Medical and veterinary research, with special reference to the tropics
By Sir LEONARD ROGERS, K.C.S.I., M.D., P.R.C.P., F.R.C.S., F.R.S., I.M.S.
That the sufferings of animals, as well as of man, have been immensely reduced through experiments on animals may safely be said to be the universal opinion of all the scientists who are best qualified to judge at the present day. What eminent mid-Victorians, still quoted for want of anything better by our opponents, said some half a century ago has, of course, no application to present day scientific knowledge.
As practically the whole physiological, pathological, bacteriological and therapeutic scientific basis of modern medicine is built up on knowledge largely acquired through experiments on animals, it would require a complete medical library to expound it. The saving of life and suffering due to physio¬logical and therapeutic experimental research have been exceeded in value in no field than tat of tropical diseases of man and of animals, of which I propose to give a brief account to-day as far as time permits.
This is one of the most terrible of deaths, owing to the rapidity with which healthy people are carried off, and all our most essential knowledge of the action, antidotes and treatment are due to animal experi¬ments. Nearly 50 years ago Sir Lauder Brunton showed the lethal action of cobra venom to be due to paralysis of respiration, and later Calmette in France made an anti-cobra serum which can neutralise the venom in the system, and save life if given in time, and sera for viperine venoms have since been made in India and elsewhere. It was also known that permanganate of potash mixed with the venom of any snake renders it inert, and Sir Lauder invented a small sheathed lancet with a compartment for permanganate, to be carried in the waistcoat pocket when out shooting, etc., for immediate use in the absence of serums, by incising the site of the bite, and destroying the venom locally before a fatal dose had been absorbed. It happened that the passage of the 1876 Act prevented Sir Lauder testing its practical value on animals, and it was consequently not until 1903, at his suggestion, that I demonstrated its value by a few experiments, as recorded in my evidence before the Royal Commission in 1907, with the result that within two years I was able to record 12 cases of persons proved to have been bitten by deadly snakes with no less than ten recoveries. Acton and Knowles later confirmed the value of permanganate locally in snake poisoning, but they prefer injecting solutions of the chemical when a syringe is available. Now no one will ever know how many persons were unnecessarily condemned to die of snake bite through the success of the opponents of animal experiments in postponing those few tests, to carry out which I had to get the recommendations of the Presidents of the Royal Society and the Royal College of Surgeons, so stringent are the conditions of the 1876 Act, under which alone an animal is allowed to recover from an anaesthetic after the smallest cutting operation.
And what was the suffering inflicted in those few experiments? The few cats which were permitted to come round from the chloroform were kept free in a room and visited from 7.30 a.m. to 10 p.m. Their small wounds were, of course, dressed antiseptically, the animals jumped up and down off boxes and shelves on their three sound limbs and showed no evidence of pain, and the only trouble I had was that several of them would come up to me at the same time to have their heads rubbed ! Yet, as the direct result of those few almost painless experiments, many human beings have been saved every year since, and will continue to be saved as long as civilisation lasts, from one of the most terrible of deaths.
Now, I am a cat lover and would not willingly have hurt one of them, but that I love my fellow beings more. Lister has well expressed the feelings of experimental scientists in his courageous letter refusing to comply with the request of Queen Victoria that he should publicly oppose experiments on animals. After stating that his own work for the good of his fellow men was due more to experiments on animals than to anything else, he added: " When they have been performed without chloroform, as has not infrequently been the case, they have been done at a very great sacrifice of my own feelings; but the greatness of the object in view has appeared to me to over-ride such considerations."
This, the most serious epidemic disease in India, carries off with great rapidity about a quarter of a million people a year, and during last century at least six pandemics spread to Europe and America ; a grave danger that experimental bacteriology has largely removed. This disease provides a good example of the way in which experimental research has furnished the scientific basis for the successful control of an epidemic disease, which in pre-bacteriological days was held by high authorities to be air-borne, and so uncontrollable. Unfortunately, owing to lack of good water supply and conservancy for the million Indian villages, we are largely dependent on preventive inoculation and treatment for the control of the deadly cholera.
Improved Treatment of Cholera.—An analysis of data from hospitals reveals how the case mortality in Calcutta hospital patients has been reduced from 59 per cent, in 1895-1905 to only 20-8 per cent, in 1,429 cases in 1915-19, or about one-third of the former rate, by the use of intravenous injections of hypertonic and alkaline salines and permanganate pills, orally, as the result of 14 years' patient investigations, mainly on the blood changes in the disease. The saline injections are based on physiological methods, and so are indirectly due to early physiological experiments. The clue to the use of permanganates was furnished by the snake venom work already dealt with, for chemically bacterial toxins and snake venoms are closely allied, and I was able to show by a few simple experiments on pigeons that small quantities of permanganate will neutralise the toxins of the cholera bacillus, and clinical trials of perman¬ganate pills orally proved capable of reducing the mortality in the villages to a considerable extent, under conditions not allowing of the intravenous saline method.
