Experiments on Animals

All suppuration, and all forms of "blood-poisoning"—abscesses, boils, carbuncles, erysipelas, puerperal fever, septicæmia, pyæmia—are due to minute organisms, various kinds of micrococcus. It has indeed been shown that suppuration may, in exceptional conditions, occur without micro-organisms: but practically every case of suppuration is a case of infection either from without or from within the body. There is no room here for any account of the work spent on these micrococci: on their identification, isolation, culture, and inoculation. It is the same with all the pathogenic bacteria—each kind has its own habits, phases and idiosyncrasies, antagonisms and preferences: nothing is left unstudied—the influences of air, light, heat, and chemistry; all the facts of their growth, division, range of variation, grades of virulence, vitality, and products; the entire life and death of each species, and everything that it is, and does, and can be made to do. The difficulties of bacteriology are written across every page of the text-books: above all, the difficulties of attenuating or intensifying the virulence of bacteria, and of immunising animals, and of procuring from them an immunising serum of exact and constant strength. Every antitoxin is the outcome of an immeasurable expenditure of hard international work, unsurpassed in all science for the fineness of its methods and the closeness of its arguments.

The older theories of disease had attributed infection to the intemperature of the weather, the powers of the air, or the work of the devil; later, men recognised that there must be a materies morbi, something particulate, transmissible, and perhaps alive, but it was still a "nameless something." Therefore, they over-estimated the constitutional, personal aspect of a case of infective disease, against the plain evidence of case-to-case infection or inoculation: they studied with infinite care and minuteness the weather, the environment, the family history, the previous illnesses of the patient—everything, except the immediate cause of the trouble. But modern pathology, like Pasteur, says, Tenez, voici sa figure.

The antiseptic method was based on bacteriology, resting as it did on the proof afforded by Pasteur that putrefaction was caused by bacteria, and not by the oxygen of the air, as had been previously believed. If any man would measure one very small part of the lives that are saved by this method, let him contrast the treatment of empyema fifty years ago with its treatment now. If he would measure the saving, not of lives but of limbs, let him take the treatment of compound fractures. If he would measure the saving of patients from pain, fever, and long confinement to bed, let him take the ordinary run of surgical cases, not only the major operations but all abscesses, lacerated wounds, foul sores, and so forth.

A serum has also been used of late years for the treatment of micrococcus-infection, and has given good results in many cases. It has been used, also, to avert the risk of such infection in certain operations where the antiseptic method cannot be strictly carried out. For the use of a "polyvalent" serum, reference may be made to the recent paper by Dr. W. S. Fenwick and Dr. Parkinson. (Trans. Roy. Med. Chir. Soc., 1906.)

II
ANTHRAX

In animals, anthrax is also called charbon, splenic fever, or splenic apoplexy: in man, the name of malignant pustule is given to the sore at the point of accidental inoculation, and the name of woolsorter's disease is given to those cases of anthrax where the lungs are infected by inhalation of the spores of the bacillus anthracis. The disease occurs among hide-dressers, woolsorters, brushmakers, and rag-pickers: among animals, it occurs in sheep, cattle, horses, and swine:—

"Many of the outbreaks of anthrax in England have been in the neighbourhood of Bradford, and have been traced to the use of infected wool-refuse as manure. A map published by the Board of Agriculture shows that the outbreaks of anthrax are most frequent in those counties of Great Britain where dry foreign wools, hairs, hides, and skins are manufactured into goods. In 1892, there were forty-two outbreaks of anthrax in the West Riding of Yorkshire, as against two in the North Riding, and one in the East Riding. An undoubted fact in connection with anthrax is its tendency to recur on certain farms. During 1895, the disease reappeared on twenty-three farms or other premises in England, and six in Scotland, where it had been reported in the previous year." (Dr. Poore's Milroy Lectures, On the Earth in relation to Contagia, 1899.)

