The profile of “three-person IVF” was raised during a recent Westminster Hall debate on the application of the technique to combating mitochondrial disease, and a subsequent Department of Health Press Release indicating that a public consultation “was expected” on the associated draft regulations. The latter announced the Government’s intention to introduce a final version for debate in Parliament in 2014. This is yet further legislation contrary to the beliefs of some religious and other groups, and these have been quick to condemn the move, here, here (with thought-provoking cartoon), here, and elsewhere. The current moves represent the next stage an established research programmes, which although not high-profile, have nevertheless been within the public domain.
As we and others have observed, these events have been sensationalized in the media and this has introduced a degree of confusion, not least from the use of the “three-parent” descriptor, which from many points of view is a misnomer. Whilst there has been widespread comment on the religious and ethical issues, relatively little has been reported on the legal aspects of which there are two main issues: the legality of the IVF technique when used in the manner proposed and the implications to the parties involved resulting from its use. Although the extension of IVF to this area will have significant ethical and religious impacts, relatively few changes need to be made to the existing legal provisions. Nevertheless, it is important first to understand how these techniques will be applied, and to be aware of the consultations and public discussion that has already taken place.
IVF and mitochondrial disease
An overview of the scientific issues involved, the treatments currently available, and the social and ethical issues raised by their potential use in IVF, is given in the Parliamentary Office of Science and Technology, (POST), report Preventing Mitochondrial Disease , issued in March this year. The ethical issues are considered in greater detail in the Nuffield Council on Bioethics Report Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review published in June 2012, and more recent information on the current status of the research was presented in the Westminster Hall debate in June 2013.
The Nuffield Report summarizes the technique [page vii] as follows:
“Mitochondria are tiny structures inside our cells which provide the energy for cells to function. Their failure to work properly can have devastating effects. Mitochondrial disorders can be caused by either problems in the genes in the nucleus affecting mitochondrial function, or by problems in genes within the mitochondria themselves. Recent years have seen increasing attention paid to two techniques both currently at the research stage: pronuclear transfer (PNT) and maternal spindle transfer (MST). These two IVF-based techniques seem to have the potential to prevent transmission of maternally inherited mitochondrial disorders caused by mutations in the genes of mitochondria.
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”.
In Westminster Hall, the Parliamentary Under-Secretary of State for Health, Anna Soubry, stated [25 Jun 2013 : Col. 64WH],
“This issue is about giving women a choice on whether or not their DNA is put into another woman’s egg. In effect, a woman would be hijacking the batteries, because mitochondria are the batteries that provide the energy, and when they do not work, they cause these diseases. This is not about any kind of genetic engineering, about which people would rightly be concerned. . . . . . the press have perhaps been a bit misleading in saying that . . . . . . some children will have three parents. They really will not: they will have their biological mother and father. It is simply that the batteries have been taken from another woman’s egg so that they are sure that any child does not bear some of the very serious diseases that often lead to premature death”.
With regard to ethical considerations, the Nuffield report [page 52] states:
“Provided that research shows PNT and MST to be effective and acceptably safe as potential treatments, the most obvious ethical reason to permit their use is that they would offer the possibility of preventing the transmission of mitochondrial DNA disorders, which affect some people’s health very seriously. Alongside this, they would offer women who carry such disorders, or who are affected by them, the chance to have healthy children who are also genetically related to them.
It notes that three pressing areas of ethical concern remain which, some had argued, may potentially override the positive aspects of these techniques:
- that PNT and MST are forms of germline therapy, with the problematic features of germline therapies in general, or that permitting their use would create a “slippery slope” towards permitting alterations of the nuclear germline.
- that the knowledge regarding the safety of PNT and MST is uncertain and in absolute terms will remain so until several generations of people have been born from the procedure: permitting their use creates the potential for harm to future persons.
- that a person born with three genetic contributors might have a conflicted or confused self-image, and perhaps conflicted or confused perceptions of the social roles of others in relation to themselves, as a result of this.
In addition to these ethical concerns, there are religious objections to the technique, the Roman Catholic view being summarized in paragraphs 2373-2379 of the Catechism, The Gift of a Child,
“2376 Techniques that entail the dissociation of husband and wife, by the intrusion of a person other than the couple (donation of sperm or ovum, surrogate uterus), are gravely immoral. These techniques (heterologous artificial insemination and fertilization) infringe the child’s right to be born of a father and mother known to him and bound to each other by marriage. . . . . . . . . .”
2377 Techniques involving only the married couple (homologous artificial insemination and fertilization) are perhaps less reprehensible, yet remain morally unacceptable. They dissociate the sexual act from the procreative act. . . . . . .”
Dame Catherine Wybourne commented recently that it appears as though children are no longer seen as a gift from God but as a lifestyle choice, or even a human right. Although proponents of IVF might reason
“[t]here are those who argue that the techniques create children with three parents, but the embryo would carry only a small number of genes from the donor—just 13 out of 23,000, or 0.056% of the genetic material. How much of a parent is that? The function of the 13 genes is restricted to powering the mitochondria; they do not affect personal characteristics such as eye or hair colour, or behaviour”,
clearly this is no justification for those who consider the technique as morally wrong per se. Further objections from the Roman Catholic point of view are put forward in the briefing paper by the Anscombe Bioethics Centre, a Catholic academic institute that engages with the moral questions arising in clinical practice and biomedical research. The briefing paper states inter alia
– PNT should be considered unethical because, in addition to the problems of germline genetic engineering which it shares with MST, PNT is a particularly destructive form of human cloning; PNT involves the destruction of the embryo from whom the pronuclear material is taken and the destruction of a host embryo (by the removal of its own pronuclei), [at 2.1 and 2.2].
