Oral evidence: Mitochondrial Donation, HC 730Wednesday 22 October 2014

Oral evidence, 22 October 2014.

Witnesses

Peter Thompson, Chief Executive, Human Fertilisation and Embryology Authority, Robert Meadowcroft, Chief Executive, Muscular Dystrophy Campaign, and Professor Jonathan Montgomery, Chair, Nuffield Council on Bioethics, and Professor of Health Care Law, University College London, gave evidence.

Chair

Gentlemen, welcome to the session. I think all three of you have been sitting listening. Would you be kind enough to introduce yourselves?

Peter Thompson

My name is Peter Thompson, chief executive of the Human Fertilisation and Embryology Authority.

Professor Montgomery

I am Jonathan Montgomery, chair of the Nuffield Council on Bioethics. My professional background is as an academic lawyer. I work at University College London.

Robert Meadowcroft

I am Robert Meadowcroft, chief executive of the Muscular Dystrophy Campaign.

Chair

I have a very straightforward question. Can you give some detail on what regulatory approach may be proposed for the use of mitochondrial donation technologies?

Peter Thompson

The HFEA is clearly the regulator. On the basis of the draft regulations the Department of Health consulted on in the summer, if Parliament passed them, we would be the licensing authority for these treatments. Those regulations would require us to make an assessment, on a case-by-case basis, as to whether or not a particular treatment should take place. We would be required to do that against certain criteria, notably whether the patient had a mitochondrial abnormality in their mitochondrial DNA, and whether or not there was a significant risk that a child born might suffer from a serious medical condition. We would also be required to make an assessment as to the competence of the clinic to do it. To start with the last point, at present if you want to offer IVF in this country you need to do so under licence from us. We put on clinics a whole series of requirements, which include things like their facilities, staff competence, the guidance they issue and so on. A small number of those clinics offer PGD, which you heard about during the previous session. That is a much more complicated set of processes. Accordingly, to have a licence to do that we put different sorts of requirements on clinics—rather more onerous ones: their skillset is much higher, their equipment is much more sophisticated and so on. If Parliament decided to make mitochondrial donation lawful, we would be seeking further sorts of criteria, because as you heard this morning, this is quite complicated biology and very few clinics will, certainly early on, be competent to offer it. What we would also need to do—because this is not set out in the regulations—is effectively design an application process. How would a clinic wanting a licence from us actually apply? What sort of evidence would they need to submit? We would need to work out how we would assess that evidence, but, as part of that, we would clearly be considering issues of safety and efficacy at whatever point in time we were asked to make that decision.

Chair

That would be case by case.

Peter Thompson

At the moment, my understanding is that the Government are intent on doing it on a case-by-case basis. We have sketched out a little bit of that in some of the evidence we sent to your Clerk, but there is a trickiness; until Parliament clearly signals that it wants to change the law, I do not think it is appropriate for us to have a consultation, or some sort of public debate, about exactly what an application process would look like. I hope that is a helpful indication.

Chair

Mr Meadowcroft, someone like you would have a view about what ought to be there.

Robert Meadowcroft

Regulation is very important. From the patient’s point of view, there has to be a degree of protection as well—an assurance that the process is rigorous and the clinics are well organised and following ethical standards. There is a need for that regulation. One has to accept that, when faced with devastating illnesses and the thought of children being born with severe conditions, there is a degree of vulnerability among patients. Therefore, to have confidence that there is a regulated service, which we hope will become available, will deter people from seeking unregulated and potentially riskier services, clearly not in this country. In the age of the internet, there are possibilities for people to seek solutions they would be better off not seeking. I think there is also a need for public confidence. We are looking to take the next step with these techniques to help those families, so there needs to be public confidence that there is a rigorous process and rigorous regulation. I see it as all part of that.

David Tredinnick

How do you think patients will be assessed for their eligibility to utilise these techniques? What will the criteria be?

Peter Thompson

There are criteria clearly set out in the Act, and they are the two I referred to earlier. There is a big role—we will need to talk to the clinics involved—for the particular package of evidence that comes with each application. If I look at how we currently do something related to PGD, pre-implantation tissue typing, which is still done on a case-by-case basis, there is usually a detailed letter from the treating clinician setting out the particular details of the case and why they feel this is the most appropriate treatment. In the regulation of PGD and pre-implantation tissue typing, there are already models we can successfully use as a basis for thinking about how we go about regulating mitochondrial donation.

David Tredinnick

Is it correct that generally new technologies are more lightly regulated as their use becomes more commonplace? Regulation can become less onerous. Might that apply in this instance later on?