Prevention is, however, better than cure and a table of data shows examples of the use of anti-cholera inoculation in a total of over half a million people, with a reduction in the mortality among the inoculated, as compared with that in the uninoculated in the same outbreaks of cholera, of from 92 to 99 per cent, in six of the seven trials of the double injection. During an outbreak recorded by Dr. Bentley in Xorth Bengal, in a large village, with about equal numbers of Hindus and Mahomedans, at first only the Hindus would be inoculated, and in a few days cholera only continued to occur among the uninoculated Mahomedans, whose males only were then inoculated, and very shortly only the uninoculated Mahomedan females were attacked, until they too received the protective doses, when the plague ceased.
A single dose of the present improved vaccines afford very valuable protection, and two million doses were used in Bengal alone in 1808. It is now being used to protect pilgrims returning to uninfected areas, such as the Central Provinces from infected pilgrimages, with promising results, and also to immunise all pilgrims going from the East to Mecca, so as to lessen or abolish the spread of cholera to Europe. In short, experimental research has placed in our hands both the means to check the spread and to treat effectually sufferers from cholera; although here, as in so many other instances, reaping the full benefits of such researches is lamentably retarded, for lack of education and of the funds and number of medical men required to bring these benefits within the reach of the general population of poor and backward countries.
The Reduction of Smallpox in India due to Vaccination in the Absence of any Material Sanitary Improvements
The death-dealing virulent type of smallpox is now more prevalent in India than elsewhere, so it is mainly a tropical disease. Fortunately the uneducated Indian villager is wise enough to know the protective value of vaccination, and he flies to telegraph for the vaccinator when the disease appears in his village. Nor is the apathy in this country in the matter surprising, because the present generation of our people are fortunate enough not to know what virulent smallpox is like, as we now only have a few cases of the very mild American form, thanks to the prompt discovery and vaccination or re-vaccination of all the contacts of the few virulent cases of smallpox that have been imported into Great Britain from India on at least three occasions in the last decade or so.
A chart of the yearly death rates per mille from smallpox in all India for five decades clearly demonstrates the great reduction in the severity of the outbreaks, from 2-1 per mille population in 1869 to a maximum of 0-8 per mille in recent years, coincidently with a rise in the yearly vaccinations from about four to ten millions. As there has been no appreciable change for many centuries in the sanitation of the Indian villages, in which about 90 per cent, of the people live, these data finally disprove the oft-exposed fallacy that the reduction in smallpox in the second half of last century in this country was due to sanitary improvements and not to vaccination.
The only specific curative treatment in the dangerous toxic forms of bacillary dysentery is the anti-toxic serum, which has to be made by injecting horses with increasing doses of the bacterial toxins, to which they soon become accustomed. The value of this serum is so fully established that it only requires mention.
Amoebic Dysentery and Liver Abscess
It was only at the beginning of the present century that bacillary dysentery was differentiated from the protozoal form caused by an intestinal amoeba, and it was not known that the amoebic form was common in India until in 1900 I found it to be so in Calcutta, where I also showed that tropical liver abscess was secondary only to amoebic dysentery, and that the old remedy ipecacuanha was only of value in that form. As early as 1886, ipecacuanha had been recommended empirically by McLean in hepatitis to prevent liver abscess, but it fell largely out of use after the saline treatment of dysentery had proved effective in what we now recognise was the bacillary form. The rediscovery and placing on a scientific basis of the ipecacuanha treatment of amoebic hepatitis, after its early diagnosis by the blood changes, together with the introduction of aspiration and oral ipecacuanha treatment of liver abscess, in place of the old open operation, with its almost inevitable secondary septic infection, resulted in the rapid decline from 1907 in .the British Army liver abscess incidence and mortality, with the gratifying result that the yearly average number of deaths of British soldiers from liver abscess fell from 9K in the decade ending 1906 to nil in 1981, and the liver abscess case mortality in two large series has also fallen from 60 to 2 per cent. In 1912, the treatment of both amoebic dysentery and hepatitis was much improved by the use of the active principle of the nauseating ipeca¬cuanha, by the discovery of the greater activity of emetine, due largely to the simple experiments of Wedder on a harmless water amoeba, and in Calcutta, by the speaker, on the pathogenic amoeba which causes dysentery.
