Chapter VI: Part II (1)

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]

[12] See also the admirable Life of Pasteur, by M. Valléry-Radot.
Translation by Mrs. Devonshire, vol. ii. p. 20.

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.

[13] This account of Semmelweis, reprinted by permission from the
_Middlesex Hospital Journal_, is mostly taken from Dr. Theodore
Duka's excellent paper on "Childbed Fever." (_Lancet_, 1886.)

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'OEuvre Médicale de
Pasteur_. _Agenda du Chimiste_, 1896, p. 528.)

[14] See Pasteur's Life, vol. ii. p. 89.

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]

[15] Dr. Legge, in his Milroy Lectures, 1905, on Industrial
Anthrax (_Lancet_, March and April 1905), gives a full account of
Sobernheim's work up to March 1904, and a table of seventy-six
cases, treated with Sclavo's serum.

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.

[16] See Dr. Flexner's account of the disease, in volume xix. of
Stedman's _Twentieth Century Practice_.

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

"Vaccination against _charbon_ has now been put to the test of
practice for fourteen years. Wherever it is adopted, there the
losses from _charbon_ have become insignificant. It was followed
by vaccination against swine-measles, _rouget des porcs_, the
special study of our poor friend Thuillier. But the immediate
result of Pasteur's vaccinations is their least merit: they have
given men absolute faith in a science that could show such good
works, they have started a movement that is irresistible; above
all, they have set going the whole study of immunity, which is
bringing us at last to a right way of treating infective
diseases.

"Virulence is a quality that microbes can lose, or can acquire.
Suppose we came across the anthrax-bacillus so far attenuated,
in the way of Nature, that it had lost all power to kill--of
course we should fail to recognise it; we should take it for an
ordinary bacillus of putrefaction: you must watch it through
each phase of its attenuation, to know that the harmless
organism is the descendant of the fatal virus. But you can give
back to it the virulence that it has lost, if you put it, to
begin with, under the skin of a very delicate subject, a mouse
only one day old. With the blood of this mouse inoculate
another, a little older, and it will die. Passing by this method
from younger to older mice, we come to kill adult mice,
guinea-pigs, then rabbits, then sheep, etc. Thus, by
transmission, the virus gains strength as it goes. Doubtless
this increase of virulence, that we bring about by experiment,
occurs also in Nature; and it is easy to see how a microbe,
usually harmless to this or that species of animals, might
become deadly to it. Is not this the way that infective diseases
have appeared on the earth from age to age?

"_See how far we have come, from the old metaphysical ideas
about virulence, to these microbes that we can turn this way or
that way--stuff so plastic that a man can work on it, and
fashion it as he likes._"

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._

+------+-----------+--------+----------+------------------------+
| | | | | Mortality. |
| | | | Animals +-------+-------+--------+
| | Total | |Vaccinated|After |After |During |
| | Number of | Number |according |First |Second |the rest|
| | Animals | of |to Reports|Vacci- |Vacci- |of the |
|Years.|Vaccinated.|Reports.|received. |nation.|nation.| Year. |
+------+-----------+--------+----------+-------+-------+--------+
| 1882 | 270,040 | 112 | 243,199 | 756 | 847 | 1,037 |
| 1883 | 268,505 | 103 | 193,119 | 436 | 272 | 784 |
| 1884 | 316,553 | 109 | 231,693 | 770 | 444 | 1,033 |
| 1885 | 342,040 | 144 | 280,107 | 884 | 735 | 990 |
| 1886 | 313,288 | 88 | 202,064 | 652 | 303 | 514 |
| 1887 | 293,572 | 107 | 187,811 | 718 | 737 | 968 |
| 1888 | 269,574 | 50 | 101,834 | 149 | 181 | 300 |
| 1889 | 239,974 | 43 | 88,483 | 238 | 285 | 501 |
| 1890 | 223,611 | 69 | 69,865 | 331 | 261 | 244 |
| 1891 | 218,629 | 65 | 53,640 | 181 | 102 | 77 |
| 1892 | 259,696 | 70 | 63,125 | 319 | 183 | 126 |
| 1893 | 281,333 | 30 | 73,939 | 234 | 56 | 224 |
+------+-----------+--------+----------+-------+-------+--------+
| Total|3,296,815 | 990 |1,788,879 | 5,668 |4,406 | 6,798 |
+------+-----------+--------+----------+-------+-------+--------+

