Examination of Witnesses (Questions 1120
- 1139)
WEDNESDAY 24 NOVEMBER 2004
PROFESSOR ROGER
PEDERSEN, PROFESSOR
ALISON MURDOCH
AND DR
ROBIN LOVELL-BADGE
Q1120 Dr Harris: We have been to
Italy where we heard some fascinating exchanges. The Italian Health
Minister told us that, in his opinion—and he is a doctor—far
more work was needed on animal embryonic stem cells before there
was any need or any point of work in humans. Is this a reasonable
position and, if not, why not? Separately, the Vatican gave us
a paper purporting to demonstrate, with references from scientific
literature and they were very keen to stress that, that it was
adult stem cells that showed all the signs of having therapeutic
application and there was very little evidence that embryonic
stem cells would be as good and therefore we really ought to press
ahead with adult stem cell research which did not involve the
use of embryos which is at least controversial in most jurisdictions.
Is that wrong and, if so, why?
Dr Lovell-Badge: First of all,
there are at least two reasons for working with embryonic stem
cells. One is to work towards therapies and the other is to use
them as an experimental tool to gain understanding of diseases
and other normal processes. We know that there are differences
between mouse and human embryonic stem cells in the way they are
grown, in their requirements and, in some respects, in their early
differentiation. So, I think you need to study both. There are
all sorts of things which are different between humans and mice
and we could take an example being the frequency of chromosome
abnormalities in early development. If you want to study that
using embryonic stem cells, for example, to generate gametes from
the cells and look at what is going wrong in meiosis, you cannot
do that using mouse embryonic stem cells because mice do not have
this really high frequency of abnormalities that human embryos
do. That is one example.
Q1121 Dr Harris: And in respect of
the other issue, adult stem cells? There are scientific references
on this paper.
Dr Lovell-Badge: There are lots
of examples where people are trying to take adult stem cells into
the clinic. Not all of them but many of them are difficult. It
is hard to get sufficient numbers of stem cells to treat people.
It is hard to grow these stem cells; there are all sorts of problems.
I am not saying that we should not be working on adult stem cells,
I have never said that, we have to. However, we do not know which
is best, whether it is potentially embryonic stem cell derived
therapy or adult stem cell derived therapies. We do not know which
is best and we cannot possibly know until we have looked at both
and that is what we need to do.
Professor Murdoch: I am a clinician,
not a clinical scientist, but I think all the evidence would suggest
that these are separate but parallel lines of research and it
would be very sensible, if we really want to make stem cell therapy
reach its full potential, that we move along both lines at the
same time. Some of the evidence that comes from studying adult
stem cells will help in embryonic stem cells and vice versa but,
at the moment, we do not know and no one knows where the end point
is going to be. I think you have to remember that a lot of the
people who are saying that we should only work with adult stem
cells and not with embryonic stem cells are not doing it on the
basis of scientific evidence, they are basing it on their views
about using embryos for research, which we can respect but where
their views are coming from has to be taken on board.
Q1122 Dr Harris: There are regulations
about creation of embryonic stem cell lines from embryos because
a value is placed on an embryo and there are regulations. Do you
think that once a cell line is established, there should be less
regulation and, if so, how much less regulation should there be
about what you then do with a stem cell line derived from embryos?
In other words, do you think there should be an application to
a body, the HFEA or a similar body, for permission or should it
be a research tool once it has been established that requires
funding clearly and so forth?
Professor Murdoch: If you take
an adult stem cell line from a patient to do a study on it, you
will be give permission to do that with appropriate ethical approval
that will say what you are doing in the lab but there would not
then be any specific regulation in terms of what goes on in the
test tube in the lab in terms of putting chemical X with it to
see how it grows and to see how it is handled and I do not really
see why there should be any difference therefore for the embryonic
stem cell line at that level.
Q1123 Dr Harris: As long as you have
the patient's consent for this sort of research.
Professor Murdoch: Exactly. It
does not need another outside body overseeing it as well.
Q1124 Dr Harris: So, we should be
able to genetically modify for research purposes embryonic stem
cells lines without regulation from an external body.
