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

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Animal research for understanding animal diseases

By professor G.H Wooldridge

For purposes of this address I propose to deal with that line of animal research directed to elucidating many of the problems of the causation, prevention and relief of various diseases in animals, many of which are also transmissible to humans.  

I hope to be able to show that enormous benefits are made available to animals by the methods of experimental research so that much pain and suffering are prevented or relieved. These results could never have been obtained without the help of experi­mental research. Such advantages are especially outstanding in the fields of preventive medicine with the development of sera and vaccines; with the advances in the use and safety of anaesthetics and analgesics, and pharmaceutical or therapeutic agents, and in the field of general and special nutrition.

It is unnecessary to devote much time to the question of anaesthetics, general and local, for the boon they confer is so obvious and so well recognised, and are incalculable. The vast majority of these agents were either discovered or perfected as the result of experimental research. Hundreds of thousands of essential and otherwise painful operations are annually performed on animals without the infliction of any pain or suffering whatever with the help of general and local anaesthetics (cocaine, procaine, etc.) and various barbiturates (nembutal, etc.). In my own personal clinical work such cases have mounted to hundreds, pos­sibly thousands, annually. The advances in this humanitarian phase of surgery in recent years have been tremendous, and all veterinary surgeons throughout this country as a routine measure resort to the use of anaesthetics on every possible occasion to prevent and relieve pain. The total benefits from this source alone can only be vaguely estimated.

By the methods then available, the administration of chloroform to dogs and cats was almost equivalent to signing their death warrant. Certainly we did resort to narcotics and analgesics such as opium and morphine, chloral hydrate and bromides, but it can readily be appreciated how inadequate such measures were. It was in these circumstances that Hobday carried out long series of experiments in producing anaesthesia in dogs and cats with inhalants such as chloroform and ether, either alone or combined, or with the addition of alcohol, and with or without preliminary narcotisation with morphine. Later I was privileged to assist very materially in the clinical application of these methods, which have gone on improving until the one time physical torture to the patient and mental anguish to the operator have both been practically abolished. The same may be said of the introduction and use of barbiturates, notably nembutal intra­venously administered, especially for small animals. To J. G. Wright, now of Liverpool University Veterinary School, belongs the credit for much patient work in this connection both for surgical purposes and for euthanasia. For the latter purpose it almost approaches perfection, and many suffering animals whose recovery is hopeless are given the benefit of euthanasia by nembutal. I consider this an almost ideal "passing over," so different from the old methods involving, to say the least of it, very considerable mental anguish to both the animal and its owner, and I would emphasise that it has only become available as the result of much patient experimental research.  

With regard to therapeutic agents a very great deal could be said. The recent progress in the introduction of new remedies is just colossal and it may be unnecessary to point out that such progress would have been quite impossible if the methods of experimental research had not been available.

It is only possible today to refer to a few of the many instances in which animals have benefited and are daily benefiting as a result of this great team-work and combined efforts of chemists, pharmacologists, bacteriologists, veterinary surgeons and others. I have already referred to the barbiturate group and the great advances they have effected in the direct relief of pain and suffering in animals and man.

The discovery of the sulphonamides and the perfection of their use have only been established by experimental research, and surely must be regarded as one of the discoveries of the age.  Their introduction has enabled us to give relief to, and to save the lives of, thousands of animals suffering from the pneumonias, strepto­coccal and other affections.   While many members of this group are being increasingly used in daily veterinary practice for the benefit of animals, the one most commonly used at this time is among the earliest discovered - sulphanilamide, which is very widely employed in the treatment of a form of contagious streptococcal mastitis in cows which is responsible for considerable injury to the mammary glands and a consequent great loss of milk for the community. It may surprise many of you to hear that it was conservatively estimated before the war that 25 per cent, of the total population of cows in milk in this country were affected with mastitis, i.e., about 800,000 affected cows which meant a loss of 48,000,000 gallons of milk a year. The use of sulphanilamide, particularly in the early stages of this disease, brings about favourable results in anything from 60 to 90 per cent, of cows in affected herds.   These favourable results cannot  be claimed as complete cures in such a high percentage, but they are definitely clinical cures in that no defect can be detected by ordinary clinical methods, and bacteriological methods are necessary to establish the fact that some degree of streptococcal infection still remains, and in some circumstances may give rise to a recurrence of clinical symptoms.   These results are of inestimable benefit to cattle and to the milk supply, but the fact that they stop short of complete cure serves to emphasise the necessity for the continued and painstaking experimental research which is being carried out at a number of veterinary research institutions.

