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.)
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:—
"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:—
"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.
| Years. |
Total
Number of
Animals
Vaccinated. |
Number
of
Reports. |
Animals
Vaccinated
according
to Reports
received. |
Mortality. |
Total. |
Total
loss
per
100. |
Average
loss
before
Vacci-
nation. |
After
First
Vacci-
nation. |
After
Second
Vacci-
nation. |
During
the rest
of the
Year. |
| 1882 |
270,040 |
112 |
243,199 |
756 |
847 |
1,037 |
2,640 |
1.08 |
10% |
| 1883 |
268,505 |
103 |
193,119 |
436 |
272 |
784 |
1,492 |
0.77 |
" |
| 1884 |
316,553 |
109 |
231,693 |
770 |
444 |
1,033 |
2,247 |
0.97 |
" |
| 1885 |
342,040 |
144 |
280,107 |
884 |
735 |
990 |
2,609 |
0.93 |
" |
| 1886 |
313,288 |
88 |
202,064 |
652 |
303 |
514 |
1,469 |
0.72 |
" |
| 1887 |
293,572 |
107 |
187,811 |
718 |
737 |
968 |
2,423 |
1.29 |
" |
| 1888 |
269,574 |
50 |
101,834 |
149 |
181 |
300 |
630 |
0.62 |
" |
| 1889 |
239,974 |
43 |
88,483 |
238 |
285 |
501 |
1,024 |
1.16 |
" |
| 1890 |
223,611 |
69 |
69,865 |
331 |
261 |
244 |
836 |
1.20 |
" |
| 1891 |
218,629 |
65 |
53,640 |
181 |
102 |
77 |
360 |
0.67 |
" |
| 1892 |
259,696 |
70 |
63,125 |
319 |
183 |
126 |
628 |
0.99 |
" |
| 1893 |
281,333 |
30 |
73,939 |
234 |
56 |
224 |
514 |
0.69 |
" |
| Total |
3,296,815 |
990 |
1,788,879 |
5,668 |
4,406 |
6,798 |
16,872 |
0.94 |
10% |
Vaccination against Charbon (France).
Cattle.
| Years. |
Total
Number of
Animals
Vaccinated. |
Number
of
Reports. |
Animals
Vaccinated
according
to Reports
received. |
Mortality. |
Total. |
Total
loss
per
100. |
Average
loss
before
Vacci-
nation. |
After
First
Vacci-
nation. |
After
Second
Vacci-
nation. |
During
the rest
of the
Year. |
| 1882 |
35,564 |
127 |
22,916 |
22 |
12 |
48 |
82 |
0.35 |
5% |
| 1883 |
26,453 |
130 |
20,501 |
17 |
1 |
46 |
64 |
0.31 |
" |
| 1884 |
33,900 |
139 |
22,616 |
20 |
13 |
52 |
85 |
0.37 |
" |
| 1885 |
34,000 |
192 |
21,073 |
32 |
8 |
67 |
107 |
0.50 |
" |
| 1886 |
39,154 |
135 |
22,113 |
18 |
7 |
39 |
64 |
0.29 |
" |
| 1887 |
48,484 |
148 |
28,083 |
23 |
18 |
68 |
109 |
0.39 |
" |
| 1888 |
34,464 |
61 |
10,920 |
8 |
4 |
35 |
47 |
0.43 |
" |
| 1889 |
32,251 |
68 |
11,610 |
14 |
7 |
31 |
52 |
0.45 |
" |
| 1890 |
33,965 |
71 |
11,057 |
5 |
4 |
14 |
23 |
0.21 |
" |
| 1891 |
40,736 |
68 |
10,476 |
6 |
4 |
4 |
14 |
0.13 |
" |
| 1892 |
41,609 |
71 |
9,757 |
8 |
3 |
15 |
26 |
0.26 |
" |
| 1893 |
38,154 |
45 |
9,840 |
4 |
1 |
13 |
18 |
0.18 |
" |
| Total |
438,824 |
1,255 |
200,962 |
177 |
82 |
432 |
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.
