13 Mar 2023
...(HHGE - see ‘A genome editing year’ and other posts in the archive). HHGE is the targeted modification a functional sequence of DNA in a human embryo (or human sperm or eggs, or their precursors) using one of a growing number of techniques, most saliently CRISPR-Cas9, with the intention that the modified sequence will be present in the cells of a future child. As it is now a year since the announcement of the birth of genome edited twins in China and discussions have been hotting up again recently, it seems appropriate to provide an update and brief commentary on some relevant developments.
In October the European Group on Ethics in Science and New Technologies (EGE, the expert group advising the European Commission in these areas) held a round table to inform the development of an ambitious Opinion on genome editing across various fields of application. This involved many of those who had entered the fray already, including the Nuffield Council and the Deutscher Ethikrat (German Ethics Council). It was followed by a session of the International Dialogue on Bioethics, which brought together a geographically broader range of participants. It is hard to draw any conclusions from these meetings, however, which largely took the form of a ‘show and tell’. It will be interesting to see, in the coming months, how the EGE tries to develop coherent normative advice on genome editing given that, as we concluded in our 2016 ‘conceptual’ report, Genome editing: an ethical review, each field of application raises distinctive issues, involves a different range of interests and requires a distinct approach.
HHGE is very much a live topic of discussion in the US. It was a theme for a panel at the annual meeting of the National Academy of Medicine (NAM) in Washington on 21 October. Given the varied themes of the meeting it was unlikely that the brief panel would do much more than raise the profile of the issue with the NAM members and, even then, the discussion quickly turned towards domestic preoccupations with reimbursement and the authorisation of clinical trials. As the sole non-US participant on the panel I hope I at least reminded US colleagues that much of the rest of the world, including many countries where research is actively progressing, has a different starting point (effective law) and a different background (a public sphere that is not so riven by antagonism over abortion provision as to make it difficult for it to inform public policy).
I was back in Washington DC fortnight later for the American Society for Gene and Cell Therapy policy summit, which devoted a day (November 6) to discussing HHGE, with panels on ‘the path forward’, patient perspectives, ethical perspectives on clinical use, and approach to international governance and engagement. The keynoteaddress was given by the Director of the US National Institutes of Health, Francis Collins, who used it to call clearly and unambiguously for a moratorium on clinical use of HHGE. It is easy to forget that, while a good deal of the world already has effective laws on these matters (among them the UK, via the Human Fertilisation and Embryology Act 1990, and the 29 states that have ratified the Council of Europe’s Oviedo Convention), the US is something of an outlier. (In the US, control of clinical use hangs by the thread of an annually renewable appropriations Bill rider that prevents the FDA using federal funds to review applications for HHGE over which it has asserted competence.) Furthermore, interventions of individual researchers like He Jiankui and Denis Rebrikov suggest that the public statements so far, such as those from the first and second international summit Organizing Committees, are seen by some as an invitation to researchers to decide for themselves when they believe they have met the criteria to proceed.
I have been ambivalent about the question of a moratorium for a long time and it is not addressed directly in our 2018 Nuffield report, Genome Editing and Human Reproduction: social and ethical issues. The first explicit call for a moratorium (from UNESCO’s International Bioethics Committee in 2015) was a cry into the wilderness. But despite no immediate response, the call has continued to echo. Although the international summit organisers fought shy of it in 2015 and implicitly rejected it in 2018, support for a moratorium has germinated within an important body of opinion, which includes Collins and Eric Lander of the Broad Institute in the US.
The problems of instituting a moratorium have been extensively discussed. They include the difficulty of explaining the value of a moratorium as a symbolic gesture, on one hand, or, on the other, the difficulty of agreeing concrete arrangements for overseeing, reviewing and lifting a moratorium that has practical authority. There are also concerns that a moratorium would create inertia (status quo bias) and have a chilling effect on scientific endeavour and on financial support for science. But the main problem is that of locating it at a supranational level. Fundamentally it is a question of sovereignty, and in two senses: the sovereignty of states vis-à-vis one another and of the ‘Republic of Science’ vis-à-vis political communities generally.[i]A moratorium must be enacted in a public space – HHGE is not an issue for researchers in biomedical science alone or for the assisted conception marketplace — but a supranational place of inscription is lacking.
