Examination of Witnesses (Questions 1-19)|
31 JANUARY 2007
Q1 Chairman: May I welcome our guests:
Dr Lyle Armstrong, Institute of Human Genetics, University of
Newcastle-Upon-Tyne, Professor Chris Shaw, Institute of Psychiatry
at King's College, London, and Professor Austin Smith, Wellcome
Trust Centre for Stem Cell Research, University of Cambridge,
as witnesses to our first evidence session in terms of the Government's
proposals on the regulation of hybrid and chimera embryos. Welcome,
gentleman, and may I first of all give my apologies for starting
this session nearly 10 minutes late. I genuinely regret that.
We ask that you, Professor Smith, chair your panel in case you
start having a dispute; you are going to be in charge of that.
Professor Smith: I will do my
Q2 Chairman: This session is being
televised and therefore, rather like the Big Brother House,
we need to be on our very best behaviour, or perhaps that is not
an appropriate thing to say! Professor Shaw, I would like to begin
with youand put the same question to Dr Armstrongand
I want a very, very brief answer, please. Would you give a brief
description in laymen's terms for the Committee of the research
you would like the HFEA to license. What is it that you want the
HFEA to license?
Professor Shaw: What we are asking
is to be allowed to put a human skin cell into an animal egg which
has had the nucleus removed. So, the DNA from the egg has been
removed and replaced with the human DNA. The skin cells that we
want to use are from patients who have neurological diseases and
we hope to be able to stimulate that new cell to divide and generate
stem cells. Those stem cells can be turned into the nerve cells
that we think are important in these different diseases and we
can study the disease process in the laboratory. This will tell
us about disease mechanisms and it will allow us to actually treat
those cells and see whether we can reverse the disease process
and discover new treatments. That is the purpose.
Dr Armstrong: We are essentially
asking to do a very similar thing. We will perform this nuclear
transfer or cloning technique using human cells and putting them
into animal eggs which have had their nuclear material removed.
The idea behind that is that we can derive embryonic stem cells
from those embryos and investigate things such as how the genes
in that adult skin cell from the human organism have been reprogrammed
or reset to make them express all the gene sets that would be
required to turn them into an embryonic stem cell. We want to
do that because we want to understand this reprogramming process
so much better because, if we can design strategies to reprogramme,
say, a cell from a human skin, then we can perhaps get away from
having to use this whole cloning process in the first place to
make embryonic stem cells and thereby make embryonic stem cell
technology more accessible to everyone rather than just as a research
Q3 Chairman: May I clarify from you
that the stem cells that you will be taking, the human cells that
you will be taking, will be from patients with known disease.
Dr Armstrong: Not in this case.
That is not our specific interest.
Q4 Chairman: That will be different
to the branch of Professor Shaw in that sense?
Dr Armstrong: It is different
in that respect, yes.
Chairman: Okay. Now, we need to get the
terminology right and I am going to bring in my colleague, Des
Q5 Dr Turner: We do not want public
debate to be bedevilled by loose terminology; there is already
loose enough terminology in the Government's proposals. It would
be very helpful if you were to set out what you mean and understand
by the terms "chimera" and "hybrid" in this
Dr Armstrong: A hybrid is essentially
an organism which is formed by the mixing of the chromosomes of
two separate organisms. A chimera is essentially an organism which
is formed by the mixing of the cell types from two separate organisms.
The entities that we would seek to create really fall into neither
of those categories because we would remove all of the chromosomal
DNA from the egg of, say, a cow or a rabbit. We, in our research
group, refer to them as "interspecies embryos". We do
not really think that the term "hybrid" is all that
valid although we can understand that we have to call them something
and that it is an easy title for people to attach to.
Q6 Dr Turner: Would you restrict
the term "hybrid" to a cell in which there is chromosomal
material from two species?
