The wild east and the worried west: pioneers or outlaws?

'The Wild East and the Worried West: Pioneers or Outlaws?' was the third session of the Progress Educational Trust (PET)'s Annual Conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'. As the frontiers of human reproduction move forward, the session reflected on the duties of funders, scientists, healthcare professionals and regulators in ensuring responsible progress. This is particularly relevant in the interconnected world of today where certain developments have brought up debates about boundaries being pushed too far in certain countries, whilst being too constrained in others. Pioneers in one context have become outlaws in another. But where and how should a line be drawn for when pioneers become outlaws?

The session was chaired by Sally Cheshire, chair of the HFEA (Human Fertilisation and Embryology Authority), and featured three speakers - Dr Sarah Rappaport (policy adviser at the Wellcome Trust), Dr Henry Malter (laboratory director at the Fertility Centre of the Carolinas) and Dr César Palacios-González (research associate at King's College London's Centre of Medical Law and Ethics).

In the first presentation, 'Funding Scientific Frontiers: A Global Perspective', Rappaport spoke about how over the last few years, Wellcome has taken a more global approach to its funding, policy and advocacy work. It funds research in around 70 countries and through that tries to accelerate ideas and seize opportunities. It supports not just scientists, but scientific endeavour and in this wants to be more 'cutting edge' than 'wild west'.

The number one concern for Wellcome in considering its global approach is equity: asking how will there be fair access to the scientific developments we are witnessing. Secondly, in terms of governance, Dr Rappaport raised the issue of the discrepancy between what significant scientific developments are imminent and the timescales of many developments which could be decades off. Too much excitement and attention for the latter may lead to neglect of the former. Finally she discussed Wellcome's obligations for research and the need to focus on global differences. For example, when looking at gene drives: what principles should be underlying research, how does the research work in different contexts, what are the global principles underlying the work?

The second speaker, Dr Malter talked about 'Myths of the Wild West: Outlaws and the New Frontier'. He started off by noting how his work with Dr Jacques Cohen played a role in extending boundaries and in the process he was called a cowboy. He joked that his talk should perhaps be retitled, 'Extending Frontiers from an Outlaw Perspective: A Cautionary Tale'. He went on to assert that those in the 'fertility frontier' have a moral, ethical and scientific mandate to try to help every person who comes through their door. Describing the fertility frontier in 1978 as a barren landscape, Dr Malter explained that while Sir Robert Edwards and his team solved many issues for tubal factor infertility, there remained no good solutions for male factor infertility aside from donor sperm. Only in 1992 did we see Dr Gianpiero Palermo pioneering the ICSI (intracytoplasmic sperm injection) procedure. The remaining problem was the barrier of compromised egg quality. Replacing an egg with a donor egg ameliorated this problem yet this donor conception was not the goal for many women.

In 2001, Drs Cohen and Malter sought a way to improve the quality of eggs through a technique called cytoplasmic transfer. This involved the injection of a small amount of cytoplasm from a donor egg directly into the egg of an infertile woman to 'rejuvenate' it. The technique seemed to them to work well, and Dr Malter stated that 17 healthy babies were born to 12 couples. The research was published, but much of the reporting focused on the fact that there was a minor level of donor mitochondrial DNA detectable in the resulting babies. Much reporting, including in the UK press, then described the technique as creating 'three-parent babies' as well as creating fears of the 'slippery slope' and the advent of germline genetic manipulation. Besides the public furore, the researchers came up against the US Food and Drug Administration.

Dr Malter concluded with some questions about the ethics of extending the fertility frontier. Is it ethical to extend the frontier? Who gives permission? What about patient autonomy? In answering the last question, the talk concluded with Dr Malter arguing that we owe patients the courage to make bold decisions. Such courage, tempered by safety and responsibility, does not - or should not - take us automatically into 'outlaw' territory.

The final talk, 'Mexico and Mitochondrial Replacement Techniques: What a Mess' by Dr Palacios-González, focused on the news that broke on 27 September 2016 of the first baby ever born who had been conceived with mitochondrial donation. Unlike the cytoplasmic transfer technique which was used by Drs Cohen and Malter to address infertility, mitochondrial donation techniques - which are used to avoid the transmisson of mitochondrial disease, a very different purpose - seek to replace all of a mother's mitochondria with mitochondria from a donor.

The US team responsible was led by Dr John Zhang, who is on record saying that he and his team chose to work in Mexico because 'there are no rules' there. The narrative setting out what had happened, and where, was far from clear when the news broke. It later transpired that the relevant embryo was created in New York through privately funded research, but the embryo was transferred to the patient in Mexico. Dr Palacios-González and Dr María de Jesús Medina-Arellano have shown that if the embryo had been created in Mexico (as was initially thought to be the case), then Dr Zhang would have broken federal health regulations.

Dr Palacios-González concluded that within this 'mess' certain questions remain unanswered, including which bodies were and were not consulted by Dr Zhang. Certain key facts have still not been made clear, and there remains considerable uncertainty about the legal and ethical issues surrounding this case. Dr Palacios-González argued that if Mexican authorities had not been kept in the loop - as indeed seemed to be the case - then this showed considerable disregard for the medico-political landscape in Mexico, and could lead to adverse developments within that landscape.

The talks generated many questions from the floor. In response to Dr Rappaport's focus on ensuring global equity in the breaking of boundaries in human reproduction, someone questioned whether we are in danger of bifurcating the species with - for example - only wealthy parents benefiting from certain techniques. There was also reflection on the best vocabulary to use when discussing children with donated mitochondria, and whether an HFEA-like sub-agency within the FDA like could alleviate many issues in the USA surrounding the boundaries of research into human reproduction. Overall, the session showed that determining who are the pioneers and who are the outlaws is a complicated process.

PET would like to thank the sponsors of its conference - the Anne McLaren Memorial Trust Fund, the Edwards and Steptoe Research Trust Fund, the ART Institute of Washington, Ferring Pharmaceuticals, the London Women's Clinic and Vitrolife.