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Mitochondrial Transfer (Three-Parent Children)

Volume 577: debated on Wednesday 12 March 2014

I am grateful that the debate has been granted and for the opportunity to serve under your chairmanship, Mr Pritchard. I am delighted that the Under-Secretary of State for Health, my hon. Friend the Member for Battersea (Jane Ellison) will reply, because she is one of the most highly regarded Ministers in Her Majesty’s Government. I would also like to thank my hon. Friend the Member for Congleton (Fiona Bruce) for all her help in preparing for the debate, as well as Dan Boucher, Helen Watt and Luke Gormally.

It is important to begin the discussion by explaining what is at stake with three-parent babies and mitochondria. Mitochondria are the organelles within every cell responsible for the generation of cellular adenosine triphosphate energy. That passes entirely in the maternal line and can carry serious diseases.

There are two means of replacing the mitochondria. Maternal spindle transfer, or MST, takes place before in vitro fertilisation. The spindle, which carries the genes in the nucleus of the egg, is removed from the healthy donor egg and replaced by a spindle taken from the egg of the commissioning mother—that is, the woman at risk of passing on mitochondrial disease. All other parts of the donor egg, including the healthy mitochondria, are left in place. The combined egg is then fertilised by the father’s sperm, and the embryo has three parents: the spindle mother, the egg donor mother and the father. Genetic parenthood is complete in the case of the father but fragmented in the case of the two mothers.

In pronuclear transfer, or PNT, two embryos are created by IVF. One, the embryo of the commissioning women, will have its mother’s affected mitochondrial genes. The other is the healthy embryo of an egg donor. The embryos are combined using a technique somewhat similar to that in the cloning of Dolly the sheep. Interestingly, the licence for the experiment was adapted from the licence originally given for Dolly-style cloning.

Given that this is obviously an incredibly important matter, akin to cloning, with a child having several parents—I know of no other country in the world that has done this—does my hon. Friend think it should be the subject of a full debate on the Floor of the House?

I certainly think that this matter ought to come to the Floor of the House. I understand from an earlier debate that the Government are committed to full parliamentary scrutiny, but no doubt the Minister will confirm that.

To continue on PNT, at the one-cell stage the donor embryo pronuclei containing the nuclear genes are removed, killing that embryo. The partially gutted donor embryo with its healthy mitochondria is then used to form a new embryo when the pronuclei harvested from the commissioning woman’s embryo are inserted. Harvesting the pronuclei from the commissioning woman’s embryo kills that embryo.

It is important to understand that the techniques are non-therapeutic. They are in no sense a cure for children who are already born, nor do they pretend to be. Rather, the techniques create new people with altered genetic composition—genetically designed individuals who will not inherit mitochondrial disease. Although the mitochondrial DNA is around only 0.1% of a person’s total DNA, a little leaven leavens all the bread, and a different person is thereby created.

The proposed techniques all promote germ-line genetic modification. That is an infinite change that will lead to all the descendants of someone treated in this way being changed, the consequence of which cannot be known.

I thank my hon. Friend for raising this critical subject. Techniques for mitochondrial transfer deliberately create a child who has three genetic ancestors, or, in the case of PNT, four. Is that not extremely concerning, raising as it does serious issues of personal identity for those born through the technique, particularly since Government guidelines propose that such individuals will not be allowed to know the identity of their third or forth parent? Will that not then transfer into future generations, too?

I was going to come on to that. As an aside, the reason we were able to determine that Richard III’s body was his was through the female line, and because we could establish the continuity of the DNA. I do not believe Government promises of secrecy. They promised that to sperm donors historically. Governments cannot be relied upon, because society becomes more open and so demands greater openness. I have no doubt that if the technique is ultimately used the donors will be identified and people with three or potentially four parents will find out.

On that point, the worry that occurs immediately to me as I listen to my hon. Friend is that if someone does not know who the third or fourth person who created them is, through sheer chance they may well find themselves marrying their brother or sister.

That is a risk, and there are others. Already in the United States a different price is charged depending on the educational qualifications of the donor. There are worries about eugenics, a point I was going to come on to.

The head of the United States Food and Drug Administration advisory committee on this matter, Evan Snyder, has said that there are not enough clinical data to suggest that mitochondrial transfer is safe. Does the hon. Gentleman agree that the present UK regulator and the UK Government should be cautious in approaching this technique?

Another issue occurs to me with regard to knowing who the third or, indeed, fourth parent is or was. Let us suppose that, in subsequent generations, further scientific research finds that another fault is being passed down generations. Without knowing whether the third or fourth parent several generations back carried some other gene that has come to the fore only after 150 years, someone would not know whether they were affected. There is a Pandora’s box of problems.

