March 13, 2019

expert reaction to a call for a moratorium on heritable genome editing

Reactions to a called for moratorium and international governance framework for heritable genome editing as published in Nature.

Mr James Lawford Davies, Partner, Hill Dickinson, said:

“It is understandable that a moratorium is attractive to those working in countries which lack coherent regulation. In the UK, however, the law very clearly allows the use of genome editing in embryos for research, but equally clearly prohibits its clinical use in embryos. As such, a moratorium is unnecessary in the UK and may risk causing confusion about where the boundaries lie.”

Dr Hayley Clissold, Policy Officer, Wellcome Sanger Institute, said:

“Before germline editing can be used clinically in humans, the Sanger Institute believes that further vital research must be undertaken to understand the scientific, technical and medical issues associated with these technologies as well as the societal, ethical and moral implications of altering the human germline.

“A global moratorium provides the opportunity for international debate among scientists, ethicists, policymakers, the public and other key stakeholder groups to form a societal consensus before such clinical uses can be considered. A structured framework for implementation of the moratorium is required for it to be effective. This must include regulations to prohibit unethical and unregulated clinical applications of germline editing from being pursued under the radar, outside of ethical practices and without significant engagement with fellow scientists and other key stakeholders.”

Dr Beth Thompson, Head of UK and EU Policy, Wellcome Trust, said:

“Genome editing technologies may hold great promise for improving health, but at this time the technology must not be used with the intention of producing babies with altered DNA. Although we do not agree that a moratorium is necessarily the best way to navigate this issue in the short term, it is clear that we do not yet fully understand the risks or benefits of this powerful technology, and finding the right governance approach is critical.

“We agree with many of the principles outlined in the Nature comment. There must be robust national laws shaped by public consultations and informed by the latest science. Wellcome will support the work of the WHO and the National Academies of Science and Medicine to address these complex questions and develop an effective and inclusive approach.” 

Prof Barbara Prainsack, Professor at the Department of Political Science, University of Vienna, and at the Department of Global Health & Social Medicine, King’s College London; Member of the Austrian Bioethics Commission and the European Group on Ethics in Science and New Technologies (EGE), said:

“Moratoriums are a well known policy instrument in the field of medical and research policy. Moratoriums tend to be used when there are no objections to a technology in principle, but when more time is needed to find out under what circumstances the technology can be safely and ethically used on humans, or to decide whether certain applications of the technology should be prohibited in general”.

“If moratoriums are passed as laws, they are, of course, legally binding – such as the moratorium on human reproductive cloning in Israel. The authors’ emphasis that a moratorium is a ‘voluntary pledge’ is somewhat misleading in this context. What the authors seem to mean by their emphasis on the voluntary nature of the moratorium is that states should be able to decide voluntarily whether to issue a moratorium by law, instead of being obliged to do so by international law – which they, however, would have needed to agree to beforehand anyhow.”

“This ‘voluntary’ decision by states to issue a moratorium must be distinguished from moratoria where institutions – or individuals – voluntary commit themselves to do something (or abstain from something) without there being a law requiring them to do so.  An example of this latter kind is the voluntary moratorium on the use of genetic test results by the Association of British Insurers [2][3]. Such a moratorium could be revoked at any time by the insurers themselves. Another example of a moratorium as an instrument of voluntary (and revocable) self-regulation was the 1975 Asilomar Conference, where scientists voluntarily committed themselves not to carry out certain forms of combining DNA from different organisms [4]. Paul Berg, who is one of the authors of the present comment, was also centrally involved in the Asilomar conference.

“It is a pity that this Nature comment does not elaborate on the specific voluntary nature of the moratorium the authors are proposing.

To the question to what extent the differentiation of an evaluation according to the purpose of the germ line intervention – correction or improvement – makes sense:

“This distinction is problematic because even the question of what constitutes a serious disease will be answered differently by different people. Thus, the distinction between correction and enhancement typically shifts the problem rather than solving it. What is positive in this Nature comment is that the authors define very clearly what they mean by ‘correction’ in this particular case: editing a rare mutation that is highly likely to cause a severe single-gene disease.

Prof Sir Robert Lechler, President of the Academy of Medical Sciences, Academy of Medical Sciences (AMS), said:

“There is no doubt that genome editing technologies hold huge potential for the future health of patients, but I agree that the clinical use of germline genome editing should remain prohibited. There are currently just too many unanswered safety, ethical and scientific questions.

“I am pleased that the proposed moratorium does not wish to change the way scientists can use germline editing for research use, nor does it seek to prohibit genome editing in human somatic cells to treat diseases. Considerable progress has already been seen in these areas and it is essential that this kind of research and treatment development can continue. With this in mind, using the term ‘moratorium’ is unhelpful and any timeframe for a fixed term ban would be largely arbitrary. Instead, the scientific community should focus on learning from the initiatives currently being established.

“I support the development of an international framework to provide guidance on the clinical applications of germline genome editing being set up by the US National Academies of Sciences and Medicine, together with the Chinese Academy of Sciences and the UK’s Royal Society. The Academy of Medical Sciences is pleased to be contributing to this commission and alongside the work by the World Health Organization on global governance and oversight of human genome editing, and wider public engagement activities, I hope that this will shine much-needed light on whether, and when, clinical applications of germline genome editing should proceed.”

Dr Yalda Jamshidi, Reader in Genomic Medicine, St George’s, University of London (SGUL), said:

“A statement in Nature this week from scientists and ethicists, many of whom have been involved in the gene-editing field, is asking for a global moratorium on all clinical uses of human germline editing.

