Oral Evidence

Taken before the Science and Technology Committee

on Wednesday 24 November 2004

Members present

Dr Ian Gibson, in the Chair

Dr Evan Harris

Dr Brian Iddon

Mr Robert Key

Mr Tony McWalter

________________

Witnesses: Professor Robert Edwards, IVF Pioneer, Chief Editor of Reproductive BioMedicine Online; Professor Catherine Peckham, Chair of MRC/HFEA Working Group on Assisted Reproduction, Institute of Child Health, London; and Professor Henry Leese, Department of Biology, University of York, Editor-in-Chief of Human Fertility Journal, examined.

Q1046 Chairman: Thank you very much, Professor Peckham, Professor Edwards and Professor Leese for coming to help us with our inquiry. No doubt you have been hearing and reading of some of the events that have been taking place and some of the issues we are trying to address. You know that we feel it is time to revisit some of these questions and I hope you will agree, and that is why I am going to start opening the questions up by saying that if we look forward 25 years, and let us assume we are all going to be here then, what do you think are going to be the capabilities and concerns of assisted reproduction practitioners? What are they going to be worried about, and concerned about?

Professor Edwards: Your question is very timely, Chairman. We have just had a meeting at the Royal Society where one of your members was present, and many people said what they saw coming. They see coming much wider use of pre implantation genetic diagnosis, a method which runs into great problems with the disabled, and also gene injections. Now, what we call pre implantation genetic diagnosis, PGD for short, is now exploding, since the genome project came. Literally every gene can be analysed, I suppose, in the early embryos; I do not know any reason why it should not, so suddenly we can look for many genes that we did not even know existed. Already, it must be a hundred diseases that are being treated. In Cyprus, for example, the government has joined in a trial of B-thalassaemia, because Verlinsky and Kuliev, who are from Chicago, signed a deal with them that they would score all the embryos of people carrying the gene and transfer non embryos in an attempt to rid Cyprus of this terrible disease. So far twenty babies have been born; none have been affected. It will continue, and I think they will clear Cyprus, i.e. Greek Cyprus, of this disorder. Also, you could never do late on‑set diseases - cancers, Alzheimers. You are entering difficult areas here because if you diagnose the embryo and define it as Alzheimers, then the parents know they have it which is not a fact they wanted to hear. In fact, many of them would rather not know. They just say "transfer the right embryo", so do not tell them anything. So this is where we are going.

Q1047 Chairman: So there is a flurry of information coming at us. Do you think we are ready for it? Do you think we are set for it, or is the science moving too fast for the changes, the regulations?

Professor Edwards: I have faced this question all my career ‑‑

Q1048 Chairman: I know that.

Professor Edwards: ‑‑ and every step we had to come down here to Parliament or go on television or do what we could, and at times people were very hostile to us. We came through that. Even James Watson, the DNA pioneer, is now satisfied that what we did was correct and ethical, and he did not at one time think that. So it took about twenty years to get the idea over, and I think the happy event of the birth of Louise Brown was very decisive in this matter. I was speaking to Leon Kass who is adviser to President Bush, and he was very anti us but when Louise Brown was born he was totally converted, he said, in a meeting. They even now have two IVF babies so he is more than converted. I think the same with PGD is happening now, because these diseases are terrible diseases. If you look at some cancers, you see the pedigree is riddled with deaths - not one cancer but several. If you have a tumour supressor gene which has mutated the lid is off for cancers so that has made a terrific impact on many families now, and what can be done on the simple genes for cancer is being done. So I think it will swing round to us, and in the meeting that we had at the Royal Society, one or two philosophers were saying that if these stem cells are used and people get better, or maybe get better than they were before - it depends what kinds of cells you put in, the parents who have not done it may find their children are handicapped in comparison, not handicapped in the sense we take it but are running behind those who have gene technology. So when you say 25 years, that is a long time in science ‑‑

Q1049 Chairman: Should I have said five?

Professor Edwards: What I am saying may be starting in five years I would say, not 25, so I think we are entering a different world and one philosopher said that the major future for human kind was not space research but examining ourselves and looking at ourselves, and making this a better world to live in.

Q1050 Chairman: I think we would all agree with that but my question really is are we up for it? Is the regulation ready for it? Are the powers that be sold on these ideas that you are putting forward and are aware of this, and are they going to do it or are we just slow?

Professor Edwards: I think people are aware of it, and I think they will become more and more aware of it. Public awareness runs ten years behind the science, I would say. To give an example IVF took ten years and now it is everywhere, so I would say that whereas PGD is coming very fast when we hear about designer babies and children and things, it is coming very quickly indeed. It is getting an excellent press, and patients are queuing up for their treatment, so I think awareness is coming.

Q1051 Chairman: Before I ask your colleagues to come in too, can you just tell me about the issue of choice in this arena? Do you think there is enough choice available for individuals to make that decision?

Professor Edwards: I am sorry to say I am shocked at the support given to patients in the United Kingdom compared with my colleagues in Europe.

Q1052 Chairman: Could you amplify that, please?

Professor Edwards: We have just reluctantly given one free cycle of IVF. Belgium gives six; Germany gave three but it is now bankrupt so it has gone down to one; France gives four; Sweden, Finland give a lot - I do not know how many. We and the United States are terrible. Our scores are far lower. In Finland, for example, I think now well over 3 per cent of all births are IVF; Patrick Steptoe and I thought it would be eight per cent; it is heading that way. If you add PGD on it will be more still, and then when you come to stem cells this afternoon there will be more still there. I think we have not treated our patients very well.

Q1053 Chairman: I am sure we will take that up. Professor Leese, Professor Peckham, would you like to amplify that? Do you disagree?

Professor Peckham: I would say one of the prime things would be to reassure the public that these technologies or procedures are safe and we need to have systems up and running to be able to address that and this certainly came out of the recent MRC working group. The public need to know that technologies are safe and are properly evaluated because unless you know that ‑‑

Q1054 Chairman: Are you suggesting they do not at the minute?

Professor Peckham: I am saying we have not got the systems in place to look at the consequences both immediate and long term.

Q1055 Chairman: It is not being done, is that right?

Professor Peckham: We are moving towards that but at the moment that is not done and it has not been possible. With the new information systems that are becoming available, data linkage systems are going to become possible. We have to address the difficulties, the ethical issues and the governance around some of these factors when we are thinking about monitoring long term, what the outcomes are of some of these new technologies.

Q1056 Chairman: So you share Professor Edwards' frustrations?

Professor Peckham: Somewhat yes, because unless we can reassure people this will not be possible.

Professor Leese: I agree with what has been said. I share the frustration from the point of view of the equity issue. PGD is very expensive and I agree as well that the major implication 25 years ahead for our field is the new genetics, the human genome project, etc, which has arrived at the early human embryo. Until three or four years ago we could not do all the genetics we can now but now we can amplify single human embryos. What I find very difficult, and I just do not know the answer, is whether PGD will extend to fertile couples who have a predisposition for disease in later life, and the Biobank will come in here providing information on predispositions, so it will all come together. I think for the infertile it is obviously less problematic; they have a known susceptibility to a genetic disorder, PGD. If you have the chance of one in later life, are fertile couples going to go through this quite traumatic procedure? I really do not know. On the regulation side, I am quite an optimist here. I was on the HFEA and, by and large, I think it has done a very good job and I do not see why we cannot put in appropriate systems to regulate in this area. It is back to you people, ultimately; I have always been quite clear about that. The buck stops with Parliament. Arguably perhaps a few more things might have been put to you but the HFEA is a body that has performed well. I think we should see this whole field as an opportunity not a threat. It can be managed; the opportunity is there. The equity issues, the affordability, is a real problem but I am quite an optimist for the future here.

Q1057 Dr Iddon: I want to pursue the tension that we believe exists between the HFEA and research, and you, in a way, Professor Leese, answered my first question but I would like the views of our other two witnesses. Do you think the development of IVF and PGD, which I understand predated the Act, would have been possible had the Act been in place at the time, and of course we have one of the pioneers here today so perhaps we should ask you, Professor Edwards.

Professor Edwards: That is an incredibly difficult question. When IVF started there were hardly any ethical committees in hospital. It was a sort of American invention that was entering our practice, and when I started working with Patrick Steptoe we had to strengthen the ethical committee. It was doing nothing. We had to make it much stronger, and we had to tell someone else to appoint the people otherwise we were biasing it towards ourselves. I think in those days you talked to your colleagues and your friends and your doctors and you decided things were safe and you had to make a lot of decisions by yourself, and this is what we had to do, but at every step we took immense advice from everybody. For example, from Chang who was working in the States, who had large problems of IVF in mice; from epidemiologists and terotologists who all told me to go ahead and that what I was doing was safe. So I never had any problem on the safety issue. I think in committees today, if you gave them the same evidence, they may just agree with me. If we could imagine they were now re‑invented I think they probably would agree that it was safe, or that it would be safe to go ahead.

Professor Leese: I agree with that quite strongly. I served for two years as chair of the working group on the HFEA that is now called something else that dealt with research applications, and I have been asked, "If you had received the application from Professor Edwards and Steptoe in the mid‑70s 'Can we go ahead and attempt to produce a baby", I think the answer would have been "yes", with cautions thrown in, etc, because there was a very strong evidence base going back 60 or 70 years. The first embryo transfer was carried out around 1900. There had been a lot of work on mouse, rabbit, primate models. It had been shown that you could create human embryos in a dish; to the best of our knowledge it was time to proceed with caution and do it, so I think then the evidence base is pretty strong. For some of the recent things the science has been moving fast. We did our best on the working group; we took the best evidence we could, and maybe later on I could give you specific examples if you like, but there is general recognition the evidence base is not as robust as it should be. The field has been largely techniques driven, I would say; things like intra cytoplasmic sperm injection, PGD itself, biopsy, cryopreservation, etc, largely about techniques, and the underlying science has to catch up, and we were struggling against the lack of good evidence, of safety and efficacy when I was a member of that Committee, and I think the implications of the report that Professor Peckham has produced will strengthen the evidence base immeasurably, and that is why I support it. But I think in the original case the evidence was good enough to proceed.

