Part II — Experiments in Pathology, Materia Medica, and Therapeutics
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
And, of course, the application of that principle is not limited to the performance of the major operations of surgery. It is in daily use in every hospital, and in every practice all the world over, for the safe and quick healing of whole legions of injuries, “casualties,” and minor operations.
But what of Semmelweis, and his study of puerperal fever? Did he not, before Lord Lister, and without the help of experiments on animals, discover antiseptic surgery? His claim is urged by those who are opposed to all such experiments. And the answer is, that his work was lost just for want of experiments on animals. If he could have demonstrated, as Pasteur did, the living organism, the thing itself, there in the tissues of an infected rabbit, and in a test-tube, and under a microscope, he might have stopped the mouths of his adversaries. He could not. He could only demonstrate to them the fact that their patients died, and his patients lived: and that some sort of direct infection was the cause of the deaths. The tragedy of his life cannot be told too often, and may be told again here.13 For want of the final proof that bacteriology, and the inoculation of animals, alone could give, he was unable to hold out against his enemies till Pasteur could rescue him.
In 1846, when he was twenty-three years old, Ignaz Semmelweis was appointed assistant-professor in the maternity department of the huge general hospital of Vienna. For many years, the mortality in the lying-in wards had been about 1.25 per cent., and no more. Then, under a new professor, it had risen; and, for some years before Semmelweis came on the scene, it had been 5 per cent., or even 7 per cent. In October 1841, there had been an epidemic that had lasted till May 1843. In these twenty months, out of 5139 women delivered, 829 had died; that is to say, 16 per cent.
There were two sets of wards in the maternity department. The one set may be called Clinique A, and the other Clinique B. For many years, the mortality had been the same in each. In 1841 a change was made: Clinique A was assigned to the teaching of students, and Clinique B to the teaching of midwives: and, so soon as this change had been made, the mortality in Clinique B became less, but the mortality in Clinique A did not. Commissions of inquiry were held, and in vain. It was suggested that the foreign students were somehow to blame, nobody knew why; and many of them were sent away. Still the deaths went on. Women admitted to Clinique A would go down on their knees and pray to be allowed to go home; almost every day the bell was heard ringing in the wards, for the administration of the Sacrament to a dying woman. People talked about atmospheric influences, and overcrowding, and the tainted air of old wards, and the power of the mind over the body: and Semmelweis set to work.
He observed that cases of protracted labour in Clinique A died, almost all of them; but not in Clinique B. He observed also that cases of premature labour, nearly all of them, did well, whichever Clinique they were in; so did those women who were delivered before they came to the hospital, and were admitted after delivery. He observed also that a row of patients, lying side by side, would all be attacked at once in Clinique A; which never happened in Clinique B. He tried everything: he altered the details of treatment; he used various subterfuges to prevent one of the professors from examining serious cases; he enforced this or that rule in Clinique A, because it was the custom in Clinique B; he slaved away at the notes of the cases—and at last the truth came to him, by the death of one of his friends from a dissection-wound. He says, “My friend’s fatal symptoms unveiled to my mind an identity with those which I had so often noticed at the deathbeds of puerperal cases.” He saw now that the students, coming straight from the dissecting-rooms, had infected the patients during examination.
In May 1847 he gave orders that every student, before examining, should thoroughly disinfect his hands. But, though he had reckoned with dissecting-room poisons, he had forgotten to reckon with other sources of infection. In October of that year, a woman was admitted who had malignant disease; of twelve women examined after her, eleven got puerperal fever, and died. In November, a woman was admitted who had a suppurating knee-joint, with sinuses; and eight women were infected from her, and died. Therefore Semmelweis said, “Not only can the particles from dead bodies generate puerperal fever, but any decomposed material from the living body can also generate it, and so can air contaminated by such materials.” Henceforth he isolated all infected cases, he enforced the strict use of disinfectants: and the mortality in Clinique A, which in May 1847 had stood at 12.24 per cent., fell in December to 3.04, and in 1848 was 1.27.
His work was taken up with enthusiasm by Hebra, Skoda, and Haller; the news of it was sent to every capital in Europe. In February 1849 Haller read a paper on it before the Medical Society of Vienna, and said, “The importance of these observations is above all calculation, both for the maternity department and for the hospitals in general, but particularly for the surgical wards.” A committee was nominated to report on the whole matter; but it was opposed by the professor in charge of Clinique A, and nothing came of it. In May 1850, Semmelweis opened a great debate on puerperal fever, which occupied three sittings of the Vienna Medical Society. His opponents were there in full force, all the Scribes and Pharisees of the profession. They brought about a vague distrust of his figures and his facts; they got people to believe that there must be “something else” in puerperal fever, as well as the local infection. Semmelweis began to be discouraged. The University authorities made a dead set against him—they refused to renew his appointment, they got him out of the hospital, and out of Vienna. He went to Pesth, and was Professor of Midwifery there; but the same opposition and hostility were at Pesth as at Vienna. Slowly he began to lose his hold over himself, went down hill, became excitable and odd. The end came in July 1865. At a meeting of University professors, he suddenly took a paper from his pocket and read aloud to them a solemn oath, to be enforced on every midwife and every doctor. His mind had given way: he was moved to an asylum at Vienna, and died there a few weeks later. He was only forty-two when he died—What a wounded name, Things standing thus unknown, shall live behind me.
The contrast between the work of Semmelweis and the work of Pasteur cuts like a knife here. The failure of Semmelweis’ teaching may be estimated by the fact that it had all to be done over again. The year of his success at Vienna was 1848. Eight years later, in the Paris Maternity Hospital, between 1st April and 10th May 1856, came such an outbreak of puerperal fever that out of 347 patients 64 died. In 1864, out of 1350 cases, 310 deaths. In Jan.-Feb. 1866, out of 103 cases, 28 deaths: “Women of the lower classes looked upon the Maternité as the vestibule of death.” In 1877-78, came the use of carbolic acid and perchloride of mercury at the hospital, thirty years after Semmelweis’ work: and, about the same time, Pasteur’s discovery of the streptococcus in puerperal fever.14 Pasteur could demonstrate to his opponents the visible cause of the infection, the thing itself. Roux tells the story:—
“Dans le pus des abcès chauds et dans celui des furoncles on constate un petit organisme arrondi, disposé en amas, qu’on cultive facilement dans le bouillon. On le retrouve dans l’ostéomyélite infectieuse des enfants. Pasteur affirme que l’ostéomyélite et le furoncle sont deux formes d’une même maladie, et que l’ostéomyélite est le furoncle de l’os. En 1878, cette assertion a fait rire bien les chirurgiens.
“Dans les infections puerpérales, les caillots renferment un microbe à grains arrondis se disposant en files. Cet aspect en chapelet est surtout manifesté dans les cultures. Pasteur n’hésite pas à déclarer que cet organisme microscopique est la cause la plus fréquente des infections chez les femmes accouchées. Un jour, dans une discussion sur la fièvre puerpérale à l’Académie de Médicine, un de ses collégues le plus écoutés dissertait éloquemment sur les causes des épidémies dans les maternités. Pasteur l’interrompt de sa place: Ce qui cause l’épidémie, ce n’est rien de tout cela: c’est le médecin et son personnel qui transportent le microbe d’une femme malade à une femme saine. Et comme l’orateur répondit qu’il craignait fort qu’on ne trouve jamais ce microbe, Pasteur s’élance vers le tableau noir, dessine l’organisme en chapelet de grains, en disant, Tenez, voici sa figure.” (Roux, L’Œuvre Médicale de Pasteur. Agenda du Chimiste, 1896, p. 528.)
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.)