Examination of Witnesses (Questions 220-239)
Professor Tak Lee, Dr Diana Dunstan, Mr Dave Allen
and Professor John Westwick
18 DECEMBER 2006
Q220Chairman: Thank you very much for coming
today. I know some of you have listened in to the previous session
so there may be additional points you would like to make. We do
have a lot of questions we want to ask so if you could try to
keep the answers short. To be quite clear, we are being web cast
and the information note of declaration of interests is available
to the public so, as I said before, we will not be reiterating
those. I wonder if I could start off by asking you to say who
you are and then we will go to questions.
Professor Lee: I am Tak Lee. I work at King's
College, London and I am the Director of the MRC-Asthma UK Centre
in Allergic Mechanisms of Asthma.
Dr Dunstan: Diana Dunstan, I am Director of
Research Management at the Medical Research Council.
Mr Allen: Good afternoon, I am Dave Allen. I
am a Senior Vice President in GSK, Head of Respiratory Drug Discovery.
Professor Westwick: My name is John Westwick,
I am the Global Head of Respiratory Diseases for Novartis Institutes
for Biomedical Research.
Q221 Chairman: Thank you. Could I
remind you that this room has a very high ceiling and an echo,
so if you can speak up. Do not worry about shouting at us; clarity
is all. I wonder if I could start by just asking you how the various
charities and professional bodies in the UK, such as the British
Society for Allergy and Clinical Immunology, Asthma UK and Research
Councils UK, work together to promote research into allergic disease.
Dr Dunstan: The MRC and, indeed, the other research
councils, work closely with charities when it is appropriate.
I think perhaps the best illustration I have got of that is in
the respiratory medicine area we have been working very closely
over the past two or three years with Asthma UK, the British Thoracic
Society and other charities to develop respiratory medicine in
the UK and, of course, a large part of that is asthma work. We
have funded, together with Asthma UK, the centre that Tak Lee
directs. We also support with the Wellcome Trust a number of studies
jointly and one of those that might be of interest in view of
your previous discussion is a longitudinal study of patients and
children in the Bristol area, 14,000 children, so we are following
them right through and they are now 14.
Professor Lee: In the last few years there have
been three national consultations on strategy for asthma research
sponsored by Asthma UK. The most recent one has just been published.
Those consultations, which are national, involve a number of bodies.
They involve the MRC, the British Thoracic Society, the Wellcome
Trust, NICE, the Department of Health and industry in various
capacities. There are liaisons and collaborations mostly in asthma.
If you are talking about allergy in the wider context there is
not much of that going on.
Q222 Chairman: Are there areas where
you feel communication could be improved between different bodies?
Professor Lee: I do. I think we have a lot to
gain by working in collaboration and in conjunction. As I am sure
we will touch on, my view is that the way forward in allergy research
in the future will depend on multi-disciplinary partnerships and
on large cohort studies and multi-centre bodies, which will be
very expensive. I think it is very likely that if we are going
to pursue a strategy to impact on the epidemic of allergy in this
country it will have to be funded through some sort of partnership
arrangement.
Q223 Earl of Selborne: Dr Dunstan
has told us something about the work of the Medical Research Council
and its funding on research into allergies. I wonder if we could
hear more about how the research councils determine what projects
are suitable for funding. She also referred to the 14 year longitudinal
study in Bristol and this is a long timescale for a research cohort
and I suspect that other such research into allergies will require
studies over a longer period than is normally convenient for funding
lines. Could we hear something about whether there are any difficulties,
therefore, in funding some of these long-term studies?
Dr Dunstan: Talking about the general mechanisms
for funding research, people come to us in response mode and if
their proposals are good enough, and they have to be pretty good
actually to get funded by MRC, then they are funded. We do have
other mechanisms. Recently we have had calls for proposals for
experimental medicine and there have been some respiratory medicine
asthma proposals funded in that call. We had a call for biomarkers
and there were none. I looked before I came today and there were
no proposals in that that were relevant to allergy. We fund training,
so individuals apply to us for training grants. We fund PhD studentships,
fellowships, senior fellows, that kind of thing, so there is a
wide range of things there. As you say, we do fund long-term work.