"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).
| Years. |
Total
Number of
Animals
Vaccinated. |
Number
of
Reports. |
Animals
Vaccinated
according
to Reports
received. |
Mortality. |
Total. |
Total
loss
per
100. |
Average
loss
before
Vacci-
nation. |
After
First
Vacci-
nation. |
After
Second
Vacci-
nation. |
During
the rest
of the
Year. |
| |
{ |
|
|
|
|
|
|
|
|
|
| |
For these
two years |
|
|
|
|
|
|
|
|
| 1886 |
France |
49 |
7,087 |
91 |
24 |
56 |
171 |
2.41 |
20% |
| |
and other
countries |
|
|
|
|
|
|
|
|
| 1887 |
are put |
49 |
7,467 |
57 |
10 |
23 |
90 |
1.21 |
" |
| |
together. |
|
|
|
|
|
|
|
|
| 1888 |
|
15,958 |
31 |
6,968 |
31 |
25 |
38 |
94 |
1.35 |
" |
| 1889 |
|
19,338 |
41 |
11,257 |
92 |
12 |
40 |
144 |
1.28 |
" |
| 1890 |
|
17,658 |
41 |
14,992 |
118 |
64 |
73 |
254 |
1.70 |
" |
| 1891 |
|
20,583 |
47 |
17,556 |
102 |
34 |
70 |
206 |
1.17 |
" |
| 1892 |
|
37,900 |
38 |
10,128 |
43 |
19 |
46 |
108 |
1.07 |
" |
| Total |
|
111,437 |
296 |
75,455 |
534 |
188 |
345 |
1,067 |
1.45 |
20% |
"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.
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.
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.)
Of course there will still be bad diphtheria years and
good diphtheria years: for example, the death-rate of
the population of England, from diphtheria, was higher
during the years 1893-1899 than during the years
1889-1892. Antitoxin can no more prevent a bad
diphtheria year than an umbrella can prevent a wet day.
But in limited outbreaks of diphtheria, such as occur in
a village, an asylum, a school, or a large family of young
children, it can be used, and is used, as a prophylactic,
and with admirable results. The example of Dr. Kármán,
just quoted, is one of the earliest instances of this
preventive use of antitoxin: other instances, of equal
importance, are given in the Boston Medical and Surgical
Journal, December 1897 and March 1898; and in the
Lancet, 2nd April 1898, and 28th January 1899. A
summary of later experiences of this preventive use of
antitoxin in different countries is given by Dr. Wilcox
of New York, and Dr. Stevens of Philadelphia, in Gould's
Year-Book for 1902:—
"At a meeting of the Société de Pédiatrie (Paris),
held June 1901, a resolution was adopted affirming that
preventive inoculations present no serious dangers, and
confer immunity in the great majority of cases for some
weeks, and recommending their employment in children's
institutions and in families in which scientific surveillance
cannot be exercised. Netter stated that he had collected
32,484 observations (cases) of prophylactic injections, and
after eliminating cases in which the disease developed in
less than twenty-four hours after injection, or more than
thirty days after, there were 6 per cent. of failures. On
the other hand, the author stated that he had recently
made ninety preventive injections with but 2.17 per cent.
of failures. Potter reports a series of twenty-four families
in which preventive injections were used. Only one case
of diphtheria occurred. In another series of cases, in
which no prophylactic injections were given, the disease
occurred secondarily in one-third of the houses, and one-sixth
of the inmates contracted the disease, in spite of the
fact that a large number of the primary cases were removed
to the hospital. Blake reports a series of thirty-five
prophylactic injections. The treatment was instituted
after three cases of diphtheria had developed in a children's
home. No secondary cases developed. Voisin and
Guinon describe an epidemic of diphtheria in the Salpetrière
Hospital among idiots and epileptics. Prophylactic
injections were given to all those exposed to the contagion.
After that, but four cases appeared, all mild in character.
One severe case developed, however, two weeks later,
ending fatally in twenty-four hours, showing that the
prophylactic action of the antitoxin, while efficacious, is
not of very long duration."
It would be easy to prolong ad infinitum the proofs of
the curative and preventive efficacy of the antitoxin: it
would be impossible to find any evidence to be weighed
for one moment against these proofs. There are three
early records that ought to be quoted more fully: the
1894 report from the Hospital for Sick Children, Paris;
the 1896 report of the American Pædiatric Society;
and the 1898 report of the Clinical Society of London.
The report from the Hospital for Sick Children,
Paris, is contained in a memoir, Sérum-Thérapie de la
Diphtérie, the joint work of MM. Roux, Martin, and
Chaillon (Annales de l'Institut Pasteur, September 1894).