Q1058 Dr Iddon: Perhaps we should have the view of Professor Peckham?

Professor Peckham: I would say we need to strengthen what is in place and I think the HFEA have done a very good job, but they are not a research organisation. We need to make sure that the evaluation of the new technologies is underpinned by scientific evidence and that we can build on that and feed back into the loop and identify areas of research that need to be addressed and pursued, and I think this is happening in other areas. It is not just assisted reproduction. Any area that involves interventions, technologies or drugs in pregnancy you need to address and look at the scientific overall evaluation of what you are doing. Assisted technology has become increasingly complex, increasingly difficult, and I think it needs a much stronger structure to underpin it and build on what is already there, which I think has been very good.

Q1059 Chairman: Have the social values that set the 1990 Act changed as well as the science?

Professor Peckham: Yes, but I think there are clear needs for change, because many of the issues addressed such as the long‑term consequences, on the health of the child and the mother, are not possible to pursue because the legislation is such that that information cannot be passed across. Therefore the database, which is an incredibly rich, quite unique database, is not being maximised and used to address new questions which perhaps were not asked in the same way previously. But there is huge opportunity to build on and strengthen rather than say that what is done now is not good.

Q1060 Dr Iddon: It sounds, Professor Peckham, as if you are saying that we need a regulatory body but there is something wrong with the HFEA so can I tease out of you how you perhaps would improve the regulatory body, if it were an expansion or a development of the HFEA or a completely new organisation, and I would ask the other witnesses to throw their ideas in too.

Professor Peckham: I am probably not the one to say how that should be done but I think that the science underpinning might mean that you need more careful regulation of the early assessment of some of the new technologies so that you might license for limited use for a duration of time while information is accrued, and that you get the proper evaluation before it is more widely used across clinics. I think probably Professor Leese would be in a better position to answer that.

Professor Leese: I would agree. We were able to give either a red, amber or green light to the new advances but we were not really then able to follow them through as they were being practised in the clinics, and clinics do things in different ways. If we had a more systematic approach to following through the recommendations that HFEA made you could do a lot of research, but you would need input of probably a different mix of researchers who were experienced in doing randomised studies and trials, etc, so we would recommend something and attempt to see it was followed through in the clinic but we were not a research body, and could not dictate the research they should do, but there is a lot of different practice going on out there and if it was managed more effectively we could get a lot of data on how these different procedures work.

Q1061 Dr Iddon: Do you think the HFEA are trying to regulate things that should have been passed on to other bodies like the other regulatory medical organisations, for example, IVF? We have had the view presented to us that IVF is such routine medical practice that really the HFEA should hand it on to the other regulatory organisations and concentrate on the newer technologies.

Professor Leese: I do not feel very strongly about this. As long as the system is in place I am not a what‑is‑the‑best‑way‑to‑regulate type of person. I am a great believer in getting the best people that you can get round the table and coming to a decision. As to how that is, as it were, systemised or put into practice I do not have a strong view on. The HFEA when I was on it did its best with limited information, and that I thought worked quite well. I do not feel strongly whether this part of its function should be given to someone else.

Professor Edwards: Could I make a comment? I think the introduction of ICSI is an example of what you may be searching for. That was discovered by accident and within three months it was crossing the world, not only Britain. I was amazed that it worked - I still am but it does work. There was never any foresight in what might happen to that. The second example which may be more relevant is that some of our American friends ‑‑

Q1062 Dr Iddon: Could I just interrupt you and ask do you think the HFEA held back the development of ICSI?

Professor Edwards: I think it probably came in just before the ICSI was formed.

Professor Leese: No, it was not. 1993.

Professor Edwards: ICSI was 1991, I think.

Professor Leese: I felt they could not have done. It worked. Infertile men were being able to have babies and the floodgates were opened. It would have been inconceivable to stop it. In an ideal world you would; you would have gone back to animal studies, work on surplus human embryos, work on clinical trials. Ten years later, the green light. It is now 50 per cent of all practice in the clinics. It would have been impossible on emotional, pragmatic, and practical grounds to stop it.

Q1063 Chairman: Legal grounds as well?

Professor Leese: Maybe.

Professor Edwards: The group that has done more to follow up ICSI is the Belgian group, headed by Andre van Steirtighem and Paul Devroey, that started it and I would say if you wanted an example of a clinic that is incredibly responsible, that is Professors van Steirtighem and Paul Devroey in Brussels, where their follow‑up studies have been astonishing, and I take my hat off to them. But also to your point, a technique came in five days ago of seeing if you could donate ovaplasm from a good egg to a poor egg. It ran into a problem with mitochondria. In relation to the question you asked, the FDA in the States called it in. Now, they have the power to call researchers in. I know that many of my colleagues were very apprehensive about what might happen in the committee. In the end the FDA did a thorough study; decided there was no adverse evidence; and said, "Carry on with caution or report back". I think that is what you are getting at actually, and the model I would strongly suggest you go to is the American FDA, the Federal Drug Agency, which is responsible for all drugs but now responsible for all new techniques, and not only drugs, so I think it is the organisation you are looking at.

Q1064 Dr Iddon: What I am really getting at is a simply yes or no. Do any of our witnesses feel that the HFEA have held back, first of all, research and then, secondly, the translation of that research into a medical practice?

Professor Edwards: No.

Professor Leese: It has always been one of the pillars on which it has worked, the HFEA, the need to promote good research, to get a good evidence base as with any area of medicine, along with welfare of the child, respect for the embryo, for example. The need to promote research has always been there and as someone who has had a research licence, even a voluntary licence prior to the Act, I have had firm management of the licence and rigorous application but I have always been encouraged to do research.

Professor Edwards: Could I amplify that comment? In two years before the HFEA developed as a scientist I had to bring a libel action in the High Court in London against the BMA, BBC and several newspapers. We were right in the forefront of ethics. If you argued you went to law, there was nothing else. If you made a decision and somebody did not like it, they were able to sue you. The HFEA ended all that and I would say since then that we in Britain have been very lucky indeed, and I really want to state that, because when I go abroad the admiration of the HFEA is unbounded. Many countries have copied it, copied us, yet if the HFEA makes a decision, in my field - I do not know if it goes to the public at large - the decision goes around the world. That is what we have created in Britain. I think we should be very proud of it but I do agree with you that you may need an FDA as well that takes over the research once it is under way. I think I would agree with you on that one. But the HFEA to me has been fantastic. We have disagreed with them. We disagreed on the second case of the designer baby. There was a child's life at stake - to me that is number one, and it did not seem to be number one with the HFEA, but there may be a reason for it, and I know they gave reasons at the time. So that is where we stand. The HFEA I think has been wonderful.

Q1065 Dr Harris: What was the reason they gave at the time?

Professor Edwards: I have to think back. The case was not a definite genetic case. It may have had environmental effects.

Q1066 Dr Harris: Were you on the HFEA at the time?

Professor Leese: I was on then. They were concerned about the risks of biopsy and the super-ovulation on the woman, and that until there was long term or better evidence for the safety of the biopsy technique that would be required they should delay on this one. I think eventually they got it right, but it was a kind of precaution when it first came to the authority, if I recall.

Q1067 Dr Harris: Yes. Now, I would like to ask the panel, on that issue, because we have just been talking about the use of evidence by the HFEA, in the Whittaker case, as you say, they say that they said that they were not going to allow the existing child to be treated in this way because of the risks of biopsy, and then they changed their minds on a later case. Was that because, in your view, the science had changed? That there was a study published in the interim that showed that the biopsy was safe?

Professor Leese: I think I came off the authority at that point - which is not a very good excuse. I think there was a general rethink and maybe the climate changed as well. You would really have to ask the people who made the subsequent decision. I think the prevailing culture had been "If we are not very happy, we will say no". I really believe that. We are desperate to help these couples but if we feel there is a problem it is beholden on us to say no, and I think the first time round there was a lot of novelty to it.

Q1068 Dr Harris: But the Whittaker child could have died, so some people argued you have to have a good reason to adopt a cautionary approach even though PGD had been going on for a while and there had been no ‑‑

Professor Edwards: The risk of damage to an embryo by taking a cell off appears to be minor, if at all. The embryo is able to adjust. Secondly, the case that they made against going ahead was that they wanted clear‑cut cases where there was a clear gene involved and not something else that may or may not happen. I cannot remember the situation that may or may not happen in this case but you will find it in the HFEA report.

Q1069 Dr Harris: But they had a similar case where there was not a gene involved that they could select out?

Professor Edwards: Yes. Now, when that same couple who had been declined because it was purely genetic went to the States, the case was done immediately by a group over there. So this ended happily but at the time I thought the HFEA made a mistake. If there is any risk to a child I think you go ahead. That is my own feeling.

Q1070 Dr Harris: So to generalise, what is your view of the way the HFEA uses clinical evidence in supporting policy decisions? That is one example. Ending donor anonymity is another; the number of embryos transferred.

Professor Edwards: Yes. If it was strictly clinical evidence in this question I would say they have very good advices. The scientists on the HFEA are no pushovers. They will judge on the evidence. It is usually the social side I think I disagree more on. In the case of Diane Blood, in the case of this DBA baby - but these are very rare cases. On the whole the HFEA handles the clinical evidence properly and the scientific evidence properly.

Q1071 Dr Harris: Professor Peckham, do you agree?

Professor Peckham: I think they have very good expert advice when making individual decisions and they are very science‑aware but I think the climate changes and I think, as already mentioned, there are social factors that come into this, not just science.

Q1072 Dr Harris: It has been well known, for example, that multiple embryo transfer gives a significant risk obviously of multiple births and that the outcomes there are poor, and other countries in Europe - Sweden, for example, is very clear about single embryo transfer, has higher success rates than we do per cycle I understand, although I know it is hard to compare like with like but in the ICSI data we have seen, so why did it take so long for there to be even the limits there have been in this country on multiple embryo transfer?

Professor Edwards: Louise Brown was a single embryo transfer. When we started we did single embryo transfers for years because we thought the human embryo was the same as animal embryos. It turned out that only 15 per cent of all human eggs will implant. We are in a disaster area here so you have to select the embryos, and we now know how to select them - just to find the 15 per cent. So the single embryo transfer has been on the cards for a very long time. The Scandinavians advertised it but other people did it as well, I would say.