It was inevitable, then, that the discovery of penicillin with its remark­able effect on various organisms brought to light an agent that seemed to give promise in the treatment of mastitis. It was investigated in America where penicillin was readily available. A report was issued last year (1946) by the Committee on Animal Health, National Research Council, U.S.A., on “The intramammary therapy of bovine mastitis." Agents used included Acriflayin, Silver Oxide, Tyrothricin and Gramicidin, Sulphanilamide and Penicillin. This last named produced a cure in the majority of cases of Streptococcus agalactiae infec­tions. Penicillin also shows greater promise against Staphylococcus aureus in the udder than any of the other therapeutic agents now in use. These various agents have been tested in this country and the American results largely confirmed, so that with the exception of sulphan­ilamide and penicillin other agents are falling into disuse, especially since penicillin has been made available for the treatment of bovine mastitis in this country. A group of workers who participated in trials for the Agricultural Research Council reported (Vet. Record (1946) 138) that a high percentage of Streptococcal agalactiae infections can be sterilised with a minimum amount of udder disturbance by injection of penicillin by the teat canal and that the injection of 20,000 units on two occasions at daily intervals is the method of choice. The results up to date are therefore most encouraging but much has yet to be done in the way of experimental research to discover and  to develop the best methods of its application.

The discoveries of therapeutic agents for the treatment of various affections have resulted from extensive experimental. It should be noted that the discovery of such remedies marks only the later stages of research into the particular disease and that essential earlier work was necessary to elucidate the aetiology and methods of spread of the disease.

The disease redwater in cattle used to take a tremendous toll of life in most tropical countries. It is due to parasites (Babesia bigeminum) which invade and destroy huge numbers of red corpuscles—up to 75 per cent of them in bad cases—and which are inoculated by ticks of several types. By the use of an agent (trypanblue) discovered by experiments on animals this loss and the attendant suffering sustained by the victims can now be reduced to almost insignificant numbers. In some countries the disease has been almost exterminated by repeated dipping as a means of tick control. A similar affection in dogs in tropical Africa and Asia due to Babesia canis carried off 80 per cent of all dogs in affected areas. It is now curable by a single injection of trypanblue. Redwater in cattle also occurs in the British Isles due to a somewhat similar blood parasite (Babesia divergens), also tick-borne. It causes a high mortality in some areas and often a prolonged illness. This can now be reduced to a “three-day” illness by the early use of acaprin (piroparv or pirevan).

While dealing with these intra-corpuscular parasitic blood affections, reference should be made to the most spectacular result of the campaign in the Union of South Africa against the East Coast Fever due to the tick-borne Theileria parva. This disease invades as many as 75 per cent of red blood corpuscles, however, unlike redwater they are not destroyed. The average time from the day of infection until death is about 30 days. It usually results in 95 to 100 per cent, mortality, and so presents one of the greatest problems in the cattle industry in South Africa. This will be appreciated from the fact that there are approximately 9,000,000 head of cattle in the East Coast Fever areas and potential East Coast Fever areas. As the result of experi­mental research preventive inoculation was practised in the earlier days of control with effective protection of 80 per cent. This, however, was not sufficient and the other line of approach in the way of tick control by repeated dipping was adopted. In this campaign approximately 6,000,000 cattle are subjected to regular dipping in 0.16 per cent, sodium arsenite solution once a week in summer and once in two to four weeks in winter. As you will realise, this is a tremendous task and a very expensive one, but is more than justified by the fact that the number of cases in 1944-45 was only 92 and in 1945-46 there were only two cases.

Rinderpest or cattle plague at one time threatened to exterminate the cattle in South Africa. The last really large-scale outbreak occurred in 1896-98. In very many instances whole herds were completely wiped out and over 2,000,000 cattle are said to have died. Methods of im­munisation, crude as they were in comparison with present methods, saved many thousands of cattle. But the great triumph as the result of intensive experimental research has been the perfection of immunisa­tion technique and the total eradication of cattle plague from the Union of South Africa. But the authorities must be ever watchful to prevent its re-introduction from territories to the north which might easily take place when one considers the extent of the frontiers across which infected cattle could stray or be driven. In Tanganyika territory the position is improving every year, but here and in Central Africa the position is seriously complicated by the fact that many species of game are sus­ceptible and the presence of cattle plague amongst these animals is a constant source of anxiety. The point is that if it were possible to apply vaccination to game, the game themselves would be saved and so would the spread of the disease to cattle by game.

