DR LYLE ARMSTRONG, PROFESSOR CHRIS SHAW AND PROFESSOR AUSTIN SMITH

31 JANUARY 2007

  Q1 Chairman: May I welcome our guests: Dr Lyle Armstrong, Institute of Human Genetics, University of Newcastle-Upon-Tyne, Professor Chris Shaw, Institute of Psychiatry at King's College, London, and Professor Austin Smith, Wellcome Trust Centre for Stem Cell Research, University of Cambridge, as witnesses to our first evidence session in terms of the Government's proposals on the regulation of hybrid and chimera embryos. Welcome, gentleman, and may I first of all give my apologies for starting this session nearly 10 minutes late. I genuinely regret that. We ask that you, Professor Smith, chair your panel in case you start having a dispute; you are going to be in charge of that.

  Professor Smith: I will do my best.

  Q2  Chairman: This session is being televised and therefore, rather like the Big Brother House, we need to be on our very best behaviour, or perhaps that is not an appropriate thing to say! Professor Shaw, I would like to begin with you—and put the same question to Dr Armstrong—and I want a very, very brief answer, please. Would you give a brief description in laymen's terms for the Committee of the research you would like the HFEA to license. What is it that you want the HFEA to license?

  Professor Shaw: What we are asking is to be allowed to put a human skin cell into an animal egg which has had the nucleus removed. So, the DNA from the egg has been removed and replaced with the human DNA. The skin cells that we want to use are from patients who have neurological diseases and we hope to be able to stimulate that new cell to divide and generate stem cells. Those stem cells can be turned into the nerve cells that we think are important in these different diseases and we can study the disease process in the laboratory. This will tell us about disease mechanisms and it will allow us to actually treat those cells and see whether we can reverse the disease process and discover new treatments. That is the purpose.

  Dr Armstrong: We are essentially asking to do a very similar thing. We will perform this nuclear transfer or cloning technique using human cells and putting them into animal eggs which have had their nuclear material removed. The idea behind that is that we can derive embryonic stem cells from those embryos and investigate things such as how the genes in that adult skin cell from the human organism have been reprogrammed or reset to make them express all the gene sets that would be required to turn them into an embryonic stem cell. We want to do that because we want to understand this reprogramming process so much better because, if we can design strategies to reprogramme, say, a cell from a human skin, then we can perhaps get away from having to use this whole cloning process in the first place to make embryonic stem cells and thereby make embryonic stem cell technology more accessible to everyone rather than just as a research tool.

  Q3  Chairman: May I clarify from you that the stem cells that you will be taking, the human cells that you will be taking, will be from patients with known disease.

  Dr Armstrong: Not in this case. That is not our specific interest.

  Q4  Chairman: That will be different to the branch of Professor Shaw in that sense?

  Dr Armstrong: It is different in that respect, yes.

  Chairman: Okay. Now, we need to get the terminology right and I am going to bring in my colleague, Des Turner.

  Q5  Dr Turner: We do not want public debate to be bedevilled by loose terminology; there is already loose enough terminology in the Government's proposals. It would be very helpful if you were to set out what you mean and understand by the terms "chimera" and "hybrid" in this context.

  Dr Armstrong: A hybrid is essentially an organism which is formed by the mixing of the chromosomes of two separate organisms. A chimera is essentially an organism which is formed by the mixing of the cell types from two separate organisms. The entities that we would seek to create really fall into neither of those categories because we would remove all of the chromosomal DNA from the egg of, say, a cow or a rabbit. We, in our research group, refer to them as "interspecies embryos". We do not really think that the term "hybrid" is all that valid although we can understand that we have to call them something and that it is an easy title for people to attach to.

  Q6  Dr Turner: Would you restrict the term "hybrid" to a cell in which there is chromosomal material from two species?