Professor Leese: I think with hindsight the HFEA could probably have moved a bit quicker to lower the limit from three to two and I suspect there is no question eventually we will go to single embryo transfer. It is a matter of when that happens. I think they could perhaps have gone a bit quicker. There were some quite vociferous complaints from some clinics that this was going to reduce success rates, which of course it would do, but I think they could have moved a little bit quicker. But they are there now and I think they will go to single embryo transfers eventually.

Professor Edwards: May I say I would not accept a criticism of the HFEA on this score because it came in slowly, as various nations moved towards it. Finland deserves a lot of credit here but it was on all our agenda. We wanted go to two and one embryo transfers, if we could. It became possible when we knew how to select the best embryos. Then it became possible. Now, that was the breakthrough, and that breakthrough started about 1990 or something like that. That is when it became clear you could transfer single embryos and get 50 per cent pregnancy rates and that was the breakthrough. Without that you were forced to transfer two or three. There was no other way round it.

Q1073 Dr Harris: Lastly in this area is my question about whether the HFEA or societies should restrict clinics from offering treatment and tests where the value and outcomes are still unclear. One example might be anuploidy screening where there is not a huge amount of evidence to suggest that it increases the chances of a live birth, but it is being offered by some clinics. Should we say "Wait, stop, let us trial it in some areas", or should we say "Let's just give information and allow patient to make the choice with their doctors"?

Professor Edwards: I think you met Dr Verlinsky in the meeting. He has done now 5000 cases I think ‑ well, maybe not that number but an immense numbers of chromosome analyses on embryos, and the group led by Jack Cohen and Santiago Munne must have done about the same. These are two American groups. We have done very few in comparison. Their data I think, and I have to agree it is recent, is getting very convincing indeed - that you reduce the number of abortions because you select out those who are going to abort. You choose the best embryos, so even some women of 42 have managed to have their pregnancies where before they may never have had them, because they only have one embryo in ten to transfer. This is the situation we are in, you see.

Professor Leese: It has to be said, though, that there was a large study in Belgium which was the first really properly randomised study that showed no advantage so I think the jury is out on aneuploidy screening, and I think it rather picks up your question. It is very difficult to know what to do. HFEA license it in a few cases. I think it would lend itself to the sort of approach that Professor Peckham's committee are advocating where you follow the procedure much more rigorously once it has been started. I think HFEA would allow it and we would have reports back but in no way was this a systematic examination of this new technique, and I think that is where your work would come in really well.

Q1074 Chairman: Very quickly, on the licensing process itself is there too much peer review in the licensing process, including the funders, and is the Freedom of Information Act going to make a difference too about information and the anonymity of reviewers and so on, and should the funders be encouraged to apply criteria set out by the HFEA before funding research projects? There are changes going on in licensing applications.

Professor Leese: What was the last one again?

Q1075 Chairman: When you fund something, should the criteria set out by the HFEA be picked up by the research funders as well, or should they just ignore them?

Professor Leese: I think there needs to be a dialogue between bodies like the MRC and the HFEA because much of what we said obviously costs money to get the evidence base where if it were in better shape it would cost money. I think there is no question about that. But it still comes back to the HFEA not being a research body. That is not what it was set up for.

Q1076 Chairman: You can see what I am driving at. There is too much of it going on. Why do they not get together and form one body?

Professor Leese: The HFEA requested that your committee be formed.

Professor Peckham: I think that showed great responsibility and I have heard nothing but good about the HFEA, particularly internationally. I think it showed responsibility to come to the MRC because of their concern that they wanted to ensure that the scientific evidence ‑‑

Q1077 Chairman: Let me cut the cackle. Should the HFEA have a research function, do you think? You have investigated it. All the playing around, peer review to the right, to the left, for the licensing application - why do we not just give them the function and get on with it? If you trust them so much, if they are so damned good?

Professor Leese: The HFEA were so good because they created a climate in which this could operate. I do not think they should be a research body.

Q1078 Chairman: Why?

Professor Peckham: You cannot do research in that sort of environment. You have to have the scientists working together; you have to have the back‑up for research; you have to have the interdisciplinary groups ‑ it has a totally different function. Legislation is quite different from a research activity.

Q1079 Chairman: You can have sub‑committees and sub‑organisations?

Professor Leese: I can see them putting up the projects for tender maybe and then you would have to have the MRC or even the department responding to the tenders and saying "This is the project I would seek to -

Chairman: I do not think we have thought this out at all. There are too many people with fingers in the pie, I think. You may disagree but that is how I am reading things.

Q1080 Mr McWalter: On ethical oversight, Professor Peckham, your report mentions the development of a "balanced ethics and governance framework" to regulate data collection and follow‑up studies. Who should do this?

Professor Peckham: I think it has to be independent. I think we have many examples in other areas in science now, whether it is the newborn screening or whether it is Biobank where an independent approach has been shown to be very successful, particularly if it is done with public consultation. When we are talking about issues like monitoring children and following up children who have been conceived by different methods in order to ensure safety, and I think that is a good procedure, I think that is vigilant and something we are doing in other areas, you have to think about the public concerns. You have to think around the issues of confidentiality, the issues of consent, the issues of what you are doing and you have to bring on the public. You have to have the public behind you or these things cannot work, and I think it needs an independent body to look at what is going on, and that can be very successful.

Q1081 Mr McWalter: This Committee has just come back from talking at Vatican City to some of the people there, and one of the things they were very interested in was whether using techniques like PGD you might get over the long‑term a contraction in the gene pool so that removing something that looks as if it has highly negative, like, say, a gene for Alzheimers or whatever, may in the end give you a gene pool whose members who participate in that then have other vulnerabilities that were not previously identified. Would you think that is a danger? Do you think that is something that should be part of the consideration for such an ethics committee?

Professor Peckham: I think one should always be looking at the effects which may be immediate or even more long term; that is appropriate for many different areas of medicine. We know that the intrauterine environment is very important and that it has implications for the child and implications much further than the child - for the adult - and I think we have to be very aware of the long‑term effects as well as the immediate effects of what we are doing, and that is a precautionary approach and something we need to do, and we have to balance the concerns of the individual and confidentiality with the benefits to society as a whole, and I think that debate is something that we have not addressed sufficiently and we need to address, because we have to think of the public good versus the benefit to the individual, particularly when you are not harming an individual, you are just merely wanting individuals to work together to produce something so that you can monitor what you are doing. So I think it is quite complex; it is not easy; it is not something you can just set up; you have to think it through and you have to do it properly, particularly with the ability that there will be soon, and this is certainly something Biobank is addressing, which is the linking with other data sets and linking with other health information within the NHS. That can tell you a lot. It can tell you if something is going seriously wrong. It might not be subtle things but if you can link databases and relate the information back to the individual technologies you are applying, it can alert you if there is anything you need to investigate further. So I think there is huge progress in data linkage that we are just beginning to apply in other areas that would be appropriate for the assisted reproductive technologies.

Professor Edwards: Answering that question from the point of view of a geneticist, if we use PGD - and we are talking about five years - for disease, I should be delighted if we get a decline in the frequency of genetic disorders. I think that would be wonderful for the human race. That is our target, so I am not the slightest worried on that point. I cannot understand what the questioner was saying to you. But if we can go later, you have to think that down the line already we are starting to look at multiple gene situations - not single gene but multiple genes - and when you enter that area you are talking about the more human characteristics of the embryo, if I can put it that way. Even though you may be putting new genes in, I would have thought the chance of risking any change in gene frequencies in a population of 60 million people would be incredibly minute. I would strongly recommend you consult a population geneticist, but I think his answer would be "Not a chance", that the effect would be very minor.

Q1082 Mr McWalter: Are you suggesting we cannot eliminate Huntington's Chorea?

Professor Edwards: We can probably eliminate any of these genes if we are prepared to pay for the screening. When people say PGD is expensive, I always say what is the price of a disabled baby who is born. What is the cost for anyone to bear? That is a terrible price for anybody to bear, and the financial cost is immense. A PGD by comparison is a very small sum of money. On PGD, I fully agree, we have to do it responsibly, but if done responsibly then I think it is a very new and challenging thing for us to accept.

Q1083 Mr McWalter: Professor Leese, do you have any observations about the performance of ethics committees in the private sector?

Professor Leese: I do not quite understand your question. They are always properly constituted as far as I know, and I used to be an HFEA inspector. They would have strong lay representation and we would always check on that to make sure the person responsible was not a member or left for items concerning his clinic. No, I do not have a view on that. I am going really back to when I used to chair inspections and all the paperwork and the ethics dimension. I always felt they were of course immensely valuable for difficult cases. If the clinic had a difficult case we would put it to the ethics committee, but I cannot recall anything that would distinguish ethics committees and private clinics from NHS Committees really.

Q1084 Mr McWalter: So people do not just appoint their pals? "So‑and‑so is worthy", or "I met Jo Bloggs down the lodge", that kind of thing?

Professor Leese: There is always an element of the great and the good, as it were, but how you resolve that one I just do not know. That is one I would put back to you in every walk of life. The expert versus the lay, and how you balance the two.

Q1085 Mr McWalter: So they might have a collective blindness?

Professor Leese: I think they are doing their best, really.

Q1086 Chairman: Do you think we can regulate private clinics at all, or do they just tell us to run away? What about the regulation of them? How do you feel about that in comparison with the regulations that you feel are strongly enacted through the system we have in the public sector.

Professor Leese: In the private clinics?

Q1087 Chairman: Yes.

Professor Leese: I am struggling to find a problem here, I really am. There is obviously something in your mind but I would have ‑‑

Q1088 Chairman: We are cynical, suspicious people. We read the newspapers and we see things going wrong and we find that people who are privatised tend to ‑‑

Professor Leese: Perhaps they were not the clinics I inspected but we would always look at the constitution of the ethics committee. It was one of the questions. "Do you have a properly formulated ethics committee?" We would always look at it and see who was on it. I cannot recall the problem, anyway.