This disease presents the most remarkable example in history of how an old-time mysterious pestilence, on its reappearance after a long interval in civilised parts, was so effectively investigated by modern bacteriological and experimental methods that the means of controlling it were discovered within about one decade. Within historical times, plague has on several occasions caused world-wide and very fatal pestilence, such as the Black Death of 1848-9, which is said to have carried off one-fourth of the population of Europe, 90 per cent, of the people in some British monastries, while 70,000 people of London, one seventh of the then population, died in 1664-5, soon after which plague ceased to be epidemic in this country. In 1894, it was carried to Hong Kong from the remote interior of China, which afforded the first opportunity for modern investi¬gation, and in a few months the plague bacillus was Nutated and proved by animal experiments to be the cause of the disease. Bombay was infected in 1896, and within two years an efficient plague vaccine had been discovered by Haffkine, and since then much improved, and the first Indian Plague Commission, as the result of a critical study, demonstrated that by its means the incidence was reduced to one-fifth and the case mortality to one-half, thus reducing the death rate to one-tenth of that of the uninoculated in the same outbreaks, and a recent volume of further data shows a very similar reduction of the death rate to one-eighth.
Further, an anti-plague serum was prepared which did not prove very efficient, but in the last two years F. P. Mackie and B. Naiiu, by further research, have made a serum which has undoubtedly saved some otherwise inevitably fatal septicaemia cases of plague. But that is not all, for within about a decade of the outbreak in Bombay, all the old ideas of direct contagion, with consequent great waste of money on useless disinfection measures, were swept away through experiments mainly carried out on such vermin as rats by W. Glen Liston, confirmed by the Second Indian Plague Commission under Sir Charles Martin, which proved the infection to he by the indirect method through rat-fleas. Thus it became possible to check the spread of the pandemic over the world by killing the rats and their fleas. The mysteries of this ancient pestilence, perhaps the worst the world has ever known, have been solved by modern experimental research methods in one decade, with untold saving of life and suffering.
Surely only those who are wilfully blind can fail to see in such epoch-making results full justification for animal experiments, mostly carried out on vermin, on whose destruction large sums are annually expended.
Malta or Undulant Fever
This is a very debilitating fever of some six months' duration as you will see from the temperature chart displayed. It is widely prevalent in Europe, Africa, North India and the United States, while a form of the disease associated with contagious abortion of cattle occurs in this and many other countries. All our most important knowledge of the disease has been derived from animal experiments, for the causative organism was discovered in 1880, and proved by experiments on monkeys to be the cause of the disease, by one of the greatest of British research workers, David Bruce. Yet sanitary measures failed to reduce its serious incidence in our military forces at Malta, until a medical commission under the same worker in 1906 discovered the mode of infection in a most unlikely source; namely, through the milk of perfectly healthy goats, an animal particularly insusceptible to bacterial diseases as a class, and consequently its role was only detected by a thorough experimental investigation guided by a master mind. The diagram of the data illustrates at a glance the immediate graphic reduction in the Malta fever cases from the middle of 1906, when the goats' milk supplied to our troops and sailors was regularly boiled. The average yearly incidence in our forces in the three years up to 1905 had been 456, in the three years after 1906 the average fell to 6 only, a reduction of 98-7 per cent, and the benefit of the discovery was reaped during the Great War in saving thousands of our sailors from this serious and sometimes fatal disease.
How the British were narrowly saved from betrayal during the Great War through anti-typhoid inoculation not being compulsory
This is such a serious matter that the evidence for the above statement will be given as far as possible by means of extracts from official and other publications. The first is from page 16 of the Official History of the War. Medical Services General History, Vol. I. “The question of making anti-typhoid inoculation compulsory was considered by the (Medical) Advisory Board in February, 1912. The board considered that despite the most careful sanitary organisa¬tion there must continue to be grave danger of typhoid fever becoming epidemic during operations in the field, and expressed the opinion that, in view of the increased resistance to infection conferred by anti-typhoid inoculation, and the impossibility of inoculating the expeditionary force after mobilization was ordered, the only method of securing the maximum of immunity would be by the adoption of anti-typhoid inoculation as a routine matter in times of peace. The board, therefore, strongly recommended to the Army Council that these anti-typhoid inoculations should be made compulsory for all soldiers on attaining the age and service at which they become available for active and foreign service; they drew attention to the procedure then adopted in the Army of the United States of America and the results obtained during its recent mobilisation on the Mexican frontier. The Army Council, however, did not consider it advisable that anti-typhoid inoculation should be made compulsory, but directed that the soldier should be encouraged by lectures and by leaflets to take advantage of the safety conferred by it.”
