El recurso internacional para la evidencia científica en la investigación con animales

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Is Discovery Worth The Pain?

The fifty-sixth Stephen Paget Memorial Lecture, 11 November 1987
Emeritus Professor Sir Stanley Peart, MD, FRCP, FRS St Mary's Hospital Medical School, London W2

The relation between man and animals and the question posed in the title turns on the rights of man as a supposed superior being to satisfy various appetites and curiosities at the expense of animals, particularly by the infliction of pain or suffering. Usually the case that is argued in favour of vivisection and the right to inflict pain is the medical one that therapeutic good is the main aim and that not only may man benefit, as by the production of new effective drugs, but so also may animals as by the prevention or amelioration of their painful diseases. This is not the issue I want to address principally but rather to explore the argument that to restrict human curiosity about nature, by restricting experiments on animals involving pain or suffering, would be a serious limitation on the continuing necessity to deepen and broaden human understanding of the universe we all inhabit and which has been essential to maintaining most of our species, but certainly not all, in a more flourishing condition as decade succeeds decade.

I believe it is necessary to see how we have arrived at our present position and to examine the bases of the arguments used in the past which lie behind opposition to experimentation on man as well as animals in the present. Objec­tions can only be answered by putting logically argued cases, however violent and unthinking some of the opposition may seem. The changing relation of man to man within society and of man to animals will be of particular value in this analysis.

Interrelationships
The hierarchical principle
The consequences of repression
The growth of the experimental approach
The social background in which vivisection was practised
The growth of the anti-vivisectionist movement
The growth of natural knowledge of experimentation and its subsequent influence
Examination of the present position and the arguments used against vivisection

Interrelationships

The association of animals with man as domestic friends and guardians with the emotional inter­play that is involved is extreme, and of course lies at the bottom of the natural distaste and even violent hatred that most feel for the infliction of pain involving such domestic animals as cats and dogs, who respond to us in human terms. So I have to pose the question how can a scientist with such a relationship to his dog undertake experiments on other dogs which cause suffer­ing. Put another way, why could I hardly bring myself to kill a mouse in my home and yet I have done so frequently in a laboratory. Naturally this dichotomy involves a judgment about purpose­less killing or suffering and the purpose of killing or suffering in an experimental setting.

The hierarchical principle

Many important interrelationships are based on some sort of hierarchy. In the wild, strength is the major criterion, so that carnivores feed on herbivores, as the lion on the zebra, but as it is usually the lioness that does the hunting, the lion at least believes that the male is superior to the female. There is no question of the zebra or the lion having rights, and the zebra has to accept its fate, but the wiser zebra, presumably knowing all about Darwinism, grazes or drinks towards the middle of the herd. However, very strong herbivores, such as gorillas, are relatively immune from attack. Most animals eventually in nature are part of the food chain, since some animal is always killing and eating some other animal, just as man does, but the difference is that man, because of his intellectual stature, has the choice of being a carnivore or a herbivore and the decision is of the same nature as that relating to experimentation. The difference is the pleasure of taste or nutritional needs set against the need to kill to satisfy that need, and experiments to increase knowledge set against killing or pain and suffering. The susceptibilities of man are such that the fatted calf may be butchered out of sight so that the veal cutlet, which does not suggest the large eyed helpless beast, may be eaten without a thought except as to its succulence. There are other hierarchies and they are always changing within species, but man is the species in which they change most, as shown by slavery and the ill-treatment of the weak, and of course by the varying treatment of animals. Hence the aristocratic horse with aristo­cratic owners able to afford Stubbs or Munnings to paint them compared with the hacks sent off to Europe as food, or the lap dogs in a Gains­borough compared with those abandoned to their fate at the Battersea Dogs Home and put down.