  Dr Armstrong: We would prefer to do that. Obviously, we understand that there is DNA from the mitochondria from the animal oocyte, but really that has very little contribution to the actual information content of the final cell. It would not instruct the embryo on how to produce an embryonic stem cell or how to make the distinction between the different types of cell you would find at the blastocyst stage embryo. All mitochondria serve to do is to produce power effectively for the cell and to partake in certain processes in programmed cell death, but they really are not terribly important for instructing the embryo as to what structures it has to form and how it has to behave.

  Q7  Dr Turner: Professor Smith, do you want to add to that?

  Professor Smith: Yes. I think what Lyle has said is absolutely correct. The traditional definition of a hybrid in biology is the fusion of two chromosome sets to make a new genetic entity. People are familiar with that particularly in plant breeding. So, when we use the word "hybrid", it conjures up a wrong image. I think that the correct scientific terms is "cybrid", which is the terminology that people used in somatic cell genetics in the 1960s and 1970s when they transferred the nuclear material of one cell into the cytoplasmic material of another, which is actually an example of what has been done in nuclear transfer. So, you have only a small component, which is the mitochondrial component.

  Q8  Dr Turner: We already seem to have the possibility of the loose use of the term "hybrid" in particular threatening research in terms of the latest HFEA decision. Do you think that unless the Government are quite clear and accurate about this use of terminology in terms of the creation of chimeras and hybrid embryos, existing areas of research are going to be threatened?

  Dr Armstrong: If the use of the term "hybrid" were to lead to sufficient opposition to the work that we want to do which led to it being disallowed, then it is possible that other areas of science such as the disease-specific stem cell lines that Professor Shaw and Dr Minger at King's College want to produce would be threatened and I would think that that would be a disadvantage for British science. It would prevent or hinder the possible development of cures using this technology which, in my view, would be a sad thing to do.

  Q9  Dr Turner: Despite the slightly improper use of terminology which has created a problem, if permission were given to allow the creation and use of these embryos purely for research purposes, would that be sufficient for your immediate purposes?

  Professor Shaw: Yes, I think it would be. This is a very discrete area and we have resorted to this because of the challenges that are faced by using human oocytes which is already licensed to work. Professor Ian Wilmut and I have a licence to work on Motor Neurone Disease in this respect. The problem with human eggs of course is that they are a very rare commodity. The eggs that we are allowed to use are those that have failed to fertilise and so they are already, if you like, pretty exhausted eggs before we can get to use them. I think it is correct to say that nobody has actually generated a mature blastocyst from which you can derive stem cells anywhere in the world.

  Q10  Dr Turner: Do you have any thoughts on the provisions that you would like the proposed Bill to take bearing in mind that this Committee has been around this course before and it left the recommendation that the creation of such embryos should be legal for research purposes provided that they are destroyed in line with the 14-day policy, the current 14-day rule for human embryo cultures, and prohibit their implantation in a woman?

  Professor Shaw: Absolutely.

  Dr Armstrong: We would be perfectly happy with that.

  Q11  Dr Turner: May we have your thoughts about what the provision for the legislation should set out.

  Dr Armstrong: Obviously, we should have the capacity to apply for licences to permit this work from a body such as the HFEA. It should state that we are allowed to do this work under very similar remit to the present HFE Act where we are allowed to do this work to gain more knowledge about embryonic development, to gain more knowledge about stem cell development and about the progression or possible progression of disease.

  Q12  Dr Turner: Would you agree with me that the framework as set out by the current HFE Act has been sufficiently clear to enable British stem cell research to reach the position that it has had  and that the proposals which have not been licensed by the HFEA were in fact fully in accordance with the existing framework?

  Professor Shaw: We believe that. Neither of us are lawyers and it is not really our area of expertise but, from the simply reading of the HFEA remit, we believe that this work should be licensed by them. These are essentially human cells that we are deriving.

  Q13  Dr Turner: What would be the consequences if this work is permanently stopped both for the disease areas and for the future of stem cell research in the UK?