That must be right. It ends up being a multi-generational experiment with the lives of people.

To return to the PNT technique, it is effectively cloning. As I said, it is telling that the licence for the experiment was adapted from the licence given to create Dolly the sheep. Cloning is widely regarded as a dangerous technique. Essentially what is being done is eugenic.

The company that developed Dolly the sheep received funding from an organisation of which I was chairman. I remember visiting it and expressing a concern that it was one step from cloning sheep to cloning humans. I was reassured that no such thing could possibly ever happen, as the human race was far too sensible. This issue challenges that, big time.

As so often, my hon. Friend is right.

The dictionary definition of “eugenic” is:

“Of or bringing about the improvement of the type of offspring produced”.

The 1922 Eugenics Congress called it

“the self direction of human evolution”.

There is grave question mark about eugenics. It frightens almost every sensible person. It is not only people who share my views who think that. In a letter to The Guardian dated 15 March 2013, that fear was made explicit by a number of medical experts. It is interesting that they chose The Guardian, which is not a bastion of right-wing reaction, to make that point. In a country nervous about genetically modified crops we are making the foolhardy move to genetically modified babies.

There are three categories of risks and dangers that have not been fully considered. The first is the category raised by the hon. Member for Stoke-on-Trent South (Robert Flello), namely practical risks relating to the long-term efficacy of the therapy. An article published in Nature in October 2012 said:

“Pioneering work in nonhuman primates is critical for the development, and safety and efficacy evaluations, of new treatments.”

That view has been discounted by the Human Fertilisation and Embryology Authority without any good reason being given. Current research using PNT in macaques has yet to be shown to be successful. Macaque zygotes do not survive the PNT process well, even though their oocytes are less prone to abnormal activation and fertilisation than human ones. If that is the case, surely we should continue with such experiments first, rather than relying on the fact that four monkeys have reached the age of three.

On that point, the research that has been done talks about generations of mice or of monkeys, but that does not address the fact that until there have been three, four, five or 10 generations, we will not know what the long-term effects are.

I agree with the hon. Gentleman. I also think that mankind is of a different order of magnitude from other animals. I do not view myself merely as a senior ape—nor indeed do I view Opposition Members as merely being senior apes or monkeys. I think much more highly of them than that. [Interruption.] I will gloss over that point. In their article in Nature, Mitalipov et al showed that they had discovered that 52% of human embryos created through MST had chromosomal abnormalities. If there is a high failure rate early on, how can we be certain that there will not be a similar failure rate later, potentially when people are in their 30s or 40s? It is a life-long, generational experiment.

There are also difficulties with the experiments on fruit flies.

An article in Science on 20 September 2013 states:

“MR in fruit flies had little effect on nuclear gene expression in females but changed the expression of roughly 10% of genes in adult males. The mitochondrial haplotypes responsible for these male-specific effects were naturally occurring, putatively healthy variants. Hundreds of mitochondrial-sensitive nuclear genes identified in that study had a core role in male fertility. For example, one of the five combinations in which mitochondrial-nucleus interactions were disrupted by mismatching was completely male-sterile but female-fertile. In other fly studies MR resulted in male-biased modifications to components of ageing”—

that is very important because we do not know what the effects will be as people get older—

“and affected the outcomes of in vivo male fertility. Together, these results suggest that core components of male health depend on fine-tuned coordination between mitochondrial and nuclear gene complexes and thus the HFEA conclusion that ‘there is no evidence for any mismatch between the nucleus and any mtDNA haplogroup at least within a species’ is incomplete and unsubstantiated.”

It has also been discovered from research in mice and invertebrates that deleterious effects on mitochondrial replacement would not be discovered until adulthood, which goes back to the point that we would have to wait decades.

The second category of risk is moral and ethical. I make no bones about the fact that my thinking on this matter is strongly influenced by the Catholic Church concerning the dignity of the human person. Equally, the Minister and the Government should respond to non-theological, non-religious concerns. I will set out briefly the religious concerns.

Thomas Aquinas wrote in his “Summa Theologica” that

“the soul is in the embryo”.

I certainly believe that to be the case. It means that tampering with embryos is tampering with human souls—tampering with what sets us apart from animals. As Benedict XVI in the Instruction “Dignitas Personae” said,

“the body of a human being, from the very first stages of its existence, can never be reduced merely to a group of cells. The embryonic human body develops progressively according to a well defined programme with its proper finality, as is apparent in the birth of every baby.”

