Genomic Medicine - Science and Technology Committee Contents

Examination of Witnesses (Questions 1 - 19)


Dr Colin Miles, Professor Veronica van Heyningen FRS, Professor Joyce Tait, Professor John Dupré and Dr Declan Mulkeen

  Q1  Chairman: Good afternoon. Can I welcome our witnesses and also those members of the public who have joined us. Thank you all for coming. I am afraid this room is not very satisfactory for such a session. First of all, you seem to be miles away from us and unfortunately we cannot bring your table nearer for technological reasons, I am told. I hope you can hear me and I will be hoping that these microphones are effective. Sometimes they are also a problem. For the members of the public, you have some information sheets at the back which give you information about the inquiry but also about the interests declared by Members of this inquiry. To our witnesses, thank you for coming. We note there has been a change of representation from the MRC but we welcome you both, Dr Mulkeen and Professor van Heyningen. You probably caught an early plane this morning from Edinburgh. Welcome to the others. There has been no change in your names. We have known that you were coming. What I would like to do is for you to introduce yourselves first and who you represent and if any of you has an opening statement to make—I do not know if one of you is going to lead and the others join in, but we leave it to you as to how you intend to do that. Then if you want to make any opening statement, please do so, otherwise we will go straight into some questions we have for you.

  Dr Mulkeen: Thank you very much. I am Declan Mulkeen. I am the Director of Research and Training at the Medical Research Council. We had not decided to make an opening statement. We thought it was better for you to question us as you see fit.

  Professor van Heyningen: I am Veronica van Heyningen. I am a research scientist at MRC Human Genetics Unit and I have been asked by the MRC to come and represent them, but I work on human genetics.

  Professor Tait: I am Joyce Tait. I am Scientific Adviser to the ESRC INNOGEN research centre based in the University of Edinburgh.

  Professor Dupré: I am John Dupré. I am a philosopher of science, particularly biology. I am the Director of the ESRC Centre for Genomics in Society (EGENIS), but I am here representing the AHRC as the grant holder.

  Dr Miles: I am Colin Miles and I am Head of Molecular & Cell Biology for the Biotechnology & Biological Sciences Research Council.

  Q2  Chairman: Thank you very much. Does any one of you want to make an opening statement? I know Dr Mulkeen said he did not intend to.

  Professor van Heyningen: One thing we have all been thinking about is that it would be really useful to have some sort of definition of what is meant by "genomic medicine".

  Q3  Chairman: Would you like to comment as to what definition might be more appropriate?

  Professor van Heyningen: I think I prefer a broader definition than just looking at human variation in relation to disease, because I think all that leads us into a great deal of important biology which underlies the disease mechanisms which we need to explore in much more detail so that the variation studies which we seem to be talking about in the questions are just the beginning.

  Q4  Chairman: Does anybody else want to comment on that definition issue?

  Professor Tait: I would also prefer a broad definition.

  Professor Dupré: Yes, I think we are all of the same mind, and of course it is not only that it is very much the beginning but I think it is very unclear where the end will be, so we want to leave it as open as possible.

  Q5  Chairman: Thank you very much for that and for bringing that out. I would like to go back and start with your submissions, the RCUK submission, which states that there are significant increasing opportunities for the translation of genomic information into improved therapies, and I would like to pick up on that theme and my questioning is related to that theme. The question I would like to ask arising from that is, if that is the case, what funding is allocated to such research and particularly to the translation of such research and are there gaps for missed opportunities in any of the funding opportunities, and what proportion of this funding is aimed at the translation of genomic data into useful information for healthcare and disease prevention and have the Research Councils done this ad hoc or have there been calls put out to support this kind of funding? I know that is a long question, but I hope you got it all?

  Dr Mulkeen: I wonder if the best thing to do is to take that in stages. On the question of cross-council coordination, from previous spending reviews we have had cross-council lined up strategies on genomics and genetics which have covered everything from the need for increased investment in genomics through to increased investment in Research Councils in social sciences and legal, regulatory and economic issues. That coordination I think has served us well, and from where we see it there is a good balance of effort across all the councils. The submission we gave you included some figures for spend, I think from BBSRC. The figure we think would best represent MRC's level of investment in genomics would be £50 million as a narrow definition or £78 million if you include areas such as the genetics of cell cycle, cell division control, which you may or may not feel is relevant to every area of human health research. Within that £78 million per annum, MRC's investment has been concentrated to a fair degree in multi-faceted centres of excellence, such as the Human Genetics Unit in Edinburgh, such as Clinical Sciences Centre and newer centres such as the Genomics and Global Health Centre in Oxford, and these serve a number of different functions. They can be important linkers for activities. The Dominic Kwiatkowski Centre in Oxford links with infectious disease and global health research across a wide range of developing countries. They can be important training and career development centres and they can provide resources for other areas. MRC has had a substantial increase in the last spending review in the funds available for translational research and we could say more about that later, but maybe the best way to structure the answer is for other Research Councils to say a bit about what their baseline level of investment in genomics is and what the activities are.

