By Caroline Simons
There were just over a hundred participants at the workshop organized by the Federation of European Academies of Medicine, the UK Academy of Medical Sciences and the Académie Nationale de Médicine France. That number included experts in the fields of science, medicine, law and bioethics. They came from Europe, the US and China (and, I think I may have heard, one French politician).
Some were engaged in active research, others represented national academies, policy making bodies, patients, research funders and industry. I noted one participant from the US represented DARPA, a reminder that gene-editing technologies may have harmful as well as therapeutic applications. There were about a dozen journalists, of whom two may cover this event in English – Anna McKie of Research Fortnight and Oliver Moody of The Times.
The aim of the workshop was to consider current scientific activities in the European Union (EU) regarding genome editing and the regulatory landscape across the EU member states for this research and its clinical application in humans. The stated intention was to foster discussion between experts, provide information to the public and stakeholders and to consider whether an EU regulatory framework to govern the safe and acceptable use of human genome editing is desirable, and how it could be achieved. There were no agreed conclusions or recommendations from this workshop, but many interesting presentations and observations. A paper which will draw on the workshop discussions is to be published.
Readers of The Niche are, as they say here, ‘au courant’ with many of the potential applications for this technology.
These applications, regulatory orientations and international governance will be discussed again (but with different speakers) at the NAS and NAM Committee on Human Gene Editing meeting in Paris later today.
Readers may register to watch the livestream. It begins 09.10 CET
Readers of The Niche are also aware of the excellent paper of Motoko Araki and Tetsuya Ishii regarding international regulations on this subject.
Here, in no particular order, are this lawyer’s take-aways from the workshop –
- The EU cannot determine what research may or may not be carried out in member states. That is the prerogative of the member states. This will change under EU regulations on clinical trials which will come into force in the next two years. With one exception, member states will no longer be able to refuse clinical trials in their own countries. Refusal will only be permitted if the research is damaging to the embryo.
- We don’t know enough about genes. Gene editing technology is an amazing investigative tool but is not nearly ready for clinical investigation. Current gene editing technology is inefficient and data about safety is lacking. A significant participant from the industry sector emphasized the point that data about safety in vitro and in vivo in animals is a prerequisite before any application in humans. He expressed his concern in particular about the lack of published data on chromosomal rearrangements and translocation. There was a general agreement that more preclinical models in animals are required and that a very efficient, safe and good animal outcome is necessary before translation into humans.
- Regret was expressed that certain journals may act as ‘ill-defined gatekeepers’ by sitting on submitted papers while waiting for consensus to emerge. This is said to give rise to ‘a new science of development of normativity’.
- Objections to human gene editing are made on the grounds of safety and/or on a principled/religious/’playing God’/dignity basis. The first can be answered by research. The concerns of the second category of objectors can’t be assuaged. They might be asked how it might be in the interest of an embryo to be born with an avoidable heritable disease or condition and how that might be compatible with the concept of dignity.
- Medical tourism: Concerns were raised in the case of a scientist working in a jurisdiction which permits germline gene editing, who on return to a conservative jurisdiction might face criminal sanction (such as Germany which criminalizes alteration of the human genome), notwithstanding that the offence occurs outside that jurisdiction. Criminal sanctions also exist for anyone who incites, aids or is complicit in any act which is criminal in German law, even if done in another jurisdiction. This might implicate colleagues.
- Early testing in hospital on exceptional compassionate grounds is not necessarily unlawful, but deprives the scientific community of data on accuracy, control etc. for future progress. Where early gene therapy is needed, there might be an adjustment of the regulatory bodies’ rules in order to preserve this data.
- In the UK, scientists can use embryos in research up to 14 days, create embryos for research, research germ cell development and can use CRISPR to experiment on early human embryos. In Poland ‘nothing is allowed’. We need to be mindful of the different cultural norms and beliefs, the differing status of the embryo in clinical research and application among the member states. For this reason a vision of European harmonization of the laws governing research on embryos and gene editing technologies is unfeasible. The UK cannot transpose its model to the US or to other EU member states. A vision of ‘European equivalency based on agreed principles’ was suggested as an alternative.