An admirable account of the disease, as it occurs in man, is given by Dr. Hamer and Dr. Bell, in the valuable series of monographs edited by Dr. Oliver of Newcastle, under the title Dangerous Trades (London, John Murray, 1902). Happily, the disease is very rare among men, even among those most exposed to it. For its treatment in man, an antitoxin has been used with some success: but the cases are too few to be of much importance.[15]

The bacillus anthracis was first seen more than fifty years ago: "Anthrax has the distinction of being the first infectious disease the bacterial nature of which was definitely proven."[16] Pollender in 1844, Roger and Davaine in 1850, noted the petits bâtonnets in the blood of sheep dead of the disease, and thought they were some sort of microscopic blood-crystals: it was not till 1863, after Pasteur's study of lactic-acid fermentation, that Davaine realised they were living organisms. Afterward, Koch succeeded in making cultures of them, and reproduced the disease by inoculating animals with these cultures; yet it was said, so late as 1876, that the bacillus anthracis was not the cause of anthrax, but only the sign of it: "Along with the bacilli, there are blood-cells and blood-plasma, and these contain the true amorphous virus of anthrax." Then came Pasteur's work, and reached its end in the experiments at Chartres, and the famous test-inoculations (1881) at Pouilly-le-Fort.

In the Agenda du Chimiste (1896) M. Roux gives the following account of this work, which he watched from first to last:—

Pasteur's note on the attenuation of anthrax was presented to the Académie des Sciences on 28th February 1881; and the test-inoculations at Pouilly-le-Fort were made in May of that year. It was hardly to be expected that every country, in every year, should obtain such results as France now takes as a matter of course; and at one time, about twenty-one years ago, there was in Hungary a "conscientious objection" to the inoculation of herds against the disease. But in Italy, from 1st May 1897 to 30th April 1898, the issue of anti-charbon vaccine from one institute alone, the Sero-Therapeutic Institute at Milan, was 165,000 tubes, enough to inoculate 33,734 cattle and 98,792 sheep. And in France, between 1882 and 1893, more than three million sheep, and nearly half a million cattle, were inoculated.

The work done in France was published by M. Chamberland, in the Annales de L'Institut Pasteur, March 1894. The following translation of his memoir—Résultats pratiques des Vaccinations contre le Charbon et le Rouget en France—shows something of the national influence of the Pasteur Institute:—

1. Charbon

"After the famous experiments at Pouilly-le-Fort, MM. Pasteur and Roux entrusted to me the whole method and practice of the vaccinations against charbon. Twelve years have passed, and it is now time to put together the results, and to make a final estimate of the value of these preventive inoculations.

"Every year we ask the veterinary surgeons to report—

1. The number of animals they have vaccinated.

2. The number that have died after the first vaccination.

3. The number that have died after the second vaccination, within the twelve days following it.

4. The number that have died during the rest of the year.

5. The average annual mortality before the practice of vaccination.

"The sum total of all the reports is given in the following tables:—

Vaccination against Charbon (France).
Sheep.

Vaccination against Charbon (France).
Cattle.

"Comparing the figures in the fourth column with those in the second, we see that a certain number of veterinary surgeons neglect to send their reports at the end of the year. The number of reports that come to us even tends to get less each year. The fact is, that many veterinary surgeons who do vaccinations every year content themselves with writing, 'The results are always very good; it is useless to send you reports that are always the same.'

"We have every reason to believe, as a matter of fact, that those who send no reports are satisfied; for if anything goes wrong with the herds, they do not fail to let us know it at once by special letters.

"Anyhow, thanks chiefly to new veterinary surgeons who do send reports, we see that in the twelve years, up to 1st January of this year, we have had exact returns as to 1,788,879 sheep and 200,962 cattle—about half of all those that were vaccinated.

"The mortality among sheep and cattle is slightly higher after the first vaccination than after the second. This fact seems to us easy to explain. The animals reported dead include both those that died as the result of the vaccinations, and those that, being already infected at the time, died of the actual disease. But, at the time of second vaccination, the animals are already more or less protected: hence a lower mortality from the actual disease, and a lower sum total.

"The whole loss of sheep is about 1 per cent.: the average for the twelve years is 0.94. So we may say that the whole average loss of vaccinated sheep, whether from vaccination or from the disease itself is about 1 per cent. The loss of vaccinated cattle is still less: for the period of twelve years, it is 0.34, or about 1/3 per cent.