The apprehension this decision of the Army Council caused in the medical department on the outbreak of the Great War is brought out by the following opening sentence of Chapter IX on the Enteric Fevers of the volume on Pathology of the Official History of the War. “Enteric fevers during the war might well have been the subject of the blackest chapter in its medical history. The Army Medical Department has never had any illusions as to the grave potentialities of these fevers in the war, only too securely based on the medical records-of the British and other armies. This knowledge was shared by the civil population, since it had not forgotten how heavy a toll had been paid to enteric in the South African War.”
In the section on Protective Inoculation, commencing on page 247 of the same volume it is first pointed out that great improvement in the protective value of the vaccine was effected, subsequently to the South African War, by the late William Leishman and his R.A.M.C. colleagues, and the report correctly states that this " is but one more illustration of the fact that progress in such matters is continuous " and " it can hardly be doubted that the vaccine of the future will probably leave the present vaccine still further behind in protective value," a forecast that a paper published in the April issue of the R.A.M.C. journal seems destined to fulfil.
The conditions as regards inoculation on the Western Front in the early stages of the war are next described as follows: “The Medical Department laboured under a heavy handicap in lacking compulsory powers in this matter, powers conceded before or during the war to the medical departments of
Table 1. The relative incidence and mortality from the enteric fevers amoung the British troops enaged respecively in the South African war and in the war of 1914-1918
|Total cases||Total deaths||Case mortality percent||Mean annual strength||Annual incidence per 1000 strength||Rate per 1000 strength|
|South African War, 1899-1902||57684||8022||13 – 9||208226||10500||14 – 6|
|The Great War, 1914-1919||20139||1191||5 – 9||2000000 (approx)||2 – 35||10|
Incidence in Great War, one forty-fifth. Death Rate in the Great War, one-hundredth
the American, French, Italian and German armies.” The result was that our medical officers were only able " to inoculate with a single dose, about 25 to 30 per cent, of the original expeditionary force before they crossed the Channel," and it is recorded that it was altogether out of the question to increase the percentage during the early battles, and the retreat from Mons, and " it was not until the fighting on the Aisne had been in progress for some time, and until the army had been able to take breath, and to make progress in its reconstruction and the incorporation of its reinforcements, that it became possible to press for and to carry out fresh inoculations on any considerable scale. By this time, towards the beginning of October, 1914, the urgent need for this became manifest to those whose duty it was to keep their fingers on the epidemic pulse of the army. Typhoid fever had made its appearance, was showing an alarming tendency to spread in certain units, and was presenting itself, only too often, in the grave form familiar to those who had served in India during the pre-inoculation days, and in the South African War. . . . There was nothing to prevent a violent conflagration except general preventive measures and the special protection conferred by inoculation."
Soon after the line on the Western Front became stabilised “strenuous and unremitting efforts commenced by means of lectures, etc., to persuade the men to be inoculated. Fortunately, the task was fairly easy, the position as regards the arguments and proofs which could be brought forward being far more satisfactory than was the case formerly. The percentage of the inoculated rose with remarkable rapidity, influenced naturally to a large extent by the fact that the reinforcements coming from home and elsewhere presented an increasingly high inoculation strength. ... It was not long before the inoculation strength of the troops in France rose to a figure which fluctuated between 90 and 98 per cent."
Figures in the Official History of the War show the reduction of the incidence per thousand of typhoid among a yearly average of two million of our troops on the Western Front to only one-forty-fifth of that among an average of over 200,000 men in the South African War, and a reduction of the death rate to only one-hundredth.
Similar data for the South African War of 1899-1902, the German Herrero War of 1904-07 and of the British Campaign in the same area in German S.-West Africa in 1914-15 show the typhoid death rate per thousand in the 1914-15 campaign was one-fiftieth or less of that of the earlier campaigns in the same country, due to the greatly improved vaccine latterly available.
We only have to recall how the typhoid epidemic held up Lord Roberts' advance and greatly prolonged the South African War, and the impossibility of adequate sanitary measures in the trenches in France, together with the narrow escape of our Channel Ports from being seized by the Germans in the first year of the war, and used for cutting off our food supplies by submarines and for the invasion of our Southern Coasts, to realise that when typhoid was "showing an alarming tendency to spread" on the Western Front in the autumn of 1914, owing to the expeditionary force having had to be sent to France with few men inoculated, without protective inoculation Kitchener's brave volunteer army could not for long have withstood the onset of the fully inoculated German troops, and our country would have been betrayed into the hands of our enemies.