Peter Thompson

It might. When we first started to license PGD, it was done on a case-by-case basis. Some years ago we moved to a condition-by-condition basis. Instead of approving every case, we approved every new condition. Over time, the range of conditions that can be tested has increased enormously as testing technology has developed. We have a number of clinics across the country that are licensed to do PGD. When one of them makes an application to do a new condition, if we grant that condition as sufficiently serious to warrant PGD, any of those clinics can offer that condition as part of a suite of conditions. That has developed over time. It is quite possible over time, should Parliament decide to pass this, that that may be the better view. Robert Meadowcroft has already hinted at it. I think there is a sense early on that with new and novel techniques a particularly rigorous form of regulatory oversight is probably appropriate.

Professor Montgomery

From an ethical perspective, it depends whether the questions are new ones or old ones. If the issue is about the seriousness of the risk prevented—from the particular condition—it makes sense to resolve that once carefully and not reopen it every time but keep it under review. If the issues are uncertain and developing, you would want to keep close scrutiny. I am not sure whether light or rigorous regulation is quite the right model; it is about questions which remain very uncertain and questions which seem to be getting some clarity. It makes sense not to have a bureaucratic hurdle that asks a question every time to which we already know the answer, but in the areas where we do not know the answer we should be able to keep looking closely.

Robert Meadowcroft

I would agree with that. I think that a case-by-case basis initially is the way to go forward on this. Patients will be cautious but not over‑cautious. If there is evidence that this technique will help them and their families, they will be keen to explore it further and discuss it with their consultant, and measure the benefits and potential risks very carefully, but when evidence emerges that this is shown to be safe, all being well, I think there will be less concern on the risk side but more concern about the appropriateness for them and their family of the choices they will be looking at.

Stephen Metcalfe

That reassurance will be created by a wider and wider evidence base that things are performing as they should be. One way of doing that would be through long-term follow-up. How would you envisage the regulatory framework around follow-up working?

Peter Thompson

I think the issue here has already been touched on in the first session. I do not think that ethically one can compel follow-up. What we can do, however, is make it a condition of a licence for a mitochondrial donation centre that they should be required to have all the processes in place to ensure follow-up, and that part of the guidance they ought to give patients is what are the benefits of follow-up. It has already been touched on that it is not possible to compel a patient to sign up to follow-up, but we can certainly put a framework around a clinic about that and inspect against it. If a clinic that was licensed to do mitochondria could show us no evidence that they had processes in place to encourage follow-up, that might be a serious regulatory matter.

Professor Montgomery

I think we should distinguish levels of coercion in terms of encouraging follow-up. It is an area where we need to bear in mind that the parents using this technology are not the only people whose interests are at stake. It is perfectly reasonable, as we do in relation to other assisted conception techniques, to make sure we record enough information that makes it possible to track back, should it turn out that children born have some issues that may possibly be related to the technologies. We need to have the mechanisms in place to be able to track that back. I think it is reasonable for us to say to parents using these technologies that a certain level of recording is mandatory. It is also reasonable to have conversations with prospective parents using these techniques about the expectations of the system to try to learn to give better care in the future. We know from the provision of intra-genetics services and other areas of donation in terms of assisted conception that it is possible to establish what seem to be good things to do without making them mandatory. We would expect, from Nuffield in this context, the expectation to be raised that it is important to learn more about this, and we hope that people who use it would also be engaged in follow-up. I do not think we would expect it to go as far as there being a mandatory requirement to undergo tests, or anything of that sort.

Robert Meadowcroft

It would be extremely difficult to require a mandatory requirement, particularly for children yet to be born. Their parents may well be committed to taking part in the follow-up and may see the benefits and importance of that, and younger children would clearly be brought by their parents to the clinic. In a sense, there would be that kind of encouragement, but, beyond that, children would take their own decisions if they are healthy and not in touch with the medical services. If they had difficulties, for whatever reason, they would be back in touch, and I am sure that the clinic, the centre, would wish to follow them. From our point of view, the difficulty for most people with rare muscle conditions is getting to see a specialist. They are desperate to go. These are very rare conditions and, therefore, they are keen to see the specialist and I do not think that would change, but if the children, through this technique, do not have the condition they would be in a different place, although I am sure the parents would be keen to bring them through.

Stephen Metcalfe

As with all things, there is a cost involved. Who do you think should be carrying the cost of operating this long-term follow-up? Is long-term follow-up a significant cost, or can it just be absorbed in the functioning of the clinics?

Peter Thompson

Doug has already mentioned the national federation in which he is involved. I do not know about their resource position. From the HFEA’s position, all assisted reproduction treatments are reported to us as part of a statutory register, so to that extent these treatments—we have already touched on the fact there will not be many of them—can simply form part of that register, which we would mark up in a particular way. That element, of at least holding some kind of national information at HFEA level, I do not anticipate being of any significant financial concern. We have an infrastructure that is already doing this for 60,000 IVF cycles a year, and a few are not going to make any difference.