The importance of the rinderpest problem is emphasised by the follow­ing extract of a report from a conference of veterinary experts held in Nairobi in February this year. It says: " Three times during the last half century rinderpest has swept southwards through East Africa, pass­ing from game to cattle, and from cattle to game with disastrous effects on both. The last large-scale outbreak occurred during the war and this was stopped at the southern border of Tanganyika by prompt and vigorous action in immunising very large numbers of cattle with the assistance of officers sent from South Africa and other territories lying to the south of the critical area." The report stresses the numerical inadequacy of the field staff of veterinary officers which should be aug­mented as soon as possible. It is officially stated that the capital repre­sented by cattle, sheep and goats in East Africa is not less than £30,000,000. The veterinary department of Kenya has supplied 8,000,000 doses of biological products in the year.

I would like here to emphasise the enormous amount of suffering which defies imagination and from which animals have been saved. Cattle plague is an extremely painful disease due to the nature of the local lesions occurring in this virus-produced affection. There are multiple ulcerative and necrotic lesions in various parts of the body and particu­larly in the alimentary tract resulting in severe and cramping abdominal pain, grunting, grinding of the teeth, arched back, the beast constantly looking round at its flanks in pain, and a blood-stained diarrhoea with severe straining often resulting in eversion of an inflamed rectal mucous membrane. Emaciation is rapid and weakness very pronounced, and death follows in susceptible stock in from four to eight days.

Anthrax affords another example of the benefits to animals of experi­mental research. Fortunately in this country anthrax is not very com­mon and there is no necessity to resort to vaccination to prevent it. In tropical and semi-tropical climates, however, the causal organism - Bacillus anthracis - is capable of living and multiplying outside the animal body. In this way the soil once infected may, and often does, become increasingly dangerous to animals grazing on it, with a mortality amongst infected animals approaching 100 per cent, after a comparatively short, but in many species of animals an excruciatingly painful, illness. As in the case of rinderpest no curative measures are of any avail, and preventive inoculation is the only possible method of control. South African authorities regard anthrax as affording one of the best examples of the potency of vaccines. This is emphasised by the fact that in the calendar year 1945 the Onderstepoort Laboratory issued over 6,000,000 doses of anthrax vaccine. A personal statement to me from an official source by one of my former students says: “A few years ago anthrax was very rife in Northern Zululand and the Transkei Territory, entirely native areas where there are about one and a half million cattle. Annual block inoculation was introduced with the result that it is very rare now to meet with a case of anthrax." But let us come a little nearer home!

A disease of young cattle known as blackleg or black-quarter is due to a soil organism (a Clostridium) normally present in the soil in many parts of the world and quite extensively in this country.   It is a most painful affection involving the skeletal muscles in any part of the body, but most commonly those of the hind quarter, with violent in­flammatory symptoms and gas formation. It is almost invariably fatal. It is heavily enzootic and in infected areas it is quite impossible to prevent exposure to infection since the young cattle must be permitted to graze. The only possible means of control is preventive inoculation. I have known farms where over 50 per cent, of the calves born died of blackleg before they were 18 months old. In one acute outbreak on a small farm 19 out of 20 calves died within a week and after a violently painful illness. Immunisation of calves is, however, amazingly effective and reduces the death-rate to less than 1 per cent, of animals vaccinated. From two laboratories alone over 50,000 doses of vaccine are issued each year—a small proportion of the total for this country alone. From one laboratory in South Africa last year's issue exceeded one and one-third million doses, and in India they must have been greater still. In fact many millions of calves are vaccinated annually  and saved from severe suffering. One year in India (1929-30) careful records were made and showed that amongst 127,981 animals inoculated against black-quarter the death-rate was 1/85th of that of the uninoculated in the same outbreaks, and since that date methods of immunisation have made very considerable improvement.

One can cite numerous instances in this country where, although the numbers are so very much smaller, the results of vaccination are equally spectacular. On one particular farm in my personal experience it had been very difficult to rear calves. Most of them died of black­leg before they were a year old owing to the heavy infection of the grazing pastures. The farmer was advised by his veterinary surgeon to adopt preventive inoculation. This was done and for several successive years there was a total absence of the disease. As he was losing no calves from this disease the farmer thought infection must have become eradi­cated from the farm and that continued vaccination was an unnecessary expenditure. Contrary to his veterinary advice he decided to discontinue it with the result that three-fourths of the calves born on the farm that year died of black-quarter.