More Specific Curative Remedies for serious widespread Diseases have been discovered by Animal Experiments in about thirty years than accrued from three thousand years of Empiricism.
Cinchona bark for malaria and ipecacuanha for amoebic dysentery appear to be the only really curative remedies for serious specific diseases that have been discovered by empirical measures in three thousand years of therapeutic history. Moreover, there is scarcely an important and commonly used drug in the British Pharmacopoeia, the efficient employment of which is not dependent on knowledge obtained by animal experiment. Once more, Professor Cushny, in his evidence before the last Royal Commission, showed that all the best soporifics, all local anaesthetics, the whole group of antipyretics, diuretics for kidney disease, physostigmine for the excruciating glaucoma, vaso-dilators for the agonising angina pectoris, and many other valuable drugs had been discovered within the previous forty years by animal experiments, under which, in his long experience, "no animal had suffered pain." Yet within the same period he could only recall one drug of moderate value, apart from some local antiseptics, that had been found without such experiments.
This new science makes use of the knowledge of the relationships between chemical constitution and therapeutic action, acquired by earlier animal experiments, to make very numerous new chemical compounds likely to prove active against the parasites of particular diseases, which must then be tested on small animals infected with the particular microbe, for they are too numerous and toxic to be tried first directly on man. The following are the most important of such remedies used in tropical medicine.
The Salvarsan Group of Drugs in Yaws and Relapsing Fever
Salvarsan and neosalvarsan were discovered by Ehrlich and first called 606 and 906, because that large number of toxic substances had to be made and tested before those very potent anti-syphilitic remedies were obtained after years of research. The tropical disease, Yaws, is caused by a closely allied organism to that of syphilis, but one innocently contracted chiefly by children by direct contagion. It is so prevalent in very extensive areas of the East Indies, Oceana, Tropical Africa and the West Indies, that few of the indigenous population of large areas escape suffering from the numerous long continued loathsome sores it produces, photos of which, before and after treatment, I show you. Yet a single injection of these new synthetic drugs often causes rapid healing of all the ulcers, although additional doses are advisable to complete the cure and prevent the permanent crippling that may result from the lesions. In the Dutch East Indies Winkel reported that 1,600,000 doses of salvarsan had been given in yaws up to 1924 alone, while in Africa the effects of its use have been so graphic that they have popularised European medicine, in place of the crude treatment of witch-doctors, to the immense benefit of millions of poor people, in hundreds of thousands of square miles of country.
Relapsing Fever, formerly confused with typhus, and very prevalent and fatal in Eastern Europe, immense tracts of Northern and Tropical Africa and parts of India, is also readily curable by salvarsan during the first few days of this usually short fever. In fact, only the cost of the drug checks the illimitable relief of suffering it can produce, but it cannot be used at all without each batch of the drug being standardised by tests on small animals, so that if the abolitionists could have their way they would perpetuate unlimited and quite unnecessary suffering throughout the world, mostly in innocent children.
The Cure of Sleeping-Sickness by Bayer 205 and Tryparasamide
Sleeping-sickness was known a century ago to West African Arab slave dealers as always fatal. It spread to Uganda, where it reduced the population around the north of Lake Victoria Nyanza from 56,000 in 1990 to 13,000 by 1907, and it has for long been decimating extensive areas of British, French, German, and Belgian tropical Africa. The causative trypanosome and infection through the bites of the tsetse fly were established mainly through the animal experiments of David Bruce, but as those flies could not be exterminated nothing but the discovery of an effective treatment could stay the ravages of the disease. Fortunately many animals suffer naturally from trypanosome infections, and mice can be readily infected with the human forms and used for testing drugs on the parasites. Atoxyl and other arsenical compounds proved of some value in the early blood infection with trypanosomes, which later develops into sleeping-sickness when the central nervous system is invaded by the parasite, so numerous new synthetic compounds were made and tried in mice, with the result that two very valuable preparations were discovered, the German Bayer 205, which clears the blood of mice of innumerable trypanosomes within twenty-four hours, and is effective in human infections in the early stage ; and the complementary American discovered Tryparsamide, which cures most cases in the second stage of sleeping-sickness and some in the last stages of the disease.
A sleeping-sickness invasion of the Southern Sudan has already been practically stamped out by searching out and treating the early cases, and valuable results have been obtained through these new drugs in many other areas of Africa, so there is little or no doubt that immense fertile areas of tropical Africa will be thus saved from decimation and ruin—thanks to animal experiments largely carried out on rats and mice. Moreover, some animal trypanosome infections have also been cured by the same drugs, including surra in camels in India, and if we may judge by value or weight the saving of one camel should be worth the sacrifice of a large number of mice.