Stephen Metcalfe

Presumably, the same answer would apply to the confidentiality of data; it is the same process.

Peter Thompson

Yes, it is already governed by the HFEA Act, which puts confidentiality requirements on the data we hold. They are at least as severe—if that is the right word—or possibly more so, for confidentiality as for any other medical data, so all that infrastructure is already in place.

Professor Montgomery

From the Nuffield report one can add two elements. One is that, given the uncertainties we heard talked about earlier, we would expect all this work to take place within carefully structured and designed trials so that it could be learned from. That implies that the obligations for seeing through that follow-up need to sit with the people leading those trials, and need to be costed as part of the funding of those trials. We also recommended that these techniques should be not just within the context of clinical trials but also in specialist centres. That relates to the informed consent questions we heard about earlier. You need people to be able to support decision making, and that implies that the funding for this should be wrapped into providing a high-quality service.

Chair

Will the existence of that data lead to insurance problems in the future? Have you made any assessment of that?

Peter Thompson

I have not.

Chair

We have a lawyer in front of us. You must have thought about it.

Professor Montgomery

Perhaps I could answer as former chair of the Human Genetics Commission. The answer lies in the moratorium that has been agreed about the use of genetic information in the insurance industry. We currently have a system that has held up pretty well and ensures there is quite a long-term process whereby any changes need to be negotiated with a decent lead-in time. I have not been in that role since 2012, so I cannot tell you about the current state of play in the negotiations on continuation of the moratorium, but I do not think this raises a new set of issues. It is rather less pressing than the issues that would be available were widespread molecular genetic testing to become available. I think it would be under that umbrella.

Jim Dowd

I want to look briefly at the status of the mitochondrial donor. I know you are all aware of the consultation and the Government’s response to this issue. Do you broadly agree with the position of the donor that the Government have outlined in the draft regulations?

Peter Thompson

The short answer is yes. There are two positions on this. Mitochondrial donation is unique. Should it be treated like gamete donation where, since 2005, the donation is known, or should it be treated more like tissue donation? For a whole series of reasons, the HFEA’s position is that it should be non-identifiable, in other words treated more like tissue donation.

Jim Dowd

The Government took the view that it was somewhere in between, but more towards the tissue end of that particular spectrum, did they not?

Professor Montgomery

We need to recognise that there is quite a lot of nuance in the status question. We are very clear that, if the question is around parental responsibility and upbringing, we do not see mitochondrial donation as being in the same category as other attributions of parenthood, and not even in the same category as egg donation. If you are asking questions about identification to the child, one of the issues to do with mitochondrial donation is that it is not unique just to the donor, in the same way as an egg donation is. Therefore, it did not seem appropriate to think of it in the same way as an egg donation—linking someone to a unique genetic parent—so we would also be supportive of that decision.

Robert Meadowcroft

We see it in exactly the same way. We do not see this as being in any way a third parent, or a second mother, but comparable with tissue donation.

Jim Dowd

I was going to ask what access should children born following these techniques have to information identifying the donor, but I think you have just covered that point, Professor Montgomery. Do you think there should be a voluntary database for information and contacts arising from this? If so, who should compile, police and monitor it?

Professor Montgomery

Nuffield did go as far as to say that that definitely should happen and we would be supportive of that. When we did our analysis of whether there were links between children who might be born from these techniques and their origins, we identified how complicated people’s sense of their identity and their parenthood was. While at the moment, on our analysis, we do not see a sense that the link mitochondria would produce is thought to be equivalent to a parental link, there is obviously the possibility that people might feel that for themselves in the future. As we have learned in relation to other assisted conception techniques, it would feel wrong to rule out the possibility that affected communities could establish something of that sort. I do not think we thought it should be a regulatory requirement, but we could see why people might want to do that, and therefore would not want to obstruct it.

Peter Thompson

I do not need to go into detail, but our position is broadly the same.

Jim Dowd

Who will be responsible for instituting it?

Peter Thompson

If you look at tissue donation, my understanding is that there are already local voluntary arrangements for doing that. I am sure that, if there was felt to be a need, those sorts of things could be developed within the wider system. We certainly did not think it would be appropriate for a stand-alone national register.

Professor Montgomery

You would expect this to grow out of the people who use services. You would expect it to be linked to the specialist centres doing it, and driven by the patients using the services, not by providers.

Robert Meadowcroft

I was going to make the same point. I think that in 2013 the HFEA in their advice to Government made the point that the specialist clinics should keep these records and have them available on an opt-in voluntary basis.

Stephen Mosley

If Parliament passes these regulations, we will be the first country in the world to allow the introduction of these techniques. You talked about regulation and how you look at the family, the clinic and so on. How will it work when it comes to overseas patients? If we are the only country doing this, you can see a situation where parents from other parts of the world will want to come here to take advantage of the technique.