It gives the results of the serum-treatment during February
to July 1894. The cases were not selected: the
antitoxin was given in every case that was proved, by
bacteriological examination, to be diphtheria—with the
exception of 20 cases where the children were just
dying when they were brought to the hospital. No
change was made either in the general treatment or in
the local applications to the throat; these were the same
that had been used in former years: le sérum est le seul
élément nouveau introduit.
In 1890-1893, before the serum-treatment, 3971
children were admitted to the diphtheria wards, and 2029
of them died. The percentage of these deaths was—
In 1890 55.88
" 1891 52.45
" 1892 47.64
" 1893 48.47 |
} |
Average = 51.71. |
The serum was used from 1st February to 24th July
1894. During this period 448 children were admitted,
of whom 109 died = 24.5.
During the same period (February to June) the
Trousseau Hospital, where the serum was not used,
had 520 cases, with 316 deaths = 60.0.
The cases at the Hospital for Sick Children must be
divided into those that required tracheotomy and those
that did not require it:—
Mortality among Cases not requiring Tracheotomy.
In 1890 47.30
" 1891 46.64
" 1892 38.8
" 1893 32.02 |
} |
Average = 33.94. |
During the serum-period, the mortality of these cases
was 12.0. At the Trousseau Hospital, without the
serum, the mortality of these cases during the same
period was 32.0.
Mortality among Cases requiring Tracheotomy.
In 1890 76.35
" 1891 68.36
" 1892 74.6
" 1893 73.45 |
} |
Average = 73.49. |
During the serum-period, the mortality of these cases
was 49.0. At the Trousseau Hospital, without the
serum, the mortality of these cases during the same
period was 86.0.
Setting aside, out of the 448 children, those cases
of "membranous sore throat" or "pseudo-diphtheria,"
in which the Klebs-Loeffler bacillus was not found, there
remain 320 cases where it was found. Of these 320
children, 20 were just dying on admission, and did not
receive the serum. Of the 300 who received it, 78
died = 26.0. Before the serum-period, the mortality of
these cases at the same hospital was about 50.0. The
complications of diphtheria, such as paralysis, were
much less frequent during the serum-period than they
had been before it.
Report of the American Pædiatric Society's Collective
Investigation into the use of Antitoxin in the treatment
of diphtheria in private practice. (Eighth Annual
Meeting, Montreal, May 1896.) From the New York
Medical Record, 4th July 1896.
This vast collection of cases is of special interest,
because they occurred in private practice. In most of
them the nature of the disease was proved by bacteriological
examination; in the rest, the clinical evidence
was decisive: "It is possible that among the latter we
have admitted some streptococcus cases, but the number
of such is certainly very small." All other doubtful
cases, 244 in number, were excluded.
Three thousand three hundred and eighty-four cases
were reported by 613 physicians from 114 cities and
towns, in 15 different States, the District of Columbia,
and the Dominion of Canada. To these 3384 cases
were added 942 cases from tenement-houses in New
York, and 1468 cases from tenement-houses in Chicago.
The New York and Chicago cases were, most of them,
treated by a corps of inspectors of the Health Board of
the city; and the municipal surveillance was very strict
at Chicago:—
"There are very few hospitals in America that receive
diphtheria patients.... It was the custom in Chicago to
send an inspector to every tenement-house case reported,
and to administer the serum unless it was refused by the
parents. These cases were therefore treated much earlier,
and the results were correspondingly better than were
obtained in New York, although the serum used was the
same in both cities, viz., that of the New York Health
Board."
The sum total of results was 5794 cases, with 713
deaths = 12.3 per cent., including every case returned;
but 218 were moribund at the time of injection, or
died within twenty-four hours of the first injection.
"Should these be excluded, there would remain 5576
cases in which the serum may be said to have had a
chance, with a mortality of 8.8 per cent.
| Of |
996 |
cases injected |
on the first day of the disease, |
49 |
died |
= |
4.9 |
% |
| " |
1616 |
" |
on the second " |
120 |
" |
= |
7.4 |
" |
| " |
1508 |
" |
on the third " |
134 |
" |
= |
8.8 |
" |
| " |
758 |
" |
on the fourth " |
147 |
" |
= |
20.7 |
" |
| " |
690 |
" |
on or after the fifth " |
244 |
" |
= |
35.3 |
" |
And in 232 cases, where the day of injection was unknown,
there were 19 deaths = 8.2 per cent.