The consequences of repression

There have been many attempts to repress human curiosity by death, torture or isolation, and fortunately they have usually eventually failed because man has an irrepressible nature. All repressive movements aim at the preserva­tion of dogma and I will give some relevant examples. Galen, who died in AD 200, described the circulation of the blood as a tidal system with ebb and flow between the heart and the individual organs that generated heat; and the solid barrier between the two ventricles of the heart was pierced by pores to allow communica­tion between the two sides of the heart. The function of the lungs was that of cooling. The influence of Galen on biological thinking was to last for another 1,400 years. In part this was due to repression by the invading hordes who ran­sacked Europe, and all that survived of scholar­ship was within religious foundations. Unfortun­ately religious scholars are known, among their virtues, for two other characteristics; the first adherence to dogma, and the second violent repression. This showed itself in such ways as opposition to human dissection and even Leonardo da Vinci was guilty of placing animal structures within human anatomy. As accurate anatomy is the necessary prelude to questions about function, the importance of dissection of human cadavers had to be emphasised, and the days when Vesalius (1514-1564) lectured to Harvey in Padua in that renowned anatomy theatre, which led directly to the river for quick disposal before the arrival of the police, should serve as a reminder that the Renaissance was not uniform and that the connection with Burke and Hare in the 19th Century arose directly out of a suppression of gain of natural knowledge and ultimately society had to respond in a positive way so that knowledge of human anatomy could progress legally to the benefit of all. The British Anatomy Act was only passed in 1832.

Knowledge of the circulation of the blood underwent similar vicissitudes, starting with Serverus (born 1511) who wrote a description of the pulmonary circulation clearly based on direct observation in Restituto Christianismi (1553), which together with other heresies led Calvin to have him burned at the stake, together with his book But direct observation prevailed, led by Vesalius (born 1514), Colombo (born 1560), Fabricius (born 1537) and Caesalpinus (born 1519), who established the direction of blood flow in veins towards the heart, and clearly they must have observed by vivisection in animals the direction of flow which raised the initial doubts about the Galenic interpretation. Then came Harvey to synthesise and consolidate knowledge of the circulation related in de Motu Cordis, pub­lished in 1628, and the culmination of years of anatomical observation, vivisection and experi­ments in man. It took some time before the difference in colour of arterial and venous blood was explained and it remained as a point of attack for the Galenical unbelievers. It was left to Hooke in 1667 and Lower and Mayow in 1668 to establish the respiratory role of the lungs by direct experimentation in animals. This part of the air used up in respiration or in burning was of course shown over one hundred years later in 1777 by Lavoisier to be oxygen. He suffered another type of repression on the guillotine at the age of 51 on the 9th May 1794. The necessity of vivisection to counteract dogma has therefore been well shown by that long struggle to over­come the theories of Galen where accurate observation without prejudice could even finally remove those pores in the intraventricular septum of the heart which did not exist, the king's new suit syndrome. The last twitches of the dying beliefs were maintained by Riolan but Harvey died on the 3rd June 1657 with general acceptance of his description of the organisation of the circulation.

The modern somewhat diluted equivalent of the repressive instincts of man is shown in a more subtle fashion, which to me is equally mis­guided, and is contained within the statement that 'We now have enough knowledge and one of our main problems is to apply what we know effectively'. This is related also to the belief that only knowledge with an obvious immediate target or measurable practical outcome merits support. If it were not for the ability of man to get round these repressive themes, we would have to feel even more depressed than many do at the present time, but remember that the famous Nixon initiative on curing cancer led to a large injection of money which, unbeknown to the administrators, was fed into cell biology, and we may be seeing a similar emergence of good out of evil with the money that is being poured into AIDS research.

The growth of the experimental approach

On the whole the enormous increase in bio­logical knowledge is a product of the last 300 years and it is important to now consider its relation to the varying views of society on this development. Many would now look with horror at Stephen Hales, a curate at Teddington, tying a white mare to a farm gate and inserting a cannula into the carotid artery without anaes­thesia (Haemastaticks, 1733). Naturally not many people would have observed this happening and even if they did, it probably would not matter to most of them against a background where beasts of burden were badly treated and animals, other than those at the top of their hierarchy, regarded as having few feelings and perhaps existing for human needs only. It would hardly occur to anyone to question the propriety of eating animals, hunting them, killing them, and by using them in various ways for human enjoyment as in bear-baiting, cockfighting, coursing and dog-fighting. Behind this lay the customs of thousands of years, not only linked to survival of the human species, but allied to prevailing religious beliefs that man was created separately and that other animals were intended for his use, without let or hindrance or regard for their feelings. The views of Descartes, expressed in Discours de la Mèthode, 1637, still held sway since they con­veniently fed religious belief. He argued that man was separated from beast by the possession of a soul and reason, and that beasts were there­fore like machines and were unable to feel pain or suffering. While few but scholars in England would be aware of his view, it allowed religious scholars to condone obvious cruelty and these beliefs still lingered on into the 19th Century and must have caused some internal conflicts when the battle between Creationism and Darwinism was joined. Paradoxically in the 19th Century it led to physiologists behaving in relation to animals as if they were Creationists, and some religious leaders, though they would have vehemently denied it, partially embracing Darwinism with the notable exception of the Catholic Church. Soon after the experiments of Stephen Hales, Jeremy Bentham was born (1748), and in his persuasive 'Introduction to the Princi­ples of Morals and Legislation' (1789), expressed the point of view which has carried through to the present with increasing force. He considered that animals form a party with man and an inter­est in the absence of pain and deserving of con­siderate treatment. He regarded human interests as higher than animal interests, therefore he held that they might be killed for food or to prevent damage, but not for torment. He prophesied that the day might come when the rest of animal creation might acquire those rights which never would have been withholden from them but by the hand of tyranny. He could see no real differ­ence between man and animal and drew analogies with the state of slaves. He left to us his belief that the most compelling question which we should now address is not “Can they reason?”, not “Can they talk?”, but “Can they suffer?”