Peter Thompson

We license only treatment that takes place in the UK. If somebody comes here and is treated at a licensed centre, effectively the processes are the same. The questions about deciding what kind of evidence you might use in order to decide whether or not it is appropriate to do treatment are the same. It is for the clinic themselves to decide whether or not they treat UK or overseas patients, but if the treatment is to take place in this country, they will have to go through the same regulatory steps as a home-based patient would.

Professor Montgomery

There is a layer of complexity created by international movements. Although we are probably likely, if we approve this, to be the first country with legislation on it, we are not the only national ethics committee discussing the issues and techniques. I am aware of that from meeting the German and French national ethics committees a couple of weeks ago. The Nuffield report flagged up a couple of significant issues. One relates to the legal status of any children who might be born. There is certainly a theoretical possibility that we might be treating people whose legal status in the country they return to is uncertain. This would be nothing like as widespread a problem as we already see internationally in relation to surrogate motherhood, where many countries have to grapple with the challenge created by the attempt to have good regulatory systems in their own jurisdictions, and citizens avoiding those or finding a cheaper way of doing it by going abroad. They then bring back their children and the legal systems have to work out how to accommodate that. They are mostly resolved worldwide by a combination of two main ways of dealing with it. One is around the woman giving birth counting as the mother, which is the most common position. The second is that, if you find that does not give you very stable outcomes, you tend to look at what is in the best interests of the children. I think that, if this technique was used, it would be much easier to fit into those frameworks than surrogate pregnancy is, because it is the nuclear DNA that is usually used in tracking identity. It would be very surprising if anybody rushed into thinking this made it more uncertain than it was previously. There is a clear set of questions which lawyers in other countries would need to sort out. Because we know they have already grappled with them, I do not think they are a reason for our not taking that step, if there are other reasons why we would go in that direction. The second concern Nuffield identified was around follow-up. Follow-up is clearly much less reliable if you lose touch with the families. There might be a number of ways you might deal with that. Depending on where people come from, you may be able to partner with centres that are providing support in other areas, but the most important thing about follow-up is to make sure we learn from the techniques and whether any safety concerns emerge. If you found that all the people using this technique were lost to follow-up, we should be concerned about it, but if you lose a few, that may be no different from the people who decline to participate. While there are things to work on, they do not seem to be reasons for not taking the step, if for other reasons it makes sense.

Stephen Mosley

Professor Montgomery, you went through my questions and answered them all, so I don’t have any other comments.

Chair

On follow-up for people who are overseas, either British people who have left the UK and taken up residence elsewhere or people who have come here specifically for the treatment, obviously there is good clinical need for that follow-up, not just for the well-being of the patient but for the broader patient group. Have you given any thought to how you strengthen relationships with other countries so that you can get the follow-up data, or is it simply a matter of giving encouragement patient by patient, not quite as one of the conditions for treatment, but saying, “We really do want you to engage in follow-up”?

Professor Montgomery

I would have to take forward the discussions from the working group we held on this, because it was not elaborated in any detail. I think the answer lies in how the patients reach the treatment centres we are talking about. If they are referred because they are identified as having family histories, you can make a link with the referring clinicians and the referring centres. That is where I would start. You would expect the treatment centres to be building up partnerships, and then you would allow for follow-up in the places they came from. The most important things to pick up will be any health issues that emerge for the children who are born, and you would expect that to be the focus in the places people go back to. If you have links with the hospitals or clinicians likely to be caring for them, you can hope they would seek those patients’ permission to transfer the information. I think that is where you would build up the partnerships. Hoping to have something that is more legalistic or regulatory-based is unlikely to deliver anything better than those sorts of partnership arrangements.

Robert Meadowcroft

We are very fortunate in the UK that the science we are taking forward is exemplary; it is outstanding at times. This is an area where I think we are leading the world. It is first-class. We as a charity, thanks to the generosity and commitment of our supporters and patients with these conditions, have been able to fund research through Professor Turnbull’s centre for more than 10 years, driven by the patients and their needs. The point I want to add to the international dimension is that in other countries there are organisations like the Muscular Dystrophy Campaign who are watching what is happening in the UK. They will be keen to follow our lead, so in a sense I think this will play out in an entirely different way from the way it appears today.

Chair

That is a good point on which to finish. Gentlemen, thank you very much indeed. Examination of Witnesses

Witnesses

Jane Ellison MP, Parliamentary Under-Secretary of State for Public Health, Department of Health, and Professor Dame Sally Davies, Chief Medical Officer, Department of Health, gave evidence.

Chair

Minister and Professor Davies, welcome to the session this morning. This is the third panel. We have had a fascinating morning listening to the science community and the regulators. Minister, the Government announced that a number of further actions were necessary before regulations would be laid. Can you tell us a bit more about those actions, and when the Government intend to lay the regulations?