"No one feature of the cases of diphtheria treated
by antitoxin has excited more surprise among the
physicians who have reported them than the prompt
arrest, by the timely administration of the serum,
of membrane which was rapidly spreading downward
below the larynx. Such expressions abound in the
reports as 'wonderful,' 'marvellous,' 'in all my experience
with diphtheria, have never seen anything like
it before,' etc.
"Turning now to the operative cases, we find the
same remarkable effects of the antitoxin noticeable.
Operations were done in 565 cases, or in 16.7 per
cent. of the entire number reported. Intubation was
performed 533 times, with 138 deaths, or a mortality
of 25.9 per cent. In the above are included 9 cases
in which a secondary tracheotomy was done, with
7 deaths. In 32, tracheotomy only was done, with
12 deaths, a mortality of 37.4 per cent. Of the 565
operative cases, 66 were either moribund at the time
of operation or died within twenty-four hours after
injection. Should these be deducted, there remain
499 cases operated upon, by intubation or tracheotomy,
with 84 deaths, a mortality of 16.9 per cent.
"Let us compare the results of intubation, in cases
in which the serum was used, with those obtained with
this operation before the serum was introduced. Of
5546 intubation cases in the practice of 242 physicians,
collected by M'Naughton and Maddren (1892), the
mortality was 69.5 per cent. Since that time, statistics
have improved materially by the general use (in and
about New York, at least) of calomel fumigations.
With this addition, the best results published (those of
Brown) showed in 279 cases a mortality of 51.6 per cent.
"But even these figures do not adequately express
the benefit of antitoxin in laryngeal cases. Witness
the fact that over one-half the laryngeal cases did not
require operation at all. Formerly, 10 per cent. of recoveries
was the record for laryngeal cases not operated
upon. Surely, if it does nothing else, the serum saves
at least double the number of cases of laryngeal diphtheria
that has been saved by any other method of
treatment."
In 1898, the Clinical Society published the Report
of their Special Committee, based on 633 cases (Trans.
Clin. Soc., xxxi., 1898, pp. 1-50). The whole report
should be read carefully; but there is room here for
nothing more than the latter part of it. This is given
at length.
A
Table showing the General Mortality of cases treated, on the same
day of the disease, with and without Antitoxin.
Antitoxin Committee:
633 Cases treated
with Antitoxin. |
Metropolitan Asylums Board
1894:
3042 Cases treated without
Antitoxin. |
Difference
of
Percentage. |
| Day of the |
C |
D |
M |
Day of |
C |
D |
M |
|
| Disease on |
a |
e |
o |
Admission |
a |
e |
o |
|
| which |
s |
a |
r |
to |
s |
a |
r |
|
| Treatment |
e |
t |
t |
Hospital |
e |
t |
t |
|
| was begun. |
s. |
h |
i |
|
s. |
h |
a |
|
| |
|
s. |
l |
|
|
s. |
l |
|
| |
|
|
i |
|
|
|
i |
|
| |
|
|
t |
|
|
|
t |
|
| |
|
|
y. |
|
|
|
y. |
|
| |
|
|
|
|
|
|
|
|
| |
|
|
% |
|
|
|
% |
|
| 1st |
20 |
2 |
10.0 |
1st |
133 |
30 |
22.5 |
12.5 |
| 2nd |
92 |
10 |
10.8 |
2nd |
539 |
146 |
27.0 |
16.2 |
| 3rd |
133 |
20 |
15.0 |
3rd |
652 |
192 |
29.4 |
14.4 |
| 4th |
130 |
26 |
20.0 |
4th |
566 |
179 |
31.6 |
11.6 |
| 5th |
258 |
66 |
25.5 |
5th |
1,152 |
355 |
30.8 |
5.3 |
| and after. |
|
|
|
|
|
|
|
|
| Totals |
633 |
124 |
19.5 |
Totals |
3,042 |
902 |
29.6 |
10.1 |
B
Summary and Conclusions of the Committee's Report
"The material for the investigation of the clinical
value of the antitoxin serum in the treatment of
diphtheria was not obtained from selected, but from
consecutive, cases, reported from the general hospitals
and the fever hospitals of the Metropolitan Asylums
Board; all were made use of which fulfilled the requirements
of the Committee.