+------+-------+-----+-------+
| | | | |
| | | |Average|
| | |Total| loss |
| | Total.| loss|before |
| | | per |Vacci- |
|Years.| | 100.|nation.|
+------+-------+-----+-------+
| 1882 | 2,640 | 1.08| 10% |
| 1883 | 1,492 | 0.77| " |
| 1884 | 2,247 | 0.97| " |
| 1885 | 2,609 | 0.93| " |
| 1886 | 1,469 | 0.72| " |
| 1887 | 2,423 | 1.29| " |
| 1888 | 630 | 0.62| " |
| 1889 | 1,024 | 1.16| " |
| 1890 | 836 | 1.20| " |
| 1891 | 360 | 0.67| " |
| 1892 | 628 | 0.99| " |
| 1893 | 514 | 0.69| " |
+------+-------+-----+-------+
| Total|16,872 | 0.94| 10% |
+------+-------+-----+-------+

VACCINATION AGAINST CHARBON (FRANCE).

_Cattle._

+------+-----------+--------+----------+------------------------+
| | | | | Mortality. |
| | | | Animals +-------+-------+--------+
| | Total | |Vaccinated| After | After |During |
| | Number of | Number |according | First | Second|the rest|
| | Animals | of |to Reports|Vacci- |Vacci- |of the |
|Years.|Vaccinated.|Reports.|received. |nation.|nation.| Year. |
+------+-----------+--------+----------+-------+-------+--------+
| 1882 | 35,654 | 127 | 22,916 | 22 | 12 | 48 |
| 1883 | 26,453 | 130 | 20,501 | 17 | 1 | 46 |
| 1884 | 33,900 | 139 | 22,616 | 20 | 13 | 52 |
| 1885 | 34,000 | 192 | 21,073 | 32 | 8 | 67 |
| 1886 | 39,154 | 135 | 22,113 | 18 | 7 | 39 |
| 1887 | 48,484 | 148 | 28,083 | 23 | 18 | 68 |
| 1888 | 34,464 | 61 | 10,920 | 8 | 4 | 35 |
| 1889 | 32,251 | 68 | 11,610 | 14 | 7 | 31 |
| 1890 | 33,965 | 71 | 11,057 | 5 | 4 | 14 |
| 1891 | 40,736 | 68 | 10,476 | 6 | 4 | 4 |
| 1892 | 41,609 | 71 | 9,757 | 8 | 3 | 15 |
| 1893 | 38,154 | 45 | 9,840 | 4 | 1 | 13 |
+------+-----------+--------+----------+-------+-------+--------+
|Total | 438,824 | 1,255 | 200,962 | 177 | 82 | 432 |
+------+-----------+--------+----------+-------+-------+--------+

+------+-------+-----+-------+
| | | | |
| | | |Average|
| | |Total| loss |
| | Total.| loss|before |
| | | per |Vacci- |
|Years.| | 100.|nation.|
+------+-------+-----+-------+
| 1882 | 82 | 0.35| 5% |
| 1883 | 64 | 0.31| " |
| 1884 | 85 | 0.37| " |
| 1885 | 107 | 0.50| " |
| 1886 | 64 | 0.29| " |
| 1887 | 109 | 0.39| " |
| 1888 | 47 | 0.43| " |
| 1889 | 52 | 0.45| " |
| 1890 | 23 | 0.21| " |
| 1891 | 14 | 0.13| " |
| 1892 | 26 | 0.26| " |
| 1893 | 18 | 0.18| " |
+------+-------+-----+-------+
|Total | 691 | 0.34| 5% |
+------+-------+-----+-------+

"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).