Jane Ellison

Thank you very much for inviting me and the Chief Medical Officer here. Perhaps I could take the Committee through what we said we would do and where we are. We published our response to the consultation on 22 July, and at that point we committed to giving further consideration to the recommendations of the expert panel, to refining the draft regulations to take account of changes identified during the consultation that we wanted to take forward, and to further discussions with the HFEA. In addition, I was made aware pretty much at the end of the summer Session that we were going to have a debate at the very beginning of the September sitting. I was keen to wait on that because it would be the first full debate we had. As Minister, I had not responded to a full debate, or had the chance to hear that range of opinion before, so for me it was a step I wanted to take. The HFEA said they would undertake to produce a layman’s summary around the science and the expert panel’s view on some of the regulatory issues. I thought it would be very helpful to see that before deciding next steps, because there was some discussion around what some of the wording in the third report of the expert panel meant and what the implications were. Having heard all that and having found the debate very useful, hearing from a very wide cross-section, I am now actively seeking cross-Government approvals and clearances and asking for parliamentary time in this Session to bring the regulations before the House. I cannot be more precise at this stage, because the process has not completed, but that is an update on the position I gave the House at the end of the debate, and I am actively seeking all of those things.

Chair

So “soon” genuinely means soon.

Jane Ellison

I am actively seeking both the approvals and the time, Mr Chairman. This is something I want to take forward.

Chair

Assuming the regulations are endorsed by Parliament through its normal procedures, when would you expect, following on from that, the first real in-person trials to proceed?

Jane Ellison

I do not think I am in a position to be precise about that, because from the point at which Parliament gave its approval the HFEA would have a series of processes to go through. I am sure you have been talking to them about that. They would then need to put the regulatory regime in place, but indicating that I am actively seeking to move things forward allows the HFEA to begin to move their thinking forward on that, so it would follow on from that. I do not think I am in a position to say exactly, but I am extremely conscious that there are real families waiting on the progress of this work. I have to make sure I go through a proper process and that I have done everything correctly. Like many other Members of Parliament, I have a family affected by this. I met their beautiful daughter Poppy who suffers from mitochondrial disease, so like every other Member of Parliament, with my constituency hat on, I am conscious that this is important to some people in our country and we need to keep up the momentum.

Graham Stringer

I took part in the debate and it seemed likely that the flavour of that debate was positive towards the regulations. Assuming Parliament agrees the regulations, what do you think are the implications for this country in being the first in the world to have regulations on mitochondrial replacement therapies?

Jane Ellison

I thank those members of the Committee who took part in the debate. I thought it was a very helpful debate. Occasionally, there is a sense in some of the public comment that Britain is going it alone and is isolated in this regard. That is something I have been exploring with my officials and have asked for information on. The UK is not an outlier in this area of medicine; we are pathfinders and innovators and I am very supportive of that. That came out in the debate. In recent weeks we have received a lot of correspondence from researchers and scientists around the world—Germany, France, Holland, Sweden, Japan, Hong Kong and two states in Australia—all indicating support for and interest in what is being done here in advances in mitochondrial donation, and acknowledging that the introduction of our regulations, were Parliament to approve them, would influence the approach of those countries and states to the new technologies. That has been helpful to me to give a sense of where the UK sits in this area of science worldwide. It is extremely useful to put on record that Britain is not some sort of outlier or isolated case; we are pathfinders and innovators and I am extremely proud of that. We also have a well-respected regulatory framework. Some of the comment elsewhere in the world is of great respect for our regulatory framework, and that is, if you like, an additional safeguard we are lucky to have. What came through in the debate, and in much of the comment I have been dealing with through a large number of parliamentary questions and so on, is that there is a very high degree of respect for the HFEA and the regulatory framework put in place by Parliament some years ago. It has more than stood the test of time, and in fact has gained respect as it has gone on. There has also been international comment about that framework.

Graham Stringer

By taking evidence today we are trying to get for the House of Commons an understanding of the science, so that it is there when we consider the regulations. We can do that as far as the science is concerned, but there is a big international debate going on out there which is about not just the science but the ethics. To summarise the arguments against it, it is said that this kind of technique is incompatible with human dignity. There have been a number of discussions in international bodies about that. Have you taken into account, and can you reassure the Committee, that if the regulations are passed we will not be hit by a lot of disputes in international law? Have you fully considered all those issues?

Jane Ellison

I do not believe we will. Usually, there are one or two widely quoted examples of certain international bodies commenting, but all the advice I have is that we are proceeding in a perfectly legal way.

David Tredinnick

Could you tell us how many people in the United Kingdom you believe could benefit from these new techniques?

