofing Fertility and Embryo Law' – explored the dilemmas that regulators face when trying to create legislation to safeguard fertility treatment and embryo research. Expertly chaired by Fiona Fox, founder and chief executive of the Science Media Centre, this final session was a truly international affair bringing together speakers in New York, Boston, Maastricht and Cambridge.

The first talk of the session – 'Assisted Reproduction, Genetics and the Future of Humanity' – was presented by Dr Jamie Metzl, a technology and healthcare futurist, and member of the World Health Organisation's Expert Advisory Committee on Human Genome Editing. He started by predicting we would move towards a world where 'millions, hundreds of millions, and not too far off, billions of people will have their whole genome sequenced'.

Dr Metzl argued that this would result in a shift in our healthcare system, with generalised medicine ultimately being replaced with personalised medical treatment based on the unique genetic makeup of each individual. Dr Metzl also believed that we are moving towards a future where whole genome sequencing of newborns would become standard practice, meaning there is a growing need for appropriate safeguards to be put in place to ensure that this genomic data is not exploited.

Dr Metzl envisaged that as we learn more about the interplay between our genetic information and our biological characteristics, some parents who use IVF to create their families will want to be more discerning in terms of which embryos are used within their treatment. He even went so far as to argue that we will eventually reach a tipping point, where 'parents feel that it's safer to conceive babies through science than it is to conceive babies through the traditional way of sex'.

Dr Metzl concluded that 'where we're heading with these technologies touches on the most intimate aspects of what it means to be a human being'. Consequently, ongoing discussion involving the public is vital.

The second talk of the session – 'The Past, Present and Future of the 14-Day Rule' – was presented by Professor Sarah Franklin, director of the Reproductive Sociology Research Group at the University of Cambridge.

At present, human embryos used for research purposes can be cultured for a maximum of 14 days before they must be discarded. This '14-day rule' was first proposed in the UK by the Warnock Committee in 1983, and has been enshrined in UK law since 1990 (and emulated elsewhere). However, advances in embryo culture techniques have now advanced to the stage where it is feasible to culture human embryos beyond 14 days.

Professor Franklin explored aspects of the 14-day rule that have helped it to endure and offer reassurance for almost four decades, and considered what could potentially be lost – or gained – from extending it. Notably, she argued that the 14-day rule has been responsible for creating a high level of public trust in both fertility treatment and human embryo research.

Professor Franklin argued the 14-day rule is not a fixed biological or moral line that specifies when human life should be protected. Instead, the 14-day rule has been selected – to some extent arbitrarily – to embody the setting of a moral line by and for society. Professor Franklin explained that the 14-day rule 'is based on a principle of exchange. In exchange for allowing controversial scientific research on human embryos, that research would be subject to the strictest regulations including a time limit and criminal sanctions backed up by the will of Parliament. So importantly, from a sociological point of view, the 14-day rule is both a literal and a symbolic limit'.

It is perhaps helpful to view the 14-day rule as a social contract between regulators, researchers and the public. When considering whether the 14-day rule should change, Professor Franklin argued that any amendment would likely require a new social contract to be established with the public, in order to maintain trust.

Ana Pereira Daoud, a researcher at Maastricht University in the Netherlands, tackled 'The Ethics of Human Embryo-Like Structures: The Closer the Knit, the Tighter the Fit' in her talk. She shared how 3D models of embryo-like structures (ELSs) are being used to investigate how human embryos may behave in the womb after implantation. ELSs are formed from induced pluripotent stem cells rather than from fertilisation, and therefore do not require a source of sperm or eggs in order to be created.

The regulation of research which uses ELSs is currently a grey area, in part due to differences and potential ambiguities in the definition of an embryo. In Spain, the human embryo is defined as the product of fertilisation, and human ELSs cannot, therefore, be viewed as true embryos. In the Netherlands, by contrast, embryos are defined as a group of cells that have the potential to develop into a human being – a definition which could, either now or in future, potentially encompass ELSs.

