Examination of Witness (Questions 720-739)|
TUESDAY 4 DECEMBER 2001
720. Gentlemen, you are most welcome. Thank
you for coming to see us today. I will be asking questions, we
do not need necessarily four responses to every question but do
come in as appropriate. Would you, Sir George Radda and Professor
Brown, Professor Baker and Professor Evans, in turn like to briefly
introduce yourselves and make any opening statement you wish.
(Sir George Radda) I will start off.
I am George Radda and I am Chief Executive of the Medical Research
Council. I am also a British Heart Foundation Professor of Molecular
Cardiology so I have myself been involved with animal experiments
and still am to some extent. I am here in my capacity as Chief
Executive of the MRC. I have with me Professor Stephen Brown,
who is one of our MRC Unit Directors. Do you want to introduce
(Professor Brown) I am a Director of the MRC Mammalian
Genetics Unit and the UK Mouse Genome Centre. I have a big interest
in mouse genetics and its role in studying human disease.
(Professor Baker) I am Ray Baker. I am the Chief Executive
of BBSRC. I was previously working in the pharmaceutical industry
in drug discovery programmes which were concerned with the central
nervous system, with diseases such as schizophrenia, Alzheimer's
Disease and depression and others. I have a great interest then
in this subject. Since then, of course, as head of BBSRC, we have
been very involved in discussions of how we fund what we fund
and the justification for the programmes that we give our funding
for. I have with me Professor Martin Evans and he can say something
about his own expertise.
(Professor Evans) I chair the BBSRC Animals Committee
and have done for more than two years now. I am a Director of
the School of Biosciences in Cardiff University. My own research
has been concerned with, first of all, the discovery and then
the use of embryonic stem cells, ES cells in mice and from that
a large amount of experimental genetics in mice.
721. Thank you very much. The first question
then is how important is fundamental research on animals? What
would be the consequences if Research Councils stopped funding
all animal procedures of substantial severity?
(Sir George Radda) The answer is it is extremely important.
Many of the medical advances in the past and in the future are
expected to be based on fundamental understanding of the physiological
and biochemical processes in the whole living organism. That is
the reason why primarily we need to do animal experiments. If
we stop them, research in this country in the biomedical field
and in the biological sciences will just simply disappear from
the world scene, and we will not be competitive at all in global
(Professor Baker) More seriously still, without that,
and with the change to the science base, we would clearly lose
a good part of our economy in companies which are based on the
science base and that would be particularly bad for the pharmaceutical
industry and related industries in biotechnology which are growing
at this time.
Lord Soulsby of Swaffham Prior
722. It has been said by quite a number of people
that whole animal research in this country could be on the way
out because of the difficulties of getting the appropriate project
licence and the rest. People are moving towards in vitro
systems. Your previous answer would be that would be a very bad
thing if it did happen. Is there any evidence in MRC or BBSRC
of people using whole animal research less now than previously?
(Sir George Radda) I do not think the answer is that
they are using it less. I think there is no scientist who enjoys
doing animal experiments. I think scientists, if they have good
reliable alternative ways of solving a problem, will use that
method. Nevertheless, we all recognise that animal experiments
are important in various areas. What is happening is that scientists
move in and out of working with animals, depending on how the
science is progressing. I do not think there is any sign that
it is decreasing. The nature has changed quite considerably in
that there has been an enormous shift towards rodents, mice in
particular, and also other smaller animals like worms and fruitflies,
and that has been helpful. The experiments on large animals and
domestic animalscats and dogshas practically disappeared
in this country in the academic world anyway. I think there has
been a shift; scientists move in and out of animal experiments,
but there has not been a decrease. As for the licensing and the
slowness of the licensing, we can, I am sure, all comment on that.
I think, again, it is very important that the community does not
wish the regulations to be any laxer than they are. We are very
happy that we know we have a well-regulated system which we can
follow. We would like it somewhat simpler at times so that licence
applications could be dealt with more speedily. I have to say
that the Home Office has been making progress in the last year
or so in that respect.
(Professor Baker) We have two contrasting effects
in terms of the number of animals which are used currently. There
is no doubt that up to a few years ago there was a decrease in
the number of animals used in experimentation. This happened because
of the development of alternatives which has perhaps gone a little
bit slower than we would have hoped but there are many alternatives
which are coming forward, I think, which would decrease the number
of animals. In contrast, the development of the life sciences
and what one might describe as the genomic revolution has brought
different aspects and a different insight into the life sciences.