"The Committee rejected all cases in which satisfactory
proof of the existence of true diphtheria was
not shown, either by the presence of the Bacillus diphtheriæ
upon bacteriological examination, or by the occurrence
of paralysis in the course of the illness. All
were also rejected in which the amount of antitoxin
administered was stated in cubic centimetres and not
in normal units, the Committee having no means by
which the strength of the antitoxin could in these cases
be determined.
"Six hundred and thirty-three cases form the basis
on which the report is drawn up; 549 were treated
with antitoxin obtained from the laboratory of the
Royal Colleges of Physicians and Surgeons; the remainder,
84 in number, were injected with antitoxin
obtained from other sources. In nine instances, antitoxin
from two different sources was injected into the
same patient.
"Statistics of the disease before the use of antitoxin
are introduced as control series; these were obtained
from the fever hospitals of the Metropolitan Asylums
Board, and from the general hospitals; and, like the
antitoxin series, are compiled from consecutive and not
from selected cases.
"The general mortality, under the antitoxin treatment,
was 19.5 per cent.; a reduction of 10 on the
percentage mortality of the cases treated in the hospitals
of the Metropolitan Asylums Board in 1894.
If 15 fatal cases, in which death took place within
twenty-four hours of the first injection, be deducted,
the mortality falls to 15.6 per cent.; which is very
little more than half the mortality during 1894 under
other forms of treatment.
"The lessened mortality is especially noticeable in
the earlier years of life, the percentage mortality of
children under five being 26.3, as opposed to 47.4.
In the next period of five years, the percentage of
mortality is 16.0, as opposed to 26.0; whilst after
ten years of age the difference in the mortality is
slight.[21]
"Laryngeal diphtheria is admittedly the most dangerous
form. The laryngeal cases have a percentage
mortality of 23.6 in the antitoxin, as compared with
66.0 in the non-antitoxin series. In the cases in
which laryngeal symptoms are so severe as to necessitate
tracheotomy, the saving of life by the use of
antitoxin is very marked, the mortality being reduced
one-half, to 36.0 as opposed to 71.6 per cent.
"The strongest evidence of the value of the antitoxin
treatment is that, in addition to reducing the
general mortality by one-third, the duration of life in
the fatal cases is decidedly prolonged. These two facts
taken together conclusively prove the beneficial effects
of the antitoxin treatment.
"The incidence of paralysis is greater in the antitoxin
than in the control series. This increased number
is partly explained by the lessened mortality, and partly
by the longer duration of life in the fatal cases affording
time for the development of paralytic symptoms.
The percentage mortality of those who had some form
or other of paralysis is lower in the antitoxin than
in the control series; so that, notwithstanding the
apparent greater risk of paralysis supervening, the
probability of final recovery is greater.
"No definite conclusion can be drawn, for the
reasons stated in the body of the report, as to the
advantage of administering the whole of the antitoxin
within forty-eight hours of the first injection, or continuing
it for a longer period; but evidence is afforded
of the importance of its administration as early as
possible in the course of the disease; the percentage
mortality in cases injected on the first and second days
of the disease being 10.7, as compared with 25.5 for
those first receiving the injection on the fifth or some
subsequent day.
"No conclusion can be drawn, from the cases reported
on, as to the amount of antitoxin which should
be used to produce the best effects; but they show that
the administration of very large doses is followed by no
pronounced ill effects.
"The injection of antitoxin is responsible for the
production of rashes, joint-pains, and possibly for the
occurrence of late pyrexia. In 34.7 per cent. the injections
were followed by rashes. Some amount of
fever accompanied the rash in 60 per cent. In only
9.4 per cent. of those in whom rashes were observed
did death ensue.
"Joint-pains were observed in 40, or 6.3 per cent.
of the whole number, and all but five of them had a
rash as well.
"In 26, or 65 per cent. of the joint-pains, some rise
of temperature accompanied the pain. A rise of temperature
during convalescence, accompanied by either
rash or joint-pain, occurred in 27, or 4.2 per cent. of
the whole number.
"No connection could be traced between the amount
of antitoxin administered and the occurrence of rashes
or late pyrexia, but the pain in and about the joints
appears to have a relationship to the amount of antitoxin
used.