Contagious abortion (brucellosis) in cows is all too rife in this country as elsewhere in the world. Unfortunately this is not a scheduled disease and cases are not reported so that it is not possible to give exact figures as to its occurrence. It is, however, estimated that not less than 10 per cent of all calves are prematurely born as the result of brucella infection. The majority are stillborn and most of the rest are weak and unthrifty and rarely attain maturity. As a result of commonly retained foetal membranes infected cows frequently develop a chronic catarrhal metritis with resulting sterility and there is a considerable reduction in the milk yield.   Indeed the Survey Committee of the National Veterinary Medical Association calculates that the annual loss of milk from this source is no less than 40,000,000 gallons involving a monetary loss of several million pounds a year. The loss from dead calves and ill-health of the  cows should be added to this to get some idea of the total loss involved. As the result of experimental research in animals it has been abundantly established that vaccination of young heifers does effectively prevent infection and is preferably carried out between the ages of four and eight months. One laboratory in this country issues about three-quarters of a million doses of vaccine annually in addition to very many thousands of doses by other laboratories, probably swelling the total to over 1,000,000 doses a year.

I imagine that some reference to tuberculosis as a disease of cattle may be expected, but the subject is so vast that I propose to make only a brief reference to it—the brevity serving perhaps to emphasise its great importance. It is estimated that no less than 30 per cent, of dairy cattle in this country are affected, but no official figures are available. After infection the progress of tuberculosis in animals is usually slow and insidious and often with no clinical symptoms until well advanced. The result of this is that an infected animal may be a source of danger to others long before any suspicion is aroused, there­fore methods of early diagnosis are imperative. By guinea-pig and cattle experiments tuberculin has been shown to be a satisfactory diagnostic agent, and with its aid there is good prospect that tuberculosis of cattle may ultimately be eradicated from this country and so reduce its incidence in man. Already many attested and tubercle-free herds are established. Several million doses of tuberculin are issued annually by the veterinary laboratory of the Ministry of Agriculture for diagnostic use in cattle, swine and poultry.

With regard to horses I will mention only two of the numerous instances in which that species has received enormous benefits as the result of experimental research, namely glanders and tetanus.

Glanders used to take a big toll of equine life in Great Britain, particu­larly amongst industrial horses of large towns. All clinically recognised cases were fatal. It was readily transmissible to human beings, especially stablemen, and veterinary surgeons have lost their lives as the result of glanders contracted from equine sources. Experimental research revealed the cause (Bacillus mallei) and the channels of spread of the disease. A method of early diagnosis was evolved by means of the Mallein test so that the presence of the disease could be revealed in the preclinical stage. By the application of this test together with intensive preventive measures and thorough disinfection glanders has been exterminated from Great Britain and there has been no confirmed case here for the last 20 years.

Tetanus was, and still is, a serious disease of animals, especially horses. It is largely enzootic and due to an organism (Cl. tetani) commonly found in the soil, especially in some localities. When a horse is infected recovery is extremely rare and it is fortunate that immunisation can now be carried out with almost absolute certainty. In some heavily infected areas it is now customary to actively immunise most of the horses as a routine measure and in the case of accidental wounds and even prior to the infliction of surgical wounds anti-tetanic serum is injected to provide a passive immunity to cover the period of healing and cicatrisation of the wounds. By this practical application of the results of experimental research a very considerable amount of pain and suffering amongst horses is thus prevented.

There are several devastating and painful diseases of sheep occurring in Great Britain which can now be controlled as the result of experimental research. One of the most outstanding is so-called “Lamb Dysentery." This is a highly contagious disease of young lambs characterised by in­flammation of small and large intestine and usually accompanied by ulceration. It is caused by a special type of Clostridium welchii generally referred to as the " lamb dysentery bacillus," which is present in the intestines and tissues of lambs affected with lamb dysentery, in the intestines of adult sheep grazing on pastures on which lamb dysentery  cases occur and in the soil of such pastures. Lambs become infected very soon after birth, usually within three to five days, and in the acute type lambs apparently well one evening may be found dead next morning. In less acute cases symptoms may persist from one to three days before proving fatal. There is evidence of severe abdominal pain as shown by persistent bleating of the lamb, and frequent attempts to micturate and defaecate. Pressure over the abdomen is painful. Recoveries are very rare and treatment of affected cases is useless. The total mortality on an affected farm may be as high as 50 per cent, or more of all lambs born there.