The 18th and 19th Century saw the biggest growth of physiological knowledge based on vivi­section where the effects of cutting out organs and observing the subsequent effects in animals established them as the source of what were subsequently called hormones, and cutting various nerves led to the identification of sensory and motor pathways, as well as the discovery of the vegetative nervous system. This was mirrored by the rise of physician/pathologist in man trying to relate pathological changes in organs with disease observed in life. The lack of communication or the lack of a belief that the findings in man were in any way related to those in animals, and that the latter could be of value in the study of man, was very slow to develop. For example, Richard Bright (born 1789), who was responsible for relating renal disease to enlargement of the heart due to increased work produced, as he inferred, by narrowing of the blood vessels, did not consider blood pressure despite the experiments of Hales of one hundred years before, and it was not until the end of the 19th Century that the concept of raised blood pressure received attention. Again, although de Bordeu was the first to suggest in 1742 that sub­stances were discharged into the blood stream from most organs with distant effects, and in 1775 even suggested that secondary sexual characteristics were due to 'humors' from testicle or ovary, it was not until 1849 that Berthold showed that transplantation of the testis prevented atrophy of the cock's comb and restored its crow. The observation of Addison (1855) in patients with atrophy of the adrenals led that extraordinary accoucheur-physiologist, French/ Mauritian Brown Sequard, to extirpate the adrenal glands in animals (1856) and to prove that they were essential to life. Consider how slowly we came to understand the control and the content of the adrenal cortex compared with the medulla; from Addison (1855) to the Taits (1953) and aldosterone.

France and Germany were the leaders in the growth of physiology and there was the unusual sight of a school of veterinary medicine in France leading the way by vivisection on horses. How­ever, this was because the horse as a military weapon was highly regarded and vivisection on animals that had outlived their value to the army might ultimately be of benefit to the purpose of the army. Claude Bernard ascended the scientific tree outside the medical establishment through the College de France and by his vivisectional experiments eventually had enormous influence on its practise worldwide due to discoveries in many areas. He owed much to his master Magendie, who by his direct animal experiments disproved the sterile arguments about vitalism and soul put forward by physicians and surgeons appointed to Chairs of Physiology and Anatomy with the seeming purpose of holding back the advance of knowledge.

It was not until the end of the 19th Century that experimental physiological research started to expand in Britain and some of the first fruits were shown when Oliver, a physician at the medicinal watering place in Bath, brought an extract of adrenals and persuaded Sharpey-Schafer at University College to inject it into an anaesthetised dog, and much to the astonish­ment of Schafer, a very great rise of pressure occurred, and this led with remarkable speed to the isolation of adrenaline, its crystallisation and subsequent synthesis. It was the first hormone to be synthesised and the term 'hormone' was coined in the laboratory of Bayliss and Starling by W. B. Hardy (1902) and was related to their experiments on pancreatic secretions, when they demonstrated the release of such a substance, 'secretin', following a meal.