The Antimony Cure of Kala-Azar or Black Fever
This terrible disease in the course of 80 years swept up the western portion of the Brahmaputra Valley of Assam and literally carried off one-third of the population. As it had a case mortality of 96 per cent, on tea estates under continued skilled European medical treatment, and it took an average of seven months to kill its unfortunate victims by inches from fever, with enormous enlargement of the spleen and liver, and most of its victims were children, so the suffering, misery and economic loss caused by kala-azar can rarely, if ever, have been equalled. After my investigation of 1896-97, epidemi¬ological measures checked its progress for a time and allowed it to be stamped out of a number of previously decimated tea estates, but in accordance with my forecast that any depressing disease might start a renewed outbreak of kala-azar, this took place in the eastern part of the Brahmaputra Valley after the influenza epidemic of 1918. Very fortunately, by this time chemio-therapeutic researches on sleeping-sickness and other diseases had led to the trial of antimony salts in kala-azar, with the remarkable result that over 80,000 cases were treated for three months on end in scattered Assam villages by intravenous antimony injections, over 80 per cent, of the sufferers were saved, and the epidemic was stayed with scarcely any loss of life compared with the earlier outbreak, in 1920 the Calcutta Tea Association, at my suggestion, supplied funds in the newly opened Calcutta School of Tropical Medicine for a whole-time research worker on kala-azar, and as the result of a decade of patient work testing a number of newly discovered organic antimony compounds, Dr. L. E. Napier has proved that with eight daily injections of neostibosan, some 90 per cent, of the sufferers from this formerly deadly disease can be cured, and he has recently recorded that by systematically seeking out and treating all the cases in a group of villages near Calcutta for six years, their number has been reduced from 121 and 127 in the first two years, to 12 and 8 respectively in the last two years, or a decline of 94 per cent. It is now abundantly clear that these researches have placed in our hands the means to eradicate this terrible disease from the affected, among a population of at least 60 million Indian people, whenever sufficient funds and staff become available, while even the present indigenous medical men must be saving many thousands of lives every year. Very similar results have also been obtained in the infantile kala-azar, so prevalent all round the Mediterranean basin. Truly this is not the least remarkable of the many triumphs of modern experimental therapeutics.
The Antimony Cure of Endemic Hematuria or Bilharziasis
A good example of how one success leads to another is the fact that Dr. J. B. Christopherson, while treating a Sudan case of kala-azar with tartar emetic injections, observed that the symptoms of endemic hasmaturia also present disappeared. His patient following up of this observation has led to the establishment of a simple cure for this painful and debilitating disease, from which most of the children of the innumerable Egyptian villages dependent on irrigation suffer. Further, R. P. Leiper, through experimental work on snails and mice, has elucidated the mode of infection and prophylaxis of this widespread disease.
Carbon Tetrachloride in Hookworm Disease
The value of this drug was discovered by tests made in the treatment of the hookworm of dogs by M. C. Hall in 1921. To mention but one example of its value, in 1928 S. M. Lambert reported that three million carbon tetrachloride treatments in Fiji had proved successful in preventing the previous rapid reinfections, with the result that the disease has been controlled as an economic and debilitating factor. And hookworm infection is one of the most widespread and debilitating diseases of warm climates.
Plasmoquine and Atebrin in the Treatment of Malaria
The Health Organisation of the League of Nations has recently estimated the incidence of malaria, in India alone, annually at 100 million cases, requiring 6S0 tons of quinine for their proper treatment, or which less than one ton actually) expended, while the yearly economic loss to India due directly to malaria has been estimated at £25,000,000. Moreover, quinine fails completely to destroy the mosquito cycle of the malarial parasite through which alone the infection is ordinarily conveyed. Invaluable as has been the establishment of the mosquito infection theory as a guide to scientific prophylaxis, which was quite impossible as long as the erroneous air-borne theory held the field, it is not always practicable among poor scattered village population so improved curative and preventive drugs are required to supplement the altogether inadequate and expensive quinine supplies.
Here once more experimental therapeutics has come to our rescue, for within the last decade two invaluable synthetic remedies have been discovered, after testing numerous new compounds with the likely activity against malaria infections in small birds. The first of these, plasnioquinc, has the long sought property of destroying in very small doses the mosquito stages of the malarial parasites which quinine does not touch, and there is already clear evidence that by its systematic use in labour forces the number of new infections through mosquitoes can be reduced greatly.