Professor Davies

In the first place, we think it is about 20 families that are very severely affected, but if it proves to be as safe as we believe it will be—only time will tell—we expect that may rise to about 80 families a year, if we go forward. Let me put on record that I hope we will, both scientifically and for those families; you would not want to deny that life-saving opportunity to families where children will die before they have become adults.

David Tredinnick

We are talking about a relatively small number of people—a small number of families. Would you consider making these treatments available to overseas citizens, Minister?

Jane Ellison

Over time, we might expect that the procedure might be offered by centres to overseas patients, but it would be for individual clinics to assess each case, and of course they would all have to work within the regulatory framework. The clinics would assess the cases and prioritise, but we would expect them to have a protocol for doing that to ensure that NHS patients were the priority. I would expect it to be something the HFEA would look at on a case-by-case basis, but our expectation would be that NHS patients would be the priority.

Professor Davies

Of course, overseas patients pay the full cost. The NHS would not be subsidising that treatment.

David Tredinnick

That is another question I had. Given the current debate, it is probably helpful to have that on the record. Who would be responsible medically and financially for the ongoing care of overseas citizens? You have already said that overseas citizens would be responsible for the full cost of the treatment. What about the responsibility for their long-term care? Is that responsibility divided, given what you have just said, into responsibility for cost and moral responsibility for the care of patients? Possibly an advisory service would write to make contact if they are uncertain about how they are.

Professor Davies

I do not see the children who are born as a result of this, as with Louise Brown, as patients; I see them as future healthy children and citizens, but we would like to follow up nationals and people who live in this country so that we get the data. I would expect that the centres, if they take overseas patients, would ask for follow‑up, and will be in close contact with the physicians who look after that family abroad, because they would need to be referred from a physician who looked after the family. We have a long and proud history of collaboration on research and follow-up between many countries through our academic networks. I think we would get some, if not all, of the data.

Chair

Adding together the two points you have made, Dame Sally, the overseas patient paying the full cost would have factored into that the costs of follow-up.

Professor Davies

I assume they would be followed up locally in their own countries, but if they come back here for follow-up as private patients they are not eligible for the NHS. Those who are not eligible for the NHS will have to pay.

Stephen Mosley

We have heard some criticism of the Government’s working definition of genetic modification in humans. The Government’s definition is that genetic modification involves a germline modification of nuclear DNA that can be passed on to future generations. Do you know how that definition was decided upon?

Professor Davies

Let me take responsibility for that. We had a lot of discussions. What was happening was that people were using terms like “genetic modification,” “GM” and “germline,” sadly, in rather mixed and odd ways. It seemed to us that, in order to have the discussion we were having, it was important to lay down working definitions. Germline is anything that is done to DNA that goes through the generations, and mitochondria go from woman to child through the generations. This is clearly a germline modification because it passes through, but we needed to make the distinction between nuclear DNA, which makes us who we are and how we are—our personalities, heights, weights and whether or not we get baldness—and the 37 genes in the mitochondria which are about energy for the cell, and which we describe as the power pack. That was why we adopted that working definition. No one to my knowledge has come up with a better definition so that we can have the conversations. It is not that that is what it is; it is so that we can have a conversation and know what we are talking about.

Stephen Mosley

We have seen a newspaper article from the summer in which it was suggested that the definition might have been because “the Government is doing all it can to contain and define these kinds of terms in ways that favour mitochondrial replacement being introduced as an uncontroversial therapy.” Do you think that is a fair argument?

Professor Davies

No. I explained that we did it in order to clarify the discussion, so everyone knew what they were discussing.

Stephen Mosley

Is that definition still under review, and can people correspond with you or the Department about it?

Professor Davies

Please do, but unless they can come up with a better definition with absolute clarity so that we can continue our discussions, I would find it difficult to shift at this point. I am not saying that we will not shift, but we need definitions that give us clarity so the discussion is an honest, open and transparent one.

Jane Ellison

I think the rationale Dame Sally has presented for the definition is perfectly sensible and reasonable. If one had come up with a definition that did not have any science behind it and that you could not explain to a reasonable person, one might be accused of marking one’s own homework, but that is not the case. As Dame Sally outlined, it is an entirely reasonable way to go forward. The same accusation can sometimes be made about headlines, articles or whatever that refer to GM babies and things like that, and which are extremely misleading. That is also something people should reconsider and be asked to justify. I am very comfortable that it is a reasonable definition that has helped us to have a sensible debate.

Stephen Metcalfe

I want to go back to follow-up. I think everyone accepts that follow-up is important. How do you envisage the Government getting involved in follow-up? Do you have a view on how follow-up data should be collected and then distributed?