Dr Armstrong: We would prefer
to do that. Obviously, we understand that there is DNA from the
mitochondria from the animal oocyte, but really that has very
little contribution to the actual information content of the final
cell. It would not instruct the embryo on how to produce an embryonic
stem cell or how to make the distinction between the different
types of cell you would find at the blastocyst stage embryo. All
mitochondria serve to do is to produce power effectively for the
cell and to partake in certain processes in programmed cell death,
but they really are not terribly important for instructing the
embryo as to what structures it has to form and how it has to
Q7 Dr Turner: Professor Smith, do
you want to add to that?
Professor Smith: Yes. I think
what Lyle has said is absolutely correct. The traditional definition
of a hybrid in biology is the fusion of two chromosome sets to
make a new genetic entity. People are familiar with that particularly
in plant breeding. So, when we use the word "hybrid",
it conjures up a wrong image. I think that the correct scientific
terms is "cybrid", which is the terminology that people
used in somatic cell genetics in the 1960s and 1970s when they
transferred the nuclear material of one cell into the cytoplasmic
material of another, which is actually an example of what has
been done in nuclear transfer. So, you have only a small component,
which is the mitochondrial component.
Q8 Dr Turner: We already seem to
have the possibility of the loose use of the term "hybrid"
in particular threatening research in terms of the latest HFEA
decision. Do you think that unless the Government are quite clear
and accurate about this use of terminology in terms of the creation
of chimeras and hybrid embryos, existing areas of research are
going to be threatened?
Dr Armstrong: If the use of the
term "hybrid" were to lead to sufficient opposition
to the work that we want to do which led to it being disallowed,
then it is possible that other areas of science such as the disease-specific
stem cell lines that Professor Shaw and Dr Minger at King's College
want to produce would be threatened and I would think that that
would be a disadvantage for British science. It would prevent
or hinder the possible development of cures using this technology
which, in my view, would be a sad thing to do.
Q9 Dr Turner: Despite the slightly
improper use of terminology which has created a problem, if permission
were given to allow the creation and use of these embryos purely
for research purposes, would that be sufficient for your immediate
Professor Shaw: Yes, I think it
would be. This is a very discrete area and we have resorted to
this because of the challenges that are faced by using human oocytes
which is already licensed to work. Professor Ian Wilmut and I
have a licence to work on Motor Neurone Disease in this respect.
The problem with human eggs of course is that they are a very
rare commodity. The eggs that we are allowed to use are those
that have failed to fertilise and so they are already, if you
like, pretty exhausted eggs before we can get to use them. I think
it is correct to say that nobody has actually generated a mature
blastocyst from which you can derive stem cells anywhere in the
Q10 Dr Turner: Do you have any thoughts
on the provisions that you would like the proposed Bill to take
bearing in mind that this Committee has been around this course
before and it left the recommendation that the creation of such
embryos should be legal for research purposes provided that they
are destroyed in line with the 14-day policy, the current 14-day
rule for human embryo cultures, and prohibit their implantation
in a woman?
Professor Shaw: Absolutely.
Dr Armstrong: We would be perfectly
happy with that.
Q11 Dr Turner: May we have your thoughts
about what the provision for the legislation should set out.
Dr Armstrong: Obviously, we should
have the capacity to apply for licences to permit this work from
a body such as the HFEA. It should state that we are allowed to
do this work under very similar remit to the present HFE Act where
we are allowed to do this work to gain more knowledge about embryonic
development, to gain more knowledge about stem cell development
and about the progression or possible progression of disease.
Q12 Dr Turner: Would you agree with
me that the framework as set out by the current HFE Act has been
sufficiently clear to enable British stem cell research to reach
the position that it has had and that the proposals which
have not been licensed by the HFEA were in fact fully in accordance
with the existing framework?
Professor Shaw: We believe that.
Neither of us are lawyers and it is not really our area of expertise
but, from the simply reading of the HFEA remit, we believe that
this work should be licensed by them. These are essentially human
cells that we are deriving.