Long-term work is partly done in our units and institutes. That
is largely basic work. We do quite a bit of work in relation to
allergy in three of our units. Mainly the cohort studies are funded
in partnership with other funders because, as you point out, they
are expensive. We have mentioned the Avon ALSPAC long-term study
and there is also a Southampton Women's Survey that is relevant
to diet and food intolerance. That is a long-term study following
women prior to them being pregnant, through pregnancy, and the
children after birth. Most of the children in that study are now
three or four years old. In the long-term study area we are looking
at all the cohorts that are funded now in conjunction with other
research councils and other funders so that we can best fund the
new sweeps needed, so we have decided to have a partnership on
funding these long-term cohorts. You are quite right, they are
very expensive and it is important that we have a partnership
looking at the sweeps so that everything that needs to be included
in a particular sweep is included and nothing is missed out and
we can all contribute to the funding.
Q224 Earl of Selborne: Would you
expect the proportion of the MRC budget on these long-term studies
to increase?
Dr Dunstan: I would certainly expect them to
increase over the next few years because we know two or three
of them are coming up to their next sweep.
Q225 Lord Taverne: You obviously
have to look at how strong the particular case is for a particular
study, but do you also have an overall view about which are the
most important studies to do, which are the most urgent ones?
Is there a way of considering the priorities of these? As far
as the expense is concerned, obviously the fact that they are
long-term studies makes them expensive but how far are they somewhat
disadvantaged by the fact that you also need very large numbers
of cohorts for infants or whatever it is?
Dr Dunstan: Priority-wise, the boards that look
after these particular subject areas have priorities in their
minds. Every year they look at their portfolio and they point
out areas of priority. The boards that look at the proposals that
come to us and assess them for funding have priorities for their
areas and they will apply those priorities when they decide on
which ones are going to be funded. In the asthma area, respiratory
medicine, that is a high priority for one of our boards. We have
got about 15 proposals that we funded last year in response to
a call and clearly they were applying the priorities in that case.
Expense is always a problem but if the research is good enough
and we have enough partners to contribute to the expense then
I think we can cope, and that particularly applies to the cohort
area.
Mr Allen: I wanted to volunteer some information
from the GSK perspective. We have set up a number of long-term
academic collaborations with a number of the Centres of Excellence
supported by the MRC. We collaborate with the NHLI, with the Universities
of Southampton, Manchester and Edinburgh. These are long-term
relationships which, although they are focused around a particular
area of research at any one time, tend to have a strategic nature
because these are the Centres of Excellence so the long-term relationship
ultimately benefits these sorts of long-term studies as well.
Q226 Lord Colwyn: I think my question
has been answered. I was just finding it hard to work out the
relationship between big pharma and medical research, and it is
obviously closer than I imagined.
Professor Westwick: Yes. Most pharmaceutical
companies that are in respiratory medicine have long-term arrangements
with leading academic and clinical centres. I think one of the
most exciting things was what was touched upon by your previous
body as to whether we can produce disease suppression or immune
deviation. There is a lot of that sort of work going on now either
funded by various academic institutions or charities or pharmaceutical
companies. You heard about the various sublingual approaches and
there are other things going on where there is some evidence that
you can cause some long-term immune deviation moving away from
an allergic response to a non-allergic response which lasts for
at least between one to two years from the studies that have only
been done for about six months to date.
Q227 Lord Colwyn: So when there is
some massive breakthrough, being a commercial institution do you
not keep quiet about it?
Professor Westwick: No, there is always pressure
to publish. With things like that, the people you link up with
need to publish as well so something as significant as that would
be published.
Mr Allen: Basic research is pre-competitive,
it really is in everybody's interests to share it because you
want the scientific community to debate and input. It is very
rare that a piece of really fundamental science would break that
would be a secret for more than about 20 minutes.