The social background in which vivisection was practised

In continually emphasising the relationship between animal experimentation and the general circumstances in society, it is now essen­tial to examine matters more closely to see why experiments, which we now would not easily tolerate, seemed to pass without much comment  or generalised opposition. In Europe in the 17th, 18th and 19th Century life for many was what might be called brutish, and the word itself tells us that animals were expected to have a very hard time in general, as were many humans. The absence of effective anaesthesia other than alcohol and some opiate until the mid and late 19th Century meant that pain was the common experience of most, together with early death. For many, grinding poverty accompanied by the possibility of hanging, deportation, exploitation of the young as child labour in the mines or up chimneys, with perhaps relief by the occasional excitement of a public execution. This indicates that it was on the whole an uncaring society, where the thought that animals might have some claim on sympathy was given to only a few. After all, the roads bore gibbets, and even the Prime Minister, Lord North, was robbed by highway­men in Gunnersbury Lane after his coach was shot at in 1774. Children expected to be beaten and criminals were publicly whipped, pilloried and hung, sailors were lashed at any sign of insubordination. Life was cheap and up until 1789, women were occasionally burned alive at the stake for murdering their husbands (petty treason!), and in the same year a woman was burned at Tyburn for counterfeit coining, which was of course a major attack on the capitalism confined to the ruling classes. In Sandwich a seven year old girl was hanged for stealing a petticoat. The penal code was extremely severe and in 1800 there were 200 capital offences possible, so you might be hanged for pick­pocketing and shop-lifting, poaching and sheep stealing, and forgery. In the mid 18th Century only 72 out of 768 of those hanged were murderers. Where slaves were still sold in the mid 18th Century, the fate of other chattels such  as animals could not be of importance unless they served the higher purposes of the rulers as in hunting, or the lower purposes of others as in dog or cockfighting. In 1827 poaching accounted for one out of seven of all criminal convictions in England. The prisons housed people who were in the last stages of degradation, so animals were often better off, even though they sometimes shared the accommodation. Pigs, however, were barred from Newgate Prison after 1714. It is ironical that Stephen Hales designed the venti­lation for various hospitals, gaols and ships in the 1740's, not long after his experiment on blood pressure (1733). The human condition through­out the 19th Century showed gradual improve­ment, but there were still extremes of destitu­tion; the feared workhouse where being ‘on the parish’ led to occasional terrible acts of cruelty, since parishes wanted to move even heavily pregnant women on to the next parish to avoid giving them and their child a constitutional right to relief. This eventually led to the emergence of reformers and legislation to protect the weak.

The growth of the anti-vivisectionist movement

The growth of feeling of dedicated men, including scientists, that experiments on animals were not to be regarded in the Cartesian sense where animals were insentient machines, began in the 17th and 18th Century with doubts about Boyle's air pump machine and Hooke's  experiments on respiration, so movingly illustrated by Joseph Wright of Derby, and forcefully expressed by John Evelyn (1620-1706). Significantly he allied beaten his criticism to that of cruel blood sports, Naturally the literary and artistic world would be aesthetically affected and their traditional cynicism with respect to medical doctors could also embrace scientists, but they were particularly quick to see the false claims and poses of the medical profession, and they have always served an important iconoclastic role. Addison (1672-1719) in The Spectator, and Pope (1688-1744), a near neighbour and acquaintance of Stephen Hales, expressed current thought quite clearly when he asked, 'How do we know that we have a right to kill creatures that we are so little above as dogs, for our curiosity, or even for some use to us?' Voltaire (1694-1778) was both observant and satirical especially about medical doctors and his tradition has been well maintained by George Bernard Shaw. Samuel Johnson (1709-1784) was as usual a savage critic, citing the possible development of insensitivity in young doctors, and further claiming that the experimental method was useless as a guide to cure of human maladies. This was criticism made well in advance of the necessary knowledge of physiological function. It was of course Jeremy Bentham (1748-1832) who posed the important questions still with us today by concentrating on the rights of animals. Therefore, since the major rise of experimental physiology occurred in the19th Century, it is perhaps surprising that this century also saw the real burgeoning of antivivisection movements. What is particularly fascinating is the different ethical and moral compulsions which drove the different groups, and equally the responses of the physiologists, ranging from the extremely defensive to the frankly arrogant. There is little doubt that anti-vivisection is a movement in which the English led the way and considerably influenced the rest of Europe and Scandinavia, and much more slowly the United States of America. There was a real target for the English invasion of Europe by proselytising anti-vivisectionists, since the main thrust of physiology based on vivisection was in France and Germany, and only later did England seriously compete.