The use of transgenic animals will tend to increase the numbers
which are used because of the fresh opportunities to delve into
and define areas of biology which were previously unknown. Nevertheless,
those numbers may be misleading. They are misleading since we
count the number of animals, and many of the transgenic animals
which are bred and developed actually undergo no suffering whatsoever.
Almost certainly some of them are not used but just live life
through their period of time. Martin Evans may wish to comment
on the use of transgenics.
(Professor Evans) Yes. I think it is very true that
a large part of the increase in the numbers of animal experiments
regulated under the Act is due to transgenic animals. I think
we foresee there is likely to be an increase. The increase is
largely going to be with mice and zebra fish, other animals too
like chickens and some of the larger farm animals, in larger numbers.
Any genetically modified animal is regarded as an experimental
animal under the Act. There is obviously very reasonable concern
about genetic modification in terms, for instance, of release
to the environment, but that is not what we are concerned with
here. What we are concerned with, as I understand it, is the control
of animal suffering. Very many of these animals show absolutely
no adverse effects whatsoever and yet they and their progeny ad
infinitum remain experimental animals under the Act, subject to
all the controls, restrictions and, indeed, statistics. I would
suggest that if there is any change which might be considered
that it might be that we start to count only adversely affected
animals or matingsand just mating these animals is an experiment
under the Actwhich are either designed or expected to give
rise to adversely affected animals. If we did that, I think we
could focus then much more upon what I see as the real purpose
of these regulations, that is to control and limit animal suffering
while allowing proper responsible scientific research to go ahead.
723. A couple of questions. When you are looking
at the grant application, that involvesto take a couple
of exampleseither the creation of a very large number of
possibly genetically modified mice through random mutation or
the use of an animal model which is of arguable benefit, such
as cystic fibrosis in mice, to what extent do you perform your
own cost benefit analysis on that? Under what circumstances would
you feel able to say "This is, say, a cystic fibrosis mice
model, not something we are prepared to support because the benefits
are less than the suffering involved"?
(Professor Evans) I would like, first of all, to take
issue with you, I am afraid, on your choice of cystic fibrosis.
The cystic fibrosis miceand I have been intimately involved
with research with these mice, with their generation and, indeed,
the researchare not what you would call an exact model;
they are not little men and women with cystic fibrosis but they
have been a wonderful opening up to the insight of what is really
going on in cystic fibrosis and have allowed, for instance, developments
of methods of gene therapy which have been taken through to human
trials. I think that is unfortunately not a well-chosen example,
if I may say so.
724. It is one on which there is a good deal
of controversy. It is one where many people have spoken against
(Professor Evans) It has been used by some of those
who would wish to try and find an example of a bad model.
(Professor Evans) But I think they have entirely misunderstood
what this sort of genetic model is doing. I think you may be quoting
people who perhaps quite honestly, with respect, my Lord, have
misinformed you on that.
(Sir George Radda) Stephen?
(Professor Brown) I want to add simply one point from
the perspective of your question and that is an issue which I
am sure we will come on to discuss; that is the ethical review
process which I think we support strongly. I think it has underlined
to scientists working in laboratories and institutes the need
to think more carefully, because that is what the process requires,
about what the costs are to the animals in terms of welfare, in
relation to the benefits to the science.
726. I was more interested in your part in the
procedure. First of all, whether you would be prepared to say
that you were not satisfied with a particular animal model and,
secondly, whether you do cost benefit analysis yourself?
(Sir George Radda) You want us to speak to what happens
when we are looking at a grant application?
(Sir George Radda) The committees, first of all, are
instructed to look at whether there is a need for animal experiments
in order to carry out that particular research programme and answer
the research questions. If there is a need for animals, have they
used the lowest form of animal that can give the answer?If
a worm can give the answer, we would rather they did the studies
on a worm than on a higher species. Have they got the right number
of animals? Can they do it on fewer? Sometimes, of course, the
committee has to say "The statistics on this number of animals
is not valid" and, therefore, you have to do a larger number
of animals to get an answer. The committees look at whether you
are going to get an answer with the minimum number of animals
that you propose to use in that study and then they ask about
the severity of the procedure (which is largely a Home Office
issue, of course,) and most importantly they look at the scientific
issues. If it is generally believed that the animal model is no
use whatsoever, then obviously the research is not going to be
funded;it is not good science.