Those who call for a moratorium generally want it to provide an opportunity to reflect not on how but on whether HHGE should be permitted to move from research into practice. Recognising that genome editing is an emerging biotechnology, not a mere medical innovation, one might conclude that a moratorium with clinical translation as its object would already be insecure. Once the technique has arrived at the threshold of translation all that remains is often ‘ELSI’-type discourse (ethical, legal, and social implications), which is merely instrumental (‘how do we do this ethically?’) rather than critical (‘what is the ethical thing to do?’). This is the more narrow framing that characterises, for example, the International Commission on the Clinical Use of Human Genome Editing, supported by the US National Academies of Sciences and of Medicine and the UK Royal Society, which held its second meeting in London on 14-15 November. Despite nominally having the aim of identifying ethical requirements (alongside the scientific and medical ones), and including non-scientists, this is a largely a roadmapping exercise, initiated as a fulfilment of the second international summit statement and in reaction to He Jiankui stealing the initiative a year ago. By developing a framework to ‘inform a potential pathway from research to clinical use’, this initiative has, arguably, already overstepped the notional point at which a moratorium would be meaningful.
To be effective, a moratorium would probably have to work at the level of research, intervening in the jealously protected sphere of ‘basic’ science. Except that the science is not basic in almost any sense, and certainly not in the sense of being detached from economic, political, social and moral interests. Such an intervention wouldn’t mean that researchers would have to hang up their lab coats, however. There are many fundamental but unresolved questions that research needs to address (for example, about the cell cycle, about chromosome segregation in the early embryo, about the DNA repair mechanisms harnessed by genome editing techniques, as Kathy Niakan proposed in 2018). These would provide a focus for research before potentially translatable experiments that demonstrate the editing of clinically relevant variants (the subject of the first four published papers using CRISPR-Cas9 genome editing in human embryos) become desirable. Insofar as such research potentially also underpins less contentious somatic genome editing, research of this kind might be treated as something like ‘dual use research of concern’ (DURC), tracked through an expanded mechanism such as the WHO’s proposed registry of genome editing research. The thought behind this is that if the scientific community can define a responsible translational pathway it might also be able to coordinate a research programme rather than merely spectate on the competition that the amenability of CRISPR-Cas9 has seemingly unleashed.
The purpose of a moratorium would be to provide an opportunity to do the moral work that has long been in abeyance, namely determining whether there may be good reasons to use heritable genome modifying technologies in humans, not merely whether it is safe to do so. This has both a national dimension, reaching into the public sphere, and, because knowledges, technologies and people are internationally mobile, an international dimension. It will and should take time. As I have suggested elsewhere, one way that this international discussion can be pursued is through international human rights institutions. The object would not be that of deriving universal moral rules as the outworking of some fundamental concept like ‘human dignity’ but providing an inclusive framework and a concrete venue for the continual reworking of margins of appreciation, the ethical differences that are consistent with respectful co-existence. The Council of Europe Bioethics Committee (DH-BIO), which discussed HHGE in its plenary meeting on 21 November, is one such institution. It is currently undertaking a review of what was, in effect, a prudential or temporizing agreement to prohibit heritable human genetic modification, codified in Article 13 of the 1997 Convention on Human Rights and Biomedicine. It remains the only international legal bulwark against HGGE. But as the Committee’s 2015 statement said (which offers a fine comparison with the simultaneous statement of the first International Summit Organizing Committee), it is the better place to start.
All this happened more-or-less in the space of a single month. But I have not mentioned a number of continuing initiatives or events that I was unable to attend: the work of the WHO Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, which met for a second time in Geneva in August; a significant meeting on public debate and the future of HHGE hosted by the Innovative Genomics Institute in Berkeley, California, on 26 October; and the annual meeting of the Association for Responsible Research and Innovation on Genome Editing (ARRIGE) on 14 November in Paris. Genome editing (across different fields of application) was also the subject of the annual meeting of the Global Forum on Bioethics in Research in Singapore, on 12 and 13 November, which included a rich assortment of papers from around the world, and particularly from outside Europe and North America, from different ethical and legal traditions. HHGE was also discussed again at the annual trilateral meetingon 13 November between the Nuffield Council, the Deutscher Ethikrat (German Ethics Council) and the French Comité Consultatif National d’Ethique (National Ethics Advisory Committee), who have all delivered reports and opinions in this field, albeit taking rather different ethical approaches. Finally, I would like to mention another event that I did manage to attend: the 7th International Bioethics, Multiculturalism and Religion in Casablanca, Morocco from 11-13 November (on which I will try to post separately), which took developments in assisted reproductive technologies as its focus. It offered an important reminder that, though some of us only see these issues from the perspective of secular bioethics, secular bioethics only accounts for a fraction of the global discussion.
[i] I use this phrase after Michael Polanyi (1962) The Republic of Science: its political and economic theory, Minerva 38: 1–21.