+------+-----------+--------+----------+------------------------+
| | | | | Mortality. |
| | | | Animals +-------+-------+--------+
| | Total | |Vaccinated|After |After |During |
| | Number of | Number |according |First |Second |the rest|
| | Animals | of |to Reports|Vacci- |Vacci- |of the |
|Years.|Vaccinated.|Reports.|received. |nation,|nation.| Year. |
+------+-----------+--------+----------+-------+-------+--------+
| |{ For these| | | | | |
| |{ two years| | | | | |
| 1886 |{ France | 49 | 7,087 | 91 | 24 | 56 |
| |{ and other| | | | | |
| |{ countries| | | | | |
| 1887 |{ are put | 49 | 7,467 | 57 | 10 | 23 |
| |{ together.| | | | | |
| 1888 | 15,958 | 31 | 6,968 | 31 | 25 | 38 |
| 1889 | 19,338 | 41 | 11,257 | 92 | 12 | 40 |
| 1890 | 17,658 | 41 | 14,992 | 118 | 64 | 73 |
| 1891 | 20,583 | 47 | 17,556 | 102 | 34 | 70 |
| 1892 | 37,900 | 38 | 10,128 | 43 | 19 | 46 |
+------+-----------+--------+----------+-------+-------+--------+
|Total | 111,437 | 296 | 75,455 | 534 | 188 | 345 |
+------+-----------+--------+----------+-------+-------+--------+

+------+-------+-----+-------+
| | | | |
| | | |Average|
| | |Total| loss |
| | Total.| loss|before |
| | | per |Vacci- |
|Years.| | 100.|nation.|
+------+-------+-----+-------+
| | | | |
| | | | |
| 1886 | 171 | 2.41| 20% |
| | | | |
| | | | |
| 1887 | 90 | 1.21| " |
| | | | |
| 1888 | 94 | 1.35| " |
| 1889 | 144 | 1.28| " |
| 1890 | 254 | 1.70| " |
| 1891 | 206 | 1.17| " |
| 1892 | 108 | 1.07| " |
+------+-------+-----+-------+
|Total | 1,067 | 1.45| 20% |
+------+-------+-----+-------+

[17] "The reports for 1893 are at present too few to be utilised
for this table."

"_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]

[18] "In Zukunft wird man es im Kampf gegen diese schreckliche
Plage des Menschengeschlechtes nicht mehr mit einem unbestimmten
Etwas, sondern mit einem fassbaren Parasiten zu thun haben, dessen
Lebensbedingungen zum grössten Theil bekannt sind und noch weiter
erforscht werden. Es müssen vor allen Dingen die Quellen, aus
denen der Infektionsstoff fliesst, so weit es in menschlicher
Macht liegt, verschlossen werden."

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.

[19] At the British Congress on Tuberculosis, London, 1901, Koch
stated that bovine tuberculosis and human tuberculosis are not one
and the same disease, and that the risk of milk-infection is so
small that burdensome restrictions ought not to be enforced. In
the general judgment of men well qualified to study the subject,
he failed to prove his point.

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.

[20] For references to this paper, and to evidence put forward
against the validity of the test, and for criticism of such
evidence, see Gould's _Year-Book of Medicine and Surgery_, 1902
(Philadelphia, W. B. Saunders & Company).

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:--

Streptococci 6
Staphylococci 55
Bacilli 19
Torulæ 9
Sarcinæ 6
Streptococci and micrococci 2
Micrococci and bacilli 9
Streptococci and bacilli 1
Torulæ and bacilli 1
Micrococci and sarcinæ 6
Micrococci and torulæ 4
Many forms present together 19
----
137
----

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.)

"The most striking confirmation of the value of antitoxin has
been afforded where the supply ran short during an epidemic. In
Baginsky's clinic, the interruption of the serum-treatment
promptly raised the mortality from 15.6 to 48.4 per cent."
(_Brit. Med. Journ._, 20th October 1895.)

"In an analysis of the ratio of mortality in 266 German cities
of about 15,000 inhabitants, it was found that the ratio of
mortality per 100,000 of the living, before antitoxin was used,
varied from 130 to 84 from 1886 to 1893, while the ratio from
1894 to 1897 varied from 101 to 35. It is a significant fact
that during 1894, when, although antitoxin was used to a certain
extent, it was not in general use, the ratio was 101; that when
antitoxin was used more extensively, in 1895, the ratio was 53;
that in 1896 it was 43; that in 1897, when antitoxin was very
generally used, the rate fell to 35." (_Trans. Massachusetts
Med. Soc._, 1898.)

"Dr. Gabritchefski points out that in recent years the number of
persons (in Russia) attacked by the disease has increased, the
figures for the whole of Russia rising from about 100,000 or
120,000, ten years ago, to considerably over 200,000 in 1897.
The introduction of the serum treatment has, however, had a
marked effect on the mortality of the disease; and the actual
number of deaths from diphtheria has either not increased at
all, or has slightly diminished." (_Lancet_, 5th Aug. 1899.)