The other new remedy has a direct curative action on malaria far in excess of that of quinine, as will be evident from a glance at a recent paper by S. P. James, W. D. Nicol and P. G. Shute, for whereas repeated relapses followed the use of quinine in cases 40 and 42 a few days' treatment sufficed to really cure the four cases treated with atebrin, so further comment is unnecessary, except to mention that all the patients were infected with a particularly dangerous relapsing form of malignant tertian malaria.
Invaluable as are these two new remedies in our struggle against the most widely prevalent and lethal disease in the world, the greatest significance of their discovery and of those against sleeping-sickness, kala-azar, relapsing fever, yaws, etc., is that no limit can be placed on the possibilities of discovering even more potent cures of malaria and other widespread tropical diseases by similar experimental methods. Without the animal experiments through which these potent new remedies have been discovered, immense amount of suffering and loss of life would have resulted.
Great as are the benefits mankind has derived from animal experiments, they are less than animals as a class have obtained from bacteriological and other researches from the time of Louis Pasteur to the present day, as the following brief data will suffice to prove.
Rinderpest or Cattle Plague
This very highly contagious disease of cattle has been absent from Great Britain since 1877, but in 1896-9 it carried off over 2,000,000 in South Africa, when that country was only saved from ruin by the successful researches of Koch, Kolle and Turner in discovering one of the most potent of protective sera, which produces sufficiently long temporary immunity to be of immense life saving value during epidemics, while lasting immunity can be produced by less simple methods. It fell to my lot to make the first anti-rinderpest serum in India in 1899. I carried out a strenuous three weeks' village inoculation campaign at a day temperature of 115° F. in the shade, with the result that among about 500 inoculated cattle, directly exposed to infection, not a single one developed the disease after the incubation period, that is, was not already infected before treatment; yet of about an equal number of uninoculated animals in the same villages one-half developed rinderpest and half of those died. During the last three decades the demand for the serum has steadily increased in India, until four million doses are now prepared yearly, and it will be seen from the first line of the table of the data for the most recent year the returns for the nine provinces of India are available, 1929-30, over one million animals were inoculated during outbreaks of rinderpest with a death rate of 0-87 per cent., or one twenty-ninth of that of the uninoculated animals in the same outbreaks, and in the most advanced province, the Punjab, among nearly 800,000 inoculations in three years less than one in one thousand died of rinderpest although exposed to infection.
Haemorrhagic Septicaemia of Cattle, etc
Still better results are being obtained from protective inoculation against this very fatal, mainly soil infection, disease of cattle, with 90 per cent, mortality within twenty-four hours of onset, for the table shows that among 806,900 animals inoculated in infected areas the mortality was only 1 in 5,000, or one sixty-sixth of that among the uninoculated in the same areas.
This is another soil infection disease of young cattle, which carries them off in a day or two, and the table shows a death rate of only 1 in 25,000 among the inoculated, or one eighty-fifth of that among the uninoculated in the same areas.
Thus wet two million cattle are receiving protective inoculation yearly in India against these three deadly animal diseases alone, and one of the senior veterinary research officers of that country recently assured me that, at a most conservative estimate, not less than 500,000 are being thereby saved yearly from a painful death. To anyone who knows India, the simple fact that the highly conservative, not to say suspicious, Indian villager, permits such wholesale inoculations of his cattle, his most valuable possession, proves that he knows from practical experience, and without the smallest possibility of doubt, the immense protective and life-saving value of these inoculations. As the required vaccines and serums are prepared from a very small number of animals, compared with the numbers saved by them, the net reduction in the sufferings of the animals must be anything from one hundred fold upwards, quite apart from the economic saving, which is not to be despised in these hard times.
In the half century that has just elapsed since Pasteur's dramatic demonstration in sheep of the life-saving value of his protective vaccination against the invariably fatal effects of the inoculation of virulent anthrax bacilli, untold millions of animals have been saved from suffering and death by the use of his and of later improved vaccines. Some faint idea of this may be gathered from the evidence of Sir Stewart Stockman before the last Royal Commission who stated that in Hungary in 11 1/2 millions of vaccinated animals, the loss was reduced from 10 per cent, to less than 1 per cent., a saving of over one million animals in that small country alone.
The same leading authority recorded that "The statistics from Hungary show that in four million observations the death rate was reduced in inoculated animals to 1-6 per cent., whereas in the non" inoculated it amounted to about 20 per cent."
