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Select Committee on Animals In Scientific Procedures Minutes of Evidence


Examination of Witness (Questions 720-739)

SIR GEORGE RADDA, PROFESSOR STEPHEN BROWN, PROFESSOR RAY BAKER AND PROFESSOR MARTIN EVANS

TUESDAY 4 DECEMBER 2001

Chairman

  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 yourself?
  (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 terms.
  (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 animals—cats and dogs—has 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 matings—and just mating these animals is an experiment under the Act—which 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.

Lord Lucas

  723. A couple of questions. When you are looking at the grant application, that involves—to take a couple of examples—either 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 mice—and I have been intimately involved with research with these mice, with their generation and, indeed, the research—are 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 you.
  (Professor Evans) It has been used by some of those who would wish to try and find an example of a bad model.

  725. Yes.
  (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?

  727. Yes.
  (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 regulations.

  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 scientists—an MRC employed scientist—we 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.

Baroness Warnock

  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 us—I 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.

Lord Taverne

  737. You said that the experiments on the larger animals—dogs, cats and monkeys—have 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 gene—maybe Stephen Brown can expand on that—and 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 to—what we call—humanise 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 larger animals?
  (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 objects.

Lord Taverne


 
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