  Professor Tait: Yes, I could say something from the ESRC perspective about their baseline levels of investment, but I think before that, picking up this point about translation, translational medicine and translational research is becoming a discrete funding area and particularly the big charitable foundations have research programmes in translational research, translational medicine. There is a need to make a distinction between the process of translation within the public sector for application in the Health Service and the process of translation, which is quite different, in commercial organisations where you are looking to develop a profitable product at the end of the day. In Edinburgh we have a cross-college translational medicine master's degree being developed just now and RCUK has also funded research fellows in translational medicine. So specifically in translational medicine there has been quite a lot of activity and it is an important and enlarging area. I think the Economic and Social Research Council's funding of the genomics-related medical research is within the three genomic centres, INNOGEN, EGENIS and Cesagen, which averages out at about £2.7 million per annum, so it is a major investment for the social sciences. I think it is the biggest investment in Europe and almost the biggest in the world. It is very significant and it has really raised the UK's profile in this area. On top of that, the ESRC has specific programmes on stem cells and synthetic biology and various other specific technologies which are part of this translation process. So there is a very significant ESRC investment.

  Professor Dupré: The AHRC does not have ring-fenced funding in this area, it is just entirely responsive, but the major investment would be the centre which Professor Graeme Laurie runs in Edinburgh, but there is also a grant that I hold and some of the work is mentioned in AHRC's report. These will be the main things which I think they are currently funding in this area, but there is no ring-fenced budget.

  Dr Miles: From BBSRC's point of view, being responsible for the funding of basic biological research in all types of living organisms, the figures I have quoted in the submission refer to the gross level of investment in genomics we have had over the last few years and the data refers to investment in lots of different types of organisms, mostly dedicated through model organisms (of which I have given examples), but practically none of that research is involved in translation to human medicine. It is all about the basic biology of those organisms and about the technology development for genomics but none really about translation to humans.

  Q6  Chairman: We are told in other evidence that we have had that the science of genomics is advancing at a rate where soon it will be possible to translate it into healthcare and that therefore the healthcare delivery systems ought to be preparing for this. Is there investment made in preparing the healthcare delivery systems for that, or do you think it is pie in the sky that genomics and genetics are becoming so advanced?

  Dr Mulkeen: It is certainly moving very quickly, but we think it is important to make sure that we reap a number of different benefits from the advances in genomics. Some of the benefits it will give us will be about understanding disease mechanisms and disease pathways in ways we could not understand before, and the way in which we turn that into a benefit for health might be a quite conventional way. It might be another small molecule drug because we now understand how the network of genetic influences turns into a disease mechanism. There will be other areas, say, in assessing the environmental risk. We have seen the impact of genomics on psychiatric genetics and the ability to understand how individual variations will influence the risk of cannabis and psychosis being linked, and there will be advances in drug safety science and toxicology. Then there will be areas where we can use what we learn in genomics to better characterise some types of disease and decide which treatments are appropriate. There will be areas where we can use that to identify risk and perhaps target screening and preventative measures of those most at risk. Then there will probably be a smaller subset where there will be therapies tailored from their first design stage to address a particular genetic sub-group of the population. There are projects which MRC supports in the Human Genetics Unit which are starting to move to link genomic approaches to selective screening for colorectal cancer. The number of lines of research which have reached this stage of maturity is quite small still though.

  Q7  Chairman: So when you said earlier on that the investment for MRC is £50 million, is this broken down into the different categories you have just mentioned, or is it in one key area?

  Dr Mulkeen: Most of the research we are doing in that £50 million could have benefits in all of those areas. Once you understand the network of genes and effects, you can translate that. You have a lot of opportunities to translate that.

