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Mitochondrial Donation

Professor Nils Hoppe and Katy Rensten, both of Coram Chambers, look at the House of Commons debate and the proposed regulations concerning mitochondrial donation and argue for a serious and measured consideration of this important development.

Professor Nils Hoppe, Coram ChambersKaty Rensten, barrister, Coram Chambers

Professor Nils Hoppe and Katy Rensten, both of Coram Chambers

As practitioners of family law know only too well, the questions of what constitutes a 'family' and who are 'the parents' are constantly evolving, both in relation to the legal and to the genetic landscape: that this is a fast changing area of law, where regulation follows hard on the heels of scientific development, could not be better illustrated than by the recent parliamentary debate on mitochondrial donation.

On 3rd February 2015, following a lively debate in the  House of Commons on the draft Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015 (the Regulations), the Regulations were passed with 382 in favour and 128 against. The brevity of the debate (some 90 minutes) was the subject of criticism and caused consternation amongst MPs who had voted "against", with comparisons being drawn with the matter that  immediately followed (a debate on rural broadband connections) which was scheduled for the rather longer period of three hours. 

Mitochondrial donation has received significant attention in the press recently and it is unfortunate that a great deal of the reportage appears to be have been influenced by points of principle, which take their impetus from feelings of uncertainty or religious conviction.

In order to understand the implications of the Regulations and to dispel any misapprehensions, it is vital to understand their remit, the regulatory target, and the objections made against them.

The Regulations provide for the licensing of an innovative assisted reproduction technique (ART) called mitochondrial donation, in which a defective part of the mother's mitochondrial DNA is replaced with intact donor material.

Mitochondria are found in most cells and, amongst other control functions in relation to cell development and cell fate, they generate the chemical energy needed to keep the cells going. This is why they are occasionally referred to as the cells' 'battery packs'. The technique in question is only available during the course of using ART, such as in-vitro fertilisation (IVF) and is aimed at couples where the mother is likely to pass on an existing defect, leading to a mitochondrial disorder in her child. Mitochondrial disorders are varied but in many cases lead to significant impairment for the child, at an early stage, and in many cases, a very early death. One in 6,500 children is born with such a serious mitochondrial defect that can lead to death in early infancy.

The proposed Regulations would enable the Human Fertilisation and Embryology Authority (HFEA) to license individual treatment centres to make this intervention available to appropriate couples. The alternative choices thus far for these couples are to have no biological children at all or to take the risk of having a child with such a disorder. Mitochondrial donation provides for a procedure where they can have biological children without the risk of passing on the defective mitochondria.

The Regulations propose two forms of licensable mitochondrial donation: pronuclear transfer (PNT) and maternal spindle transfer (MST). The 2012 Nuffield Council on Bioethics Report summarises the technologies succinctly:

"PNT involves using very early (one day old) embryos. MST uses unfertilised eggs. Both techniques would create embryos in which the nuclear genetic material of the intended parents is re-housed along with healthy mitochondria from a donated egg. This could come from either an unrelated donor or a maternal relative with healthy mitochondrial DNA. A maternal relative's healthy donated mitochondria would be identical to any healthy mitochondria the intended mother had, effectively permitting her to pass on what she may regard as 'her family's' mitochondrial DNA to her child." (Nuffield Council Report 2012, vii.).

This summary of the technique already hints at two important objections raised against it: the destructive 'use' of an ovum and the alteration of the cells' germ line.

It is, first, important to realise that a great many of the objections raised against the proposed Regulations belong in the category of 'slippery slope' type arguments, usually taking the form of  'This is a dangerous road to take...', 'Whatever next?' , or 'If we allow this, we'll allow X [usually something unpleasant] next'.  Given that they evade empirical proof entirely, it is difficult to see how such objections should have any place in a reasoned debate. Similarly, objections which are made 'on principle' are usually difficult to engage with in any appropriate way, as the principle being invoked is often not defined and is employed as simply another way of saying 'I am just against this'.

That said, there are a number of valid objections which ought to be addressed in more detail. Broadly, although some of these issues are intertwined, they can be segmented into (1) safety concerns, (2) ethical concerns, and (3) consistency with EU law. Within the confines of this article, it would be difficult to do justice to the past and current debate in legislature and literature, so what follows can be only a brief outline discussion of the objections and the main counterarguments.

Firstly, it has been suggested that the evidence base for the safety of this intervention is too 'thin' to justify making the technology widely available. It is very much worth bearing in mind that no medical intervention is entirely safe, so what this question boils down to is the usual balancing exercise between risk and benefit that imbues all of biomedical practice. In presenting the Regulations, Jane Ellison MP quoted Frances Flinter, a professor in clinical genetics at Guy's and St Thomas' NHS Trust, as saying:

"There has been more scientific review of this proposed process than any other medical technology."