Q228 Baroness Perry of Southwark: I
think my first question is to Mr Allen. When pharmaceutical companies
are deciding where to put their research effort, do you tend to
put it into allergies in totality or do you go down the route
of individual disorders?
Mr Allen: The short answer is that we do both.
It is very important to us to focus on application of need when
we are looking for new medicines. To do that we need to understand
what the patients are looking for and until we can fundamentally
affect allergy then we need to treat the consequences of it. We
need to treat asthma, we need to treat the broncho-constriction,
we need to treat the inflammation that follows it, we need to
treat the rhinitis, the watery eye and that sort of thing in hay
fever. Obviously to deliver those therapies it has got to be very
different if you want to give them via an inhaler for asthma or
intra-nasally for hay fever. We try and treat the consequences
of the allergy in the appropriate way and we focus on understanding
the consequences and treating it appropriately. To go beyond that
and start to think about how we can fundamentally affect the course
of these diseases, then we need to do research into the basic
allergy mechanisms, we need to understand the way that T-cells
and the sub-populations of T-cells start to talk to each other.
That is where we collaborate a lot more with academic centres
to do more fundamental research to try and progress our understanding
long before we can start to apply it in a sense that will fundamentally
change the natural history of these diseases.
Q229 Baroness Perry of Southwark: So
the route you go down is much more to look for collaboration with,
say, MRC funded research rather than to look at what they are
doing and do something different?
Mr Allen: It is fair to say that when you look
at the more basic science then the amount of work that we can
bring to bear, even as a huge pharmaceutical company, is very
tiny compared with the amount of basic science that goes on globally,
so we look to play our part and we look to partner and we look
to do that in collaboration. Where it is applying those learnings
in a drug discovery sense that becomes something that we think
we are quite good at, so obviously we will try and do that ourselves,
but it is both parts.
Q230 Baroness Perry of Southwark: Perhaps
I could ask our witnesses more broadly, given there is great disparity
between the amount of money put by Government into allergy research
compared with what is put in by the pharmaceutical companies collectively,
do you think there is a danger that pharmaceutical companies might
determine the agenda of research?
Professor Westwick: Yes, I think that is possible.
Dr Dunstan: I was going to answer differently
actually. I am not sure what figures you have got but there is
a paper that we received quite recently about asthma that suggests
charities and Government together invest about the same amount
as industry each year.
Q231 Baroness Perry of Southwark: In
that one field.
Dr Dunstan: In that one field, yes.
Q232 Baroness Perry of Southwark:
I was talking about allergies in the broadest sense.
Dr Dunstan: I do not think there is any chance
that either of us are going to dictate the agenda. As Mr Allen
says, we are going to be working together.
Professor Lee: I agree broadly with what has
been said already but there is one slight problem sometimes that
arises when a therapeutic manoeuvre developed by a company is
extraordinarily expensive. If the programme of work that the academic
community wants answered is not necessarily within the strategic
direction of the company they may not provide you with the material
to study. If it becomes prohibitively expensive for academia to
pursue, that is one slight issue which can arise from time to
time. It does not happen very often but when it does it is awful.
Q233 Chairman: An area which concerns
me is we have heard in previous evidence there are areas of rather
unglamorous research which need to be done and people have a lot
of difficulty in securing funding from anywhere, partly because
the pharmaceutical industry has no interest in those areas particularly
at the moment and because the research funding bodies have already
committed all their money. I wonder if you want to comment. That
is really more for Professor Lee, I think.
Professor Lee: Obviously it happens. There is
no real solution to that because if the funding is not there to
do the work then the work cannot be done.
Mr Allen: I have doubts about whether the disparity
really exists. If you look at respiratory research and recognise
that allergy is only a part of that, a lot of GSK's funding, for
instance, goes into chronic obstructive pulmonary disease which
is likely to become one of the world's top three killers by 2015
to 2020, there is no allergic component, but if you capture that
spending under respiratory research it will be a very substantial
part of it. I do not think there is a disparity, generally we
partner where we have joint expertise, we invest ourselves where
we have unique expertise and I think we would expect the research
institutions to invest where they have unique expertise.