(Professor Baker) I have examples of cases in application
in which we had known that the Home Office would grant licences
but our committees have rejected those applications based on their
belief that insufficient data and information will be provided
by those experiments. I have even seen examples where suggestions
have been made for alternative experiments which have alleviated
much of the concern.
728. The second question was if, or indeed when,
the law is changed or the practice is changed so the particular
experiments are forbidden in this country, such as use of chimpanzees,
would you consider supporting a project which involved the use
of chimpanzees overseas? Clearly some people do because a number
are still being done.
(Sir George Radda) No. The answer is we would not
support experiments abroad which are not consistent with our own
729. Who in the UK is funding these experiments?
(Sir George Radda) If it is funded elsewhere, we have
nothing to do with it. We have no control over what a scientist
might do who travels abroad and does an experiment. If it is one
of our own scientistsan MRC employed scientistwe
do then have a control over that and we expect the universities
to exert the same sort of control on their scientists.
Earl of Onslow
730. I have two questions. One, I may have misunderstood
you, you said that the number of higher animals was falling and
the number of lower animals was increasing. Does that mean then
that possibly the drug licensing regulations could be amended
to reduce the number of dogs and apes that are used? That is my
first question. My second question, I may have misunderstood you,
I thought somebody implied experiments which produce no suffering
should not need a licence at all. Would this not lead to a possibility
of a value judgment as to what the suffering was and consequential
problems? Somebody might say, for instance "If I want to
jump a fence and in jumping it I bash the horse on the side with
my spurs to make him take off which is what I want him to do rather
than crash into the fence" that is causing an element of
suffering. I accept I am using a non scientific language but you
know what I mean.
(Professor Baker) I am not sure that any of us implied
that any animal experiment should go forward without licensing
on the judgment of no suffering. I do not think that was the case.
731. Obviously I misunderstood you.
(Professor Evans) Maybe I could come in there a little
bit. If one wishes to do an experiment on tissues from a normal
mouse, those mice are kept, they are not animals under the control
of the Act. There are a lot of regulations of their proper maintenance
but they are not animals under the Act. They would be killed by
what is called a Schedule 1 procedure, in other words a method
which is deemed to be humane, and then the tissues can be used
for experiments. If, however, a precisely similar type of protocol
was carried out with an animal which carried, shall I say, a transgenic
gene that marked its liver cells but did nothing which we can
detect with the most sensitive detections to adversely affect
the animal in any other way, then it would be an experiment under
the Act. That was my suggestion that maybe there are some, which
I think would have to be released by the Home Office, I think
our inspectors would have to be involved there.
732. I must admit it comes slightly as news
to me that you can do something, but not do something with a mouse,
and then bump it off and then look at slices of it under a microscope,
that does count as animal experimentation.
(Professor Baker) But the killing of the mouse would.
(Professor Evans) I am sorry, we are probably getting
into technicalities. The killing of the mouse, if it was carried
out by what is called a Schedule 1 method, which is an agreed
humane procedure, does not bring it under the control of the Act.
733. Can we continue on to my second question,
the one on whether the drugs regime requires a certain line of
experimentation going all the way down from primates to mice or
whatever it is, that is if I have understood it correctly. I rather
got the impression with your experimentation and research you
are using less higher order mammals. Therefore, do you think it
would be possible to reduce the regime of higher order mammals
in drug licensing methods?
(Professor Baker) Perhaps I could take that. The requirement
at the moment is for testing of drugs on two animal species, one
of which is normally a rat; there is a very large knowledge base
in rat and, therefore, it is done in rat. There is then the need
in many cases for a second species, which is normally monkey or,
in some cases, dog. I have my own feelings about that and I think
the regulatory authorities, I am sure, in due course, will begin
to examine the number of experiments which are needed and the
dose levels which are needed to test potential drugs. The danger
is clear. The danger is adverse effects in humans. The question
one needs to ask is what is the margin of safety one places before
one puts that drug, first of all, into a volunteer, and then subsequently
into patients. That margin of safety is the issue which the regulatory
authorities are concerned about. If we do move forward to decrease
that testing, and particularly the higher dose levels of those
drugs, then the increase in adverse effects, which will include
fatalities, will be a problem. Of course one could always say
we would not need a particular drug but there would then be a
significant impact on some patients for those diseases for which
treatments are not yet available.