It was in 1863 that the first organised anti-vivisection demonstration occurred in Florence, led by the tough English gentlewoman, Frances Power Cobbe, strongly supported by other refined and tough English women who subsequently established anti-vivisectionist societies such as the Victoria Street Society (1875). They gathered unto themselves men of like mind but it is striking that change in Germany, France, Italy and Scandinavia moved only slowly compared with the English movement based upon the aristocracy, even Royalty, who were often in the somewhat hypocritical position of using and attacking animals in what were euphemistically called sporting pursuits. Naturally there were all sorts of cross-currents within anti-vivisection movements, ranging from Francophobia, anti-Semitism, the rights of women and feminism, wrapped up with the suffragette movement and particularly with such legislation in Britain as the Contagious Diseases Acts (1864-1869), regarded as a typical male attack on women, and as the public debate grew, the arguments became more heated, more irrational and, like an Irish fight, many seemed to join in for pure enjoyment. It is not very different today, so that the alliance of belief in alternative medicine, hydrotherapy, homoeopathy, with a lack of belief in orthodox medicine, and hatred of vivisection, come together. The 19th Century also revealed the ambivalence in some scientists due to the pain and suffering inflicted on animals, and is perhaps best shown by Darwin, who at different times expressed first horror at the thought of vivi­section, and then his later reflection, 'I have long thought physiology one of the greatest of sciences, due sooner, or more probably later, greatly to benefit mankind, but judging from all other sciences, the benefits will accrue only indirectly in the search for abstract truth. It is certain that physiology can progress only by experiments on living animals. Therefore the proposal to limit research to points at which we can now see the bearing in regard to health, etc, I look at as puerile.' (Francis Darwin, Ed., The Life and Letters of Charles Darwin. Murray, London, 1888, vol. 3, pp 200-202). An important move­ment began to emphasise the importance of science in medicine and is epitomised by the addresses on medical education given in my own Medical School in 1868 by Owen, Huxley, the Archbishop of York, Dr Alderton, and the Rt. Hon. Robert Lowe. They all stressed this need, but against were the forces of the old establish­ment, the aristocracy, the law, the Church, and especially the strong minded ladies, such as Cobbe. Violent statements by one side such as that by Cobbe, suggesting that Jack the Ripper might be a physiologist delirious with cruelty, were matched by the arrogance of the other, typified perhaps by Virchow, the German patho­logist, who spoke as if he and his supporters regarded animals as  purely objects for the use of man without a second thought. Before the intro­duction of the Animal Bill in 1876, there had been a public outcry over the Handbook for the Physiological Laboratory, published in 1873 under the names of Sanderson, Klein, Foster and Lauder Brunton, based on the perceived in­humanity, due to lack of mention of anaesthesia and the description of experiments in restraining devices, together with a description of the resul­tant animal behaviour, all seeming to betray a serious lack of sensitivity to public opinion. Politi­cians and other influential formers of opinion alike must have been considerably influenced by these considerations, since the bulk of the popu­lation probably would not have strong thought on animals in general. However, it is an impor­tant feature of our society, then as now, that important ethical and moral movements begin with small groupings of people.

As an interesting illustration of public concern, the bulldog owned by August Desire Waller, the first full-time paid lecturer in Physiology at St Mary's Hospital Medical School, was the subject of questions in Parliament since it was believed that cruelty was inflicted. The dog actually stood with its paws in warm saline connected to the electrometer by which Waller first recorded cardiac electrical activity indirectly — the basis of the modern electrocardiograph. Waller possibly first became interested in the subject of 'animal electricity' through John Burdon Sanderson, joint editor of the infamous Handbook and formerly MO for Health in Paddington and First Waynflete Professor of Physiology at Oxford.

But the public debate had aroused feelings which penetrated to the Government and so it was in 1876 that legislation was introduced in the first Animal Bill, which defined the limits for vivi­section, and for the first time society, through Parliament, could express a view, and scientists became directly answerable to public opinion. However, some of their insensitive, over-stated cases reached their most important public demonstration in the very large Medical Congress in London in 1881, which attracted Pasteur, Virchow, Koch, Owen, Huxley and Stephen Paget, where the familiar arguments about the utility to man and animals of vivi­section in relation to cure of disease were advanced. The furore over the recent Act of 1986 followed a similar course and the degree of responsibility to Government and its agents has been increased and representation by society at large also increased by the composition of the assessment committees.