Professor Pedersen: If I may interject
something here. I think it is rather naïve to portray the
circumstances as if there were no current regulation or no current
body. That may be deliberately so because you like to raise the
question of whether there should be an additional body. I should
be the last person to point this out because everyone here should
know the law better than I, but the law which enabled this research
to go forward that was passed in this House required the establishment
of a body to oversee the research and that body has the authority
and the responsibility to do so: it is the Stem Cell Steering
Committee and it is chaired by Lord Patel. Everyone who works
on embryonic stem cells in the UK has to report to that committee
and seek permission from that committee in its role as overseer.
So, I do not understand why the question is being asked as to
whether there should be a body because there is one.
Q1125 Dr Harris: We are reviewing
the regulatory framework and we will issue a report suggesting
whether it is over-regulated or under-regulated. What I am trying
to tease out is whether the current regulatory system is onerous,
necessary and appropriate or whether we were just a little sensitive
at the time and we can get rid of a level of bureaucracy and rely
on the existing normal methods of scientific oversight as one
would with adult stem cells as Professor Murdoch just said. It
may be that you like filling in application forms to Lord Patel.
Some scientists tell us that they would rather not have that extra
level of bureaucracy.
Professor Pedersen: If the question
then refers to the effectiveness and the onerousness of complying
with Lord Patel's committee, I think that there have been some
responses early on to the effect that it was onerous. I think
I myself had the first response to the committee on an application
to export cells to Sweden that we had been studying. It of course
is onerous to participate in self-regulation and Lord Patel's
committee is a regulatory body, not a body that is encoded in
statutory regulations as the HFE is a self-regulatory body. Of
course it is onerous but that is the price of doing research in
full compliance with the public trust and I think that eventually
even those of us who are measuring it just on paperwork will comply
with that because it is a reasonable cost to pay for the opportunity
of doing this research.
Dr Lovell-Badge: I think I disagree.
I think that once you are doing experiments on a cell line, whatever
cell line it is, in vitro in the lab, then I think there
are going to be pretty much no circumstances where that needs
to go to a regulatory body. Maybe a local ethical committee to
some extent but I do not think it needs any other further level
of regulation. If you are going to then take those products from
the cell lines and do something with them, then obviously that
has to be regulated in some way and there are other ways that
is done. In any transplant medicine, for example, you have to
have the right sort of approval for that. I cannot see that there
is any real need. The only matter you have mentioned was public
trust but I think there is no real fear if you are just doing
experiments in the lab.
Q1126 Dr Harris: Professor Murdoch,
the casting vote!
Professor Murdoch: I would tend
to move that way.
Q1127 Dr Harris: For the record,
please.
Professor Murdoch: The UK stem
cell bank is a relatively new body and is not fully operational
yet; it is still finding its feet in terms of how it works. I
would like to see it move towards a less formal regulatory process
for what goes on in the laboratory than it has been tending to
take on board at the present time. There are a lot of issues in
the regulatory process which the UK stem cell bank has set up
which are still being debated. It is a voluntary group and there
is dialogue going on. Some of the issues that they have suggested
we have are just not practical and cannot be done, but they are
listening to what we are saying and are coming back and negotiating
on them. I think there is the potential that, if it goes as far
as it is suggested it might do, it might be disinhibitory to research
rather than actually helping protect anybody or anything from
any harm that is going to come. We should not have regulations
for the sake of it, we should look at the risks and what we are
trying to protect against and I think the risk of what you are
doing in the lab helping to learn how stem cells grow is actually
very small.
Q1128 Dr Harris: My last question
is about your evidence from the Newcastle Fertility Centre which
I found difficult to follow with this nucleus and faux nucleus
and I suspect that, if I had a bit of difficulty, then others
might have as well. As I understand it, it is not possible at
the moment to allow a defective egg to fertilise, that with a
faulty mitochondrion, and then take the nucleus and insert into
a nucleated donor egg with a good cytoplasm and good mitochondria.
That is not permitted under the existing wording of the HFE Act.
You talk in your interesting evidence about how you think that
the pronucleus is the thing to be transferred and I would be very
grateful if very briefly but in straightforward terms you can
tell me whether the things I have just raised are different issues
and, even if they are, whether you think the Act needs to relax
a little about the former case I suggested in case that turned
out to be useful.