"The results of the Committee's investigation tend
to show that by the use of antitoxin—
1. The general mortality is reduced by one-third.
2. The mortality in tracheotomy falls by one-half.
3. Extension of membrane to the larynx very rarely
occurs after the administration of antitoxin.
4. The duration of life in the fatal cases is decidedly
prolonged.
5. The number of fatal cases is less when antitoxin
is used early in the illness than in those which do not
receive it until a later period.
6. The frequency of the occurrence of paralysis is not
diminished, but the percentage of recoveries in cases
with paralysis is slightly increased.[22]
7. Rashes are produced in about one-third of the
cases, and are attributable to the antitoxin.
8. Pain, and occasionally swelling about the joints, are
produced in a number of cases.
9. Even when used in large doses, no serious ill effects
have followed the injection of antitoxin."
The foregoing reports belong to ancient history.
Let us leave them, and study the record of the hospitals
of the Metropolitan Asylums Board. They serve a
city of 121 square miles, and 4-1/2 millions of inhabitants.
The use of the antitoxin in the hospitals of the Metropolitan
Asylums Board began in 1895. It had been
used in 1894 on a few cases only, during the latter
part of the year, and had been procured with much
difficulty from various sources, chiefly from the Institute
of Preventive Medicine. On 9th November 1894,
the Board applied to the Laboratories' Committee of
the Royal Colleges of Physicians and of Surgeons,
asking them to undertake the supply. Arrangements
were made for this purpose; and the sum of £1000
was given by the Goldsmiths' Company. Dr. Sims
Woodhead, then Director of the Laboratories of the
Conjoint Colleges, now Professor of Pathology at Cambridge,
was put in charge of the bacteriological work
and the preparation of the serum, with a host of
expert colleagues: the administration of the treatment
was the work of the medical officers of the hospitals
of the Metropolitan Asylums Board. The experiences
of 1895 are given in the following passages from the
joint report to the Board from the medical superintendents:—
"The period covered by the report extends from 1st
January 1895 to 31st December of the same year.
During this time—with the exception of an interval of
three months at the Eastern Hospital, when its use was
suspended; of three months at the Fountain, and to a
considerable extent throughout the year at the South-Eastern
Hospital, when all cases were consecutively
treated, irrespective of their severity—the serum was
administered only to cases which at the time of admission
were severe, or which threatened to become so. In a
certain number, the patients being moribund at the time
of their arrival, and beyond the reach of any treatment,
no antitoxin was given. No change has taken place
during the year in the local treatment of the cases, nor
has there been any new factor in the treatment other
than the injection of antitoxin.
"It must be clearly understood that, with the exceptions
previously stated, it has been the practice at each
of the hospitals to administer serum to those cases only
in which the symptoms on admission were sufficiently
pronounced to give rise to anxiety, the mild cases not
receiving any.
"No less than 46.4 per cent. of the antitoxin cases were
under five years of age, against 32.5 per cent. in the non-antitoxin
group; and only 16.1 per cent. in the former
class were over ten years of age, against 33.8 per cent.
in the latter. The high fatality of diphtheria in the
earlier years of life is notorious.
"It is obvious, therefore, that to compare the mortality
of those treated with antitoxin with that of those which
during the same period were not so treated, would be to
institute a comparison between the severe cases and
those of which a large proportion were mild. This
would clearly be misleading.
"The only method by which an accurate estimate can
be obtained as to the merits of any particular form of
treatment, is by comparing a series of cases in which the
remedy has been employed with another series not so
treated, but which are similar, so far as can be, in other
respects. This, in the present instance, is impossible;
but, having regard to the fact that 61.8 of the 1895 cases
were treated with serum, an approximately accurate conclusion
can be drawn by contrasting all cases of diphtheria
completed during 1895, the antitoxin period, with
all cases completed during 1894.
"The year 1894 has been selected for the purpose of
comparison, not only because it is the year immediately
preceding the antitoxin period, but because the average
severity of the cases has been, in our opinion, about
equal. Moreover, the death-rate in 1894 was slightly
lower than it had been in any previous year.