Now one hundred years later on from Frances Cobbe the anti-vivisectionist movement has been given a somewhat different emphasis, principally by two authors; Singer, writing on Animal Liberation, and Ryder on Victims of Science. From this time on the issues ceased to be based purely on whether man has a right to inflict pain or suffering on animals to increase knowledge, a characteristic of the battles of the last Century, but on much broader issues, such as speciesism, where animals have rights and therefore claims on man, with the further belief that the experi­mental approach is unnecessary and in any case so unethical as to be completely unjustified. At the extremes of these views are those of the Animal Liberation Front, which would see a dissociation of animals from man with breaking of those bonds of animals as food, beasts of burden, domestic pets, and naturally objects of experimentation. As so often, important disputes may attract violent people, in this case using the argument that the violence that scientists inflict on animals should be repaid in like manner.

The growth of natural knowledge of experimentation and its subsequent influence

Since I am making the case that increase of knowledge is of ultimate benefit to man and to life in general, I think it is necessary to look at the pattern of discovery as well as the timescale over which it proves effective. It is relatively easy to point to some research at the present time, which may seem to a casual or prejudiced observer to be irrelevant to human or animal needs, but great care has to be taken before such a view is accepted. I can illustrate this best by reference to some examples and would stress that they are but few out of many.

Circulation If we start only with Stephen Hales in 1733, whose major contribution, both in animal and plant physiology, was to introduce quantity into his observations, as shown so clearly in Haemastaticks and Vegetable Staticks, we can see that the blood pressure measurement was not taken account of even by such a keen observer as Richard Bright in 1824. He noted in patients with diseased kidneys that the left ventricle of the heart was enlarged and he attri­buted this to either unwonted activity due to altered quality of the blood or increased resis­tance in the small vessels.

Strangely it did not occur to him, and one can only suppose he was unaware of the earlier observations of Hales, that the blood pressure itself might be elevated, and it was not until the late years of the 19th Century that the con­cept of a raised blood pressure was considered as of importance and the development of indirect measures of pressure in man by Riva Rocci, Korotow, and others allowed its demonstration to be undertaken. It was in 1898 that Tigerstedt and Bergmanshowed in the rabbit by direct injections of kidney extract that there was a pressor material present which they called renin. No one took any notice, probably due to lack of communication of observations by physiologists published in a journal that would have no impact on those making measurements in man. It was not until 1934, when Goldblatt, who, as a histo-pathologist, was impressed by the narrowings of the small intrarenal arteries seen under the microscope in human pathological specimens taken from patients with high blood pressure, that the next advance came. He applied a clip to the renal artery in animals and produced a rise of blood pressure. This led directly to the re­discovery of renin and further analysis of its action by a combination of animal experiments, biochemical techniques to isolate the substances involved in the pathway, renin as an enzyme acting on its substrate in the plasma to produce a decapeptide shown to be converted to an octapeptide by an enzyme which could be extracted from vessel walls, and therefore all the components in the system had been identified. This knowledge, which has played a considerable part not only in gaining understanding of possible mechanisms in human high blood pressure, which is an extremely common condi­tion causing much mortality and morbidity, but further led to greater knowledge of control of the adrenal secretion of aldosterone twenty years after the observations of Goldblatt. Precise know­ledge of the components of these systems of interrelated physiological pathways led to the ability of chemists to synthesise molecules which block the action of the enzyme which converts the biologically inactive decapeptide, angio­tensin, to the active octapeptide, and this has proved of considerable value, not just in under­standing the physiological mechanisms, but in the treatment of high blood pressure and of cardiac failure in patients with and without a raised blood pressure, and this is but a small part of the whole story.

Interferon When Alick Isaacs first described this effect in the early 1950's. I was also working in the National Institute for Medical Research at Mill Hill, and while he initially believed that this would be a key to the control of viral diseases from his initial animal experiments, there was a very long period before anyone took the effects very seriously. The monumental discovery of Watson and Crick eventually led to a growing interest and understanding of viral diseases and the way in which they affect cells. The explosive growth of cell biology and of biochemical separa­tion techniques led to characterisation of a family of substances under the heading of Interferon, and their study has led not just to knowledge of precise actions, especially on the different classes of lymphocytes, but the initial discovery in experimental animals that they could affect tumour growth. They are now used in the effective treatment of some patients with leukaemia and unusual forms of tumour, such as Kaposi's sarcoma, which is particularly common in patients suffering from the AIDS syndrome. The study of Interferon can be allied to a wider interest in general to the release of substances by cells which might even be called local hormones; this covers a wide variety of cell growth sub­stances, many of which- were only identified as effects in experiments on animals, but which led to strenuous efforts to produce more definable substances. The lymphokines, tumour necrosis factor, nerve growth factor and various angiogenetic factors arose from observations in animals which can obviously be of great rele­vance in understanding both human physiology, starting with life itself when the fertilised ovum is implanted in the uterine wall followed by the growth of blood vessels into the placenta, or to the way in which tumours, both in animals and man, cause the growth of blood vessels on which they depend for their nourishment.