Q234 Baroness Perry of Southwark: Some
of the research that we have been hearing about this morning into
the prevention of the allergic reaction in the first place, so
to speak, to de-sensitise the person, is that something that pharmaceutical
companies leave to academic blue skies research or are the pharmaceutical
companies involved in that as well?
Professor Westwick: There are a number of smaller
companies that are linked up with larger pharmaceutical companies.
There are a large number of immune deviation trials going on right
now, I am aware of at least five that are in operation. The whole
purpose is to look for a long-term loss of allergic response.
Mr Allen: There are two levels that we need
to understand. To fundamentally modify the immune system has to
be a very long-term goal. We should recognise that you do not
mess with the immune system very lightly. It is because of that
that I would fully support a strong research base in the UK that
continues to tease out the role of the immune cells, the sub-populations,
the way they talk to each other, the way antigen is presented
in all of its complexities. Where we look at the hope in the near
term, which is to re-educate the immune system not to respond
to grass pollens and tree pollens, there are good clinical studies
ongoing and it is an area of very active interest for all the
pharmaceutical companies.
Q235 Lord Rea: How does UK funding
for research into allergic disorders compare with other countries?
I am talking about all the sources of funding, Government, charity
and industry, how do those compare with what goes on in other
countries?
Dr Dunstan: I do not have the figures for anything
except respiratory work. In respiratory work, the share of the
funding that we have is proportional to the share of biomedical
funding that the UK has in relation to spend in other countries
but in some other areas of respiratory work countries such as
Australia, Finland and Sweden have a significantly greater investment
relatively speaking than the UK.
Mr Allen: From a purely GSK perspective, we
have the majority of our asthma and rhinitis work based in the
UK which means we have a disproportionate amount of our spend
internally in the UK. We do have collaborations in the US and
across Europe but because our people tend to be here, we collaborate
locally with the academics that are here. From a company perspective
we are investing disproportionately in the UK.
Professor Lee: I tried to get some information
about spend on allergy/asthma research from a number of different
bodies and the information I have is incomplete, nevertheless
I have some information. The NIH was very helpful and wrote back
to me and their spend per annum in the financial year of 2005
for asthma and rhinitis alone was £154 million.
Q236 Lord Rea: As compared with the
UK of what sort of figure?
Professor Lee: Dr Dunstan was telling us about
the MRC spend. Away from the MRC, including the Wellcome Trust,
Asthma UK and a little bit of information from the Department
of Health, the amount of money other than Research Councils is
in the order of £6 million per year.
Dr Dunstan: MRC spends a bit over £5 million
a year directly on allergy research and £15 million a year
on basic understanding of immunological mechanisms, some of which
would be relevant to allergy.
Q237 Chairman: Dr Dunstan, could
you clarify is that all allergy and of that amount how much is
asthma and how much is other allergic manifestations?
Professor Lee: That is the issue. When I tried
to find out information about this, including how different research
organisations label their funding, it was complicated. Allergy
and asthma tends to be mixed up. Looking at the portfolios, the
ones that I have seen from the titles, the majority of those is
asthma rather than allergy globally and more fundamental than
translational. The numbers are quite startling really.
Professor Westwick: I think one of the problems
when you are talking about respiratory is trying to separate how
much is allergy/asthma because respiratory now includes a very
large area within the pharmaceutical companies, but if you just
say "respiratory" it is good to know that within the
UK the three leading pharmaceutical companies worldwide have their
respiratory research, which often includes their allergy/asthma
research, located in the UK.
Q238 Lord Rea: Which allergic disorders
receive the largest amount of research funding and do you think
this is appropriate? I can foresee that you are going to say "asthma"
but then we have the problem with what part of the asthma research
is directed specifically towards allergy.
Professor Lee: I can only speak for Asthma UK.
About 30 per cent of the Asthma UK spend is directly related to
allergy.
Q239 Lord Rea: That is clear.
Dr Dunstan: I do not have those figures for
MRC. I can get them for you if that would be helpful.[1]
1 Please see MRC supplementary written evidence. Back
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