That, too, is absolutely correct. No human, whatever their stage of development, is merely a group of cells.

We must be concerned about the unknown consequences of tampering with the genes of an embryo, and for the unreligious there will be mental issues to be faced by those who find out later life that they have three or even four parents. The gravity of the change is such that it should not be made without the most careful thought and properly tested research. [Interruption.]

Order. I am sorry to interrupt the hon. Gentleman. Will whoever has their phone on please turn it off, or put it on silent or vibrate? This is an important debate and it needs to be heard with respect.

Thank you, Mr Prichard. Silence is golden.

The third risk is legal, and I am slightly reluctant to raise it because it concerns the European Union charter of fundamental rights. It is not a document I often quote in support of an argument, but there is a question about its applicability in the United Kingdom. It is not directly applicable in UK law except when it coincides with EU law. There is considerable debate about how far the overlap between UK and EU law goes. Article 3(2) refers to the

“prohibition of eugenic practices, in particular those aiming at the selection of persons”.

I have established that this is eugenics, so it would be in contravention of the Charter of Fundamental Rights. I do not believe that the Government would want to contravene that accidentally.

Essentially, the Government have started too early and are putting the cart before the horse, which makes travel difficult, by consulting on regulatory approval before sufficient research has been done into the safety of the therapy.

I apologise for not being here earlier. The Northern Ireland (Miscellaneous Provisions) Bill was being discussed in the House and I had to be there.

Does the hon. Gentleman accept my concerns on behalf of the people of Northern Ireland who are very worried by what was suggested the other day—that the Department of Health is pressing forward with regulations without full consultation and without the impact being fully known? I hope that the Minister will assure us that that will not happen.

It is essential with such a fundamental change in our understanding of humanity that it is made with the fullest consultation and parliamentary approval. I believe that the Government are sympathetic to that.

Will my hon. Friend explain what evidence he has seen of any preparatory work on the ethical considerations that would be necessary? Is it not the case that many of the regulatory approval processes have commenced, but no proper work has been done with respect to public opinion on the ethics involved?

There is consultation, but it worries me that it has been done before the prior research has been completed, so we cannot be certain about safety.

I am glad that my hon. Friend raises the issue of public opinion, which is unpersuaded. A ComRes poll for Care will be released tomorrow, and I can exclusively reveal some of the results to the House. It found that 34% are opposed and 35% are in support, so there is no strong balance of support but, crucially, 44% agree that as it is currently illegal to grow most genetically modified crops for commercial purposes on the ground of safety, it ought to be illegal to create genetically modified children.

I return to the point that change of even 0.1% leads to genetically modified children. It is not sufficient to say that that is a tiny modification so it does not matter. It is the essence of the line of inheritance that we all have from our mothers through successive generations and centuries.

Does my hon. Friend agree that it is worrying that the assumption is that this will happen and that the consultation is more about how it will happen? Would it not be better for the Minister to say today that the Government will stop the consultation and continue with the research until they are satisfied that the procedure is safe?

My hon. Friend makes a very good point. If the Minister would say that, her standing in North East Somerset would rise even higher, although it is hard to believe that is possible.

The Government’s own consultation—this is crucial—says:

“It is estimated that 1 in 200 children born every year in the UK have some kind of mitochondrial DNA disorder.”

The number of serious disorders is much lower, but one in 200 has some kind of mitochondrial disorder. It is worrying that that is in the consultation because the premise is that 0.5% of the population are born imperfect and that in future only perfect people should be born. Many of us have imperfections, but they make up humanity, and the mixed variety of interest, thoughtfulness and development that is humanity often comes from our faults, as well as our abilities. It is a fundamentally dangerous road to start down because, although the technique cannot at this stage affect eye colour, some clever scientist will eventually work out how to ensure that babies have blue eyes and blonde hair, or whatever people want. Every time something like this happens, we go to the next stage and the argument becomes, “Well, we’ve done this, so it is logical to continue.” When that line has been crossed, the argument against going further is merely a matter of degree; it is not absolute.

I fear that we have already had the push to having perfect babies. Abortion on ground E of disability means that babies with even slight imperfections do not see the light of day.

One aspect of political correctness that I like is calling disabled people “differently able”. People with disabilities have different abilities and skills, and contribute to the benefit of society in a different way from those of us who have the use of all our limbs, and so on.

Although the current aim is small, 10 children every year, who might have been born, will be replaced by 10 different babies. That is not a major problem crying out for an urgent solution, but the solution that is being proposed is a fundamental change in our understanding of our own humanity.