Q1089 Mr Key: I think the evidence so far is that the HFEA should not become a research organisation, if I understand you correctly, but this does bring us back to the question of clinical data bases. Under the Act, Section 31, the HFEA has to log information under certain circumstances and the recent MRC HFEA working group has suggested that there should be a new monitoring framework in place to collect and collate more comprehensive information than is currently done. Would that be a good idea, if there is to be no research function? What is the point? Why do we not just ask the HFEA to record very basic information like recording gametes and embryo donations?

Professor Edwards: I would find no problem in people following up our research at regular intervals, coming and checking, making sure it was safe rather than it was ethical, if you see the difference, which I think is what you are saying. I would have no problem with that at all. In fact, such a body would be welcome. First of all, they may find things we had not thought of which is always wonderful to us but it would give us the chance to show what we are doing, and this body would show that we are doing it properly. That is what we want ‑ to make sure that people see what we are doing is being done perfectly correctly. And, by the way, I think IVF is being practised correctly. There are one or two renegades, I am sorry to say, but on the whole it is practised correctly. Does that answer your question, sir?

Q1090 Mr Key: Partly, but I wonder if our other witnesses have a view particularly on this question of clinical databases and whether there is duplication here, and what would be the point of the HFEA enlarging a database if it was not for research?

Professor Edwards: When Louise Brown was born, and we opened the Oldham General Hospital we started getting a lot of data, we sent it to the Medical Research Council and they wanted to follow up all the babies for us. After a short time they wrote back saying "It is too expensive; we will do chromosomes only". After three months they said "We do not want to do chromosomes either", so our first database which could have been established in the United Kingdom in 1982 was never established, so I think the MRC must get its act right on this. If it is going to come in it must be seen as a duty of the MRC. At the moment it is a place for research applications. I have not applied for ten years, by the way, and it might have changed in ten years, but when I was around it was a place for research applications and not for checking research. I do not know if it is the right body.

Professor Peckham: I think the information database that the HFEA has is a unique information base but it has been set up to address different questions. It has a lot of information on treatment cycles, conceptions, and minimal information on outcome. What was suggested in the MRC report was that you might want to look at certain questions as demanding more details of the technology that was used in trying to tease out that in relation to the effect on the health of the child, so I do not think you would want more information; you might want selected but fairly discrete information. So you are not suggesting two databases; you are suggesting there needs to be very close collaboration to ensure that the information you would require for that purpose, which is different, is available on the database, so it is complementary. You do not want to duplicate things; you want to work together, and I think one can think of many examples where that has taken place. I think the monitoring falls in a way between good clinical audit and research but there is no doubt that such information provides a very valuable database from which to do more in‑depth research using more detailed approaches which would be more appropriate for bodies like the MRC, but at least you have a sampling frame and you know who you are investigating and you can look at issues about bias. It is difficult to follow up and we know at the moment we have not got that in place; it is not easy. So it falls between two, that monitoring process. It is good clinical practice, and it is audit.

Q1091 Mr Key: That is helpful. Can I move on to something really fundamental. I want to ask you how you define an embryo and a gamete. When Parliament decided all those years ago in the Act to define an embryo and a gamete, they used terminology which now appears to be inadequate, and the HFEA in its evidence has suggested that we need a redefinition of embryos and gametes, and the Canadians, of course, have recently done that in their Act which in March 2004 received Royal Assent, so who would like to start by advising us how you would define an embryo?

Professor Edwards: I think it matters for whom you are defining it.

 

Q1092 Mr Key: For us for the time being

Professor Edwards: For lawyers, you probably have to watch every step you take

Q1093 Mr Key: Forgive me for interrupting, professor. I am asking you to advise us as representatives of our constituents wrestling with day-to-day problems on the one hand listening to you and on the other hand reading the Daily Mail. How would you define an embryo to us?

Professor Edwards: Let me give you one example where there is a problem. You do not need fertilisation to establish an embryo; it can set off by itself and we call that parthenogenesis and we call that a parthenogenetic embryo. We do not have a problem with that. If somebody clones it, instead of fertilising it, they put a nucleus in it, we call that a nuclear transfer embryo, NT for short, and you will hear more about that in your next meeting I would think. That is how we see it. I would say that most scientists I know would be very unwilling to define too hard because we understand what we are doing and I can understand what all my colleagues are doing in the advance of research. I am not trying to be unhelpful.

Q1094 Mr Key: Do any of our other witnesses disagree with what the Professor has just said?

Professor Leese: It is very difficult to come up with a definition on the spot. It really is. It is the product of a union of two gametes for a start, an egg and a sperm. The whole thing is a continuum of course and, with any developmental process, it is where you begin and where you end but, for starters, it is the union of two gametes.

Q1095 Mr Key: How do you define a gamete?

Professor Leese: In operational terms, it is an egg and a sperm.

Q1096 Mr McWalter: It is not though, is it, because you have artificial gametes?

Professor Edwards: One of my ambitions is to take a sample of blood and take a white cell in place of a gamete for patients who do not have their own gametes. That would be wonderful and, by the way, that would involve cloning and that is why I do not agree with abandoning cloning either. I think you have to leave your mind open on all these questions. You never know where you are going to be next week! We may find that cloning helps infertile patients. I think the answer is to make your own definition. This is a very hard question off the cuff, you know.

Q1097 Mr Key: Good! That means we are doing our job!

Professor Edwards: Let us bring a group of scientists in, let them argue for a couple of weeks and then see what they say.

Q1098 Chairman: No chance!

Professor Leese: I see where you are coming from now. I would say that physiologically it is normally the union of two gametes. However, it may also be formed in the following ways and you could have somatic cell nuclear transfer and you could list them if you wish. I am not sure how useful that would be.

Q1099 Chairman: Do we need a new word? Do we need new language?

Professor Leese: No, I do not think so.

Chairman: You understand what an embryo is.

Q1100 Mr Key: For an awful lot of people - and we have listened to a lot of them in this Committee, both in Sweden and in Italy - it is all about the potential of development into a human life. Some people define an embryo as that, the potential to develop into life. Does that come into your thinking?

Professor Leese: It is a continuum; it is one stage on a continuum; it is a developmental process.

Professor Edwards: You have two problems: you have to define human life and I would not like to do that either. Secondly, you can have a human life at birth and that is a definite life from an embryo that has been injected with a donor nucleus. In rabbits and rats, cloned embryos are normal and full term. So, cloning is coming in two species. So, you have embryos that have never seen a sperm or never seen an egg Well, they have seen an egg but they have never seen a chromosome division in the egg. To ask for a definition is very difficult.

Professor Leese: I thought of this as a subtext in which you have three weeks and 10,000 words, frankly. It is very difficult to define it here and now. I accept that, for operational terms, it probably does need defining and I am sure whoever redefines the act will do a first-rate job on it.

Professor Edwards: Perhaps your Committee could do it.

Q1101 Chairman: You were trying to help us but you are not being too helpful at the minute!

Professor Leese: My response would always be to seek advice and I would put it to the professional bodies first of all and see what they say.

Q1102 Chairman: But you admit that it is a problem.

Professor Leese: I do not think it is as big a problem as you make out.

Q1103 Chairman: We are not making out that it is a problem, we are asking you a question.

Professor Edwards: I would say candidly that we in our field, within all these things we are talking about, when it is written, we understand what is meant.

Q1104 Chairman: The world moves on.

Professor Edwards: Yes and I think any attempt to start to apply a new name would lead to much verbiage. This is what I fear - pre-embryo has disappeared.

Chairman: We are talking to you about the public and constituents out there.

Q1105 Dr Harris: I just want to ask you about this idea of haploidisation to create effects of the artificial gametes. Is it your understanding that that could be useful? It is permitted subject to licence at the moment or would it not count as a gamete under the HFE Act?

Professor Edwards: It is now done in rabbits and rats, NT goes to full term and normally, as far as I can see...I hesitate because I do not have the evidence but I am told that this is true. It means that we can start to think of doing this instead of doing things such as collecting testicular sperm where you almost shred the testes to get the rare sperm out. You would simply get a drop of blood and use that instead. It probably brings the descent of the male a little further than his rather poor performance in my field because it would not be sperm. I do not know how it would go down! I think that a lot of people would get advantage from it. I am being 100 per cent serious here. If all couples where there were no gametes in one of them could use this technique, it could be very helpful to a lot of people worldwide, an awful lot of people. I cannot be more definite than that.

Professor Leese: But it would have to be tested exhaustively for safety and epigenetic effects, the potential damage if you went down this novel route. That is what I would say in terms of the regulatory body. There is great novelty but the testing required would be immense to ensure healthy offspring etcetera.

Q1106 Dr Harris: If it were shown to be safe, do you think it should be licensable, regulated and allowed both for infertile couples, in the way you have described Professor Edwards, and indeed same sex couples?

Professor Edwards: Yes, I would say definitely. I think it would be a very valuable clinical tool to help a lot of unfortunate people.

Q1107 Dr Harris: There are rules saying that embryonic stem cells should only be used in the regulations for the treatment of serious disease and there may be situations where embryonic stem cells and use of embryos could be used to treat infertility such as deriving gametes, for example, from embryonic stem cells. Do you think that infertility is a serious disease that should be covered by the terms of that condition if we keep that condition?

Professor Edwards: We have known that embryo stem cells will produce gametes since 1968 when we transferred them to see if embryos would produce gametes, so there is no problem. The question is, what quality are they? I think I agree with Henry totally. I would want detailed analyses on growing gametes in vitro because they undergo very detailed molecular changes - I do not want to go into them - which might be affected.

Q1108 Dr Harris: My question was that you can only do this research, even just checking it for whether it is viable or not, using embryos and embryonic stem cells for serious disease and would you consider deriving gametes to treat infertility to come into the remit of serious disease to justify, under the existing regulations, licensing that activity?

Professor Edwards: I have always thought that infertility is a very serious disease. It is not classified as a disease, it is a condition, but I think anything we do to help any infertile couple would be wonderful. I can actually talk about the current status of spermatic cell haploidisation. It is not working. It appears to be more complex than cloning. Maybe there are some extra things to learn that we do not know already and I think it will be some years down the line if it does come.

Q1109 Dr Iddon: One last controversial question while we have such an eminent panel in front of us, if I may say so. Professor Edwards, do you think we can draw the line between research on these interesting new technologies and eugenics?