As part of her research, Daoud has held a number of focus groups to explore the attitudes of Dutch professionals and lay citizens towards the creation and research use of human ELSs. Daoud shared that some participants felt that 'research with human ELSs would be as, if not more, contentious, than research with human embryos', whereas others argued the exact opposite. These deliberations were partly based on whether the ELSs would develop what they considered to be morally relevant features such as a heartbeat, or have the capacity for continuous development (see BioNews 1116). Nevertheless, the consensus opinion from these focus groups was that all ELS research should be regulated in some way.

For the last talk of the conference, Professor Insoo Hyun – chair of the ethics committee of the International Society for Stem Cell Research (ISSCR) – explored the question 'What Makes an Embryo "Chimeric"? And Why Does It Matter?'. He started the talk by clarifying the technical difference between 'hybrids' and 'chimeras'. Hybrids are created when you combine the sperm and eggs of two different species, resulting in a combined organism in which every cell contains more-or-less identical genetic material. By contrast, each of the cells in a chimera originates from one of two (or more) separate organisms, and so these cells differ genetically from one another.

The use of chimeras within research continues to evolve. Professor Hyun described how one research team recently transferred a small number of human stem cells into monkey embryos to learn more about how cells from different species interact, so that human organs for transplant might one day be grown in animals.

Professor Hyun discussed the ISSCR's recently updated guidance on how chimeric research should be regulated. These guidelines specify that different levels of regulation are required, depending on whether the chimera is going to be transferred into a non-human uterus or not (transfer into a human uterus is expressly forbidden). If human stem cells are incorporated into a non-human embryo, and the resulting chimera is intended to be transferred into a non-human uterus, then a full specialist review will be required. The researchers need to demonstrate that there are no 'reasonable alternative' research approaches that could be used to answer their research question.

Professor Hyun highlighted the challenges of trying to create guidance and/or legislation for technologies that are evolving very quickly. He acknowledged that the ISSCR guidelines on chimeric research will need to be further updated as the science progresses, but argued that the guidelines are 'good enough' for where the science is now.

Unsurprisingly, the four talks prompted a number of questions from the audience and the Q&A session was a particularly stimulating affair. Dr Metzl was challenged on whether he truly believed that one day most people would choose to have children via assisted conception. Furthermore, if refined methods of embryo selection or modification were demonstrated to produce healthier, smarter children, what could be done to prevent this from entrenching privilege?

Daoud was asked whether we could ever truly settle the moral status of human embryo-like structures. Professor Hyun was asked whether the formation of human-primate chimeras would bring new ethical concerns. Professor Franklin was asked whether the 14-day rule should be changed in accordance with present social attitudes, or whether it should reflect social attitudes that we aspire to hold in the future.

Fittingly, for a session sponsored by the Anne McLaren Memorial Trust Fund, Professor Franklin, highlighted how Mary Warnock and Anne McLaren had both been staunch advocates and practitioners of public engagement. Their work played a pivotal role in creating the fertility and embryo research legislation that we have today, and this session reflected something of their spirit.

The Progress Educational Trust (PET) would like to thank the sponsors of its conference – the Anne McLaren Memorial Trust Fund, the Edwards and Steptoe Research Trust Fund, ESHRE, CooperSurgical, Ferring Pharmaceuticals, Hart Publishing, Merck, the Society for Reproduction and Fertility, Theramex, TMRW Life Sciences, Vitrolife and the Institute of Medical Ethics.

Register now for PET's free-to-attend online events in 2022:

• Whole Genome Sequencing at Birth: What Research Can, and Should, Be Done with a Baby's Genome? (19 January 2022)

• Adding Up What We Know: A Global Perspective on Fertility Treatment Add-Ons (26 January 2022)

• Prioritising Patient Safety: How to Minimise Risk in Fertility Treatment (9 February 2022)

• Whole Genome Sequencing at Birth: Genomic Data, A Resource from Cradle to Grave? (16 February 2022)

• Whole Genome Sequencing at Birth: Workforce Implications for Healthcare Professionals and Beyond (16 March 2022)