  Professor van Heyningen: At the moment, I think a lot of disease association studies, the genome-wide association studies, are finding associations with single genes but many single genes and we still do not understand how all those work together so that things like predicting risk are still a little way off. I think there is still a lot of work to be done and some of that is going to involve quite a lot of computing power, which I understand from one of my colleagues, Malcolm Dunlop (who is a colon cancer specialist and has done a lot of this work), is not available in Britain or Europe to get all those comparisons and interactions analysed.

  Q8  Chairman: So what timescale might we be thinking about? A quick guess.

  Professor van Heyningen: Ten, fifteen years.

  Professor Dupré: There is some use of polygenic genetic testing sort of at the medical coalface and which we have done some research on. It is evident there are some real challenges in getting medical practitioners even to kind of understand how best to do this. We have looked at one gene, which is the susceptibility gene for thrombophilia and we found that a lot of people who have had tests of this kind did not actually know they had had a genetic test. There was a big socioeconomic class relation to how much people had understood what was going on. We have also been looking at the use of family history, which in many ways now is actually a much more effective way of looking at genetic susceptibility for polygenic disease, and there again have found there is a great deal of variation in the kind of ways this information is processed, what kind of questions are asked, how they are understood, how the relevance of this has been communicated to patients. I think there is quite a bit that could be done before major medical technologies come on-stream in terms of seeing what happens at the patient-physician interface.

  Q9  Lord Sutherland of Houndwood: You mentioned looking at the family history there. Is this being done systematically? I know about the Generation Scotland initiative in the four centres in Scotland. Are there other centres of that kind focusing on family history particularly?

  Professor Dupré: I am not aware of it being used in a systematic way, but other panellists may be. We are exploring the possibilities for its use.

  Professor van Heyningen: In the colon cancer studies which are being done in Edinburgh they certainly get the initial entry into the system by having colon cancer at an early age, but then the families are investigated in some detail. So this is a sort of progressive analysis of risk and prospective risk as well in some cases.

  Q10  Lord Sutherland of Houndwood: So that will be done after diagnosis rather than a national type survey?

  Professor van Heyningen: Yes. They come in through being affected and then, partly because the family information is so readily available in Scotland, they follow them up.

  Professor Dupré: What we are looking at is prospective cardiovascular disease and there is a very good indication that this is helpful as part of a general risk assessment, but how you use it is open to some debate.

  Q11  Baroness Finlay of Llandaff: I think my question focuses a little bit on your later answers, because I wanted to ask you about diagnostics. The diagnostic industry is playing an increasingly important role in the translation of laboratory-based research into practical and cost-effective tests for clinically relevant genetic variations. I wonder if you could tell the Committee how the Research Councils themselves are supporting research into this area and if you can give us some examples of specific projects which are being funded by the Research Councils rather than those which are being generated through industry?

  Dr Mulkeen: I will say a little bit and I think Colin will want to say a bit as well. We have issued over the last 24 months two calls for proposals on biomarkers looking at academic groups, hopefully in collaboration with industry in many areas, which can bring forward proposals for identifying ways of either identifying disease at an early stage or for monitoring the progression of disease and response to treatment. It is important to remember, though, that very often genetic understanding will lead us to understand the mechanisms of disease, that the right tests or the most economical and robust tests may be based on a bio-chemical or some other downstream consequence of having that genetic trait. So the number of biomarker projects which involve collaboration with industry on genetic tests rather than other tests is quite a small proportion of the total. Certainly what we are hoping to do is to get more and more industry interaction in this area, and with the increase in money we have got for translational research, diagnostics as well as therapy will be a key area for us.

  Dr Miles: Although BBSRC has no current examples where we have got projects with the express intention of developing diagnostics, in the quite recent past we have supported a link programme with the MRC, called Applied Genomics Link, and the link programme, as you may be aware, is one where the companies and the public sector fund projects on a 50:50 basis. There is a number of those projects which might eventually feed through into diagnostic tests. Rather than go into each one of those individual programmes, what I have done is I have printed out some information for you and I will leave this for you at the end. It describes half a dozen projects where there might be the development or leading to the development of a diagnostic test with the company, and all the companies involved in these seem to be SMEs. That is just for your information, but I shall leave that for you.

  Q12  Baroness Finlay of Llandaff: Just thinking ahead and trying to be predictive, given that the biomarkers are probably much easier and more defined to pick up and your comment, Professor van Heyningen, of not having the computing facilities to really do the complex genomics, do you think that genomics are realistically going to be part of future diagnostic research or do you think we will actually be looking at the understanding of the gene and then the biomarker that comes from it being a more refined test in terms of clinical diagnosis?