" ... Of 3042 patients of all ages treated during 1894,
902 died—a mortality of 29.6 per cent.; whereas, of 3529
cases treated during 1895, 796 died—a mortality of 22.6
per cent.; the difference in percentage between the two
rates being therefore 7.1. This, assuming that the
former rate would otherwise have been maintained, represents
a saving of 250 lives during the past year.
Influence of Age.
Table showing variations in reduction of mortality obtained with
Antitoxin at different ages.
| Ages. |
Antitoxin Cases,
1895 |
All Cases,
1895 |
All Cases,
1894 |
Diff. in
Mortalities,
1894
and
1895. |
| Cases. |
Deaths. |
Mortality
per cent. |
Cases. |
Deaths. |
Mortality
per cent. |
Cases. |
Deaths. |
Mortality
per cent. |
| Under 5 |
1013 |
379 |
37.4 |
1453 |
497 |
34.2 |
1171 |
556 |
47.4 |
13.2 |
| " 10 |
1829 |
575 |
31.4 |
2720 |
744 |
27.3 |
2246 |
836 |
37.2 |
9.9 |
| " 15 |
2056 |
606 |
29.4 |
3144 |
779 |
24.7 |
2609 |
877 |
33.6 |
8.9 |
| All ages |
2182 |
615 |
28.1 |
3529 |
796 |
22.5 |
3042 |
902 |
29.6 |
7.1 |
For every age-group, with the single exception of that comprising
the years 15 to 20 (the numbers of which are small), the percentage
mortality was less in the 1895 than in the 1894 cases. The
reduction in mortality was greatest in early life.
Influence of Time of coming under Treatment.
Table showing percentage mortality in relation to day of disease
on which cases came under treatment.
| Day of Disease. |
1894. |
1895. |
Difference. |
| 1st |
22.5 |
11.7 |
10.8 |
| 2nd |
27.0 |
12.5 |
14.5 |
| 3rd |
29.4 |
22.0 |
7.4 |
| 4th |
31.6 |
25.1 |
6.5 |
| 5th and over |
30.8 |
27.1 |
3.7 |
| Total |
29.6 |
22.5 |
7.1 |
"It will be seen that the percentage mortality of cases
admitted on the same day of disease is less in every
instance in the year 1895. The difference is most
marked in the case of those patients who were admitted
on the first and second day of illness, viz., 10.8 and 14.5
respectively.
"Both in 1894 and 1895, no less than over 37 per
cent. of the patients were admitted on, or after, the fifth
day of disease. And, moreover, while in 1894 as many
as 59.2 per cent. of the fatal cases were not brought
under treatment until the fourth day, or later, in 1895,
the antitoxin year, the proportion was even higher, viz.,
67.7 per cent.
Laryngeal Cases
"The tracheotomy results at each hospital are more
favourable in the year 1895 than in 1894, the mortality
ranging in the latter year at the different hospitals
between 90 per cent. and 59.4 per cent., whereas in
1895 the range was from 56.2 to 40.5.
"The combined tracheotomy mortality for all the
hospitals, which in 1894 was 70.4 per cent., has fallen
to 49.4 per cent. in 1895. This is a lower death-rate
than has ever been recorded in any single hospital of
the Board for a year's consecutive tracheotomies. In
other words, rather more than 50 per cent. of children
on whom the operation has been performed have been
saved since the employment of antitoxin. In one of the
hospitals no less than a fraction under 60 per cent. survived,
although the recoveries in that hospital in any
previous year did not exceed 25 per cent., and in the
preceding year—viz., 1894—were as low as 10 per cent.
"The improved results in the tracheotomy cases of
1895 have also been shared by analogous cases in which
the operation was not performed. The percentage mortality
of all laryngeal cases has fallen from 62 in 1894 to
42.3 in 1895.
"Moreover, the number of laryngeal cases which required
tracheotomy has fallen in 1895 to 45.3 per cent.,
whereas in 1894 it was 56 per cent.