Professor Edwards: Again, it depends what we mean by eugenics. Eugenics was started in the 1870s by an English geneticist who had the welfare of mankind in his mind. The work became degraded after 1930 caused by the Nazis but also by various other things where people were found not to be behaving themselves fully correctly in relation to the way they abused their children. So, the word became degraded and it is a word that you have to be very careful about using today for this reason: you cannot use this word in Germany, for example. It is impossible to go there. You have to say exactly what you are trying to do. I think we can define what we want to do without using that term and I think we can make it clear to people what we want to do without using that term. I would love to show you the minutes of our meeting last week when these things were discussed in great detail when you would have seen that the problem is complicated but could be solved.

Q1110 Dr Iddon: Is that the view of the other two witnesses?

Professor Leese: If I recall the question, I think my answer would be "yes" and that you simply need a strong regulatory body that keeps people on board.

Professor Peckham: I think it is very difficult and you would have to be very, careful when you use it because you have to separate the two and not let them merge. I agree that you have to be very careful.

Chairman: Thank you very much for helping us wrestle with the very difficult remits of today. You can be sure that the new science that is coming through will be part of our report, so your evidence has been quite crucial to help in that. Thank you very much indeed

 

Examination of Witnesses

 

Witnesses: Professor Roger Pedersen, Director, Cambridge Stem Cell Institute, Professor Alison Murdoch, Consultant Gynaecologist, Head of Department, Newcastle Fertility Centre, and Dr Robin Lovell-Badge, Head of Division of Developmental Genetics at the MRC's National Institute for Medical Research, examined.

Q1111 Chairman: Can I welcome you all. You have been sitting through the first part and enjoying the attempt to define some arenas of the activity which quite clearly did not bother the last group too much but we will be asking you questions about other issues as well and I am very pleased that you have found time to come and talk to us. You know how important this inquiry is and how organisations are getting to grips with these problems now. I am going to start off with the first question. Roger Pederson, I want to get you on line really because we have talked about this in the past. As the man who came from California to undertake stem cell research, you missed Arnie Schwarzenegger and his amazing success over there in the votes and so on in the Presidential Election and his undertaking to conduct stem cells research. Do you regret that now? Would you go back to San Francisco and engage there with them with the multi-million dollars that they are going to throw at this or do you think you are doing the right thing and are we doing enough, are we doing the right thing, or are we just playing at it in this country? I want to get you on record.

Professor Pedersen: It is an honour to be here and a privilege and I feel very special being a Californian Yankee in Queen Elizabeth's Court. Thank you for that opportunity. What I would say is that I came here for a very specific reason which was to accelerate research on stem cells to reach the patient community at the earliest possible date. I came here because it was clear to me at that juncture that the UK was the best place in the world to accomplish this. I have been asked numerous times why I reached that decision and it is very clear in my mind that the primary reason for the UK's past success and the potential future success rests on the foundation of public policy developments that have been made as a result of hard work on the part of many people including people in this room. That public policy was of course inspired by the success in in vitro fertilisation in Professor Edwards's hands some 25 years ago. So, there is a tradition really of successful public policy development in the UK that is unparalleled anywhere else including California. So, the simple answer is that I would not hear of going back to California where there is a mismatch between the initiative in California and the countrywide hostility towards stem cell research.

Q1112 Chairman: The second part, Roger and Alison, and Robin can join in this too, is, what more do we need to do in this country to stay ahead of the game, as it were, to be upfront, to have that attractive value, to bring more Roger Pedersens over, not just from the States but from elsewhere in the world of course?

Professor Pedersen: Thank you for that compliment. What I would say, if I may use vernacular with which I am familiar, is, if it ain't broke, don't fix it. I think that the HFEA works and that it is a huge part of the engine that drives forward stem cell research obviously insofar as it is related to embryo research in this kingdom. I think the important thing to do is to not dismantle or not provide a target for diminishing the effectiveness of the HFEA by opening up the doors to changes that might diminish its effectiveness. I think on the whole, at least in the timeframe that I have observed it closely, it has been incredibly effective. Obviously there are other things that need to be done. The HFEA in itself is not a sufficient cause for success in the stem cell field and I think that further public policy developments need to be undertaken, for which I compliment you and your Committee. I think this is an extraordinarily important role because what needs to be done is to look forward at the ethical, legal and social issues that are going to be brought out on to the table as a result of the progress of the technology and not stay mired in the issue of moral status of early human embryo. That is not the only issue and we will be blindsided by other issues that will come as a result of the progress in technology. I think there are other issues that need to be addressed such as long-term funding and the commitment to that, but that is a separate issue from regulatory issues.

Q1113 Chairman: When will we move into the clinic, as it were, in your opinion? When will we be treating Parkinson's, Alzheimer's or whatever because those were basically the hard-line reasons that it got through Parliament and are we moving into that position? Are we up for that? Are we organised enough to do that?

Professor Pedersen: I think that, in terms of your responsibilities for the public trust and the public welfare, you should be prepared for the risk, if I might state it that way, that the field will be ready to go to first inpatient work within five years which means that a lot of work needs to be done starting right now to consider the impact of that clinical undertaking in terms of distributive justice of the technologies - is it really going to be for everybody or is it just going to be available for the wealthy few? - in terms of the safety of the technique and in terms of the equitability of the choice of the diseases on which we focus, and I would focus on Parkinson's probably and have a treatment within five years.

Professor Murdoch: I think the first obvious answer to your question about where we go now is money and I think that is probably not the remit of this Committee, so I will stick to the issues that relate to regulation. Despite any negative things that I might have to say about the authority, I think the fact that we have an act that regulates IVF treatment and research in embryos in the UK is the single most important reason why we have taken a lead worldwide in terms of stem cell particularly and, if you look at the situation in America, it is not just stem cell regulation, it is the fact that the IVF clinics are not regulated in the same way that we are regulated and do not have that structure of control that has slowed things down and still slows things down in America. Just putting money into California is not going to get them necessarily the answers that they need. So, the need for strong regulation in terms of the use of the embryos to generate stem cells is important and has to continue. I think there is an important issue in terms of perhaps slowing down what might regulate the progress in terms of embryonic stem cells work which is if the current IVF regulation then goes on into regulating stem cells. Once you have an embryonic stem cell line, the whole process of then what goes on in the laboratory in terms of developing it, differentiating it and using it. We have to be very careful that we do not tie down that research into a regulatory process. If you put that part of the regulation into the hands of the HFEA, into the hands of requiring ethics committees for each individual study that is done in the lab, then I think we will slow things down in the UK in a big way. So, we have to find some way of identifying that an embryo has a certain specific identity that has to be given certain respect but, once it becomes a stem cell line, even though it is called an embryonic stem cell line, it has actually changed, it is not the same thing and does not require the same strict regulatory processes that we have now. There are other ethical committees that can look at regulating that in a way that is more appropriate.

Dr Lovell-Badge: I have very little to add. I think the attraction of the amount of money in California is certainly going to bring some people there. They are actively trying to recruit people and the amount of money is actually enormous.

Q1114 Chairman: Do you think we could lose out to them?

Dr Lovell-Badge: We could well lose some people to them simply because of the attraction of the money. That is an issue. Otherwise, I agree, I think it is far better to do this sort of research in an environment where you have backing from all sides and good regulation and I absolutely agree with Alison, I think it would be a big mistake to have work done in vitro in embryonic stem cells subject to any regulation apart from perhaps a local one.

Q1115 Mr Key: Could we look at the awarding of research licences. In the 2001 regulations that Parliament has produced, it extended the purposes of research to include knowledge about the development of embryos, knowledge about serious disease and to enable such knowledge to be applied. Do you think that those regulations are adequate or should they be extended in some way?

Professor Murdoch: I think they are adequate at the moment but they are in the process of being tested through the courts and I am not sure that it is the time now that we should be thinking about going back and looking at them.

Q1116 Mr Key: We are going back and looking at them whether we like it or not. That is why we are here.

Professor Murdoch: I have a particular difficulty in that the particular licence we have is now going to judicial review which rather limits what I can say to the Committee here.

Q1117 Mr Key: We understand that. Would anyone else like to add to that?

Dr Lovell-Badge: I think as always it comes to where you draw the boundaries as to what is clear. You were having this debate earlier about whether being infertile is sufficient justification to, for example, use embryonic stem cells to make germ cells.

Q1118 Mr Key: Professor Pederson has given a five-year timeframe for some of this work. How should we regulate clinical trials in the future because we are only going to get an opportunity for an act like this maybe once every 15 years? We have to look ahead. How do we need to regulate clinical trials?

Professor Murdoch: Clinical trials are already regulated. There are already considerable procedures that we have to go through. If I wanted to introduce a new drug into my clinical practice, there are various processes that I go through. If it is a drug that has been tried and tested, I would go to my Trust, I would go to the Drugs and Therapeutics Committee; I would give them the evidence to show that it was better than the existing and was cost effective and would be introduced into clinical practice. If it were a new drug, I would go through phase one, phase two and phase three so as to do it; it would go to Ethics Committee and patients would be informed and it would be appropriately funded. In terms of introducing clinical trials, I do not see any need to introduce any different model.

Q1119 Mr Key: Are we all agreed? Does anyone have any concerns about the EU Tissue Directive and do you think that will have an effect on human stem cell research?

Professor Murdoch: I have lots of views about the EU Tissue Directive. I think overall it is going to require an improvement in the quality system in terms of IVF laboratories and how they are run and, in that respect, the professional societies are supportive of anything that would improve quality. I think it is still going through the discussion process to make absolutely sure that the processes that are going to be required under the Directive are not so rigorous that actually it effectively stops the practice because theoretically it could do that. Overall, I think it is going to be an improvement on clinical service because, if you are talking about generating new embryos, the better quality embryos you have, the better the treatment will be and, the more effective it will be, the more likely it will be to be able to have patients coming through for treatment, the better embryos we will have that will be donated to research and the better stem cell research we will have. So, it will follow on. A good IVF unit is the one that is going to be working for the stem cell generation, not the bad IVF unit.