Professor Murdoch: This is an
application that is pending with the HFEA at the moment from my
scientific colleague Mary Herbert; it is not my name directly
on that at the moment. A pronucleus will only have half the number
of chromosomes as an adult nucleus. A female pronucleus will have
half the chromosomes in the female from the egg and the male pronucleus
will have half the chromosomes from the male and it is only when
you put the two together that you will actually get a full complement
of chromosomes. So, that is where the main difference comes between
nucleus and pronucleus. I think there is a fundamental issue that
is important in terms of the Act and restructuring the Act here
and that is that the existing Act puts into primary legislation
certain things that we can and cannot do and gives very specific
terms and identity. You talked before about what is meant by embryo
and it comes back to that sort of issue. If you use these words
in primary legislation, it then becomes very difficult, as new
techniques develop, to go back and interpret them and to get some
understanding of what was meant initially when people said that
in the Act and change it as things have moved on. For instance,
the other issue in relation to that that is coming up is that
we are not allowed to change the genetic structure of an embryo
and I am sure that was originally put in the Act with the intention
of making sure that people did not alter the genes in the nucleus
and do that sort of process, but of course there are genes in
the mitochondria and therefore what we are trying to do to help
people who have serious mitochondrial disease to have a healthy
baby suddenly falls under the wording in the Act which it was
never intended for. So, one possibility of restructuring the Act
is that you actually avoid putting these dogmatic statements in
primary legislation and maybe devolve that to a secondary body
of the good and great and the people who are interested to actually
look at these issues as they arise and decide whether they are
now, in the present climate, appropriate things for us to be doing
in research. That will give us the flexibility to move on much
more quickly than having to do it as we did with nuclear transfer,
go back to primary legislation and actually change the Act to
do it. As long as it is for the body that has the authority and
the confidence of Parliament and the public, I think that might
be a better way to go about it and it would get over some of those
problems.
Q1129 Dr Harris: That is secondary
legislation; you have to wait a long time.
Professor Murdoch: Yes, it still
takes time.
Q1130 Chairman: For the record, will
the day come when we will not need many stem cell lines? We may
only need 15 or 20. You shake your head, why is that? There could
be one on every street corner.
Professor Murdoch: There was a
meeting in Newcastle recently when we were looking at how many
stem cell lines . . . The North East has a fairly static population
but they reckon that, in order to meet full complement tissue
matching, you need about 700 stem cell lines just for the North
East population. Given the rate at which you can generate stem
cell lines at the moment, which would need about 100 spare embryos
in one stem cell line possibly, you are talking then about 700,000
surplus embryos. That is just for the north east of England. I
think the reality of actually being able to generate enough stem
cell lines that tissue match all the population is not realistic.
Professor Pedersen: I would say
that this discussion has only begun and the data are not yet in
the public domain with which to address it. The challenge is to
make reasonable estimates of how many embryonic stem cells lines
would be needed or, for that matter, any source of stem cells
would be needed to tissue match the UK population and then to
discover methods of obtaining those in a patient transplant quality
with the highest efficiency in order that we do not waste the
material.
Q1131 Mr McWalter: I am very interested
in many of the things that you have been saying. One of the things,
Professor Murdoch, that struck me was that you indicated that
the reason why all this is so difficult is because the stuff/material
that is in your lab is, in the first instance, an embryo and that
is obviously the reason why there is huge public concern about
it. One of the issues then is that many of the people to whom
we have talked have said that that needs to be treated with respect.
Your words were that it has an identity. I can think of a friend
of mine who has had two children through IVF and the spare embryos
are now sitting there and then the issue is, what do you do with
them? The Vatican has effectively said that you do not have IVF
really; you generate three embryos and you implant all of them;
you do not have a spare embryo from them. Assuming that one does
not want to go down that line and one wants to treat these materials
with respect, I think that my friend would actually want those
embryos to be used to further human knowledge for the overcoming
of avoidable disease and suffering. I think she would see that
as the best way forward for those materials that have come from
her and her husband. So, I do understand that treating with respect
might involve being in a lab, in the same way as keeling over
and donating your cornea to someone you have never met is also
a treating with respect of the human body, so I do understand
that. Then you said that when you generate a stem cell line from
the embryo, then the rules change and Dr Robin said. "Now
it is like sodium chlorate in a test tube. I do not want anyone
telling me this is very special sodium chlorate; I do not want
anyone telling me this is very special material when I have to
continue, for instance, to inform the people who gave the material
its identity what happened after the embryo became the originator
of the stem cell line." Why do you not accept that maybe
that material also needed to be treated with respect? You were
sort of in the middle but you went more towards Dr Robin's view.