It is a pleasure to serve under your chairmanship, Mr Pritchard. With the limited time available to me, I will set out some of the process by which we got to this point, but it goes without saying that these are extremely serious issues. I listened respectfully to colleagues’ concerns. There were some technical interventions and I will get back to colleagues about any concerns that I cannot answer now.

This is exactly why we are having consultation, and why I can confirm that the matter will be debated on the Floor of the House. The regulations will be subject to the affirmative procedure and there will be every chance to return to the issue and to debate it in full. I give that assurance. I know that I will not have time to respond to some points that are technical and scientific and I do not want to get them wrong, so I will write to hon. Members after the debate.

When the debate does come before the House, right hon. and hon. Members will look at things such as Library briefing notes and Parliamentary Office of Science and Technology notes, which normally I commend in the highest terms. My concern about the POSTnote entitled “Preventing Mitochondrial Disease”, which is Number 431 from March 2013, is that it talks about people who oppose this as simply being in a pro-life camp. That sort of language is very unhelpful, because the opposition is far wider than that.

I did not write that brief. I have never used that language and I would not. I accept—indeed, it is right—that this will be a subject of parliamentary debate, because it involves important issues. Just as Parliament has previously debated advances in science, such as IVF, and considered and weighed in the balance the concerns and the potential benefits, so that will happen again. I am certain that people will come to their own conclusion. These matters are normally decided by votes of conscience. I would be very surprised if this matter was not decided in the same way; in fact, I am sure that it will be.

Let me try to respond to some of the points and at least go through the process by which we have got to this point. I should say, though, in response to the intervention that was picked up by colleagues that we will arrange parliamentary briefings with, for example, some of the scientists involved and with the chief medical officer. I hope to be able to give hon. Members the opportunity to put questions directly to some of the people involved. There will be opportunities at all stages along the way, I hope, for colleagues to ask questions and get answers. What they think of the answers will obviously be down to them, but we will try to make it possible for people to come to a very informed view.

I am grateful for this opportunity. I am grateful that hon. Members have had a chance to put some of their concerns on the record, because that helps us in preparing for debates ahead. It gives us a heads-up on some of the areas of particular concern. Obviously, I have also been receiving correspondence about the matter.

The chief medical officer for England announced last year that the Government would go ahead with the development of draft regulations to allow mitochondrial donation in treatment. The consultation began on 27 February and will run until 21 May. I have already recognised the deep sensitivity of these issues. Since we were first approached in 2010 to make the regulations, we have been comprehensively collecting expert opinion and public views, and I will explain how that has been done. However, I understand that for many hon. Members and for many members of the public, this will ultimately be an ethical question. There will be strong views on both sides of the House, as we have seen today.

My hon. Friend the Member for North East Somerset (Jacob Rees-Mogg) touched on what mitochondrial disease is. It is a genetic condition of mitochondria—the part of the body’s cells that produces the energy that they need to function. It tends to be described, for the benefit of the general public, as the “battery pack” that powers a cell.

A person’s mitochondria come from their mother’s egg. Therefore, if a woman has mitochondrial disease, it is likely that she will pass it on to any children she may have. Mitochondrial DNA is separate from an individual’s genomic DNA, which is in the nucleus of the body’s cells. Mitochondrial DNA disease can be devastating, but the disease affects everyone differently. The range of different effects can include heart disease, liver disease, poor growth, loss of muscle co-ordination, visual and hearing problems and mental disorders. Rare conditions caused by faulty mitochondria include forms of Leigh’s syndrome, which can cause multiple symptoms in infancy, such as muscle weakness, heart and kidney failure and nervous system dysfunctions.

Some affected children live short and painful lives. They are constantly in and out of hospital. The quality of life for them and their families is seriously diminished. I have been contacted by a family in that position in my constituency and I suspect that other hon. Members will be as we continue to engage in this debate in the coming weeks and months.

The condition affects approximately one in 5,000 adults, although one in 6,500 babies are born with a severe form of the disease that can lead to death in early infancy. It is estimated that about 12,000 people live with a mitochondrial disease in the UK, and there is no cure. However, research has been ongoing at the Newcastle centre for life, among other places, for many years. In anticipation of significant advances in this field, the Human Fertilisation and Embryology Act was amended in 2008 to introduce a regulation-making power to allow mitochondrial donation to treat serious mitochondrial DNA disease. At the time that amendment was made, Parliament was made aware that there was the potential for these techniques to be developed. The Act was thus amended and that was included.

The mitochondrial donation techniques involve removing the nuclear genetic material from an egg or embryo with unhealthy mitochondria and transferring it to a donor egg or embryo with healthy mitochondria, as my hon. Friend the Member for North East Somerset said.