Jane Ellison

I do not have a detailed view, because it is something I would expect HFEA to talk to scientists about. I do not think that at this stage we have to have all of that detail outlined. It is clearly a completely sensible thing for us to know, but at this point I do not think it is an essential piece of detailed planning to have in place to go to the next stage of the process. Any clinic licensed by the HFEA to do this technique would need to satisfy the regulator that they had thought it through and had a proper regime in place. That is why we have a regulator. I know that is something they would do. We have had conversations about the fact that, in principle, it would be part of the regime they would need to put in place.

Stephen Metcalfe

If there is a cost implication, are the Government willing to put in additional funds, or do you not see the scale of the treatment as so large that it requires funding?

Jane Ellison

We have not got to that stage of discussion yet, because we have not brought regulations before Parliament. It is a reasonable question to ask, and I think there will be a discussion, but because of the size of the potential cohort at the moment it is not a group so large that thinking ahead to that conversation would be a reason to say we need to stop and think about it. At the moment we know that we are talking about a relatively small group of people, and we have no reason to think it will change very quickly, but that is a conversation we would need to work through. Let’s not forget that there is also an enormous cost in both human and financial terms in caring for children who are very sick and die young from dreadful diseases.

Stephen Metcalfe

There has been some suggestion that follow-up should be a condition of treatment, although I have not heard anyone agree with that here today. What is your view on treatment being conditional on agreement to follow‑up?

Jane Ellison

I just do not think we are at a stage to have that discussion. We have not put regulations before Parliament yet. Clearly, discussions need to be had. Should Parliament pass the regulations, it is not the case that, the day after, all these things would suddenly be happening. The HFEA would need to put in place their own regulatory regime. The science is a continuum; it is an ongoing series of experiments, and that will continue. It is not unreasonable to have not thought through all of those things at this stage. We have people and a process in place to make sure they have been thought through at the point when they need to be.

Professor Davies

I absolutely agree. As you know, I am a clinician and my subject was sickle cell disease, so I looked after disabled kids. My experience was that families wanted to know that their children were well after pre-implantation diagnosis and wanted them followed up. They also wanted to help future research. I would be surprised if our NHS patients did not want to join in.

Jane Ellison

We have seen that from some of the people we met through the Lily Foundation’s work; they have been communicating with Members of Parliament, and families have been going to meet their Member of Parliament. I have been so impressed by how many of those families have a very good grasp of the science. They have been able to have good conversations with their Members of Parliament and help to get them to understand the debate.

Mr Heath

I think that the regulations you are bringing forward at the moment will allow for maternal spindle transfer and pronuclear transfer. I do not think they would allow for other techniques. Is that correct?

Jane Ellison

That is correct, at the moment.

Mr Heath

If we have a new development, as we now have in the HFEA addendum last week—polar body genome transfer—it has a few hurdles to get over first, but it would require a future change in regulations to be brought into use. Is that correct?

Jane Ellison

Yes, it would.

Mr Heath

The process would be that various safety concerns had to be satisfied, clearly.

Jane Ellison

It would follow the same process, which has been a rigorous one, and has been followed in the case of the two techniques that are currently the subject of discussion. I have the same understanding as you that there is a third technique, and I have had some layman’s discussions with scientists about it. From my point of view, it is a little further back in the process of consideration, but it is clearly extremely interesting and encouraging. I would see it following a similar process, but it is just a little further back in the process we have been following on the other two techniques to date.

Mr Heath

On the two processes you are considering bringing within regulation, as far as you are concerned, the safety aspects have been satisfied. There may still be ethical considerations, but that is a matter for Parliament to decide.

Jane Ellison

There have been three expert panel reports during the course of this Parliament. My feeling is that we know all the things it is reasonable and possible to know at this stage. There are people who ask questions about safety and want to be satisfied, to the extent it is possible to be satisfied given the sum of knowledge and the stage the techniques are at, which is that we have not yet done them, as it were, with women. I think there is a body of opinion, and I respect their ethical concern, who express concerns about safety but in reality are opposed in principle. I would like people to be straightforward about that; it would be helpful to the debate. What I found particularly useful about the debate on 1 September was that I heard from a group of Members I do not think I had heard from before—people who did not have a strong view either way. They were not gung-ho at being at the forefront of science, nor were they opposed in principle. They came to it from the point of view of whether it was reasonable and sensible: are all the necessary steps and possible things that are knowable at this stage known? I found it very helpful that a number of Members in that third category were in favour of bringing forward the regulations. In looking at the concerns people raise about safety, I always try to ask the question: are they actually opposed in principle? In other words, would the safety horizon always be just that, or is there another horizon, or are there reasonable questions to ask that can be answered at this stage? I think the latter stage is where we are with the third report, particularly when I read the layman’s summary of the third expert panel report. There were certain words in it that caused public debate. I found it quite helpful to have that layman’s summary explaining words like “critical,” which were touched on, and what they meant, and to have it clarified that some of the experiments referred to in the third expert report could take place before or after regulations were made. I found that very helpful. That was what really tipped me towards thinking that I now needed to move forward actively.