"These results are extremely satisfactory. It is to be noted especially that the average annual death-rate from charbon, before vaccination—the average given in these reports—is estimated at 10 per cent. among sheep, and 5 per cent. among cattle. But even if we put it at 6 per cent. for sheep, and 3-1/3 per cent. for cattle, and say that the worth of a sheep is 30 francs, and of an ox or a cow 150 francs—which is well below their real value—even then it is obvious that the advantage of these vaccinations to French agriculture is about five million francs in sheep, and two million in cattle. And these figures are rather too low than too high.

2. Rouget

"Some years after the discovery of vaccination against charbon, M. Pasteur discovered the vaccine for a disease of swine known under the name of rouget. From 1886, these vaccines were prepared and sent out under the same conditions as the vaccines against charbon. The following table gives the reports that have come to us of this disease:[17] —

Vaccination against Rouget (France).

"The total average of losses during the past seven years is 1.45 per cent., or about 1-1/2 per cent.

"This average is appreciably higher than the average for charbon. But it must be noted that the mortality from rouget among swine, before vaccination, was much higher than that from charbon among sheep. It was about 20 per cent.; a certain number of reports speak of losses of 60 and even 80 per cent.: so that almost all the veterinary surgeons are loud in their praises of the new vaccination."

The rest of M. Chamberland's paper is concerned with the defects, such as they are, of the vaccinations, and the need of absolute cleanliness in the making of them: which is somewhat difficult for this vast number of vaccinations of animals all over France, and in other parts of the world. The whole story of the discovery is told in M. Valléry-Radot's Life of Pasteur: and the whole story of rouget, in the same most fascinating book, vol. ii., p. 180.

III
TUBERCLE

Before Laennec, tubercle had been taken for a degenerative change of the tissues, much like other forms of degeneration. It was Laennec who brought men to see that it is a disease of itself, different from anything else; and this great discovery of the specific nature of tubercle, and his invention of the stethoscope, place him almost level with Harvey. He founded the facts of tubercle, and on that foundation Villemin built. In 1865, Villemin communicated to the Académie des Sciences his discovery that tubercle is an infective disease; that he had produced it in rabbits, by inoculating them with tuberculous matter. En voici les preuves, he said. He appealed to these inoculations to prove his teaching:—

La tuberculose est une affection spécifique. Sa cause réside dans un agent inoculable. L'inoculation se fait très-bien de l'homme au lapin. La tuberculose appartient donc à la classe des maladies virulentes.

It was no new thing to say, or to guess, that phthisis was or might be infective. So far back as 1500, Frascatorius had said that phthisis came "by the gliding of the corrupt and noisome humours of the patient into the lungs of a healthy man." Surely, if clinical experience could suffice, men would have made something out of this wisdom of Frascatorius. They made nothing of it; they waited three hundred years for Villemin to inoculate the rabbits, and then the thing was done—En voici les preuves. Three years later, Chauveau produced the disease in animals, not by inoculation, but by the admixture of tuberculous matter with their food. Then, as the work grew, there came a short period of uncertainty: different species of animals are so widely different in their susceptibility to the disease that the results of further inoculations seemed to go against Villemin; and it was not till 1880 that Cohnheim finally established Villemin's teaching, and even went beyond it, making inoculation the very proof of tubercle:—

"Everything is tuberculous, that can produce tuberculous disease by inoculation in animals that are susceptible to that disease: and nothing is tuberculous, that cannot do this."

Then, in 1881, came the welcome news that Koch had discovered the bacillus of tubercle. In his first published account of it (24th March 1882) he says:—

"Henceforth, in our warfare against this fearful scourge of our race, we have to reckon not with a nameless something, but with a definite parasite, whose conditions of life are for the most part already known, and can be further studied.... Before all things, we must shut off the sources of the infection, so far as it is in the power of man to do this."[18]

In November 1890 he announced, in the Deutsche Medizinische Wochenschrift, the discovery of tuberculin. Its failure was one of the world's tragedies. The defeat may not be final, and we may live to see phthisis fought and beaten with its own weapons: but, for the present, it is more to the purpose to consider what other benefits have been gained, from the discovery of the tubercle-bacillus in 1881, in every civilised country in the world.

