Examination of Witnesses (Questions 1
WEDNESDAY 30 APRIL 2008
Dr Colin Miles, Professor Veronica van Heyningen
FRS, Professor Joyce Tait, Professor John Dupré and Dr
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 makeI 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
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
Professor Tait: I am Joyce Tait. I am Scientific
Adviser to the ESRC INNOGEN research centre based in the University
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.
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".
Would you like to comment as to what definition might be more
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
Does anybody else want to comment on that definition issue?
Professor Tait: I would also prefer a broad
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.
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
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
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.
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.
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
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
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
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
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
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
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
associationand this is a European projectand 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
Q16 Lord Sutherland of Houndwood:
So if you need a big enough computer, no one of you will provide
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
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
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