Professor Murdoch: I would not
say that stem cell lines should not be treated with respect. Anyone
who deals with stem cell lines knows that they have to be treated
with respect or else they die, basically. So, yes, there is some
respect there. I think it is to do not with respect that you give
them but actually how you look at them and how you process them
and care for them. Every embryo that you create in an IVF laboratory
has to be individually identified and we have to be able to account
for it to the HFE. If an HFE inspector comes in, they will say,
"Where was that embryo? Where is that embryo? Where are your
records to say what happened to it?" Once that becomes the
stem cell line, you are now talking about millions of cells. Are
you going to account for every single individual cell? If you
count them as groups of 100 cells, then is a group of 100 cells
different from the millions? They are different. I am not saying
that you do not respect a line for what it is and where it has
come from and its value, but you cannot subject it to the same
degree of regulation and monitoring in practical terms.
Q1132 Mr McWalter: The one thing
you might do, apart from telling people who, say, donate these
embryos and they regard that as the appropriate thing to do with
them, is undertake to keep them informed about the research. So
that they do not have only the thought, the embryo was in a lab
somewhere and got used in a lab but to inform them more about
the research. Then they would have a continuing interest in what
you were doing and see beyond simply the fact that the embryo
is now no longer, as it were, recognisable as the embryo they
created. I do not see why you do not have some sort of continuing
interface with the people who generated that material in fact
out of mutual love and all the other things that go into it.
Professor Murdoch: Because those
stem cell lines are not their baby.
Q1133 Mr McWalter: I understand that.
It is degrees of respect and you might find ways of integrating
that concern into the ethical framework.
Professor Murdoch: Patients who
give consent—and do not forget that the processes of consent
are rigorous; in our unit at the moment, we have a nurse who is
funded by the MRC specifically to work fulltime to talk to patients
about the research that is going on in the lab; she has nothing
to do with the clinical work at all; so, it puts an interface
between the clinical service and the research service—are
given the opportunity to get information back about anything that
might be found out that might affect their health and their children's
health in the future and they can choose to do that or to not
do that. They are not given the opportunity to be given specific
information back about what happens to any lines that might be
derived from their embryos. My own personal view is that I think
that is probably the right thing to do. Do not forget that I am
treating people with clinical problems and some of these people
do not get pregnant from treatment and some do and it is a huge
psychological problem that they have. To then burden them with
the problem of how they then regard a stem cell line that might
be generated from an embryo I think is actually too difficult
for them. If they do not feel that they want to participate in
the research on the basis that they are not getting that information,
they do not give consent, so they do not agree. It is discussed
with them and they are given that opportunity. Just to give you
some feedback, since the nurse was employed in September, previously
we had had a very sort of hands-off approach, so the number of
people consenting to give embryos for research was 50-60%, that
sort of order. Since she has been there and we have been able
to give people more information, about 17% of the people whom
we see say at their first visit when they come for IVF when I
say, "There is research going on here", say, "No,
I don't want to participate" and they are not involved any
further. Of those that go on and they ask for information and
are given further information, 87% agree to use any surplus embryos,
these are embryos that would otherwise be discarded, for research.
The reasons they give are that if people had not done research
on embryos in the first place, they would not be there having
an IVF treatment. They recognise that these embryos are going
to be discarded; they are no use to anybody; they cannot be given
to anybody else; they are there and they want them to be used
and I think the views of the patients whose embryos they are have
not been listened to previously hard enough in this debate.
Q1134 Mr Key: Scientists might say
that we are dancing on the head of a pin but a lot of other people
would say that we are dancing with angels in trying to get to
the bottom of this issue. We were told by previous distinguished
witnesses that scientists really cannot define an embryo, "it
depends who you are talking to", we were told. So, what is
so special about the moral status of an embryo if we cannot even
define one?
