Event Review: The Ethics of Mitochondrial Replacement Therapy

Ethical dimensions of the emerging technology of mitochondrial replacement were the focus of a symposium that took place on 25 June at the 12th World Congress of Bioethics in Mexico City.

Mitochondrial DNA (mtDNA) disorders are among the most commonly inherited neuromuscular diseases and can cause immense suffering and death. The development of new technologies may lead to the replacement of mitochondria carrying harmful mtDNA mutations with 'healthy' mitochondria from donated eggs. These experimental techniques may allow parents who are likely to pass on mtDNA disorders to have a genetically related child without the disorder. However, they raise challenging ethical issues.

Dr Annelien Bredenoord discussed the ethical challenges raised by the uncertainty of first using such radical new techniques. She highlighted the fact that the techniques modify the germline and modifications would thus be transmitted to subsequent generations. This raises the challenge of evaluating intergenerational risks and benefits. She also discussed the ethics of using nonhuman primates and embryos in preclinical research to reduce risks.

Dr Bredenoord argued that to be justifiable, mitochondrial replacement should present a favourable balance of risks and benefits in comparison with current alternatives, namely egg donation, prenatal diagnosis and preimplantation genetic diagnosis. She suggested that the most challenging ethical issue is justifying the leap from 'bench to bedside' in the presence of promising preclinical results. In many other risky first-in-human studies the research participant decides whether to take the risk, but in this case the couple decides and the prospective child carries the risk. It is thus of tremendous importance to rigorously evaluate preclinical safety data and to ensure long term follow up in order to enhance the ethical acceptability of mitochondrial replacement as a reproductive option.

Dr John Appleby considered the anonymity of mitochondrial donors in light of recent proposed legislation by the UK Department of Health to make mitochondrial donation anonymous, even though anonymous gamete donation is prohibited. This discrepancy appears to be based on the view that mitochondrial donation is unlikely to affect the identity of offspring and that future persons are thus unlikely to want to know who their donors were.

The mitochondrial genome is much smaller than the nuclear genome and so is thought not to have the same phenotypic effects on a future person as a nuclear genome. However, Dr Appleby argued that donor conceived persons do not typically understand their identities in a narrow genetic sense and often have other reasons for wanting to know the identity of their donors. He concluded that until we have strong grounds for doing otherwise, it would be unjustified to treat mitochondrial donors differently from other gamete donors and that neither should be anonymous.

Dr Anthony Wrigley outlined ways in which our genetic origins might play a role in determining our identity in light of mitochondrial replacement techniques. Currently, two techniques are suggested: 'maternal spindle transfer' (MST) in which mitochondrial transfer occurs before fertilisation and 'pronuclear transfer' (PNT) in which it occurs after the egg has been fertilised, and therefore after the core genetic identity of the future person has been established.

Dr Wrigley explored how Parfit's Non-Identity Problem can be applied to inform our ethical evaluation of these two techniques by asking: 'does using technique x cause a (numerically) different individual to be born than if technique x were not used?'. He argued that this would be true for MST, since the genetic identity of the future individual is created after the intervention and in this sense the intervention creates a different individual. However, it would not be true for PNT, since the genetic identity is created prior to the intervention. Therefore, in cases of MST, we cannot normally claim that individuals so created have been harmed or have benefitted from mitochondrial replacement. However, cases of PNT can be seen as modifying an existing individual and could therefore be classified as 'treatment'.

Professor Stephen Wilkinson built on this conclusion that MST is a form of selective reproduction (selecting individual x rather than y) whereas PNT is a case of embryo modification, and discussed the ethical implications of such a distinction. He argued that straightforward attributions of harm and benefit could be harder in the case of MST because of the Non-Identity Problem.

Moreover, he emphasised that concerns about eugenics and human dignity, which some critics have raised, could be stronger in the case of MST if this involves 'selecting out' embryos with mitochondrial disease (whereas PNT involves attempting to 'treat' them). Finally, he argued that parents' obligations to seek treatment could be stronger in the case of PNT, because not doing so may harm their future child and may be compared to (or even be an instance of) failing to provide needed medical treatment. This however would not apply to MST, if MST is 'selection' rather than modification or treatment.

Finally, Professor Vardit Ravitsky highlighted the extensive media coverage of the public debate surrounding this controversial technology and discussed the role the media plays in shaping public perceptions. She presented various portrayals of mitochondrial replacement in the media and offered some reflections regarding how different framings may shape the public debate. She analysed the implications of using sensationalist terminology such as 'three-parent babies' and 'genetically modified children' versus more neutral and scientific terminology such as 'transfer' or 'replacement' and even favourable terminology such as 'therapy' and 'life-saving treatment'. She argued that as experts, bioethicists and scientists have a responsibility to carefully choose terminology and framing when informing the media and the public.

The symposium was part of a five-year programme of
research titled 'The Donation and Transfer of Human Reproductive Materials', led
jointly by Rosamund Scott (Professor of Medical Law and Ethics at King's
College, London) and Stephen Wilkinson (Professor of Bioethics at Lancaster
University). It is funded by a Wellcome Trust Senior Investigator Award in
Ethics and Society and runs from 2013 until 2017. To find out more about the
project please click here.