Whether this brief statement is entirely correct might be open to discussion, but what is clear is that the sentiment expressed is one of approval with the breadth of the scrutiny which this technology has undergone. No risks have been identified at this stage which outweigh the significant benefits of counteracting the near certainty of a fatal disease in a child born with a mitochondrial disorder. In line with the usual vigilance that accompanies innovative or established medical interventions, safety data will be continuously surveyed and scientifically assessed as the intervention becomes more routine.

Secondly, there are also a number of ethical and philosophical objections to the treatment. One is that, the technology is not, in fact, aimed at curing mitochondrial disease but instead at replacing the sick child with a healthy child – in other words, rather than removing the disease from a defined individual, it is creating an altogether new individual who just happens not to have this disease. The extremely complex philosophical points about individuality and personhood to which this gives rise are impossible to encapsulate in these few lines. Suffice it to say that any selective procedure during ART (such as a choice based on morphology to determine which embryo to implant and which to discard) is also a decision which alters the person that is the product of such a procedure. The genuinely interesting question here would actually be why a scientifically informed interference with the 'raw material' is more problematic than a subsequent discarding of a morphologically undesirable embryo.

An additional issue which is raised is that the proposed procedure relies on the depletion of two ova (the creation of an embryo using one ovum, and then the rehousing in the second ovum). This part of the procedure was wholly incorrectly characterised by Fiona Bruce MP in the Commons debate, in which she made repeated reference to the 'destruction of at least two human embryos [...] to create a third'; this is simply wrong. A donor ovum is, nonetheless, required for this procedure and some might object to the 'utilisation' of an ovum in this way, in the same way as they would object to sperm donation, IVF in general or indeed blood transfusions or organ donation.

Other objections which are offered under the heading 'ethics' tend to be little more than expressions of general uneasiness about a novel technology which interferes with the course which budding life takes. It has, rightly, been pointed out that the very same objections were raised when IVF was first debated. In particular, the fear that this type of technology might lead to designer babies seems to be aimed not so much at the technology than at those who use the technology, and for what purpose.  In other words, what ought to be the subject of regulation is the context in which the technology is deployed rather than an outright prohibition of the technology itself. That is exactly what the Regulations propose to do.

Thirdly, the question of interfering with the creation of life ties in with the objections raised in relation to EU law.  Whether or not the Regulations are compatible with EU law was a matter raised vociferously by Robert Flello MP who made reference to Art. 9(6) of the EU Clinical Trials Directive (2001/20/EC), which stipulates:

"[...] No gene therapy trials may be carried out which result in modifications to the subject's germ line genetic identity."

It is without doubt the case that the replacement of mitochondrial DNA interferes with the subject's germ line genetic identity, though not in the way envisaged by the drafters of the Directive. The nuclear DNA remains unchanged and this is where the individual's identity and phenotype are encoded. Nevertheless, this norm can be taken as a clear indication against this type of modification in the context of gene therapy trials. At the same time, the licensed provision of IVF treatment including mitochondrial replacement to individual parents does not, in any way, constitute a clinical trial (as is clear from Art. 2 of the Directive).

Additionally, curative treatments are already being offered under the NHS which lead to a modification of the subject's germ line, such as lymphoma treatments and, generally, chemotherapy. It is clear that the legislator's objection was not to interventions which alter the germ line per se, but to experimentation aimed at altering the germ line as a primary effect. The objection that the Regulations fall foul of the Clinical Trials Directive is therefore, in the authors' view, misguided.

It seems to the authors of this article regrettable that the Commons debate surrounding the Regulations was driven, by and large, by non-scientific objections. In particular, the regular recourse to 'slippery slope' arguments significantly devalued the quality of the debate. What is all too often overlooked is that ethical arguments are available to both those for and against. Merely having one or more ethical argument on one's side does not unhinge the debate in its entirety – the exercise will be one of balancing the arguments on either side. 

Mitochondrial donation is a proven technique which will enable couples to make the best possible attempt at conceiving children without avoidable diseases. To force couples to have no biological children or to acquiesce to the risk of having children who suffer greatly and die early, despite having at our disposal the means to prevent this, falls considerably short of our moral obligations.

It is imperative that such important developments, placed as they are at the intersection of multiple complex ethical and legal issues, are given the serious and measured consideration they deserve, in order that the law that evolves in the wake of the science, is the best that can be achieved. 

Nils Hoppe is professor of life sciences regulation at the University of Hannover and an associate tenant at Coram Chambers. His work focuses on the regulation of innovative health technologies, genetics and genomics, and biobanks. Katy Rensten is a barrister at Coram Chambers specialising in both public and private law children cases.