“The truth is we don’t know what the consequences of genome editing the human germline will be. This approach means that the changes will be passed on to future generations. If the technical difficulties are overcome it could be entirely beneficial in some cases, or it could result in unknown long-term side effects. Thus, the implications of human germline editing extend beyond the individual embryo; and of course, the embryo itself cannot give consent. Yet the technology is immensely valuable in disease research and for the treatment of many serious inherited conditions, a distinction highlighted in the statement. As such these are areas where further work should be allowed to continue, alongside efforts to improve and refine the technology itself.

“This is not the first time the scientific community have voiced the need for regulation and societal discussion of the potential impact of gene editing technology, but the call for a moratorium also provides a suggested framework, around which individual nations can begin to address these issues in a more transparent manner and with the consensus of their “own” government and citizens. It also asks that all potential stakeholders – including hospitals, research institutes, funders, clinicians and others working in the field, actively respect and support regulation of this technology.

Importantly with the many unknowns involved, the debate over the best way forward is still very much in its infancy, a point reflected perhaps in the timeline of the proposed framework which suggests an initial ban on all clinical use of germline editing for a period of 5 years. Whilst we can never guard completely against rogue parties who choose to go outside the realms of regulation and oversight, we should keep striving towards a society where the responsibility is shared by all stakeholders, and incidents are minimized because of collective efforts to protect their citizens.”

Dr Helen O’Neill, Programme Director, Reproductive Science and Women’s Health, University College London (UCL), said:

“This letter serves to ignore rather than reiterate that a global ban is already in existence and only attempts to address what would happen in the case of another extreme scientist. 

“Currently, there are (as there was in China) legal and ethical measures in place globally which regulate the use of gametes and embryos. Let’s not forget that He Jiankui broke many rules, and was aware of this by choosing to do his work outside of the auspices of the university (and taking unpaid leave). It was not that he did this because the law allowed it. 

“Regarding the two years of public discussion: 

“There has never been a broad societal consensus about anything in any country, not even the allocation of human rights, so expecting this as a benchmark for clinical adoption of germline therapy is unrealistic. 

“They state:

“”Finally, no mechanism was created in the ensuing years to ensure international dialogue about whether and, if so, when clinical germline editing might be appropriate.” 

“This blatantly ignores the two-year work of the Nuffield Council on Bioethics Enquiry into human genome editing as well as the ongoing international dialogue and efforts of groups like ARRIGE. 

“When they state that “the bar should be set high” this is a given, and the bar has never been higher. It is in everybody’s interest to ensure this technology is employed safely and to a clinical standard but using words like “moratorium” do not feed the interest of funding bodies, which allow the research to reach such a high bar. 

“It is worth recalling that none of the mechanisms of genetic quality control were (or are) in place for the introduction of new elements of assisted reproduction before they reach the clinical embryology laboratory or fertility clinic. Embryos are inspected for their morphology and developmental potential and there is a paucity of research into the genetic disruptions that mechanisms like biopsy and culture conditions could inflict on an embryo.  

“The authors use the words “guarantees” and “ensures” when speaking of the ability of PGT-A and PGT-M (methods of screening embryos for aneuploidy of monogenic disorders), which shows blatant disconnect to the actual statistical chances of a couple to have a child free of genetic disease using current methods of stimulation and testing. Even with multiple cycles (which puts stress on the mother) to harvest a larger number of oocytes, the numbers of embryos remaining which are viable for transfer are minimal. 

“The suggestion to “continue to improve IVF and PGT” to improve their success rates, rather than allowing for germline editing to correct mutations is a naive one and only serves to show the disconnect between the authors and the current IVF and PGT trends. It disregards the simple biological fact that a high number of oocytes and embryos are naturally aneuploid, so there is a limit to IVF success due to innate biological barriers. 

“When referring to the societal implications, they state “Genetic enhancement could even divide humans into subspecies.” as though economics don’t already create a divide, between rich and poor and allow for uneven allocation of provisions and healthcare due to wealth status. 

“Under the same section, it speaks of unintended mutations which “cannot be removed from the gene pool unless all carriers agree to forgo having children, or to use genetic procedures to ensure that they do not transmit the mutation to their children. ” Surely the more pressing problem we face is that we currently DO have the mechanisms to remove highly dangerous and deadly mutations from affected families and this paper wishes to impose restrictions on their use.

“The main problem I have is that what they are saying reflects the many previous agreements of all interested or invested organisations but naming a “moratorium” sheds a negative light on the potential for germline genome editing. This will have huge consequences for research funding, many of the bodies requiring the proposal to be “clinically translatable”.”

Mr Hugh Whittall, Director of the Nuffield Council on Bioethics, said:

“This is a welcome contribution in the developing international debate about genome editing, but many crucial questions about the technique still remain unanswered. In line with the recommendations in the Nuffield Council on Bioethics’ 2018 report, Genome editing and human reproduction: social and ethical issues, we agree with the need for international action and broad societal debate before any move towards clinical implementation.”

Ms Sarah Norcross, Director, Progress Educational Trust (PET), said:

“A moratorium on the clinical use of germline genome editing is neither necessary nor useful.

“In our work, we have found that people do not worry specifically about changing the  germline. They are more concerned with whether or not specific applications of genome editing are medically warranted. This finding has also been borne out by several recent surveys of the public in the USA, the UK and elsewhere.

“We do not think a moratorium would have deterred He Jiankui, who acted secretively and in breach of a clear scientific consensus that germline genome editing should not be used in the clinic at this time. Moreover, He Jiankui’s practices were scientifically and ethically unsound in so many different ways, that they would have been wrong regardless of whether or not they involved germline genome editing.”

‘Adopt a moratorium on heritable genome editing’ by Lander et al. was published in Nature at 18:00 UK time on Wednesday 13^th March 2019.

Declared interests

Dr Yalda Jamshidi: “None to declare”

None others received.