1. It has given to everybody a more reasonable and hopeful view of phthisis and the diseases allied to it. The older doctrine of heredity, that the child inherits the disease itself, has given way to the doctrine that the inheritance, in the vast majority of cases, is not that of the disease itself, but that of a tendency or increased susceptibility to the disease.

2. It has brought about an immense improvement in the early and accurate diagnosis of all cases. The bacillus found in the sputa, or in the discharges, or in a particle of tissue, is evidence that the case is tuberculous.

3. It has given evidence, which till 1901 was hardly called in question,[19] that tabes mesenterica, a tuberculous disease which kills thousands of children every year, is due in many cases to infection from the milk of tuberculous cows. In England alone, in 1895, the number of children who died of this disease was 7389, of whom 3855 were under one year old.

4. It has proved, and has taught everybody to see the proof, that the sputa of phthisical patients are the chief cause of the dissemination of the disease. By insisting on this fact, it has profoundly influenced the nursing and the home-care of phthisical patients; and it has begun to influence public opinion in favour of some sort of notification of the disease, and in favour of enforcing a law against spitting in public places and conveyances. In some of the principal cities of the United States, laws on this subject have already been enacted.

5. It has greatly helped to bring about the present rigorous control of the meat and milk trades. The following paragraph, taken almost at random, will suffice here:—

"Bacteriological examinations during the past year have shown that more milks are tuberculosis-infected than is generally supposed, and the importance of carefully supervising milk supplies is becoming more and more acknowledged. Veterinary surgeons are practically agreed that tuberculin is a reliable and safe test for diagnosing the presence of tuberculosis in animals, but affords no index of the extent or degree of the disease. The test, however, will not produce tuberculosis in healthy animals, and has no deleterious effect upon the general health of the animals. The London County Council have decided that all cows in London cowsheds shall be inspected by a veterinary surgeon regularly once in every three months, and that a systematic bacteriological examination shall be conducted of milks collected from purveyors." (Medical Annual, 1901.)

6. Tuberculin has come into general use for the detection of tuberculosis in cattle, to "shut off the sources of the infection." A full account of this method in different countries was given by Professor Bang, of Copenhagen, at the Fourth Congress on Tuberculosis, Paris, 1898. The injection of tuberculin is followed in eight to twelve hours by a well-marked rise of temperature, if the animal be tuberculous. Of this test, Professor McFadyean, Principal of the Royal Veterinary College, London, says:—

"I have no hesitation in saying that, taking full account of its imperfection, tuberculin is the most valuable means of diagnosis in tuberculosis that we possess.... I have most implicit faith in it, when it is used on animals standing in their own premises and undisturbed. It is not reliable when used on animals in a market or slaughter-house. A considerable number of errors at first were found when I examined animals in slaughter-houses after they had been conveyed there by rail, etc. Since that, using it on animals in their own premises, I have found that it is practically infallible. I have notes of one particular case, where twenty-five animals in one dairy were tested, and afterwards all were killed. There was only one animal which did not react, and it was the only animal not found to be tuberculous when killed."

Two instances of the validity of this test will suffice. In 1899, it was applied to 270 cows on some farms in Lancashire. Of these cows, 180 reacted to the test, 85 did not react, and 5 were doubtful. Tuberculous disease was actually found, when they were killed, in 175 out of the 180 = 97.2 per cent. (Lancet, 5th August 1899.) In 1901, Arloing and Courmont published a critical account of the whole subject, and gave the following facts. In 80 calves, which on examination after death were found not tuberculous, the test was negative: in 70 older cattle, which were tuberculous, the test was positive in every case but one, though the dilution of the serum was 1 in 10.[20] It would be easy to add instances of the value of this test, for it is practised far and wide over the world.

7. More recently, the discovery of the "opsonic index," and its use by Sir Almroth Wright and others, has given a great advance to the observation and treatment of cases of tuberculosis. The administration of the "new tuberculin" is now timed and measured with an accuracy which was absolutely impossible a few years ago.