Professor Murdoch: I think that
is a real problem in terminology and I can see where the issues
are coming from in previous discussion. If you go out on to the
street and say to someone, "What do you think an embryo is?"
they will describe to you a tiny but fully formed moving foetus,
so a moving thing with arms and legs and a heart that is beating.
That is lay understanding of an embryo. The patient having IVF
thinks of an embryo as the four cells they see on the screen before
they are put back that might make them a baby. The Act of Parliament
at the moment considers an embryo as being an egg sitting in a
dish surrounded by hundreds of thousands of sperm with no intention
of ever letting any of those sperm get inside the egg but, according
to the law, that is an embryo. Clearly these are completely different
things. Therefore, we have to use different words to describe
them. There are different words to describe them—you can
use larcisis(?), you can use zygote at different stages, but I
think that we will have to find a different word because they
are different things. Clearly, there are issues in terms of public
perception, public education and understanding of what we are
doing but, if we persist in using the term "embryo",
we are going to get it wrong. One of the headlines in the newspaper
when the nuclear transfer issue came out had a picture of a fully-formed
embryo as an illustration and that is wrong. It is misinformation.
Q1135 Mr Key: Professor Murdoch,
you just said in answer to a question from my colleague, referring
to your patients, that it is too difficult for them. Our problem
is that we are trying to find a way of describing something in
law which will be applied for as long as possible. The law will
not fall into disrepute because we do not do our job properly.
Do you think there is a conflict of interest between stem cell
research and fertility treatment given that every embryo donated
for research could theoretically become a baby?
Professor Murdoch: There is potential
conflict of interest and I think part of the current regulations
which are very tough are designed to minimise that conflict of
interest. Regardless of what the HFEA would say, the licences
that we have go to the Ethics Committee before they get seen by
the HFEA and one of the remits of the Ethics Committee is to make
sure that nothing is going to be done to the patient in the process
of any research which will harm their primary treatment. So, there
are not just the HFEA but there are standard regulation procedures
already that cover that. I think that, in the UK, we probably
have it about right. One of the difficulties you have in other
countries in the world is where people are saying, "We are
going to create embryos, pay people to give eggs/sperm specifically
to make embryos specifically for research." That might turn
out to be the only way we are going to get decent embryos to do
it but I think that, at the present time, the stance that has
been taken in the UK, which is that we will use the embryos which
have already been created which are going to be thrown away otherwise,
is the appropriate way to do it and we have to come to terms with
potential conflicts of interests.
Q1136 Dr Iddon: Will it ever become
possible in your view to abstract stem cells from an embryo without
destroying the embryo? What are the benefits in doing that? How
much effort should be put into it? What is the impact on regulation
if it comes achievable?
Dr Lovell-Badge: It could be done;
the techniques are available to do that simply by beginning as
you would PGD, on an embryo, and take two cells and derive embryonic
stem cells from those.
Q1137 Chairman: Why do you not do
that then?
Professor Pedersen: This may be
an overly technical answer, but one of the rules, that is to say
a fact, that we know applies to all mammals, of which we are a
member, is that the early development of the embryo before implantation
into the uterus depends on the total mass of cells and anything
that is outside becomes the placenta. That is the rule. So, unless
you have a big enough mass to have an inside, you get no stem
cells except placenta. That is why it is very difficult to take
a bit of the embryo and achieve this. You could, in principle,
take just the inner cells out and leave the placenta alone, but
then it would not develop except for as a placenta and a placenta
does not grow without the inner cells present.
Q1138 Dr Iddon: And the impact on
regulations? Can we see how you can change regulation if this
becomes a common practice? Does the present regulation cover this
adequately?
Professor Murdoch: I am sure that
current regulation as it stands would cover it because you are
doing a manipulative process to an embryo, so it would come to
a committee which would have to decide whether it was something
that was justifiable to do and whether there was a good scientific
basis for doing it.
Q1139 Dr Iddon: Let me look at another
difficulty now and that is bringing human and animal gametes together
or cells together. Why is that necessary in stem cell research?
What are the benefits we can gain from that and do you think it
is ethical?
Professor Murdoch: Are you talking
about chimeras or co-culture?
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