– From a genetic perspective, the child of MST would have three parents: a genetic father and two genetic mothers. The mitochondrial mother provides an element of inheritance that is special to the female line – a distinctive maternal genetic contribution. The child of PNT would have genetic ancestry but no genetic parents, and no immediate living precursors. He or she would be a clone created from the deliberate destruction of two embryos, [at 4.1].
– Apart from the embryos destroyed in research along the way to developing either method, ‘successful’ pronuclear transfer will effectively involve destructive reproductive cloning from the original embryo of the woman who wants a baby. This embryo is destroyed when its nuclear genetic material is harvested and placed in the ‘shell’ of a largely-gutted second embryo. This grossly disrespects human life, and the offspring will need to come to terms with the fact that he or she was created from the bodies of embryos created and killed precisely as ‘building blocks’ for him or her, [at 4.2].
The principal legislation is the Human Fertilisation and Embryology Act 1990, (“the 1990 Act”), as amended by the Human Fertilisation and Embryology Act 2008. The latter updates parts of the 1990 Act in relation to assisted reproduction treatment and embryo research whilst the main features of the existing model of regulation: Part 1 takes account of scientific developments to reflect changes in social attitudes and updates the regulatory provisions relating to HFEA. Part 2 introduces a new concept of “parenthood” for a mother’s female partner in certain circumstances, making equivalent provision to that for opposite-sex couples. Part 3, inter alia, amends the Surrogacy Arrangements Act 1985.
On 8 September 2005, after its initial rejection, the HFEA granted licence under the 1990 Act to the Newcastle University for mitochondrial research. Although not then published, the results were reported during the House of Lords debate on the 2008 Act, [4 Feb 2008 Col. 847] when calls were made for the technique to be licensed by the HFEA for treatment.
The 2008 Act anticipated emerging advances in this field; and section 3 inserts a new subsection ZA(5) into the 1990 Act providing for a regulation-making power specific to mitochondrial disease under which, in relation to permitted eggs, permitted sperm and permitted embryos
“Regulations may provide that—
(a) an egg can be a permitted egg, or
(b) an embryo can be a permitted embryo, even though the egg or embryo has had applied to it in prescribed circumstances a prescribed process designed to prevent the transmission of serious mitochondrial disease,”
The 2008 Act’s Explanatory Notes state that:
“[i]n the future, it may be possible to create embryos using an affected woman’s egg, her partner’s sperm and healthy donated mitochondria. This regulation-making power will enable such embryos and eggs to be implanted in a woman if the technology became available and was proven safe. Further provision regarding mitochondrial donation is made in section 26, which inserts new section 35A into the 1990 Act.”
With regard to parenthood in cases involving assisted reproduction, section 33 re-enacts section 27 of the 1990 Act: i.e. the woman who carries a child following assisted reproduction regardless of where this is carried out is regarded in law as the child’s mother, unless the child is subsequently adopted or parenthood is transferred through a parental order. Section 33(1) provides that
“[t]he woman who is carrying or has carried a child as a result of the placing in her of an embryo or of sperm and eggs, and no other woman, is to be treated as the mother of the child.”
In March this year, HFEA published the findings of a public consultation on the social and ethical implications of mitochondria replacement, the latest step in evaluating the scientific, social and ethical aspects of these treatments for clinical use. Its recommendations to government for the proposed Regulations include:
- Specific licensing by HFEA of clinics wishing to offer mitochondria replacement.
- Approval by HFEA of each use of mitochondria replacement, though Regulations should permit a degree of flexibility to modify this in the future.
- Follow-up research on the children born to be undertaken
- Mitochondria donors regarded as equivalent to “a kind of tissue donor”: the resulting child should not have a right to identifying information about the donor, although information exchange and contact could be arranged locally by mutual consent.
- Further assessment of the safety and efficacy to be commissioned by HFEA once a clinic has submitted an application to carry out one of the techniques.
During the Westminster Hall debate, Anna Soubry stated
“Our considerations are being led by the chief medical officer. It is right, if we are to move forward, that she should be the person to lead on the proposals—she may reject them—and, as the CMO, to make any announcement and to be at the forefront of any decision. I am told that her considerations are almost complete”
“[t]he chief medical officer has given the issue her careful consideration in the light of the advice and the findings of the Human Fertilisation and Embryology Authority, following the consultation period. I anticipate that she will set out the Government response before the summer recess and, even with my poor mathematics, I can work out that that should certainly be within the next few weeks.”
The House of Commons rises on 18 July.
 POSTnote 431, Preventing Mitochondrial Disease: The Parliamentary Office of Science and Technology (POST) is an office of both Houses of Parliament, with the responsibility for providing independent and balanced analysis of policy issues that have a basis in science and technology.