Cell fusion When cells were caused to fuse together to see if the characteristics of one could be incorporated in the other, it could not be seen that this seemingly simple experiment would lead to one of the most important contributions to immunology, and from experiments in animals, with leaps of the imagination, has led to enormous advances in knowledge of human genetics by isolation of genes and their products. Understanding of diseases patterns and their inheritance has followed. The production of monoclonal antibodies with far reaching uses as well as the production of pure substances on a large scale which otherwise could not be attempted are other obvious benefits not just confined to physiology, biochemistry and thera­peutics.

Receptors A large area of pharmacology has depended upon the concept that important sub­stances, such as hormones and drugs, attach to specialised areas on cell surfaces called receptors. This concept is quite old and is due to Langley in Cambridge (1907), who proclaimed his belief in a receptive substance on the membrane of muscles which would be responsive to chemical stimulation. It is perhaps not surprising that in 1904 Elliott, working in his laboratory, had enunciated the concept of chemical transmission of nervous impulses, since he believed the sympathetic nervous system released adrenaline at the nerve endings.  There was little general belief in this until Loewi (1922), in his experi­ments on the isolated animal heart, showed the release of 'acceleranstoff’ and ‘vagustoff’, later to be identified as noradrenaline and acetyl­choline. Elliott's initial discovery depended upon Schafer and Oliver (1894) but it was not until 1946, again from animal experiments, that the substance liberated at sympathetic nerve endings was shown to be noradrenaline, thanks in the main to the work of von Euler. Put together with much other work, the idea of receptors of differ­ent types now came of age and Ahlquist (1948) first categorised, by careful pharmacological studies in animals, the different type of sympa­thetic receptors as alpha and beta, with different biological  results of stimulation, and of course enabled James Black to successfully produce sub­stances that selectively block the beta receptor which not only led to a better understanding of physiology, but to a therapeutic advance in the treatment of heart disease and high blood pressure.

When Kosterlitz examined the effect of morphine on receptors in the isolated gut of animals, I doubt if it was his original thought to wonder if there were natural morphine like sub­stances attaching to the same receptors, but when he later studied morphine receptors in brain the thought did occur and the outcome was the discovery of enkephalines in brain extracts and the start of a completely new chapter in autopharmacology with discovery of whole groups of new substances - some in search of a function!

I think it is impossible to look at these sequences showing alternation between study of animals and of man, with sometimes observa­tions on one species being followed by confirma­tion in others, without feeling that the search for knowledge has had very far reaching  benefits, not just in knowledge of human physiology but of application to all species.

Examination of the present position and the arguments used against vivisection

There is a line in the argument which runs through from Jeremy Bentham, the most vocal of critics, to Singer and Ryder in the present, whose views can perhaps be summarised as follows:

1. Man has no right to inflict suffering on other animals and the ends can never justify the means.

2. Man has no right to distinguish himself from other species, and if he does so by exploita­tion, he is then guilty of 'specieism'.

3. Animals have rights expressed as a special claim on man.

I must now address these arguments. I believe that 'rights' is a completely false concept since I cannot accept that any living being has any rights, but that man is in the special position of having obligations of varying degree, both to his own species and to others. Other species have no obligations and what they do to each other and to other species, including man, is not governed by any other force than by their nature and circumstances. This seems so obvious to me that it hardly requires stating, but the question of obligations may next be examined.