If my hon. Friend will forgive me, I will not. I have been left with very little time to respond. I doubt that I will even get through the remarks that I have prepared. However, I would be very happy to talk to him after the debate, and of course we will have much lengthier opportunities to debate the issue, so I do not think that I am cutting off debate.

Allowing the new treatments would give women who carry mitochondrial DNA mutations the choice to have genetically related children without the risk of serious disease. Recent estimates from the scientists leading the UK research in this area are that about 10 to 20 families a year could be helped initially. The scientists and clinicians at Newcastle university believe that allowing these techniques will also advance their understanding of mitochondrial function and mitochondrial diseases. It will enable them to gain a greater understanding of the way in which mitochondrial DNA mutations are passed from mother to child. It could also provide them with a better understanding of how mutations vary in different cells, which may lead to the development of new treatments for those currently suffering from mitochondrial conditions.

The use of the techniques would also keep the UK at the forefront of scientific development in this area and demonstrate that the UK remains a world leader in facilitating cutting-edge scientific breakthroughs. I know that that might be an uncomfortable point for some hon. Members, but other hon. Members have expressed great support for that. There are different sides to the argument. I completely accept that.

I understand that some hon. Members—this has been touched on today—are concerned about a slippery slope. Let me be very clear. Parliament has only provided a power to allow

“a prescribed process designed to prevent the transmission of serious mitochondrial disease”.

That is all that is prescribed in relation to the regulation-making power. We are proposing only to allow the donation of mitochondrial DNA, not nuclear DNA, so that is a further strengthening in terms of the regulation-making power. There is no intention or legal mechanism to go any further.

The draft regulations that are now out for consultation set out how the techniques would be allowed in treatment, the regulatory tests that the Human Fertilisation and Embryology Authority would have to use to give approval to a clinic on a case-by-case basis and how the mitochondrial donor would be treated in terms of information available to any children conceived through the new techniques.

In 2010, the Newcastle researchers approached the Department and requested that, in the light of their progress, we give consideration to the introduction of regulations. Recognising the complexity and sensitivity of this subject, we asked the HFEA to arrange public consultations and oversee a number of independent scientific reviews. An expert advisory group was established and a report passed to the Department in spring 2011. It found that the techniques were not unsafe, but recommended that some further research be undertaken.

After careful consideration of the report, the Department of Health and the Department for Business, Innovation and Skills commissioned the HFEA in autumn 2011 to undertake a comprehensive public dialogue and set of consultations in order to understand the public’s views on and understanding of this issue. The HFEA consultation was held between July and December 2012. It looked at the social and ethical issues raised by mitochondria replacement, as well as addressing a range of practical regulatory issues. Sciencewise, which plays a key role in helping the public to understand complex scientific issues, commended that public dialogue and the HFEA as an exemplar in its approach to gathering public views on a complex issue. As I am sure colleagues can understand, it is never enough, on an issue as complicated as this, to do a press release-style consultation. A simple “for and against” does not suffice to explore the complexity of the issue and ensure that when people express an opinion, they are doing so with a slightly wider understanding of it.

The HFEA gave a full set of advice to the Government in March 2013 based on the findings of the public dialogue and including further advice from the expert panel that it had reconvened. That concluded that although there continues to be nothing to indicate that the techniques are unsafe, further research on some specific aspects should be undertaken. Overall, the advice from the HFEA, informed by the balance of views from the public and stakeholders, was that the new treatment techniques should be allowed so long as they are safe and carefully regulated.

We have also taken account of other published reviews—for example, the 2012 report by the Nuffield Council on Bioethics entitled “Novel techniques for the prevention of mitochondrial DNA disorders: an ethical review”.

Some press headlines have suggested that a child born as a result of the new techniques would have three parents. My hon. Friend the Member for North East Somerset also alluded to that. I do not have time now to go into the detail of why we do not believe that that is the right characterisation. It is important to understand that mitochondrial DNA comprises a very small proportion—0.1%—of total DNA. However, these are issues that we can explore further. I have heard the concerns that have been put on the record today. It is also the Department’s view that this process does not constitute a form of human cloning. The techniques are not equivalent to reproductive cloning, because any children resulting from the use of the techniques would have arisen from fertilisation and be genetically unique.

However, there is clearly a great deal more for us to explore. Today’s debate has been a very helpful chance to hear the concerns of hon. Members expressed on the record. It gives me time to go away, look at the issue with officials and with the experts and ensure that we put in place the right advice and the right level of consultation as we go through the parliamentary process, in terms of—