Examination of Witnesses (Questions 227-239)|
5 FEBRUARY 2007
Q227 Chairman: Can I welcome our third
panel today. Professor Colin Blakemore, welcome again, Professor
Martin Bobrow and Mr David Macauley. Could I ask you to introduce
yourselves, in no more than one minute, to say who you are and
who you represent; we will start with you, David?
Mr Macauley: Thank you, Mr Chairman.
David Macauley. I am the Chief Executive of the UK Stem Cell Foundation.
The Foundation exists to develop what we would define as translational
medicine. If you could imagine a continuum of basic research at
one side, across to, say, industry developing the therapy and
marketing it, translational medicine is really the bit where we
believe there is a funding gap existing currently in the United
Kingdom, where typically the Research Councils and the Medical
Research Council would take the research and normally it would
be the preserve of industry then to pick up the science and develop
it. Currently it is not the case in the United Kingdom and really
we exist to bridge that gap; so it is an important funding step
for typically academics and clinicians who come together to develop
a model therapy or the basis of a therapy. We exist to fund that
Professor Bobrow: I am a superannuated
medical geneticist and academic. I am here as Deputy Chairman
of the Wellcome Trust, which is a research-funding organisation.
Professor Blakemore: I am Chief
Executive of the Medical Research Council, which is a leading
funding body in the area of stem cell research. I am a neuroscientist.
A little of my work has been concerned with stem cell science.
Chairman: Thank you. Starting this session
Q228 Graham Stringer: When you are
evaluating grant applications, how do you judge the likelihood
Professor Blakemore: I think it
depends very much what you mean by success.
Q229 Graham Stringer: Are embryonic
stem cells going to be produced; that would be success in what
we are talking about?
Professor Blakemore: Clearly,
the potential for productivity, in terms of science or possible
medical benefit, is the most important criterion in deciding whether
a grant should be awarded; so it would not be attractive to fund
a project in which the likelihood, let us say, of stem cells being
produced, if that was what was proposed in the research, was extremely
Q230 Graham Stringer: I am sorry;
is that not rather restating the question as a form of answer:
how do you do that? We all want success. How do you judge the
likelihood of that success; how do you assess it?
Professor Blakemore: In this case,
the peer review process would try to assess the probability of
success on the basis of what was known about previous research,
including the track record of the applicant. If what you are driving
at here is the question of how successful we are in creating human
embryonic stem cells, the background in research suggests that
the probability is rather low and producing stem cells by somatic
nuclear transfer is even lower, in fact, virtually zero, on present
Q231 Graham Stringer: I am confused
now. You think it is worth funding this kind of research, even
with that background?
Professor Blakemore: What is being
offered in this case is the possibility of a very significant
improvement in the success rate through the use of animal oocytes
combined with human somatic cell nuclei to explore the methodological
problems which are the obstacle that has been revealed in attempts
at using human oocytes in combination with human somatic nuclei.
Given the fact that the success rate in other species, for both
somatic nuclear transfer and the development of stem cells from
conventional embryos is rather higher than that for humans, there
is the hope that if we can find what the practical obstacles are
we will be able to make better progress. Clearly, there are ethical
reasons why such exploratory research, essentially methodological
research, should not be done with human oocytes, because of the
difficulty of obtaining them and, in a sense, their huge moral
Q232 Chairman: Just before you go
on, Professor, can I ask you, Professor Blakemore, whether you
are convinced that the research done by Professor Sheng in China
Professor Blakemore: I know Professor
Sheng personally. The laboratory is very well established and
I think widely respected. I do not have any reason to be doubtful
about those results.
Q233 Chairman: He was questioned
earlier, so I just wanted to put that on the record. Sorry, Professor.
Professor Bobrow: My answer, briefly,
is going to be very similar. If we were to receive an application
to fund this sort of work, we would send it to one of our judging
panels, which contain a number of people who would be expert.
Also we would send it to somewhere between four and 10 international
experts in precisely that field of science, asking them to look
in some detail at exactly what is proposed and to give us their
opinion on whether it is likely to run or not. There are not guarantees
in this; if you actually knew the answer you would not be doing
the research. That is an established process and it is what we
do with everything, and it is not a policy question, it is a pragmatic
question related to that individual proposed set of experiments.
The criteria that we would want the panel to look at in general
are, is this addressing an important question; does this person
have a good track record in this type of science, do they know
what they are doing; do the experiments make sense and, of course,
are they decent, ethical and legal. Lastly, we would want to know
if it is innovative, because it is relatively easy to forget that
if you do not concentrate specifically on things which are novel
then nothing progresses very fast. Clearly, this is a field where,
although there are lots of areas of promise and you hear all these
good words, it is tough going at the moment. That is the time
to be prepared to be a bit inventive and to put a bit of money
in general into funding things which look like a bit of a flyer,
where the risks are high, because the possible returns are high,
with the provisos about ethical and legal and moral issues which
I have given already.