One can imagine the immensity of such problems; with newly-born, highly susceptible lambs exposed almost immediately after birth on pastures that cannot possibly be sterilised, developing an acutely painful condition for which no curative measures are available. In these circumstances the discovery by Dalling of an effective means of control by the use of serum or vaccine was really a godsend, and it was only arrived at as the result of much patient experimental research. There are two methods by which the disease can be almost completely controlled. One method is by the inoculation of the newly born lambs with hyper-immune serum. This is nearly 100 per cent, effective. In one series of experiments carried out by Dalling, the mortality amongst 456 inoculated lambs was 1.9 per cent, compared with 22.6 per cent, among 425 uninoculated lambs on the same farm. It is essential that the serum be injected as soon as possible after birth - within twelve to 24 hours. The other method consists of inoculating the breeding ewes by means of a formalinised culture of the lamb dysentery bacillus about ten days or a fortnight before the mating season begins and again about ten days before lambing begins in the flock. The ewes thus develop an active immunity which, however, is apparently not transmitted to the lamb in utero. In the actively immune ewe there is a high concentration of antibody in the colostrum and on sucking the lamb receives the anti­body which is absorbed from the intestine and a passive immunity is conferred. This is the method adopted on hill farms where it is not possible to handle lambs within twelve hours or so after birth, and on such farms losses from lamb dysentery have been reduced to a minimum by vaccination of ewes.

For the prevention of this and other sheep diseases such as braxy, strike or blackleg, etc., well over a million doses of serum and vaccine are employed every year in Great Britain with the prevention of an incalculable amount of suffering.

Sway back in lambs. This name, commonly used, is really descriptive of the chief symptoms of a nervous disorder of newborn and young lambs, the outstanding symptom of which is ataxia. It is characterised by progressive and sometimes massive destruction (demyelination) of cerebral white matter which results in severe and usually fatal paralysis. It occurs in various parts of Great Britain, and though in many districts it has a low incidence there are districts in which it is enzootic and occurs with disastrous periodicity.

The primary cause of swayback is unknown but it is definitely linked with a trace element deficiency since the administration of small amounts of copper to ewes throughout gestation prevents the disorder appearing in lambs. Yet it is not due to a copper deficiency per se as it may occur on farms where the copper content of the grass and soil is normal, and the copper reserves in the blood and liver of affected lambs and their mothers may not be altered. The disease appears identical with one occurring in Australia, India, S. America and Sweden. The symptoms are very characteristic but vary in degree of severity. All show ataxia, some appear paralysed at birth, some are unable to stand or walk and lie helpless and some show only a slight weakness of the hind quarters and a rocking or straddled gait. Many are blind. There is no fever and remissions do not occur. In the severe cases the mortality is 100 per cent, particularly of those showing marked symptoms at birth. The mildest cases may not be observed until some weeks after birth and may only show slight unsteadiness when walking. Some of these may survive and may be fattened later.

On post-mortem examination the viscera are normal unless intercurrent pneumonia has occurred. The cerebral white matter shows a diffuse gelatinous degeneration and in the severe cases there may be liquefaction and cavitation. There are no haemorrhages and the meninges appear normal. The proof of the trace element deficiency is furnished by the fact that swayback can be prevented from appearing in the progeny of sus­ceptible ewes by allowing the latter throughout the gestation period to have access to salt licks containing 1 per cent of copper. Copper licks should be used regularly in all areas where the disease appears to be enzootic.

In pigs in this country there are perhaps two outstanding diseases which should be referred to, namely, Swine Erysipelas and Swine Fever.

Swine erysipelas is very prevalent and until a few years ago was responsible for very great losses amongst pigs, estimated at about 20 per cent of those affected. Vaccination has reduced the incidence to much smaller numbers, and in any outbreak the early use of serum prevents its extension to other pigs exposed to infection and cures most of those in the early stages of the disease. By this means the death-rate in an outbreak may be reduced to less than 1 per cent. The amount of vaccine and serum now being used annually in this country is very large indeed. It is interesting to note that Stockman stated that in Hungary of four million observations the death-rate amongst inoculated animals was reduced to 1.6 per cent, (from 20 per cent or more).