Among other important diseases of animals, recorded in standard works on veterinary medicine and bacteriology, in which much saving of suffering and life has been effected by the use of serums and vaccines discovered or made through animal experiments, I only have time to enumerate : Braxy of sheep, prevalent in Scotland, Joint-ill of foals, Tetanus, Swine fever, Contagious bovine pleuro-pneumonia ; and of the diagnostic use of mallein in Glanders it is recorded : " Experience in Great Britain and elsewhere has shown that by this method alone the disease may be eradicated."
Further curative remedies have been discovered by animal researches for certain animal Trypanosome infections, Tropical ulcers of dogs and man and Piroplasmosis of bovines, sheep and dogs, the last of which used to carry off 90 per cent, of dogs in very extensive tropical areas, such as in Africa, but is now readily curable. Nor can any limit be placed on the relief to animals that will undoubtedly accrue from further such investigations, as a single recent example will suffice to prove.
Distemper of Dogs
Every one knows the truth of Professor Hobday's statement that hundreds of thousands of dogs die annually of distemper, so it is not surprising the dog lovers, both here and in the United States, raised funds to finance, with the help of the Field newspaper, the very successful investigation of distemper by the Medical Research Council, whose last report for 1931-32 records the following results : " In dog communities, such as packs of hounds, distemper in epidemic form often had a mortality of 50 to 80 per cent. No trustworthy preventative was known." " It was found, in due course that a healthy dog could be given lasting protection against distemper by the inoculation of a vaccine containing the killed distemper organisms, followed by inoculation of living virus a fortnight later. Preparations of antiserum were made, and it was found that the dog could also be protected by a simultaneous inoculation of antiserum and virus, and that the antiserum used alone was valuable in diminishing the severity of the disease in an unprotected dog if given early enough." "Trials were made on a large scale, especially in foxhound kennels. ... Highly successful results were obtained. A survey showed that, taking cases only where exposure of young dogs to infection was definitely known to have occurred, the incidence of distemper among 650 inoculated hounds belonging to 23 different hunting packs was only 1-4 per cent., and the death rate 0-3 per cent. Without inoculation the incidence among young foxhounds in this country is nearly 100 per cent., while the death rate is usually 50 per cent., and may exceed 75 per cent." Such facts speak for themselves (Chart IV.).
It is worthy of note that Mr. Baldwin, when recently asked in the House of Commons, if this discovery could have been made if the Dogs' Protection Bill had been passed, replied that he understood that it would have been quite impossible. Yet the abolitionists have for long agitated for its passage, so, if successful, they would have prolonged indefinitely unlimited suffering of the dogs themselves.
The certainty that before long, all over the world, millions of dogs will be saved from the most painful and fatal disease they are liable to, as the direct result of the distemper researches, is likely ultimately to prove but a minor benefit compared to the good prospect of its leading to the conquest of a number of the most widespread infectious diseases of man and animals, produced by the ultramicroscopical viruses of which that of distemper is the first to be conquered. In fact, a protective vaccine against the deadly yellow fever, of a very promising nature has already accrued from the application of the principles developed during the distemper work. Now the virus infections thus opened up to new and profitable lines of research include such important and widespread diseases of man as typhus, smallpox, rabies, encephalitis, poliomyelitis, measles, five short tropical fevers, and common colds. Moreover the standard British work on bacteriology describes no less than 25 virus diseases affecting such a wide range of animals as horses, cattle, sheep, goats, swine, dogs, cats, fowls, rabbits, guinea-pigs and monkeys, and including the widespread rinderpest, and foot and mouth disease, as well as one form at least of cancerous tumour.
The success of the recent distemper researches is thus likely to be just as epoch-making as the early bacteriological triumphs of Pasteur and Koch, and it is quite clear that the necessity for the continuation of experimental researches on animals, which was established by the 1912 report of the Royal Commission on the subject, in the interests of the animals themselves, as well as of mankind, is far more imperative at the present time than it has ever been in the past.
The foregoing evidence will suffice to prove that literally millions of animals are being saved in civilised countries every year by the use of serums, vaccines, etc., discovered and made through unavoidable animal experiments, and the number is being added to each decade. Now no scientist of standing will deny that some suffering is inflicted on animals in this work, but I maintain, with confidence, that the reduction of the sufferings of the animals as a class, is many thousand times that inflicted on them in the discovery and preparation of the serums and vaccines I have dealt with. I therefore come to the conclusion that the examples I have given to-day from the limited field of tropical medical and veterinary science alone, suffice to prove that the reduction in the suffering that results year by year to animals, as well as to man, from the discoveries made in about three decades through a limited number of animal experiments, is incalculably greater than the pain inflicted on the animals under our humane laws.