Dr Lovell-Badge: I agree with that and I think it is very important. I am looking into some of this. I do not work directly on human material at all but, looking into some things that go on in different places, you see in IVF widely different rates of success, different rates of success of growing embryos, to blastocyst stages, and I think anything that can be done to improve the overall success rates of all the methods being used ...

Q1120 Dr Harris: We have been to Italy where we heard some fascinating exchanges. The Italian Health Minister told us that, in his opinion - and he is a doctor - far more work was needed on animal embryonic stem cells before there was any need or any point of work in humans. Is this a reasonable position and, if not, why not? Separately, the Vatican gave us a paper purporting to demonstrate, with references from scientific literature and they were very keen to stress that, that it was adult stem cells that showed all the signs of having therapeutic application and there was very little evidence that embryonic stem cells would be as good and therefore we really ought to press ahead with adult stem cell research which did not involve the use of embryos which is at least controversial in most jurisdictions. Is that wrong and, if so, why?

Dr Lovell-Badge: First of all, there are at least two reasons for working with embryonic stem cells. One is to work towards therapies and the other is to use them as an experimental tool to gain understanding of diseases and other normal processes. We know that there are differences between mouse and human embryonic stem cells in the way they are grown, in their requirements and, in some respects, in their early differentiation. So, I think you need to study both. There are all sorts of things which are different between humans and mice and we could take an example being the frequency of chromosome abnormalities in early development. If you want to study that using embryonic stem cells, for example, to generate gametes from the cells and look at what is going wrong in meiosis, you cannot do that using mouse embryonic stem cells because mice do not have this really high frequency of abnormalities that human embryos do. That is one example.

Q1121 Dr Harris: And in respect of the other issue, adult stem cells? There are scientific references on this paper.

Dr Lovell-Badge: There are lots of examples where people are trying to take adult stem cells into the clinic. Not all of them but many of them are difficult. It is hard to get sufficient numbers of stem cells to treat people. It is hard to grow these stem cells; there are all sorts of problems. I am not saying that we should not be working on adult stem cells, I have never said that, we have to. However, we do not know which is best, whether it is potentially embryonic stem cell derived therapy or adult stem cell derived therapies. We do not know which is best and we cannot possibly know until we have looked at both and that is what we need to do.

Professor Murdoch: I am a clinician, not a clinical scientist, but I think all the evidence would suggest that these are separate but parallel lines of research and it would be very sensible, if we really want to make stem cell therapy reach its full potential, that we move along both lines at the same time. Some of the evidence that comes from studying adult stem cells will help in embryonic stem cells and vice versa but, at the moment, we do not know and no one knows where the end point is going to be. I think you have to remember that a lot of the people who are saying that we should only work with adult stem cells and not with embryonic stem cells are not doing it on the basis of scientific evidence, they are basing it on their views about using embryos for research, which we can respect but where their views are coming from has to be taken on board.

Q1122 Dr Harris: There are regulations about creation of embryonic stem cell lines from embryos because a value is placed on an embryo and there are regulations. Do you think that once a cell line is established, there should be less regulation and, if so, how much less regulation should there be about what you then do with a stem cell line derived from embryos? In other words, do you think there should be an application to a body, the HFEA or a similar body, for permission or should it be a research tool once it has been established that requires funding clearly and so forth?

Professor Murdoch: If you take an adult stem cell line from a patient to do a study on it, you will be give permission to do that with appropriate ethical approval that will say what you are doing in the lab but there would not then be any specific regulation in terms of what goes on in the test tube in the lab in terms of putting chemical X with it to see how it grows and to see how it is handled and I do not really see why there should be any difference therefore for the embryonic stem cell line at that level.

Q1123 Dr Harris: As long as you have the patient's consent for this sort of research.

Professor Murdoch: Exactly. It does not need another outside body overseeing it as well.

Q1124 Dr Harris: So, we should be able to genetically modify for research purposes embryonic stem cells lines without regulation from an external body.

Professor Pedersen: If I may interject something here. I think it is rather naïve to portray the circumstances as if there were no current regulation or no current body. That may be deliberately so because you like to raise the question of whether there should be an additional body. I should be the last person to point this out because everyone here should know the law better than I, but the law which enabled this research to go forward that was passed in this House required the establishment of a body to oversee the research and that body has the authority and the responsibility to do so: it is the Stem Cell Steering Committee and it is chaired by Lord Patel. Everyone who works on embryonic stem cells in the UK has to report to that committee and seek permission from that committee in its role as overseer. So, I do not understand why the question is being asked as to whether there should be a body because there is one.

Q1125 Dr Harris: We are reviewing the regulatory framework and we will issue a report suggesting whether it is over-regulated or under-regulated. What I am trying to tease out is whether the current regulatory system is onerous, necessary and appropriate or whether we were just a little sensitive at the time and we can get rid of a level of bureaucracy and rely on the existing normal methods of scientific oversight as one would with adult stem cells as Professor Murdoch just said. It may be that you like filling in application forms to Lord Patel. Some scientists tell us that they would rather not have that extra level of bureaucracy.

Professor Pedersen: If the question then refers to the effectiveness and the onerousness of complying with Lord Patel's committee, I think that there have been some responses early on to the effect that it was onerous. I think I myself had the first response to the committee on an application to export cells to Sweden that we had been studying. It of course is onerous to participate in self-regulation and Lord Patel's committee is a regulatory body, not a body that is encoded in statutory regulations as the HFE is a self-regulatory body. Of course it is onerous but that is the price of doing research in full compliance with the public trust and I think that eventually even those of us who are measuring it just on paperwork will comply with that because it is a reasonable cost to pay for the opportunity of doing this research.

Dr Lovell-Badge: I think I disagree. I think that once you are doing experiments on a cell line, whatever cell line it is, in vitro in the lab, then I think there are going to be pretty much no circumstances where that needs to go to a regulatory body. Maybe a local ethical committee to some extent but I do not think it needs any other further level of regulation. If you are going to then take those products from the cell lines and do something with them, then obviously that has to be regulated in some way and there are other ways that is done. In any transplant medicine, for example, you have to have the right sort of approval for that. I cannot see that there is any real need. The only matter you have mentioned was public trust but I think there is no real fear if you are just doing experiments in the lab.

Q1126 Dr Harris: Professor Murdoch, the casting vote!

Professor Murdoch: I would tend to move that way.

Q1127 Dr Harris: For the record, please.

Professor Murdoch: The UK stem cell bank is a relatively new body and is not fully operational yet; it is still finding its feet in terms of how it works. I would like to see it move towards a less formal regulatory process for what goes on in the laboratory than it has been tending to take on board at the present time. There are a lot of issues in the regulatory process which the UK stem cell bank has set up which are still being debated. It is a voluntary group and there is dialogue going on. Some of the issues that they have suggested we have are just not practical and cannot be done, but they are listening to what we are saying and are coming back and negotiating on them. I think there is the potential that, if it goes as far as it is suggested it might do, it might be disinhibitory to research rather than actually helping protect anybody or anything from any harm that is going to come. We should not have regulations for the sake of it, we should look at the risks and what we are trying to protect against and I think the risk of what you are doing in the lab helping to learn how stem cells grow is actually very small.

Q1128 Dr Harris: My last question is about your evidence from the Newcastle Fertility Centre which I found difficult to follow with this nucleus and faux nucleus and I suspect that, if I had a bit of difficulty, then others might have as well. As I understand it, it is not possible at the moment to allow a defective egg to fertilise, that with a faulty mitochondrion, and then take the nucleus and insert into a nucleated donor egg with a good cytoplasm and good mitochondria. That is not permitted under the existing wording of the HFE Act. You talk in your interesting evidence about how you think that the pronucleus is the thing to be transferred and I would be very grateful if very briefly but in straightforward terms you can tell me whether the things I have just raised are different issues and, even if they are, whether you think the Act needs to relax a little about the former case I suggested in case that turned out to be useful.

Professor Murdoch: This is an application that is pending with the HFEA at the moment from my scientific colleague Mary Herbert; it is not my name directly on that at the moment. A pronucleus will only have half the number of chromosomes as an adult nucleus. A female pronucleus will have half the chromosomes in the female from the egg and the male pronucleus will have half the chromosomes from the male and it is only when you put the two together that you will actually get a full complement of chromosomes. So, that is where the main difference comes between nucleus and pronucleus. I think there is a fundamental issue that is important in terms of the Act and restructuring the Act here and that is that the existing Act puts into primary legislation certain things that we can and cannot do and gives very specific terms and identity. You talked before about what is meant by embryo and it comes back to that sort of issue. If you use these words in primary legislation, it then becomes very difficult, as new techniques develop, to go back and interpret them and to get some understanding of what was meant initially when people said that in the Act and change it as things have moved on. For instance, the other issue in relation to that that is coming up is that we are not allowed to change the genetic structure of an embryo and I am sure that was originally put in the Act with the intention of making sure that people did not alter the genes in the nucleus and do that sort of process, but of course there are genes in the mitochondria and therefore what we are trying to do to help people who have serious mitochondrial disease to have a healthy baby suddenly falls under the wording in the Act which it was never intended for. So, one possibility of restructuring the Act is that you actually avoid putting these dogmatic statements in primary legislation and maybe devolve that to a secondary body of the good and great and the people who are interested to actually look at these issues as they arise and decide whether they are now, in the present climate, appropriate things for us to be doing in research. That will give us the flexibility to move on much more quickly than having to do it as we did with nuclear transfer, go back to primary legislation and actually change the Act to do it. As long as it is for the body that has the authority and the confidence of Parliament and the public, I think that might be a better way to go about it and it would get over some of those problems.

Q1129 Dr Harris: That is secondary legislation; you have to wait a long time.

Professor Murdoch: Yes, it still takes time.

Q1130 Chairman: For the record, will the day come when we will not need many stem cell lines? We may only need 15 or 20. You shake your head, why is that? There could be one on every street corner.

Professor Murdoch: There was a meeting in Newcastle recently when we were looking at how many stem cell lines ... The North East has a fairly static population but they reckon that, in order to meet full complement tissue matching, you need about 700 stem cell lines just for the North East population. Given the rate at which you can generate stem cell lines at the moment, which would need about 100 spare embryos in one stem cell line possibly, you are talking then about 700,000 surplus embryos. That is just for the north east of England. I think the reality of actually being able to generate enough stem cell lines that tissue match all the population is not realistic.