  Professor van Heyningen: I think probably under different circumstances for different diseases both of those scenarios will be correct, that in some cases we are going to have to carry on looking at the level of the gene, at DNA, but in other cases I think it will be much better to go back to perhaps very old-fashioned biomarkers, which can often distil the effect of multiple genes but actually it is the biomarker level that is the critical one. So I think the new knowledge is going to allow us to understand in much more detail what it is that we should be looking at, at relatively simple diagnostic levels in many cases but not in every case.

  Dr Mulkeen: In looking at the overall landscape of the UK science base and its interaction with industry, I think we would certainly agree that this is an area where there is a lot of, as yet, unrealised potential both in genetic technology, biomarkers and other markers. It is an area where we would really like to see a lot more academic industry collaboration in the coming years.

  Baroness Finlay of Llandaff: Thank you.

  Q13  Lord Sutherland of Houndwood: I want to go back really to the Chairman's opening question about funding, but to expand that a little bit. That was specifically on translational research. The RCUK have told us that they believe significant levels of investment are required for relevant development of our biomedical capacity in this country, which we all recognise is very high. We have a very good reputation for our work in biomedical and biological sciences. The question is, RCUK have told us the investment is needed. Apart from asking for more money from RCUK, what are the Research Councils doing about this?

  Dr Mulkeen: It is worth highlighting a few of the areas where we see the money going in the future. Continuing to build multidisciplinary and multifaceted centres of excellence and to keep the strengths we have got will be key. The whole genome association studies which MRC has funded and Wellcome has funded on a larger scale have put the UK in a very strong position. They create an opportunity and a need to follow through with more detailed sequencing using new generation technologies, and then, following on from that, more work on the biological function of disease. From an MRC and also an NIHR point of view there is a need to build up not just very large population sample bases and very large cohorts but also smaller, intensively phenotyped patient cohorts, because only by having the balance of both will we be able to really tease apart the networks of effects that we are looking for. There is a lot to be done on informatics and on human capacity and skills in these areas.

  Q14  Lord Sutherland of Houndwood: Can I just push on informatics, because again Professor van Heyningen raised this question quoting Malcolm Dunlop? One of the things which concerns us, obviously, is competitiveness and we look across the Atlantic and the volume of cash being spent in the USA far outstrips anything here, so we have got to be quick on our feet. Is there, for example, an informatics gap there that we need to think about plugging?

  Professor van Heyningen: I do not fully know what funding is available for informatics. All I heard from Malcolm Dunlop was that they have got all the data with new single gene association—and this is a European project—and there is not a computer even in Europe which can cope with the volume of association analyses which need to be done. He says that they have to put on some data and then take some off in order to be able to look at the associations. But I do not know where the money is coming from or what plans there are to expand all this, but I wanted to flag it up, obviously.

  Dr Mulkeen: Both MRC and BBSRC had good settlements in the last spending review and we are very grateful for that, and we will be reviewing with some input from BBSRC how we help our research computer access some of the newer high-cost technologies. On informatics, there are important issues around coordination and cooperation as well and the skills base. That brings us on to areas like Connecting for Health, but it might be that, Colin, you wanted to come in on that.

  Dr Miles: I was going to start at a very broad level and say that to me there are things which RCUK needs to do for the Government, if you like, to sustain the input of funding which is going on at the moment. It seems to me that there are three essential things which the RCUK needs to achieve. First of all, we need to maintain our ability to identify and exploit new areas of scientific opportunity. That seems to be one of the main things, if you like, of having a research-led organisation. We all have our own strategy panels, we all have our own committees whose job it is to do just that, and we have long-term visions and strategies, and we have ideas which have come out of that. In the submission you will have read about systems biology as an example of a new area which is coming out and you may also have read about synthetic biology, which at the moment is a new emerging area, one which is just about coming to the fore ready for research grant support for the Councils. We also have to respond to the needs of government, providing a strong research and training base, and that is desirable because not only does it offer the opportunity to answer and address some of the questions the Government has and to provide advice and input to the Government, but also it is an opportunity to attract investment from the private sector, particularly external investment from the private sector, if we create the UK as a good place to do scientific research. I guess the final part from this is encouraging the development of a broader skills base to encourage people to think about how they might exploit the research, the results they are producing.

  Professor Tait: Could I just add to that? The Economic and Social Research Council has just extended the funding of its genomics network through to 2012, so our funding is secured and we are actually going to continue to do very useful parallel work on the socio- economic and ethical aspects of these new technologies as they come forward.