Man is so obviously superior in intellect, and the ability to have conscience and therefore ethical and moral dilemmas, that to deny that he is vastly different seems to me quite ridiculous. Man is different by magnitudes from other species and despite superficial anatomical like­nesses and emotional responses, has to be distin­guished by those characteristics of reason and conscience leading to those moral and ethical considerations. For this reason I think Bentham was wrong and the question was not 'Can they suffer?', since they obviously can, but 'Should man ever make them suffer in the cause of increased knowledge?' Is that his real present obligation? The same considerations in lesser degree apply precisely to man conducting experi­ments on his fellows. One of the possible answers to this dilemma is that it is morally wrong to inflict pain and suffering without a reason that, is generally acceptable to 'society'. There is never any absolute point or principle which governs this balance lying behind the word acceptable. No one would accept now Stephen Hales' experi­ments but 'society' did then for reasons which I think are quite understandable. What 'society' will now accept is quite different and the reason advanced by those conducting experiments today will not be acceptable in ten or twenty years time. Therefore at present we must examine what type of experiment is acceptable to 'society' and how does the wide range of man­kind encompassed in that word gain understand­ing of the proposed experiments. At present kill­ing animals for food, while lavishing affection on pets, and even in some societies the same species, can exist side by side, since 'society' decides the benefit to themselves outweighs any moral con­sideration put forward by others and is not at present prepared to be vegetarian or to prohibit types of animal husbandry, battery farming, fox or stag hunting, described quite vocally by others as despicable cruelty. Man can exist in different compartments and make decisions which seem incompatible but are based on benefit or pleasure on the one hand, dislike of cruelty and infliction of pain without justifiable cause on the other, and finally and the most difficult, the inflic­tion of pain or suffering with presumed benefit by increase of knowledge.

I have tried to convey my own view that examination of the historical progress of human knowledge reinforces belief in the experimental approach, including that on man himself. I believe it is a fundamental need of man to explore all aspects of nature and that pain and suffering will always have to be justified to society as a whole and to be legislated for, since I have no confidence that experimental man left purely to his own devices will always and uniformly behave decently, even though I do believe that most do so behave. The recent debate in Parliament over research on human embryos and the legislation needed exemplified how necessary is continued public dialogue, as well as the need to face facts which are unplea­sant and yet need an answer that is not merely like that of the early anti-vivisectionists, nor of some of the present violent anti-vivisectionists. The consequences of the  repression of man's obligation to discovery in the face of all the historical evidence that repression has allowed for the supremacy of dogma, lead me to the inevitable conclusion that the acquisition of further knowledge, is worth the imposition of pain and suffering, since there is no such thing as absolute truth and the experimental approach is always testing today's concepts as well as yester­day's.

We live in a permanently hostile environment and our survival as a species depends on our ability to respond to each fresh challenge as by viruses, bacteria, parasites and insects. Our success as a species is because our superior intelli­gence is allied to rapid adaptation, but other species rapidly adapt to changing circumstances and they are not interested in our survival except indirectly as a host or as part of their food chain. Unless we continually expand our knowledge of biological phenomena we will suffer seriously as a species and therefore I willingly accept the charge of 'specieism' and believe we must main­tain our position at the top of the hierarchy against considerable natural opposition. Our obligations are to all living beings especially to those with the largest emotional demands of us and there is a price to be paid not only for greater understanding of nature, but, without exaggeration, for the future existence of all species.

This view has important consequences. There is need for continual public debate, communica­tion and interactive forums at all ages, and those intent on increasing human knowledge by experimentation must communicate and argue their case without dissembling or softening the edges of their arguments (eg, by sacrificing animals instead of killing them), and always by justifying any pain or suffering in a way which everyone can understand. Naturally at a time when science in general can be equated with the risks of a Chernobyl disaster, and with the supposedly unthinking release of radio-active chemicals from power stations, or the use of harmful chemicals as fertiliser for cereal crops: and biological science with experiments on human embryos, explanations have to be made very clearly and continually. If animals are to be shown on television programmes with electrodes sucking out of their skull, particularly if they are primates and therefore identified more readily with man himself, then the experimenter must not only just describe the experiments he is carrying out, but at all stages must show a sensitivity for the feelings of his audience and a justification for the type of experiment that satisfies not just his conscience and that of his peers but that also of others less well informed. I hope that this will be an ever expanding exercise in human relationships. Scientists must welcome critics and not just dismiss their arguments, since they are helping to shape society's views, and the way in which knowledge is to be gained, just as much as are the scientists.

I started by asking how it was that I could kill a mouse in the laboratory and yet would not readily do so in other circumstances. I hope I may have made clear my particular reasons and hope that most of those who deny my right to make these decisions will continue to attempt conversion by argument and not by violence.


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