Professor Pedersen: I would say that this discussion has only begun and the data are not yet in the public domain with which to address it. The challenge is to make reasonable estimates of how many embryonic stem cells lines would be needed or, for that matter, any source of stem cells would be needed to tissue match the UK population and then to discover methods of obtaining those in a patient transplant quality with the highest efficiency in order that we do not waste the material.

Q1131 Mr McWalter: I am very interested in many of the things that you have been saying. One of the things, Professor Murdoch, that struck me was that you indicated that the reason why all this is so difficult is because the stuff/material that is in your lab is, in the first instance, an embryo and that is obviously the reason why there is huge public concern about it. One of the issues then is that many of the people to whom we have talked have said that that needs to be treated with respect. Your words were that it has an identity. I can think of a friend of mine who has had two children through IVF and the spare embryos are now sitting there and then the issue is, what do you do with them? The Vatican has effectively said that you do not have IVF really; you generate three embryos and you implant all of them; you do not have a spare embryo from them. Assuming that one does not want to go down that line and one wants to treat these materials with respect, I think that my friend would actually want those embryos to be used to further human knowledge for the overcoming of avoidable disease and suffering. I think she would see that as the best way forward for those materials that have come from her and her husband. So, I do understand that treating with respect might involve being in a lab, in the same way as keeling over and donating your cornea to someone you have never met is also a treating with respect of the human body, so I do understand that. Then you said that when you generate a stem cell line from the embryo, then the rules change and Dr Robin said. "Now it is like sodium chlorate in a test tube. I do not want anyone telling me this is very special sodium chlorate; I do not want anyone telling me this is very special material when I have to continue, for instance, to inform the people who gave the material its identity what happened after the embryo became the originator of the stem cell line." Why do you not accept that maybe that material also needed to be treated with respect? You were sort of in the middle but you went more towards Dr Robin's view.

Professor Murdoch: I would not say that stem cell lines should not be treated with respect. Anyone who deals with stem cell lines knows that they have to be treated with respect or else they die, basically. So, yes, there is some respect there. I think it is to do not with respect that you give them but actually how you look at them and how you process them and care for them. Every embryo that you create in an IVF laboratory has to be individually identified and we have to be able to account for it to the HFE. If an HFE inspector comes in, they will say, "Where was that embryo? Where is that embryo? Where are your records to say what happened to it?" Once that becomes the stem cell line, you are now talking about millions of cells. Are you going to account for every single individual cell? If you count them as groups of 100 cells, then is a group of 100 cells different from the millions? They are different. I am not saying that you do not respect a line for what it is and where it has come from and its value, but you cannot subject it to the same degree of regulation and monitoring in practical terms.

Q1132 Mr McWalter: The one thing you might do, apart from telling people who, say, donate these embryos and they regard that as the appropriate thing to do with them, is undertake to keep them informed about the research. So that they do not have only the thought, the embryo was in a lab somewhere and got used in a lab but to inform them more about the research. Then they would have a continuing interest in what you were doing and see beyond simply the fact that the embryo is now no longer, as it were, recognisable as the embryo they created. I do not see why you do not have some sort of continuing interface with the people who generated that material in fact out of mutual love and all the other things that go into it.

Professor Murdoch: Because those stem cell lines are not their baby.

Q1133 Mr McWalter: I understand that. It is degrees of respect and you might find ways of integrating that concern into the ethical framework.

Professor Murdoch: Patients who give consent - and do not forget that the processes of consent are rigorous; in our unit at the moment, we have a nurse who is funded by the MRC specifically to work fulltime to talk to patients about the research that is going on in the lab; she has nothing to do with the clinical work at all; so, it puts an interface between the clinical service and the research service - are given the opportunity to get information back about anything that might be found out that might affect their health and their children's health in the future and they can choose to do that or to not do that. They are not given the opportunity to be given specific information back about what happens to any lines that might be derived from their embryos. My own personal view is that I think that is probably the right thing to do. Do not forget that I am treating people with clinical problems and some of these people do not get pregnant from treatment and some do and it is a huge psychological problem that they have. To then burden them with the problem of how they then regard a stem cell line that might be generated from an embryo I think is actually too difficult for them. If they do not feel that they want to participate in the research on the basis that they are not getting that information, they do not give consent, so they do not agree. It is discussed with them and they are given that opportunity. Just to give you some feedback, since the nurse was employed in September, previously we had had a very sort of hands-off approach, so the number of people consenting to give embryos for research was 50/60 per cent, that sort of order. Since she has been there and we have been able to give people more information, about 17 per cent of the people whom we see say at their first visit when they come for IVF when I say, "There is research going on here", say, "No, I don't want to participate" and they are not involved any further. Of those that go on and they ask for information and are given further information, 87 per cent agree to use any surplus embryos, these are embryos that would otherwise be discarded, for research. The reasons they give are that if people had not done research on embryos in the first place, they would not be there having an IVF treatment. They recognise that these embryos are going to be discarded; they are no use to anybody; they cannot be given to anybody else; they are there and they want them to be used and I think the views of the patients whose embryos they are have not been listened to previously hard enough in this debate.

Q1134 Mr Key: Scientists might say that we are dancing on the head of a pin but a lot of other people would say that we are dancing with angels in trying to get to the bottom of this issue. We were told by previous distinguished witnesses that scientists really cannot define an embryo, "it depends who you are talking to", we were told. So, what is so special about the moral status of an embryo if we cannot even define one?

Professor Murdoch: I think that is a real problem in terminology and I can see where the issues are coming from in previous discussion. If you go out on to the street and say to someone, "What do you think an embryo is?" they will describe to you a tiny but fully formed moving foetus, so a moving thing with arms and legs and a heart that is beating. That is lay understanding of an embryo. The patient having IVF thinks of an embryo as the four cells they see on the screen before they are put back that might make them a baby. The Act of Parliament at the moment considers an embryo as being an egg sitting in a dish surrounded by hundreds of thousands of sperm with no intention of ever letting any of those sperm get inside the egg but, according to the law, that is an embryo. Clearly these are completely different things. Therefore, we have to use different words to describe them. There are different words to describe them - you can use larcisis(?), you can use zygote at different stages, but I think that we will have to find a different word because they are different things. Clearly, there are issues in terms of public perception, public education and understanding of what we are doing but, if we persist in using the term "embryo", we are going to get it wrong. One of the headlines in the newspaper when the nuclear transfer issue came out had a picture of a fully-formed embryo as an illustration and that is wrong. It is misinformation.

Q1135 Mr Key: Professor Murdoch, you just said in answer to a question from my colleague, referring to your patients, that it is too difficult for them. Our problem is that we are trying to find a way of describing something in law which will be applied for as long as possible. The law will not fall into disrepute because we do not do our job properly. Do you think there is a conflict of interest between stem cell research and fertility treatment given that every embryo donated for research could theoretically become a baby?

Professor Murdoch: There is potential conflict of interest and I think part of the current regulations which are very tough are designed to minimise that conflict of interest. Regardless of what the HFEA would say, the licences that we have go to the Ethics Committee before they get seen by the HFEA and one of the remits of the Ethics Committee is to make sure that nothing is going to be done to the patient in the process of any research which will harm their primary treatment. So, there are not just the HFEA but there are standard regulation procedures already that cover that. I think that, in the UK, we probably have it about right. One of the difficulties you have in other countries in the world is where people are saying, "We are going to create embryos, pay people to give eggs/sperm specifically to make embryos specifically for research." That might turn out to be the only way we are going to get decent embryos to do it but I think that, at the present time, the stance that has been taken in the UK, which is that we will use the embryos which have already been created which are going to be thrown away otherwise, is the appropriate way to do it and we have to come to terms with potential conflicts of interests.

Q1136 Dr Iddon: Will it ever become possible in your view to abstract stem cells from an embryo without destroying the embryo? What are the benefits in doing that? How much effort should be put into it? What is the impact on regulation if it comes achievable?

Dr Lovell-Badge: It could be done; the techniques are available to do that simply by beginning as you would PGD, on an embryo, and take two cells and derive embryonic stem cells from those.

Q1137 Chairman: Why do you not do that then?

Professor Pedersen: This may be an overly technical answer, but one of the rules, that is to say a fact, that we know applies to all mammals, of which we are a member, is that the early development of the embryo before implantation into the uterus depends on the total mass of cells and anything that is outside becomes the placenta. That is the rule. So, unless you have a big enough mass to have an inside, you get no stem cells except placenta. That is why it is very difficult to take a bit of the embryo and achieve this. You could, in principle, take just the inner cells out and leave the placenta alone, but then it would not develop except for as a placenta and a placenta does not grow without the inner cells present.

Q1138 Dr Iddon: And the impact on regulations? Can we see how you can change regulation if this becomes a common practice? Does the present regulation cover this adequately?

Professor Murdoch: I am sure that current regulation as it stands would cover it because you are doing a manipulative process to an embryo, so it would come to a committee which would have to decide whether it was something that was justifiable to do and whether there was a good scientific basis for doing it.

Q1139 Dr Iddon: Let me look at another difficulty now and that is bringing human and animal gametes together or cells together. Why is that necessary in stem cell research? What are the benefits we can gain from that and do you think it is ethical?

Professor Murdoch: Are you talking about chimeras or co-culture?

Q1140 Dr Iddon: Yes.

Dr Lovell-Badge: There are three: there would be chimeras, there would be co-culture and there would be the nuclear transfer as well.

Q1141 Dr Iddon: Well, how long do we have?

Dr Lovell-Badge: Let us start with the nuclear transfer experiments going across species and there have been lots of attempts at this mostly in China taking, for example, human somatic cell nuclei and putting them into rabbit eggs. That was used to derive embryonic stem cells which, according to the work published, have all the properties of human embryonic stem cells. The reason for doing those experiments was simply to get over the shortage of having human cell lines and that seems to me to be a perfectly good reason for doing it. You can imagine other reasons for trying to do this. There was a paper published recently where people, again in China, had taken cells from early chicken embryos and put them into rabbit enucleated eggs and they claimed to get blastocysts from those. A lot of this work has not been easy, so it is to be taken with a pinch of salt. I think that as long as that sort of work is done for purely experiments in culture, I see no real problem.