734. I imagine you are very much conscious of
public perception of the kind of work you do, you can hardly not
be. I wondered whether you thought there was a great difference
between public perception of fundamental research and on the other
hand of toxicity testing or the development of new drugs, or has
the general public not grasped the difference?
(Sir George Radda) Our MORI poll I think has asked
that question which we did a few years ago. I think the answer
is that the public is much more ready to accept basic experiments
which might lead to medical advances than experiments which are
related to toxicology or products particularly, perhaps, in the
cosmetic industry and so on.
735. Yes. It is very difficult in the case of
fundamental research obviously to know whether this is going to
have a beneficial outcome or no outcome at all or just turn out
to not have been worth doing. Are people prepared to accept this
aspect of fundamental research?
(Sir George Radda) I think the answer was that 56
per cent of the people asked that question said yes, they were
prepared to accept it either always or soemtimes. Only a relatively
small number said they would not accept it and the rest said "Well,
we do not know".
(Professor Baker) I would add a rider to that. I think
it is quite clear that if you ask most of usI would include
myself in the same way as the general public"Are you
happy to use animal research in research to discover how to treat
cancer?" the answer will be "Yes". In contrast,
if you ask the general public "Are you happy to use animals
in research on the way that cells signal messages both intra cellular
and inter cellular ..." that is inside cells and between
cells, then the answer is a larger number would say "no".
That is the perception I think that you are referring to.
736. That is right.
(Professor Baker) It is a very difficult one. It does
need quite hard work. I think both our Councils do work hard at
this particular issue.
737. You said that the experiments on the larger
animalsdogs, cats and monkeyshave been virtually
eliminated. From the point of view of the animal welfare side
of the equation, this is something which is very widely welcomed.
Has the other side of the equation, the benefits of research suffered
as a result? We note that some of the people who have given evidence,
like Huntingdon Life Sciences, still have to carry out certain
experiments on dogs. Do you lose any of the potential benefits
of research by the virtual elimination of the larger animals and
if so which?
(Sir George Radda) First of all, I think that many
of the studies that are done at Huntingdon Life Sciences are because
of regulatory reasons, for production or testing of drugs, and
we have covered that. In terms of fundamental experiments to understand
basic biological processes or to do studies in relation to certain
diseases, we can now, for example, take a human genemaybe
Stephen Brown can expand on thatand put it in the mouse
to study a receptor that would be a target for a drug, whereas
previously we were only able to study such processes in a higher
organism. Now we can do all kinds of manipulations which allow
you to use a species like the mouse to study human gene expression.
Stephen, do you have an example?
(Professor Brown) This is the power of genetic modification
in the mouse; not simply to ask questions about the function of
an individual gene in the mouse but also towhat we callhumanise
the mouse, give it an immune system which looks like that of a
human; ie has some human genes as opposed to certain mouse genes.
Then that allows us to ask questions which previously we might
have only been able to answer by working on primates, for example.
This is a big step forward enabling us, I think, still to see
the benefits of this kind of molecular genetic research and not
lose any of the benefits that you are alluding to.
738. Are you saying that in fundamental research
it is no longer, as far as you see, really necessary to use the
(Professor Brown) In molecular genetic research, studying
the function of genes, there is no work in this country that I
am aware of that is using larger animals to study fundamental
genetic processes and how they impact upon disease, either for
animals or for humans. I think most scientists welcome this shift.
It is an important scientific development and it is reflected
in the animal figures that you referred to.
Baroness Richardson of Calow
739. Would you comment on the way animals are
used in terms of training surgeons? For example, does that require
the higher animals particularly in neuroscience and so on?
(Sir George Radda) I actually thought that now you
are not allowed to use animals to train surgeons. You are only
allowed to use animal experiments in order to come up with a new
surgical procedure or move forward the whole field. The training
element is not allowed now under the Animals Act. Surgeons now
have to be trained by virtual surgery and on various artificial