PROFESSOR COLIN BLAKEMORE, PROFESSOR MARTIN BOBROW AND MR DAVID MACAULEY

5 FEBRUARY 2007

  Q227 Chairman: Can I welcome our third panel today. Professor Colin Blakemore, welcome again, Professor Martin Bobrow and Mr David Macauley. Could I ask you to introduce yourselves, in no more than one minute, to say who you are and who you represent; we will start with you, David?

  Mr Macauley: Thank you, Mr Chairman. David Macauley. I am the Chief Executive of the UK Stem Cell Foundation. The Foundation exists to develop what we would define as translational medicine. If you could imagine a continuum of basic research at one side, across to, say, industry developing the therapy and marketing it, translational medicine is really the bit where we believe there is a funding gap existing currently in the United Kingdom, where typically the Research Councils and the Medical Research Council would take the research and normally it would be the preserve of industry then to pick up the science and develop it. Currently it is not the case in the United Kingdom and really we exist to bridge that gap; so it is an important funding step for typically academics and clinicians who come together to develop a model therapy or the basis of a therapy. We exist to fund that particular work.

  Professor Bobrow: I am a superannuated medical geneticist and academic. I am here as Deputy Chairman of the Wellcome Trust, which is a research-funding organisation.

  Professor Blakemore: I am Chief Executive of the Medical Research Council, which is a leading funding body in the area of stem cell research. I am a neuroscientist. A little of my work has been concerned with stem cell science.

  Chairman: Thank you. Starting this session is Graham.

  Q228  Graham Stringer: When you are evaluating grant applications, how do you judge the likelihood of success?

  Professor Blakemore: I think it depends very much what you mean by success.

  Q229  Graham Stringer: Are embryonic stem cells going to be produced; that would be success in what we are talking about?

  Professor Blakemore: Clearly, the potential for productivity, in terms of science or possible medical benefit, is the most important criterion in deciding whether a grant should be awarded; so it would not be attractive to fund a project in which the likelihood, let us say, of stem cells being produced, if that was what was proposed in the research, was extremely low.

  Q230  Graham Stringer: I am sorry; is that not rather restating the question as a form of answer: how do you do that? We all want success. How do you judge the likelihood of that success; how do you assess it?

  Professor Blakemore: In this case, the peer review process would try to assess the probability of success on the basis of what was known about previous research, including the track record of the applicant. If what you are driving at here is the question of how successful we are in creating human embryonic stem cells, the background in research suggests that the probability is rather low and producing stem cells by somatic nuclear transfer is even lower, in fact, virtually zero, on present experience.

  Q231  Graham Stringer: I am confused now. You think it is worth funding this kind of research, even with that background?

  Professor Blakemore: What is being offered in this case is the possibility of a very significant improvement in the success rate through the use of animal oocytes combined with human somatic cell nuclei to explore the methodological problems which are the obstacle that has been revealed in attempts at using human oocytes in combination with human somatic nuclei. Given the fact that the success rate in other species, for both somatic nuclear transfer and the development of stem cells from conventional embryos is rather higher than that for humans, there is the hope that if we can find what the practical obstacles are we will be able to make better progress. Clearly, there are ethical reasons why such exploratory research, essentially methodological research, should not be done with human oocytes, because of the difficulty of obtaining them and, in a sense, their huge moral value.

  Q232  Chairman: Just before you go on, Professor, can I ask you, Professor Blakemore, whether you are convinced that the research done by Professor Sheng in China is sound?

  Professor Blakemore: I know Professor Sheng personally. The laboratory is very well established and I think widely respected. I do not have any reason to be doubtful about those results.

  Q233  Chairman: He was questioned earlier, so I just wanted to put that on the record. Sorry, Professor.

  Professor Bobrow: My answer, briefly, is going to be very similar. If we were to receive an application to fund this sort of work, we would send it to one of our judging panels, which contain a number of people who would be expert. Also we would send it to somewhere between four and 10 international experts in precisely that field of science, asking them to look in some detail at exactly what is proposed and to give us their opinion on whether it is likely to run or not. There are not guarantees in this; if you actually knew the answer you would not be doing the research. That is an established process and it is what we do with everything, and it is not a policy question, it is a pragmatic question related to that individual proposed set of experiments. The criteria that we would want the panel to look at in general are, is this addressing an important question; does this person have a good track record in this type of science, do they know what they are doing; do the experiments make sense and, of course, are they decent, ethical and legal. Lastly, we would want to know if it is innovative, because it is relatively easy to forget that if you do not concentrate specifically on things which are novel then nothing progresses very fast. Clearly, this is a field where, although there are lots of areas of promise and you hear all these good words, it is tough going at the moment. That is the time to be prepared to be a bit inventive and to put a bit of money in general into funding things which look like a bit of a flyer, where the risks are high, because the possible returns are high, with the provisos about ethical and legal and moral issues which I have given already.