Mr Macauley: When it comes to
the UK Stem Cell Foundation, we share an advisory board, a scientific
advisory board, with the Medical Research Council. Our criteria
are somewhat different. This type of work we would deem not to
be translational, in the sense that we would wish to fund it,
but it is a recognised stepping-stone on the way to translational
science. In fact, the Cooksey Review, completed recently, addressed
the whole issue of translational research in the United Kingdom
and it is an area of debate at the moment. In terms of review,
the criteria we would use in assessing an application are very
similar to this; in fact, we are looking at a number of applications
at the moment, Parkinson's disease is one example, where these
techniques, that the Government currently propose to be banned,
would actually hinder the development of the work that we would
propose. On translational medicine, which is often a reduction
to process, it is often not very exciting, it does not lead to
Nobel prizes, in many cases, it is pathological, it is process-driven,
but again a lot of the same criteria, the quality of the research
team; in many cases, the amount of money is a good indicator of
the likelihood of success. Many of the challenges we face are
resource issues, as opposed to major scientific hurdles; all of
the work that the MRC and Wellcome fund is to get over the scientific
hurdles and then it becomes an issue of taking that science and
developing it into a sort of working prototype or therapy that
we can move forward with.
Chairman: We understand the process.
Q234 Graham Stringer: Just one more
question on this line and then a slightly different question,
if I may. Having the peer review and all the other criteria you
may use, do you judge alternative lines to go down, or do you
not? Do you consider whether using adult stem cells is likely
to be more effective and productive, or is that left to one side,
as not being part of the grant application? On scheduling, we
have heard some evidence that people do not want this research
to take place at the present time. Should we be rushing into this
Professor Blakemore: On the question
of adult stem cells, certainly the Medical Research Council, and
I am sure the Wellcome Trust as well, funds research on adult
stem cells. We have a unit in Oxford, the Molecular Haematology
Unit, which is devoted largely to work on stem cells, on blood
stem cells. I think the general feeling is that although adult
stem cells, eventually, when we learn how to manipulate them,
might provide alternatives to some of the possible anticipated
uses of embryonic stem cells, we need to learn from the study
of embryonic stem cells what might be possible with adult stem
cells. The research needs to go ahead on a broad front, certainly
involving embryonic stem cells as well, if we are to learn how
to benefit from adult stem cells fully. I will give a particular
example in the context of your discussion. There are claims that
adult stem cells, in some cases, can have similar multipotency,
that is a capacity to form different types of adult cells, to
that of embryonic stem cells. For instance, I heard very recently
about work in Japan which suggests that in mice adult fibroblasts,
which help to repair skin, bone, and other tissues, and can be
converted quite simply into cells that appear to behave like stem
cells. To prove that, one would need ultimately to introduce such
cells into a developing blastocyst to see whether those cells
which are claimed to be stem cell-like, can contribute indeed
to all tissue types. That would involve creating a chimera. If
we were able to pursue that in humanslet us say it were
possible to make stem cells out of fibroblasts in humansthat
would be a wonderful advance. But to test the extent of multipotency
really it would be necessary to produce chimeras, introducing
them into an embryo of another species, rather than a human, in
order to see whether they could contribute to all tissue types.
Q235 Graham Stringer: Thank you.
On just a slightly different tack, if I may, you heard the discussion
previously this is an area of great controversy. In coming to
conclusions about whether to push forward with this research,
how important do you consider public opinion? I asked the previous
witnesses, if public opinion was 80% against would they still
want to go ahead; do you have a view on this?
Professor Blakemore: It would
depend very much, first, on how public opinion had been measured,
in other words, whether it was properly representative; and, secondly,
on what background understanding of the facts that opinion was
based. In the case of the debacle around GM food science a few
years ago, the hostility of the public was very clear; but I think
one could question the extent to which the public really were
properly informed about the facts, both the facts around benefit
and the facts around risk. The problem is, and this has clearly
been identified already, that the notion of combining human and
animal material generates a `yuck' factor which actually might
reflect the lack of knowledge of the public about the reality
of what is involved, and indeed the benefits which are already
flowing from just such approaches.
Professor Bobrow: I do not think
that, for a moment, we would consider that science could progress
without the backing of the public in the most general sense. Where
there is serious public unrest one has to take some account of
that; but the way that we are sensitive to that is by processes
of the sort which bring us here this afternoon. We would not go
out ourselves and look for public opinion and influence our funding
decisions specifically on that basis.