In the case of swine fever extensive immunising experiments have been carried out with crystal-violet vaccine and this is stated by the Veterinary Laboratories of the Ministry of Agriculture to give nearly complete protection for twelve months. It is now being issued to veterinary surgeons by the Ministry and other laboratories for general use and will undoubtedly result in great benefits to the swine population.

The story of the benefits enjoyed by animals as the result of experi­mental research could be enormously extended, and indeed, it has only been possible for me to touch the fringe of the subject. But in order to make the circle more complete I suppose I should to refer to domesticated animals, and I do so very briefly.

In poultry, Fowl-pox (a highly contagious disease with high mortality) is well under control as the result of vaccination. The vaccine is pro­duced from pigeons and a quarter of a million doses are issued by the Ministry of Agriculture and Fisheries annually.

Bacillary White Diarrhoea (Pullorum disease) causes great losses in chicks and in poultry and egg production in widely dispersed areas in this country. It is now getting under control as the result of easier methods of early diagnosis by agglutination, and there are now about 3,000 accredited flocks of poultry in the country in which the disease is practically non-existent.

With regard to dogs and cats those of us who are engaged in clinical work have the best opportunity of assessing the great benefits received as the result of experimental research, and the consensus of opinion is that its value exceeds all imagination. One or two examples must suffice.

The experimental work on nutrition by Mellanby and others has resulted in the reduction of the incidence of Rickets almost to vanishing point and when it does occur its cure is simple and easy. This applies equally well to all other species of domesticated animals. Mellanby's later work on the part played by treated flour in the cause of nervous affections offers great encouragement and emphasises the necessity for still further experimental research in these fields.

Distemper and Rabies are probably the greatest scourges affecting the canine race. We are fortunate in that of those two diseases we have only distemper in this country. I estimate that not less than 50 per cent of dogs born in this country used to die of distemper and many of the survivors suffered from troublesome sequels throughout their lives. With the advent of distemper prophylaxis the incidence is enormously reduced and in my wide experience I assert that the Laidlaw & Dunkin method of immunisation is effective in over 90 per cent of dogs vaccinated. Perhaps just at the present time this should be somewhat modified as there have recently been a considerable number of cases where it has failed. It would seem to me that the probable cause of this unfortunate occurrence is the introduction of a new strain of virus against which the antibodies of the Laidlaw-Dunkin virus are ineffective, i.e., that as in the case of foot-and-mouth disease, there are more than one strain of virus and that these strains have no cross-immunising antibodies. If that is so, the solution of the problem must be the introduction of a poly-valent vaccine and serum. Much more experimental research is necessary in the hope of solving this problem.

Rabies (hydrophobia) occurring in dogs and other animals and man is certainly one of the most terrible of all diseases. In many countries it is a constant menace. Affected dogs are uncontrollable. They run from home and are disposed to attack and infect any animals and human beings in their way. As the result of experimental research we know the cause and methods of transmission of this awful disease and we have been able to exterminate it from this country and prevent its re-introduction by means of rigid quarantine of all imported dogs. As dogs are the main source of infection, an incalculable benefit to animals and man has resulted from a systematic immunisa­tion of dogs in countries where rabies is rife. The effect is most successful and I will quote an extract from a personal com­munication received just before the war from the Commissioner of Inspection and Sanitation for Kansas City. He says: “For a number of years prior to 1927 this city was visited regularly with an epidemic of rabies in which a large number of animals died of the disease. Many persons were bitten and were compelled to take Pasteur treatment. The prevalence of rabies in this city in 1927 was high. Action was taken by the City Council and the compulsory law (vaccination of dogs) was enacted. As a result there has been a steady decline of rabies in so far that today we have scarcely any at all, and such cases occur in out­lying districts where the enforcement law has failed. We have vaccin­ated some 150,000 animals and find that less than five breaks have occurred in the vaccinated group. To any city desiring to control rabies and do an act of human kindness to animals the vaccination of all dogs is recommended. The experiences of this city disprove any claim of anyone that vaccination is harmful to the animal."

I fear I may have gone on far too long and quite exhausted the patience of my listeners. There is so much more that could be said, but I trust I have amply shown that practically all species, of domesticated animals at any rate, do reap and enjoy most remarkable benefits as the result of experimental research, and no veterinary surgeon could pos­sibly do his duty to the animal world unless he took full advantage of the remarkable discoveries by various research workers, and particu­larly those of his colleagues in the veterinary research institutes.

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