Heritable genome editing: navigating the red line

By Tanya Brigden

20 August 2018


Nuffield Council on Bioethics (the Council) released last month their eagerly anticipated report Genome editing and human reproduction: societal and ethical issues. Prompted by developments in genome editing technologies, in particular the rapid emergence of CRISPR Cas-9, the report explores the range of ethical issues raised by the prospect of genome editing becoming available as a reproductive option.

The focus is specifically on heritable editing (where changes can be passed on to offspring) as opposed to somatic cell editing (where only the treated individual is affected.) Whilst the report is advisory, the Council’s recommendations on similar topics such as mitochondrial donation have subsequently informed legislation in the UK.

The report

Against a backdrop of increasing genomic information available to parents, and the advent of a greater range of assisted reproductive technologies (of which genome editing may be a powerful addition), the report considers the ethical pros and cons for individuals, society, and humanity in general, with thought for the competing interests and moral claims at stake.

Their inquiry employs a critical moral framework, to question not ‘How we offer this technology in a manner that is ethically acceptable?’ but ‘Should we offer it, and what is at stake if we do or choose not to?’

It assesses a range of arguments including those surrounding reproductive interests, the implications for future generations, the interrelation between individual decisions and available options, and the burden of disease and related values such as the experience of fragility. The report concludes that genome editing interventions to influence the characteristics of future generations could be ethically acceptable, provided that two overarching principles are satisfied:

  • That such interventions are intended to secure, and are consistent with, the welfare of a person who may be born as a consequence, and
  • That any such interventions would not increase disadvantage, discrimination or division in society.

The media coverage

This conclusion has been met with a mixed response, criticised by some for not explicitly restricting genome editing to therapeutic applications (as the US National Academies of Science and Medicine did in their 2017 report), and sparking inflammatory media claims that ‘designer babies’ have been ‘given the go ahead’. Such criticism misinterprets the report and disregards the fact that adherence to these two principles ensures that certain safeguards are met. The decision whether or not to permit genome editing does not hinge solely on avoiding (or securing) a specified condition.  As the Council argues, medical, social and governance contexts are crucial. Only under specific circumstances is heritable genome editing deemed ethically acceptable, and the Council is clear that “these circumstances do not obtain at present”.

Under the Human Fertilisation and Embryology Act 1990 as amended, it remains unlawful to use edited gametes or embryos in treatment.  As the report acknowledges, legislative change, should it be required, is many years away and would be strictly regulated, permitting genome editing by license only after the risk of adverse outcomes has been assessed on a case-by-case basis.

Thus, it is unlikely that genome editing for anything other than serious genetic conditions could ever satisfy the second principle, which suggests that the ‘permissive stance’ reported by the media is a misrepresentation.

Challenges associated with heritable genome editing

Despite the potential of this technology to deliver therapeutic benefits, there are fundamental and pressing considerations that need to be addressed.

Unresolved safety concerns: There is considerable unease about the safety of genome editing tools. Whilst Chapter 2 of the report acknowledges the limitations of our current knowledge, much of the discussion is based on the assumption that genome editing is safe. This is understandable to the extent that safety is a prerequisite to clinical implementation and to foresee and ethically evaluate responsible pathways for translation. But many would disagree that heritable genome editing has “now become a real and distinct possibility” as monogenic diseases cannot yet safely be corrected in humans, let alone complex polygenic conditions or traits.

Studies, including one published last month by the Wellcome Sanger Institute, demonstrate that new and complex safety concerns are continuing to be discovered.  The challenges associated with ensuring the safety of the treatments being developed, trialled and delivered cannot be understated.

Alternative reproductive options and the ‘right’ to genetically related children: Prospective parents wishing to have a healthy child already have several reproductive options open to them; to adopt, to use a gamete donor, or to undergo preimplantation genetic testing. Therefore, it is important to establish what genome editing can contribute over and above existing technologies, and whether it can provide sufficient benefit to justify the potentially significant harms. Although there are rare instances where prospective parents are unable to have a genetically related child free from genetic disease, for example where both parents have Cystic Fibrosis or Huntington’s disease, these instances come with their own ethical considerations. As emphasised in one response to the Council’s Call for evidence – 'the most important, if not constitutive element of parenthood is that one is able - or, more radically, alive - to care for the child'.

A report that focused on the uses of somatic genome editing that are closer to implementation would have provided useful ethical insight into this technology whilst also providing a basis for assessing further applications

For most couples the desire to have a healthy, genetically related child is a powerful moral claim, but this does not constitute a ‘right’ under which the state has a positive obligation to act. It also must be placed within the broader context of potential harms to the child and to society. If, as the report notes, 'it is hard to foresee acceptable uses of heritable genome editing intervention other than as an alternative to existing procedures for the avoidance of heritable genetic disease' then perhaps it should remain behind a red line until we are confident that it can deliver safe and practical benefits. A report that focused on the uses of somatic genome editing that are closer to implementation would have provided useful ethical insight into this technology whilst also providing a basis for assessing further applications.

The Council give a comprehensive account of the relevant ethical considerations in their report and suggest a rigorous framework within which heritable genome editing could be delivered. But before we consider implementing this technology, even for therapeutic applications, we must be more confident that potential harms are minimised, and that the justifications for proceeding are fully met - and this includes assessing the risks and costs associated with enabling people to have genetically related children. 

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