  Mr Macauley: When it comes to the UK Stem Cell Foundation, we share an advisory board, a scientific advisory board, with the Medical Research Council. Our criteria are somewhat different. This type of work we would deem not to be translational, in the sense that we would wish to fund it, but it is a recognised stepping-stone on the way to translational science. In fact, the Cooksey Review, completed recently, addressed the whole issue of translational research in the United Kingdom and it is an area of debate at the moment. In terms of review, the criteria we would use in assessing an application are very similar to this; in fact, we are looking at a number of applications at the moment, Parkinson's disease is one example, where these techniques, that the Government currently propose to be banned, would actually hinder the development of the work that we would propose. On translational medicine, which is often a reduction to process, it is often not very exciting, it does not lead to Nobel prizes, in many cases, it is pathological, it is process-driven, but again a lot of the same criteria, the quality of the research team; in many cases, the amount of money is a good indicator of the likelihood of success. Many of the challenges we face are resource issues, as opposed to major scientific hurdles; all of the work that the MRC and Wellcome fund is to get over the scientific hurdles and then it becomes an issue of taking that science and developing it into a sort of working prototype or therapy that we can move forward with.

  Chairman: We understand the process.

  Q234  Graham Stringer: Just one more question on this line and then a slightly different question, if I may. Having the peer review and all the other criteria you may use, do you judge alternative lines to go down, or do you not? Do you consider whether using adult stem cells is likely to be more effective and productive, or is that left to one side, as not being part of the grant application? On scheduling, we have heard some evidence that people do not want this research to take place at the present time. Should we be rushing into this research now?

  Professor Blakemore: On the question of adult stem cells, certainly the Medical Research Council, and I am sure the Wellcome Trust as well, funds research on adult stem cells. We have a unit in Oxford, the Molecular Haematology Unit, which is devoted largely to work on stem cells, on blood stem cells. I think the general feeling is that although adult stem cells, eventually, when we learn how to manipulate them, might provide alternatives to some of the possible anticipated uses of embryonic stem cells, we need to learn from the study of embryonic stem cells what might be possible with adult stem cells. The research needs to go ahead on a broad front, certainly involving embryonic stem cells as well, if we are to learn how to benefit from adult stem cells fully. I will give a particular example in the context of your discussion. There are claims that adult stem cells, in some cases, can have similar multipotency, that is a capacity to form different types of adult cells, to that of embryonic stem cells. For instance, I heard very recently about work in Japan which suggests that in mice adult fibroblasts, which help to repair skin, bone, and other tissues, and can be converted quite simply into cells that appear to behave like stem cells. To prove that, one would need ultimately to introduce such cells into a developing blastocyst to see whether those cells which are claimed to be stem cell-like, can contribute indeed to all tissue types. That would involve creating a chimera. If we were able to pursue that in humans—let us say it were possible to make stem cells out of fibroblasts in humans—that would be a wonderful advance. But to test the extent of multipotency really it would be necessary to produce chimeras, introducing them into an embryo of another species, rather than a human, in order to see whether they could contribute to all tissue types.

  Q235  Graham Stringer: Thank you. On just a slightly different tack, if I may, you heard the discussion previously this is an area of great controversy. In coming to conclusions about whether to push forward with this research, how important do you consider public opinion? I asked the previous witnesses, if public opinion was 80% against would they still want to go ahead; do you have a view on this?

  Professor Blakemore: It would depend very much, first, on how public opinion had been measured, in other words, whether it was properly representative; and, secondly, on what background understanding of the facts that opinion was based. In the case of the debacle around GM food science a few years ago, the hostility of the public was very clear; but I think one could question the extent to which the public really were properly informed about the facts, both the facts around benefit and the facts around risk. The problem is, and this has clearly been identified already, that the notion of combining human and animal material generates a `yuck' factor which actually might reflect the lack of knowledge of the public about the reality of what is involved, and indeed the benefits which are already flowing from just such approaches.

  Professor Bobrow: I do not think that, for a moment, we would consider that science could progress without the backing of the public in the most general sense. Where there is serious public unrest one has to take some account of that; but the way that we are sensitive to that is by processes of the sort which bring us here this afternoon. We would not go out ourselves and look for public opinion and influence our funding decisions specifically on that basis.