Q13 Dr Turner: What would be the
consequences if this work is permanently stopped both for the
disease areas and for the future of stem cell research in the
Professor Shaw: In terms of the
disease areas, I think we are looking at a very huge task in terms
of achieving this with human eggs. Certainly it is not something
that is likely to happen within the next few years or possibly
several decades. That would be a major problem for us. The diseases
we are looking at are all devastating diseases in which we have
very little understanding of disease mechanisms. It is very difficult
to develop an effective treatment if we do not actually know what
is going wrong and, as I think we show in the models, they not
only tell us about what is going wrong but they provide an immediate
resource to screen for drugs that will be effective. If you stop
that, then you are really putting a halt on all that sort of work
and I think that is not only bad for science but is bad for our
patients and is bad for the community and sends a very negative
Q14 Chris Mole: Would you all agree
that the term Professor Smith used of "cybrid" is well
enough and widely enough understood to be used as a definition
in law and are there any others that could be helpfully put on
the table at this time to ensure that the legislation controls
what needs to be controlled and does not control other bits?
Professor Shaw: One possibility
that I believe has been mentioned previously in the discussions
is that a pseudo-hybrid. The embryo is not a real hybrid but a
pseudo-hybrid, they are essentially human pseudo-hybrid embryos.
I think that the definitions are very important but it is not
for me to tell you what should be done. I would feel comfortable
with either "cybrid" or with "pseudo-hybrid"
terminology. I think that would help us distinguish our work from
some of the other work that may require further restriction in
Q15 Chairman: I do think it is important
that we get a definition because so far this morning we have asked
that specific question for us to try to get clarification and
we have had "interspecies embryo", "cybrid",
"hybrid chimera" and "pseudo-hybrid" all mentioned.
If that is confusing us as a committee that is trying to make
some clear recommendations, then, in terms of the public debate,
it is going to be very, very difficult indeed, particularly more
broadly in the House at the draft bill stage. You have all agreed
on "cybrid" and you have all agreed on "pseudo-hybrid"
as the two clear definitions. Is "cybrid" the preferred
Professor Smith: I would say so
because, if you use the word "pseudo", this will raise
questions with journalists and politicians and the public. I think
that there has been a bit of a problem in the scientific community
in thinking how to describe these entities that are created by
nuclear transfer because the only word we have is "embryo"
but they are not normal embryo and this has become conflated with
when you have an interspecies situation. My understanding of the
somatic cell genetics field is that "cybrid" is the
word that has been used in the past and would seem to be a perfectly
legitimate word to use in this context that would make it very
clear that this is a different thing from a hybrid. Of course,
as we know, you still have people/journalists who will use the
word "hybrid" but it is very important for this Committee
and Parliament to know what the law says.
Q16 Chairman: It was really important
to get that firmly on the record. Dr Armstrong and Professor Shaw,
in response to Dr Turner's question, you were quite definite that
you were in fact going to grow these cybrids for 14 days.
Professor Shaw: Yes.
Q17 Chairman: Stem lines would be
taken during that time and at the end of that time.
Professor Shaw: Yes.
Q18 Chairman: And then it would be
Professor Shaw: Absolutely.
Q19 Chairman: Why do you not wish
to grow them to full term?
Professor Shaw: It certainly is
not in my scientific remit to do that. It is no the biological
experiment we are interested in. Indeed, I think it is a whole
area that I would not feel comfortable working in myself. That
is my own personal opinion.
Dr Armstrong: For my research,
there is no scientific value in doing that. All of the events
which will reprogramme the somatic genome will have taken place
by the blastocyst stage generally which develops at day five to
six. There is no real remit for my going on any longer beyond
that. We would derive embryonic stem cells from blastocysts at
day six and that would be the termination of that embryo's existence.
There would be nothing further to do with them after that. Apart
from anything else, the differentiation events that are taking
place in an embryo at 14 days would probably mean that it would
not survive in culture anyway. The 14-day limit has been applied,
but I do not know of anyone who has actually cultured an animal
or a human embryo to that limit because they are outside the context
of a uterus in which they would expect to have been implanted
and, outside of that context, there is very little possibility
that they would survive in culture.