Q1142 Dr Harris: The Chinese thing is unlawful in this country at the moment.

Dr Lovell-Badge: Is it? I do not know that.

Professor Murdoch: Yes, it is.

Dr Lovell-Badge: I have asked and have never received an answer.

Professor Murdoch: I understood that it was.

Dr Lovell-Badge: You are not using any human gametes. I guess you would have to call it a sort of human embryo at one point.

Professor Murdoch: I may be wrong. It is actually that you cannot put an embryo into an animal which is not the same thing.

Dr Lovell-Badge: So, I think it probably is. It is possibly regulated by the Home Office and Procedures Act.

Chairman: Does that help you, Brian?

Q1143 Dr Iddon: Not really! It is obviously a very experimental area and it needs further looking at.

Professor Murdoch: One issue that is important is that, if we are going to develop stem cells of a therapeutic product, then we actually need to be growing them and deriving embryonic stem cells from embryos in an animal-free environment which at the present time is difficult to do. So, from that point of view, we need to separate them out. Just because there is always the risk potentially of making a therapeutic product that has animal ...

Dr Lovell-Badge: That is also the co-culture thing. Most people have today made their human embryonic stem cell lines, growing them on feeder cells from the mouse but that situation has changed.

Q1144 Dr Iddon: It looks as if there might be a clash of legislation, and Parliament will obviously have to deal with that.

Dr Lovell-Badge: The third type of experiment is the chimeras if you want me to talk about that too which is where you are deliberately trying to mix cells from two different species. For example, we know that with mouse embryonic cells, if you introduce those back into an early mouse embryo, they will contribute to the development of that embryo and will give you a live born animal with a mixture of cells derived from the embryo and cells that were in culture. So, it has been proposed that people might want to do these experiments to test whether, for example, embryonic human stem cells are also really and truly pluripotent, that they can give rise to all sorts of cell types by transferring them into the embryo of another species. I personally think that this is very unlikely to work taking the embryonic stem cells themselves. However, I think there are good reasons for making chimeras at later stages where you have a particular cell type that you want to, if you like, replace in the mouse. Perhaps you want to humanise the mouse in order that that mouse has a particular set of cells, like the immune system, which is then derived from humans. And then you can use them for study as a model of human diseases.

Q1145 Chairman: This is a good lecture!

Dr Lovell-Badge: I am sorry, I will stop. There are good reasons for doing it is all I am saying.

Q1146 Dr Iddon: That is what we were looking for.

Professor Pedersen: Can I respond in the spirit, I think, of your question as to whether there would be any further regulation needed with respect to these proposed experiments. I think that, in the first instance, they would be precluded from clinical use because they combine what we have to avoid, namely animal product contribution to medical material, so nobody would use that ultimately in clinical use and I do not think there are any additional regulations needed beyond that disincentive.

Q1147 Dr Iddon: Let me finish by trying to provoke you. We have had other witnesses in front of us who have said that the stem cell scientists are overselling the benefits of stem cell research and the chances of helping people with various diseases is pretty small. I am giving you a chance to react to those witness statements which we have on the record.

Professor Pedersen: I would like to react. I think it is entirely self-evident that blood stem cells are clinically effective because they have been in use for decades now clinically to treat people if they are undergoing chemotherapy or have had forms of anaemia for example, but the difficulty of extending that therapy to other tissues is that we cannot grow those adult stem cells in a Petri dish. They simply do not grow. When you take them out of the body, they start growing and specialise and that is even true of blood stem cells. So, how we expand this field of knowledge is to study what we can study in fact and that is embryonic stem cells which grow in a Petri dish and have the capacity to turn into every tissue of the body which means that the other stem cells ... What we expect is to break this entire field of knowledge open by studying embryonic stem cells. This is an area where we know exceptionally little at this present time, that is to say how our body works as an organised system. It is like any field of knowledge at the very beginning, you cannot guarantee where it is going to deliver but we can say with certainty that it will deliver. It will probably deliver vastly in excess of our narrow expectation which is simply transplantation. What we probably will discover is how to get our body stem cells to perform better in their place and that is the pot of gold at the end of the rainbow. If I now may take just a moment to finish ...

Q1148 Chairman: Please try and be brief.

Professor Pedersen: In the interests of having this goldmine as heart of the knowledge-based economy, I think it is exceptionally important not to make the mistake that the US has made which is not simply to put negative regulation in the way of the research but to keep changing the policy. The volatility, in my mind, is what has lost the advance of this research in the States. It is because it changes with every administration and I would therefore caution you against making unnecessary changes in the regulatory structure because it is the stability of regulation that allows people to go out with confidence and invest their lives and their student's lives in this research area.

Q1149 Dr Iddon: While we have you on this stand, can I just remind the Committee that, in the American elections just gone, stem cells featured quite prominently in the debate leading up to the election. Would you be hesitant if that happened in the next General Election which is imminent in Britain and could you defend yourselves on the general public's platform to defend the work you are doing if it happened here and would you welcome a debate during a General Election campaign in Britain?

Professor Pedersen: I would certainly welcome it. It seems unlikely in view of the fact that both major parties ---

Q1150 Dr Harris: Both?

Professor Pedersen: Forgive me!

Q1151 Dr Harris: You are forgiven!

Professor Murdoch: In terms of the American debate, the polls in America suggested that 70/80 per cent of the population supported stem cell research despite the stands that were taken within the debate and I am sure that it is at least the same in the UK. I would be really surprised if there is a polarisation of views considering that Parliament has already debated and voted on this issue relatively recently. I do not think it would help in moving us forward to have that issue raised in a public debate. The issue we are talking about of stem cells being overhyped raises two issues. The first, which I think is important, is that we recognise the timescale involved and that sometimes the media will say that a cure for Parkinson's is going to happen tomorrow and it is not. There is a huge amount of work to do and, if we raise expectations too soon and if we move to clinical trials too soon ---

Q1152 Dr Iddon: We have been told five years in this session.

Professor Murdoch: That is fine but that message is sometimes not getting over to the people who are against it. I think sometimes you need to recognise the position of the people who say it is hype. If you come from the viewpoint that there should not be IVF and there should not be embryo research and that is why you should not be a member of stem cell research, you have to be clear where those views come from.

Dr Lovell-Badge: Do not forget also the research purpose of using embryonic cells. You can use embryonic stem cells to study genetic diseases and you can use them to try and find alternative ways of curing people than as transplants.

Q1153 Mr McWalter: Your remarks about elections, the public and so on connects with my earlier point which was to try and get some sense of ownership of the wider public of some of this stuff because, to be honest, that 22 per cent for whom it was an issue, that, for them, often is the number one issue and so they discount everything else. They are like foxhunters. They discount everything else. That is the only issue they are going to vote on and that is the one they go on and I think that, from that point of view, even if it is a minority of people, it is extraordinarily electorally potent and that is why we need to make sure that there is much greater public understanding and public ownership of both the ethical and the scientific basis of a lot of the materials we have talked about today.

Professor Murdoch: I would entirely agree and I spend a lot of my time talking to various people about it.

Dr Iddon: At the moment, licence applications and the peer review of those licence applications are dealt with by the HFEA without transparency and one of the criticisms that we have had from other witnesses is that the whole process should be transparent. Of course, the Freedom of Information Act is about to impinge upon us in January next year. Is there concern among professionals that the whole process will have to become transparent, the licensing application and the peer review reports or not?

Q1154 Chairman: You will have to see the reports.

Professor Murdoch: I am being careful what I say because of the legal issues that are going on at the present time in terms of the process. I do not have any problem. There is nothing that we have given to the HFEA in terms of any research licence applications that we have put through that I would consider could not be available in the public domain.

Dr Iddon: I am pleased to hear that.

Q1155 Chairman: I was just thinking that, since Norwich MPs have a great relationship with Prince Charles, if we could get him to speak out for stem cell research, it would be game, set and match but I have my doubts at the minute. Do you think there is duplication of ethical and scientific review processes? Do you think they could be combined better or do you think they are kept very separate for a good reason?

Professor Murdoch: The ethical procedures have been changed enormously over the last five years and have been tightened up. There is a 60-paged document that I have to fill in to get local Ethics Committee approval for these sort of procedures and all the consent forms have to be approved by them. So, for them to be looked at again by a separate authority could end up with a situation where someone does not like that word, it goes back to the other person, they change that sentence and you could just bounce backwards and forwards. There should be one organisation that does that but, having sat on a local Ethics Committee for some time, I do not think they have the expertise to deal with some of the scientific issues that relate to whether the procedures we are dealing with are legal.

Q1156 Chairman: Do you have confidence that the HFEA comes to an informed judgment on that basis? You have been singing their praises, international stars and so on. Can they make that judgment best in this country in terms of licensing and taking the scientific evidence?

Professor Murdoch: Which judgment? Whether there should be a licence or not?

Q1157 Chairman: Yes as an example. Do you have great confidence in them being able to assimilate all this data and make a judgment? Are they the organisation to do it?

Professor Murdoch: There has to be an act of Parliament that regulates to a certain extent what we do and therefore there will have to be an authority that implements that Act. I do have some concerns about the process that the HFEA goes through at the present time. I would not sing its praises 100 per cent. There are lots of things that could be improved. I think it is slow. It is over-bureaucratic because it is necessary to do that because of the legal requirements it has to fulfil in its due process. The procedures for inspection and for reports are a negative influence in terms of research. The particular research with stem cells is only one form of research. If you are talking about research relating to basic ART techniques, I think that regulation is very disinhibitory to basic research that goes on in the laboratory and could be improved. I would not want to say that the HFEA is perfect by any means. There are lots of things that could be improved.

Q1158 Chairman: Would you concur with that, Robin? Yes or no?

Dr Lovell-Badge: Yes.

Chairman: Thank you very much indeed. I am sorry to bring it to an end but thank you very much for coming, it has been very helpful. I know that it is a tortuous process for you but thank you very much for answering our questions enthusiastically and, I think, accurately. Thank you very much.