  Q236  Dr Iddon: Gentlemen, as distinct from those who have strong moral or ethical objections to the way that Newcastle and Kings want to go, are there any strong scientific reasons why this work should not go ahead, which you are picking up from other groups perhaps?

  Professor Bobrow: My understanding of this, and I am taking advice from others who are much more expert than I, is that this is high-risk, high-gain research, so there is no absolute reason to say that this work could not succeed, and there are some indicators, that you have already heard about, that it might, but that is not to say that it is a certain bet on the block. That is no reason not to pursue individual applications if they are structured properly. I have not been asked to look at the specific applications which have been to the HFEA and so I would not comment on them, but for the field in general that would be my view. If they hit the desk at the Trust they would be sent off to the sort of review process that we mentioned earlier.

  Q237  Dr Iddon: Professor Blakemore, are you picking up any anti feelings about this area?

  Professor Blakemore: Of course there are scientific doubts about any new area of science, and the principal one, I suppose, will be about whether one could generate stem cells from a hybrid embryo by somatic nuclear transfer of human genetic material into an animal oocyte shell, which behave truly like human stem cells. One issue here is the influence of the mitochondria in the cytoplasm of the oocyte. Mitochondria contain a small component of the total DNA in the cell and they might play a part in the function of any hybrid stem cells produced. In fact, the preliminary results as reported from China and also from the groups in New York and in Cyprus strongly suggest that it is possible to create stem cells which behave very much as if they are human, but we have to confirm that. The only way is by experiment.

  Q238  Dr Iddon: Is there objection on the grounds that maybe viral contamination would be a problem; is that a serious risk?

  Professor Bobrow: I am not sure that there is any factual basis which has been brought out for that being a risk in this specific instance. For me, it is quite important to put this against a slightly different background. One of the things which have really knocked me back, over the past 15 years, as a scientist, is the extent of similarity between genetic material from wildly differing species, really wildly differing. I think it is just astonishing that many, many genes can be taken from yeast, which is a long way away from people, and put into human cells and work perfectly and do the right thing, and vice versa. There are hundreds of other examples. At the front end of biology, the distinction between different species in culture, as opposed to things walking around on four legs, is nothing like as clear-cut as it seems in the newspapers. I am now retired. I cut my scientific eye-teeth fusing human and mouse cells together to make it into a specific cell hybrid, and tens of thousands of those experiments were done 30 years ago. There is no suggestion that anything has happened untoward as a result of those experiments. It would have to be incredibly specific to this sort of cell type, in this sort of situation. There are two separate risks. One is the risk to the world and to the researcher, which is what I have dealt with; the other is the risks if you were actually to go another step and turn that into a therapeutic procedure. I think those risks are unknown, uncharted and nobody that I know of is suggesting the reimplanting of such embryos at this stage; we would need to know a massive amount more.

  Q239  Chairman: Would you agree that would be the next step, and that is what many people are concerned about, that it will be that next step, and, going back to the Japanese research, Professor Blakemore, that implanting an embryo to see how certain stem lines develop is the logical next step, or is it not?

  Professor Bobrow: My brief answer would be, putting it back into a person is not the logical next step. Putting it back into an experimental animal for a short period of time may well be the next logical step.

  Professor Blakemore: I think what this discussion is revealing is the diversity and the complexity of possible uses of the general methodology of combining human and animal material. I can just try to clarify my understanding of the range of areas in which this approach might be useful. The first is essentially methodological, to try to find a way around the current problems in creating human embryonic stem cells and particularly stem cells by somatic nuclear transfer. We are up against a real barrier there. It is unreasonable to continue that research through the use of human oocytes; using empty animal oocytes will help enormously. There is absolutely no intention of implanting going beyond the 14-day rule and implanting those embryos, or even using the stem cells for therapy. That is just one area. The second is to develop models, in vitro, in the test-tube, of disease conditions, i.e. stem cells from embryos that are created by nuclear transfer, where the human nucleus is known to be carrying a genetic defect. Again, there is no possibility of using those cells to treat people, and having no intention of reimplanting the embryo; but only of creating very valuable models of disease, which, in turn, might be used to help the development of drugs or to test the toxicity of drugs in different types of individual. The third is the one which I referred to earlier, of the possibility of testing the claimed multipotency of stem cells derived from other sources, for instance, adult stem cells; it might be necessary to create chimeras. Finally, there is the issue of the scientific benefit, the advance of knowledge that could be produced about developmental processes through this area of research, again, with strict controls. For instance, this question of the interactions between nuclear DNA and mitochondria DNA; this is clearly an experimental approach to that important question.