Mr Heath

That is very helpful. When we were talking to the practitioners earlier we referred to the two techniques which are on the table, as it were. I put it to them that there was a discernible ethical difference between the two—one was using embryos rather than eggs—and perhaps it might be appropriate for patients to have an element of choice between two techniques. They might feel more satisfied with one rather than the other in ethical terms. They agreed with that. Would the NHS be able to encompass that?

Professor Davies

It may well be that the NHS can, but if you look at advanced technologies used with patients, whether it is in the NHS or elsewhere, success usually improves with practice. I would be worried if at the beginning you were doing one of this and one of that and flipping around. The outcomes are likely to be better, which means successful embryos coming through and children being born, rather than the safety of the technique, if you stick to one and get it to work successfully and then develop the other alongside if you want to offer choice. It is not that I am against choice, but pragmatically high technology usually has a practice curve to go up to get the best results.

Mr Heath

You want to back a winner, but you do not know which one it is going to be at the moment.

Professor Davies

That is absolutely true, but it is a practical issue that we should recognise.

Jim Dowd

There have been many references by yourself and others around the table to the earlier debate. You will know from that that some colleagues have reservations along the lines of the so-called slippery slope and designer babies, which are clichés much beloved by the tabloids. What reassurance can you give that by providing a legal platform for this kind of work we are neither on a slippery slope nor making it easier?

Jane Ellison

You are right; that is something that is said. Actually, in the debate I took the opportunity to give an example from the 1990s when legislation was put in place about the date up to which embryos could be used in experimentation. That has not changed. I gave an example of something put into statute that had not changed, yet debate at the time said it was a slippery slope; it would soon go and the date would stretch. It has not changed. Sometimes it is important to challenge easy assumptions, because particularly in my area of public health people make those assumptions all the time. It is quite important to go back and challenge them. I think we can give that reassurance because we can point to where it has not happened. We also have a well-respected regulatory regime, and that is important. The regulator now has a lot more experience than when those debates on IVF were taking place. We should give the regulator credit for having given successive Governments and our population confidence that they can handle these issues in a sound and sophisticated way. That is the other reassurance people can have. There are some countries that do not have a similar regulatory regime, so you would have just a legislative framework and individual clinics. I think the fact that we have this important body sitting between the two is something from which everyone can take significant assurance.

Professor Davies

I think the HFEA have proved themselves in not allowing a slippery slope. They are there to protect all of us.

Jim Dowd

I certainly remember—I think the Chair does as well—those arguments around the embryology issue. They have not changed. You are satisfied that there are sufficient safeguards in place under the regulations as proposed to prevent any broader application or extrapolation of them. They are discrete and they are confined wholly and solely in addressing this issue.

Jane Ellison

Yes. The regulations are quite tightly drawn. In 2008 it was anticipated that this might be something on which we would want to bring forward regulation. As several people pointed out in the debate, it illustrates for how long careful consideration has been given to this issue. The regulations are carefully and thoughtfully put together. We have a regulator that not only has to license the places for doing it but has to look at each individual case and give approval on a case-by-case basis. I think that is a robust regime.

Professor Davies

Perhaps I could highlight—though the Minister would be better at speaking to it—that the Government have taken on board in the regulations a number of aspects that came up through the consultation, so they are changed in some small ways from where the Government started. Do you want me to list them?

Jane Ellison

We can list those for the Committee. I always think it gives people assurance that something is a genuine consultation, because as a result of the consultation there have been amendments or whatever, so that is quite important. If Sally wants to run through those, I am very happy for her to do so.

Professor Davies

Would that be helpful?

Jane Ellison

I do not know whether the HFEA mentioned it earlier.

Jim Dowd

You might as well put it on the record.

Professor Davies

It includes amending the definitions to take account of the presence of polar bodies in eggs or embryos; modifying the consent provisions to ensure clarity; amending the determination required from the HFEA as to the risk of serious mitochondrial disease so that it can be made in relation to a specific woman rather than being needed for specific eggs or embryos; clarifying that there must be a significant risk that a person with those abnormalities would have, or develop, serious mitochondrial disease; and some other minor and technical drafting amendments.

Chair

Thank you, Minister and Dame Sally. The session today, when all the record is there, hopefully will help to inform the parliamentary process. For the record, we will publish from all the additional correspondence we have had, where we have the authority so to do, anything that has come to us that has not already been published elsewhere. Hopefully, the transcript of this morning’s session, plus the additional correspondence that goes on our website, will help to inform the parliamentary process during the passage of the regulations. Thank you very much for your attendance this morning. Oral evidence: Mitochondrial Donation, HC 730 28