Q236 Dr Iddon: Gentlemen, as distinct
from those who have strong moral or ethical objections to the
way that Newcastle and Kings want to go, are there any strong
scientific reasons why this work should not go ahead, which you
are picking up from other groups perhaps?
Professor Bobrow: My understanding
of this, and I am taking advice from others who are much more
expert than I, is that this is high-risk, high-gain research,
so there is no absolute reason to say that this work could not
succeed, and there are some indicators, that you have already
heard about, that it might, but that is not to say that it is
a certain bet on the block. That is no reason not to pursue individual
applications if they are structured properly. I have not been
asked to look at the specific applications which have been to
the HFEA and so I would not comment on them, but for the field
in general that would be my view. If they hit the desk at the
Trust they would be sent off to the sort of review process that
we mentioned earlier.
Q237 Dr Iddon: Professor Blakemore,
are you picking up any anti feelings about this area?
Professor Blakemore: Of course
there are scientific doubts about any new area of science, and
the principal one, I suppose, will be about whether one could
generate stem cells from a hybrid embryo by somatic nuclear transfer
of human genetic material into an animal oocyte shell, which behave
truly like human stem cells. One issue here is the influence of
the mitochondria in the cytoplasm of the oocyte. Mitochondria
contain a small component of the total DNA in the cell and they
might play a part in the function of any hybrid stem cells produced.
In fact, the preliminary results as reported from China and also
from the groups in New York and in Cyprus strongly suggest that
it is possible to create stem cells which behave very much as
if they are human, but we have to confirm that. The only way is
Q238 Dr Iddon: Is there objection
on the grounds that maybe viral contamination would be a problem;
is that a serious risk?
Professor Bobrow: I am not sure
that there is any factual basis which has been brought out for
that being a risk in this specific instance. For me, it is quite
important to put this against a slightly different background.
One of the things which have really knocked me back, over the
past 15 years, as a scientist, is the extent of similarity between
genetic material from wildly differing species, really wildly
differing. I think it is just astonishing that many, many genes
can be taken from yeast, which is a long way away from people,
and put into human cells and work perfectly and do the right thing,
and vice versa. There are hundreds of other examples. At the front
end of biology, the distinction between different species in culture,
as opposed to things walking around on four legs, is nothing like
as clear-cut as it seems in the newspapers. I am now retired.
I cut my scientific eye-teeth fusing human and mouse cells together
to make it into a specific cell hybrid, and tens of thousands
of those experiments were done 30 years ago. There is no suggestion
that anything has happened untoward as a result of those experiments.
It would have to be incredibly specific to this sort of cell type,
in this sort of situation. There are two separate risks. One is
the risk to the world and to the researcher, which is what I have
dealt with; the other is the risks if you were actually to go
another step and turn that into a therapeutic procedure. I think
those risks are unknown, uncharted and nobody that I know of is
suggesting the reimplanting of such embryos at this stage; we
would need to know a massive amount more.
Q239 Chairman: Would you agree that
would be the next step, and that is what many people are concerned
about, that it will be that next step, and, going back to the
Japanese research, Professor Blakemore, that implanting an embryo
to see how certain stem lines develop is the logical next step,
or is it not?
Professor Bobrow: My brief answer
would be, putting it back into a person is not the logical next
step. Putting it back into an experimental animal for a short
period of time may well be the next logical step.
Professor Blakemore: I think what
this discussion is revealing is the diversity and the complexity
of possible uses of the general methodology of combining human
and animal material. I can just try to clarify my understanding
of the range of areas in which this approach might be useful.
The first is essentially methodological, to try to find a way
around the current problems in creating human embryonic stem cells
and particularly stem cells by somatic nuclear transfer. We are
up against a real barrier there. It is unreasonable to continue
that research through the use of human oocytes; using empty animal
oocytes will help enormously. There is absolutely no intention
of implanting going beyond the 14-day rule and implanting those
embryos, or even using the stem cells for therapy. That is just
one area. The second is to develop models, in vitro, in the test-tube,
of disease conditions, i.e. stem cells from embryos that are created
by nuclear transfer, where the human nucleus is known to be carrying
a genetic defect. Again, there is no possibility of using those
cells to treat people, and having no intention of reimplanting
the embryo; but only of creating very valuable models of disease,
which, in turn, might be used to help the development of drugs
or to test the toxicity of drugs in different types of individual.
The third is the one which I referred to earlier, of the possibility
of testing the claimed multipotency of stem cells derived from
other sources, for instance, adult stem cells; it might be necessary
to create chimeras. Finally, there is the issue of the scientific
benefit, the advance of knowledge that could be produced about
developmental processes through this area of research, again,
with strict controls. For instance, this question of the interactions
between nuclear DNA and mitochondria DNA; this is clearly an experimental
approach to that important question.