Experiments on Animals

by Stephen Paget

I
INFLAMMATION, SUPPURATION, AND
BLOOD-POISONING

Pathology, the study of the causes and products of diseases, is a younger science than physiology: the use of the microscope was the beginning of pathology; and the microscope, even so late as sixty years ago, was very different to the microscope now. The great pathologists of that time had not the lenses, microtomes, and reagents that are now in daily employment; they knew nothing of the present methods of section-cutting and differential staining. But the publication in 1839 of Schwann's cell-theory marks the rise of modern pathology. In 1843, Darwin wrote his first draft of the doctrine of the origin of species; and Pasteur, that year, was in for his examination at the École Normale. The work of Schwann, Virchow, and Pasteur had such profound influences on science that the span of sixty years seems to cover the modern development of pathology: and this span of years is marked, half-way, by the rise of bacteriology. In 1875, when the Royal Commission on Experiments on Animals was held in London, the evidence was concerned practically with physiology alone: very little was said about pathology, and of bacteriology hardly a word. The witnesses say that they "believe they are beginning to get an idea" of the true nature of tubercle: and the evidence as to the nature of anthrax, given by Sir John Simon, reads now like a very old prophecy:—

"We are going through a progressive work that has many stages, and are now getting more precise knowledge of the contagium. By these experiments on sheep it has been made quite clear that the contagium of sheep-pox is something of which the habits can be studied: as the habits of a fern or a moss can be studied: and we look forward to opportunities of thus studying the contagium outside the body which it infects. This is not a thing to be done in a day, or perhaps in ten years, but must extend over a long period of time. Dr. Klein's present paper represents one very important stage of a vast special study. He gives the identification of the contagium as something which he has studied to the end in the infected body, and which can now in a future stage be studied outside the body."

Thirty years ago, there was no bacteriology, in the present sense of the word: and now the "habits" of these "contagia" have been studied, outside and inside the body, with amazing accuracy. It has been proved, past all possibility of doubt, that the pathogenic bacteria are the cause of infective diseases; they have fulfilled Koch's postulates—that they should be found in the diseased tissues, be cultivated outside the body, reproduce the same disease in animals, and be found again in the tissues of those animals. By an immeasurable amount of hard work crowded into a few years, this New World of bacteriology has been subdued. The Royal Commissioners of 1875, speaking of physiological experiments only, said, "It would require a voluminous treatise to exhibit in a consecutive statement the benefits that medicine and surgery have derived from these discoveries." If physiology in 1875 required a treatise, bacteriology in 1906 requires a library: and it is impossible here to give more than the faintest outline of some of the work that has been done.

But all pathology is not bacteriology; and it would take a treatise of prodigious length to set forth the work of modern pathology in the years before anything was known of bacteria. The microscopic structure of tumours and of all forms of malignant disease, the nature of amyloid, fatty, and other degenerative changes, and the chief facts of general pathology—hypertrophy and atrophy, necrosis, gangrene, embolism, and many more—all these subjects were studied to good purpose, before bacteriology. Above all, men were occupied in the study of inflammation under the microscope. It was this use of the microscope that revolutionised pathology; especially, it made visible the whole process of inflammation, the most minute changes in the affected tissues, the slowing and arrest of the blood in the capillaries, the choking-up of the stream, and the escape of blood-cells out of the capillaries into the tissues. Everything had been made ready for the fuller interpretation that was coming from bacteriology: the old naked-eye descriptions of inflammation were left behind; men set aside the definition of Celsus, that it was rubor et tumor cum colore et dolore—words that sound like Molière's jest about the vis dormitiva of opium—they watched inflammation under the microscope, in such transparent structures as the frog's web and mesentery, the bat's wing, and the tadpole's tail. It was thus that Wharton Jones discovered the rhythmical contraction of the veins in the bat's wing. The discovery of the escape of the white blood-cells, diapedesis, through the walls of the capillaries, was made by Waller and Cohnheim. To those who are opposed to all experiments on animals, it may seem a very small thing that a blood-cell should be on one side or the other of a microscopic film in a tadpole's tail; but this diapedesis, the first move of the blood in its fight against disease, is now seen, in the light of Metschnikoff's work, as a fact of very great importance.

The history of this transitional period, from the study of inflammation in transparent living tissues to the use, in surgery, of the facts of bacteriology, is told in Lord Lister's Huxley Lecture, October 1900. He describes how the foundations were laid in surgical pathology, by microscopical and experimental work on inflammation, coagulation, suppuration, and pyæmia, for bacteriology to build on: how his own share of the work began when he was house-surgeon to Sir John Erichsen at University College Hospital, and afterward to Mr. Syme in Edinburgh, and how it was continued through all his Edinburgh and Glasgow life:—

"After being appointed to the Chair of Surgery in the University of Glasgow, I became one of the surgeons to the Royal Infirmary of that city. Here I had, too, ample opportunities for studying hospital diseases, of which the most fearful was pyæmia. About this time I saw the opinion expressed by a high authority in pathology that the pus in a pyæmic vein was probably a collection of leucocytes. Facts such as those which I mentioned as having aroused my interest in my student days in a case of pyæmia, made such a view to me incredible; and I determined to ascertain, if possible, the real state of things by experiment....

"While these investigations into the nature of pyæmia were proceeding, I was doing my utmost against that deadly scourge. Professor Polli, of Milan, having recommended the internal administration of sulphite of potash on account of its antiputrescent properties, I gave that drug a very full trial as a prophylactic.... At the same time, I did my best, by local measures, to diminish the risk of communicating contagion from one wound to another. I freely employed antiseptic washes, and I had on the tables of my wards piles of clean towels to be used for drying my hands and those of my assistants after washing them, as I insisted should invariably be done in passing from one dressing to another. But all my efforts proved abortive; as I could hardly wonder when I believed, with chemists generally, that putrefaction was caused by the oxygen of the air.

"It will thus be seen that I was prepared to welcome Pasteur's demonstration that putrefaction, like other true fermentations, is caused by microbes growing in the putrescible substance. Thus was presented a new problem: not to exclude oxygen from the wounds, which was impossible, but to protect them from the living causes of decomposition by means which should act with as little disturbance of the tissues as is consistent with the attainment of the essential object.... To apply that principle, so as to ensure the greatest safety with the least attendant disadvantage, has been my chief life-work."[12]