  Professor Shaw: In terms of the disease areas, I think we are looking at a very huge task in terms of achieving this with human eggs. Certainly it is not something that is likely to happen within the next few years or possibly several decades. That would be a major problem for us. The diseases we are looking at are all devastating diseases in which we have very little understanding of disease mechanisms. It is very difficult to develop an effective treatment if we do not actually know what is going wrong and, as I think we show in the models, they not only tell us about what is going wrong but they provide an immediate resource to screen for drugs that will be effective. If you stop that, then you are really putting a halt on all that sort of work and I think that is not only bad for science but is bad for our patients and is bad for the community and sends a very negative signal.

  Q14  Chris Mole: Would you all agree that the term Professor Smith used of "cybrid" is well enough and widely enough understood to be used as a definition in law and are there any others that could be helpfully put on the table at this time to ensure that the legislation controls what needs to be controlled and does not control other bits?

  Professor Shaw: One possibility that I believe has been mentioned previously in the discussions is that a pseudo-hybrid. The embryo is not a real hybrid but a pseudo-hybrid, they are essentially human pseudo-hybrid embryos. I think that the definitions are very important but it is not for me to tell you what should be done. I would feel comfortable with either "cybrid" or with "pseudo-hybrid" terminology. I think that would help us distinguish our work from some of the other work that may require further restriction in the legislation.

  Q15  Chairman: I do think it is important that we get a definition because so far this morning we have asked that specific question for us to try to get clarification and we have had "interspecies embryo", "cybrid", "hybrid chimera" and "pseudo-hybrid" all mentioned. If that is confusing us as a committee that is trying to make some clear recommendations, then, in terms of the public debate, it is going to be very, very difficult indeed, particularly more broadly in the House at the draft bill stage. You have all agreed on "cybrid" and you have all agreed on "pseudo-hybrid" as the two clear definitions. Is "cybrid" the preferred option?

  Professor Smith: I would say so because, if you use the word "pseudo", this will raise questions with journalists and politicians and the public. I think that there has been a bit of a problem in the scientific community in thinking how to describe these entities that are created by nuclear transfer because the only word we have is "embryo" but they are not normal embryo and this has become conflated with when you have an interspecies situation. My understanding of the somatic cell genetics field is that "cybrid" is the word that has been used in the past and would seem to be a perfectly legitimate word to use in this context that would make it very clear that this is a different thing from a hybrid. Of course, as we know, you still have people/journalists who will use the word "hybrid" but it is very important for this Committee and Parliament to know what the law says.

  Q16  Chairman: It was really important to get that firmly on the record. Dr Armstrong and Professor Shaw, in response to Dr Turner's question, you were quite definite that you were in fact going to grow these cybrids for 14 days.

  Professor Shaw: Yes.

  Q17  Chairman: Stem lines would be taken during that time and at the end of that time.

  Professor Shaw: Yes.

  Q18  Chairman: And then it would be destroyed.

  Professor Shaw: Absolutely.

  Q19  Chairman: Why do you not wish to grow them to full term?

  Professor Shaw: It certainly is not in my scientific remit to do that. It is no the biological experiment we are interested in. Indeed, I think it is a whole area that I would not feel comfortable working in myself. That is my own personal opinion.

  Dr Armstrong: For my research, there is no scientific value in doing that. All of the events which will reprogramme the somatic genome will have taken place by the blastocyst stage generally which develops at day five to six. There is no real remit for my going on any longer beyond that. We would derive embryonic stem cells from blastocysts at day six and that would be the termination of that embryo's existence. There would be nothing further to do with them after that. Apart from anything else, the differentiation events that are taking place in an embryo at 14 days would probably mean that it would not survive in culture anyway. The 14-day limit has been applied, but I do not know of anyone who has actually cultured an animal or a human embryo to that limit because they are outside the context of a uterus in which they would expect to have been implanted and, outside of that context, there is very little possibility that they would survive in culture.