  Q15  Lord Sutherland of Houndwood: Whose responsibility is it to bring thinking together on this? Is it RCUK, whatever, this great body maybe, is it the director-general of Research Councils, is it the departments, or do you just have to get together as a good idea occurs?

  Dr Mulkeen: The first responsibility is for Research Councils to get together sort of in twos, threes, fours or fives, as needed to address the question, and that is how most of the job gets done. From time to time around big spending reviews there are very big cross-cutting issues. RCUK will facilitate that process.

  Q16  Lord Sutherland of Houndwood: So if you need a big enough computer, no one of you will provide that?

  Professor Tait: Could I just add, from the point of the individual researchers at the academic end of the scale it is actually proving increasingly easy to collaborate with other kinds of researchers, so as social scientists it is increasingly easy to collaborate with medical and natural scientists and there are schemes which cross the Research Councils that we can apply to, and that is an increasingly improving situation.

  Lord Sutherland of Houndwood: Good. Thank you.

  Q17  Baroness Finlay of Llandaff: I just wanted to go slightly lateral to that but picking up on previous responses from both Dr Mulkeen and Dr Miles. With this investment and with partnership, how much of that do you envisage providing financial returns to the UK from developments in the long-term, because one of the problems with some aspects of industry is that actually their main basis and their shareholder basis and profits basis is outside the UK? So whilst we might do very high quality research and go into partnership with them for developing, when it actually comes to providing a commercial product the UK seems remarkably thin on seeing some of the profit from that very major investment, particularly when there needs to be money back into the system over something like a major IT investment.

  Dr Mulkeen: On the whole the biomedical sector seems to have a good track record in turning UK science into high-skill and high-tech jobs in the UK and contributing to the balance of payments and we would hope that by investing in the way we are doing we would keep the UK as one of the best places in the world to engage in research in this area, and there are certainly opportunities. There are, of course, many major biomedical companies which are not yet investing in the UK as much as they could, but I think we have a good track record here and scope to pull in even more interest over the next decade.

  Q18  Baroness Finlay of Llandaff: But does our legislative framework work counter to that and our regulatory framework on research?

  Dr Mulkeen: I should probably hand over to colleagues from other Research Councils there. From where I sit, I do not have detailed involvement in the regulatory issues. I do know that other countries, including the USA, worry about their regulatory framework as well, so I would not say that the UK was the only country in the world which had anxiety about how encouraging its regulatory framework was in this area.

  Professor Tait: I can comment a little bit on the regulation and its impact at two different stages. There is the increasing tendency for biological sciences to regulate the research itself and in that kind of area there are increasing concerns about the lack of coordination of various kinds of ethical requirements and permissions which have to be acquired before one can even begin to do the research. Veronica has already mentioned that making an even modest change in an existing programme maybe to catch up with some new science which has emerged requires going right back to the beginning again, to the ethical processes. So if we are talking about the research, then I think there are things we can do to make it easier and more productive to do the research. I think there is another whole question about how one regulates the outcomes of the research as it is developed into products. I do not know if you want me to go into that just now or to save that until later.

  Chairman: We will at some stage go into that.

  Q19  Lord Colwyn: I want to ask you what the MRC have done to support national activities in genomics since the closure of the Human Genome Mapping Project in Hinxton and whether in fact it is important that we do do something in view of the superior spending in the States. Is it important that we do carry on with the work?

  Dr Mulkeen: The MRC's investment, and I think BBSRC's investment as well, in genomics has been increasing steadily over the last decade. The volume of training in bioinformatics, the degree to which we are supporting links between genomics and clinical medicine, the investment in large population cohorts and increasingly small, well-phenotyped cohorts and the development of methodologies for analysing and interpreting genetic data are all areas where we have seen a lot of growth. The centres of excellence that we support, such as the Human Genetics Unit, our centres in Oxford, provide a very strong coordinating role and they often collaborate very actively across the UK, often brokering international collaborations. So we see it as quite a tightly knit community with very good cross-linkage between the various centres and a very good collective understanding of what is needed next to move the research forward.

  Professor van Heyningen: There are really many areas where the MRC has very new initiatives but also ongoing ones, but, for example, some new ones to set up, an MRC centre in cognitive aging and cognitive epidemiology.

  Chairman: I am afraid there is a vote called, so we will have to stop while the Members go and vote.

The Committee suspended from 4.15pm to 4.23 pm for a division in the House

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