- There was general agreement that broad societal consent would be needed before this technology should move to the clinic. In considering the desirability of avoiding the strongly held views of minorities at opposite ends of the spectrum of public opinion and the imperative to engage those on the middle ground, it was generally agreed that the UK public consultative process prior to the recently approved ‘mitochondrial replacement’ techniques would provide a useful template. A similar process was used in the General Public Discussion on the Revision of the French Bioethics Law. A representative of patients’ interests observed that at least 6% of monogenic disorders affect 5% of the world population and have no cure. He asserted that societies that do not allow favourable innovation are responsible for disorders for which nature was formerly blamed. The use of language in the public arena was discussed. It was suggested that words such as ‘eugenics’, ‘playing God’, ‘manipulate’ should be avoided, as people are more likely to oppose techniques described in this manner. Words like ‘therapy’ would engender public approval and are to be preferred. While public consultation was desirable and recommendations of the public might be reflected in regulations, the meeting did not feel that it should be constrained by those recommendations.
- I asked Dr. Lovell-Badge if all research efforts involving ‘CRISPRing’ of human embryos without reproductive intent should be allowed or if a compelling rationale should be required. He answered that research should be allowed, but that clinical application of somatic and germline gene editing need to be regulated. He reiterated that we don’t know enough about specific genes or the possible consequences of germline gene editing for it to proceed to clinical application.
I asked Professor Joannet if the use of viable human embryos rather than 3PNs should proceed at this point. Dr. Robin Lovell-Badge responded that this is already happening and is preferable as the 3PN embryo may be stressed in terms of repair mechanisms.
I asked Professor Bartnik if gene editing holds greater promise and less risk than ‘mitochondrial replacement’ for some diseases caused by mtDNA mutations and cited the recent papers. She responded that the research on mitochondrial replacement technology (MRT) is more advanced and that it has been given serious consideration and safeguards proposed such as restricting the clinical application of MRT to the production of male embryos for reproductive endeavor. (MRT appears imprecise and inelegant to me by comparison, but hey, I’m not a scientist. Might gene editing be worth the wait?)
Some questions were unrelated to our discussion topic. One was an enquiry as to whether there were any regulations which prohibit the production of ‘artificial gametes’ (derived from iPSCs). The lunch break provided a welcome escape from any obligation to respond. The second question came from Dr. Lovell-Badge. He enquired as to whether an infertile man might act as a surrogate to incubate another man’s sperm (produced by treatment of that man’s spermatogonial stem cells) by transplanting them to his testes. This has apparently been done in mice and some non-human higher primates. That does seem rather a big ask for the unfortunate sterile man….
Looking at the line-up for today, I’m sure it will be a great meeting. I haven’t heard Nick Bostrom before and anticipate that he will make a ‘disruptive’ contribution. Guido Pennings always engages his audience with lots to ponder. I heard Hans Clevers at the COGEM meeting in November and hope he gives the same presentation. His research and graphics were ‘awesome’.
I am pondering Edmund Burke’s declaration to Rousseau that society is a contract, ‘but it is a contract between the living, the unborn, and the dead.’ The public must be educated and engaged in the decision to direct our own evolution. It is such a contract. Meetings like these are a good start.
 International regulatory landscape and integration of corrective genome editing into in vitro fertilization. Reproductive Biology and Endocrinology 2014, 12:108.
About the author. Caroline Simons is a BCL Dip Eur Law LLM (International and European Intellectual Property Law) Solicitor. She is currently a candidate for an MA in Bioethics and Medical Law at St Mary’s University, London. She did her dissertation for LLM at Trinity College Dublin in 2014, which was on subject of 3-Person IVF. Currently she is researching legal issues around germline editing techniques for MA dissertation. You can follow her on Twitter here.