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IVF and the prevention of mitochondrial DNA disease: the moral issues

3 May 2011
By Professor Alison Murdoch
Professor of Reproductive Medicine, Newcastle upon Tyne
Appeared in BioNews 605
'And since it is always more agreeable to think in simple than in complicated terms, and since moral indignation is one of the most delightful of passions to indulge in, I believe that there is a real danger that the indignant will win the day and all research using human embryos will be brought to an end. Those who believe in the need for this research have a duty to argue their case as widely, but also as intelligently, as possible' Mary Warnock, 1985 (1).

Medicine has faced many controversial milestones, none more so than those involving reproduction. IVF was one but, after 30 years, it is now accepted medical practice enabling previously infertile couples to become parents. IVF has also evolved to help couples with other problems. For example, PGD (preimplantation genetic diagnosis) enables those who carry a serious risk of having a child with cystic fibrosis to transfer an embryo without that genetic fault.

Technology has developed in other areas too, such as reproductive cloning. However, this has been agreed internationally to be a step too far and is prohibited in humans. The UK Government must now decide whether we can use IVF technology to reduce the risk of transmission of mitochondrial DNA abnormalities. Will they accept it or reject it?

The UK's Secretary of State has before him a report on the scientific progress towards finding techniques that will reduce the risk of a mother transmitting abnormal mitochondria to her children (2). We now have a clear plan, with a foreseeable timescale, for the implementation of these techniques. Government approval is required to permit this treatment.

The new techniques will help a woman who carries abnormal mitochondrial DNA to have a healthy baby. The nuclear DNA of her embryo (carrying the information that determines her baby's characteristics) will be transferred to an activated, enucleated egg of a donor with normal mitochondrial DNA.

Although the scientific path is clear, the moral issues are undefined. Three main issues emerge. First, are we stepping over an acceptable line by manipulating embryos? Second, are techniques acceptable if the results will be passed to the next generation? Finally, is it right for society to deny treatment because of these concerns?

Routine IVF treatment creates more embryos than will be transferred. They have been knowingly created to increase the chance that at least one will result in a baby. 'Using' embryos in this way is accepted practice. 'Disrupting' embryos (e.g. taking a biopsy for PGD) is also a routine procedure. Although challenged by some, in these respects the proposed techniques are not new.

When we use IVF to prevent mitochondrial DNA disease, we will also have transplanted intracellular structures from egg donor to child. Is this really novel? A child who has had a bone marrow transplant will be healthy because cells from another person are integrated into their body; they have genetic material originating from three people. This may be argued to be an issue of scale, not one of fundamental moral concern.

Some will argue changes to a baby's mitochondrial DNA are different because the change will pass to the next generation. This is termed 'germ line therapy', a technological Rubicon. Changes in the nuclear DNA would be passed through the germ line - sperm and eggs - to the next generation. By association, we need to consider eugenics, if only to dismiss it.

Modification of the nuclear DNA in human embryos is illegal in the UK. Breaking the inheritance chain is currently achieved by selecting healthy embryos for transfer, for example, PGD or abortion after prenatal diagnosis. Although permitted in the UK, both have been challenged because of the risk that they promote the philosophy of eugenics.

Mitochondrial DNA is passed intact down the maternal line and does not influence a person's characteristics, despite affecting their heath. While not underestimating the issues, they mainly arise by similarity of terminology not intent. Like PGD, preventing mitochondrial DNA disease falls within the good medical practice of preventing serious illness, not eugenics.

The most difficult ethical issues are those faced by the potential parents of children, not politicians making the decisions to permit these techniques. Parents must live with the consequences of giving birth to a child with serious disability, using donated gametes, having no children or risking this new technique. When debating the issues above, we must consider the patients living with these real dilemmas. Society is not harmed by these techniques, neither are any other people within society.

The use of sensational or exaggerated comments in this debate is irresponsible. Similar discussions before IVF resulted in unwarranted social stigmatisation of early IVF babies. The family that take home a baby that has been 'cured before implantation' or even 'cured before conception' will inevitably receive attention, but responsible terminology and debate now may reduce future stigmatisation.

Their child will contain genetic material from more than its mum and dad. They may be labelled 'miracle babies', but to mum and dad they will just be their own healthy baby. Where is the moral right in denying them that choice?

1) The Warnock Report
British Medical Journal |  20 July 1985
2) Scientific review of the safety and efficacy of methods to avoid mitochondrial disease through assisted conception
Human Fertilisation and Embryology Authority (HFEA) |  18 April 2011
22 July 2013 - by Professor Stephen Wilkinson 
Why are potentially positive developments like mitochondrial replacement therapy and next-generation sequencing greeted with talk of 'designer babies', and is such language justified?
18 February 2013 - by Professor Alan Handyside, Dr Karen Sage, Michael Summers and Dr Alan Thornhill 
The Human Fertilisation and Embryology Authority recently announced plans to review the list of approved inherited conditions for which preimplantation genetic diagnosis is currently licensed to ensure that it is only available for conditions which meet the statutory requirements in the UK...
17 September 2012 - by Sarah Norcross 
Mitochondria don't normally get much press attention, they like to keep a low profile generating energy in the cells and leave nuclear DNA to grab the headlines...
13 February 2012 - by Professor Mary Herbert 
The advent of PGD extended the scope of IVF beyond the treatment of infertility. PGD is predominantly used to prevent transmission of genetic defects arising from mutations in nuclear DNA. However, it can also be used to reduce the risk of transmitting mutations in mitochondrial DNA (mtDNA), which cause a range of debilitating and life-threatening diseases...
13 February 2012 - by Dr Kristina Elvidge 
Mitochondrial diseases are soon to be brought to the attention of the general public, as the Government seeks to gauge the attitude of the nation towards a ground-breaking IVF treatment that could prevent these conditions being passed from mother to child...
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