It is a far cry, from the present method of counting how many tubercle-bacilli are taken up by a single blood-cell, back to Villemin's rabbits. Every inch of the way, from 1881 onward, the pathological study of every form of tuberculosis, medical or surgical, human or bovine, has been dependent on bacteriology; that is to say, on experiments on animals.

IV
DIPHTHERIA

The bacillus of diphtheria, the Klebs-Loeffler bacillus, was first described by Klebs in 1875, and was first obtained in pure culture by Loeffler in 1884. Its isolation was a matter of great difficulty, and the work of many years, because of its association in the mouth with other species of bacteria. The following table, from Hewlett's Manual of Bacteriology, is a good instance of one of many practical difficulties. Out of 353 cases of diphtheria, bacteriological examination found the diphtheria-bacillus alone in 216 cases. In the remaining 137 it was associated with the following organisms:—

In December 1890 came the news that Behring and Kitasato had at last cleared the way for the use of an antitoxin:—

"Our researches on diphtheria and on tetanus have led us to the question of immunity and cure of these two diseases; and we succeeded in curing infected animals, and in immunising healthy animals, so that they have become incapable of contracting diphtheria or tetanus."

Aronsen, Sidney Martin, Escherich, Klemensiewicz, and many more, were working on the same lines; and in 1893, Behring and Kossel and Heubner published the first cases treated with antitoxin. Then, in 1894, came the Congress of Hygiene and Demography at Budapest, and Roux's triumphant account of the good results already obtained. Thus the treatment is not many years old; but, if the whole world could tabulate its results, the total number of lives saved would already be somewhere above a quarter of a million. Men found it hard at first to believe the full wonder of the discovery: the medical journals of 1895 and 1896 still contain the fossils of criticism—all the may be and must be of the earlier debates on the new treatment. The finest of all these fossils is embedded in the Saturday Review of 2nd Feb. 1895—It is a pity that the English Press should continue to be made the cat's-paw of a gang of foreign medical adventurers. To get at the truth, we must reckon in thousands: take, out of a whole mass of evidence, all just alike, the reports from London, Berlin, Munich, Vienna, Strasbourg, Cairo, Boston, and New York; these to begin with. Or the following facts, cut almost at random out of the medical journals:—

"The medical report of the French army states that since the introduction of the serum-treatment of diphtheria, the mortality among cases of that disease had fallen from 11 per cent. to 6 per cent." (Brit. Med. Journ., 3rd September 1898.)

"Professor Krönlein (Zürich) exhibited statistical tables, showing that the prevalence of diphtheria in the canton of Zürich had been nearly uniform during the past fifteen years; and that the mortality rapidly decreased as soon as antitoxic serum was used on a somewhat larger scale. In his clinic, all the patients were examined bacteriologically, and serum was administered in every case of diphtheria without exception. Of 1336 cases treated before the serum-period, 554 = 39.4 per cent. died; whilst during the serum-period there were 55 deaths among 437 cases = 12 per cent. In cases of tracheotomy, the death-rates before and during the serum-period were 66 and 38.8 per cent. respectively." (Lancet, 7th May 1898, Report of German Surgical Congress at Berlin.)

"Dr. Kármán was entrusted by the Hungarian Government with the task of instituting measures for preventing the spread of diphtheria in a village and its neighbourhood. As general hygienic regulations accomplished nothing, he tried preventive inoculation.... Among 114 children thus treated, there was during the next two months no case of diphtheria, although the disease was prevalent in the village up to the date at which inoculation commenced, and continued to rage in the surrounding villages afterwards. During those two months, only one case of diphtheria appeared in the village, and that was in an uninoculated child; while, in the previous five months, 18.3 per cent. of the village children had been attacked, of whom eight died, six not having been treated with serum. Considering the wretched hygienic condition of the village, the harmlessness of preventive inoculations, and the continuance of the disease in the neighbouring villages, where diphtheria-vaccination was not carried out, the extraordinary value of the inoculations, in the prophylaxis of diphtheria, can hardly be denied." (Brit. Med. Journ., 16th January 1897.)