"The following tables briefly summarise the foregoing
results. As no returns for 1894 were furnished by the
Fountain Hospital by reason of the smallness of the
numbers, the Fountain cases have also been omitted
from the 1895 figures, in order that the two series may
be rendered strictly comparable:—
1. Comparative Mortality of Laryngeal Cases at all Hospitals,
except the Fountain.
| Year. |
Cases. |
Deaths. |
Percentage
Mortality. |
| 1894 |
466 |
289 |
62.0 |
| 1895 |
468 |
196 |
41.8 |
2. Comparative Results in Tracheotomy Cases at all Hospitals,
except the Fountain.
| Year. |
Cases. |
Deaths. |
Percentage
Mortality. |
| 1894 |
261 |
184 |
70.4 |
| 1895 |
219 |
108 |
49.3 |
3. Comparative Number of Laryngeal Cases which required
Tracheotomy at all Hospitals, except the Fountain.
| Year. |
Cases. |
Tracheotomies. |
Percentage of
Tracheotomies. |
| 1894 |
466 |
261 |
56.0 |
| 1895 |
468 |
219 |
46.8 |
"On these tables further comment seems unnecessary.
Summary
"The improved results in the diphtheria cases treated
during the year 1895, which are indicated by the foregoing
statistics and clinical observations, are—
1. A great reduction in the mortality of cases brought
under treatment on the first and second day of illness.
2. The lowering of the combined general mortality to
a point below that of any former year.
3. The still more remarkable reduction in the mortality
of the laryngeal cases.
4. The uniform improvement in the results of tracheotomy
at each separate hospital.
5. The beneficial effect produced on the clinical course
of the disease.
Conclusions
"A consideration of the foregoing statistical tables
and clinical observations, covering a period of twelve
months, and embracing a large number of cases, in our
opinion sufficiently demonstrates the value of antitoxin
in the treatment of diphtheria.
"It must be clearly understood, however, that to obtain
the largest measure of success with antitoxin it is essential
that the patient be brought under its influence at
a comparatively early date—if possible, not later than
the second day of disease. From this time onwards, the
chance of a successful issue will diminish in proportion
to the length of time which has elapsed before the treatment
is commenced. This, though doubtless true of
other methods, is of still greater moment in the case of
treatment by antitoxin.
"Certain secondary effects not unfrequently arise as a
direct result of the injection of antitoxin in the form in
which it has at present to be administered, and even
assuming that the incidence of the normal complications
of diphtheria is greater than can be accounted for by the
increased number of recoveries, we have no hesitation in
expressing the opinion that these drawbacks are insignificant
when taken in conjunction with the lessened
fatality which has been associated with the use of this
remedy.
"We are further of the opinion that in antitoxic serum
we possess a remedy of distinctly greater value in the
treatment of diphtheria than any other with which we
are acquainted."
Now let us take the whole record of all the hospitals
together. The disease was first admitted in 1888; this
year is therefore to be reckoned as incomplete.
| Year. |
Percentage
Mortality. |
Year. |
Percentage
Mortality. |
| 1888 |
59.35 |
1897 |
17.69 |
| 1889 |
40.74 |
1898 |
15.37 |
| 1890 |
33.55 |
1899 |
13.95 |
| 1891 |
30.63 |
1900 |
12.27 |
| 1892 |
29.35 |
1901 |
11.15 |
| 1893 |
30.42 |
1902 |
11.04 |
| 1894 |
29.29 |
1903 |
9.69 |
| 1895, first antitoxin year |
22.85 |
1904 |
10.08 |
| 1896 |
21.20 |
1905 |
8.3 |
These results, of course, are but one instance of what
has happened, since 1895, in every country all over
the civilised world. Securus judicat orbis terrarum. We
have Siegert's tables (1900), based on no less than
40,038 cases admitted in nine years to sixty-nine
hospitals in Germany, Austria, Switzerland, and Paris.
He divides these nine years into a "pre-serum period,"
an "introduction year," and a "serum period." In the
pre-serum period the general mortality was 41.5, and
the mortality of cases requiring operation was 60; in
the serum period, the general mortality was 16.5, and
the mortality of cases requiring operation was 37.5.
Any bad results that have been recorded from the
use of the antitoxin are so rare, in comparison with the
hundreds of thousands of injections made, that they do
not come to be considered here. And, even though a
few have occurred, we may be sure that some of them
were due, not to the antitoxin, but to the natural course
of the disease.[23] The lesser drawbacks, the occurrence
of joint pains and of rashes, are transient and in no
way serious.
It has been supposed, and said, that the use of the
antitoxin increases the complications of the disease.
On this point, the best authority is Professor Woodhead's
monumental Report (1901), dealing with the
Metropolitan Asylums Board cases for 1895 and 1896.
He sums up the matter thus:—
"The free use of antitoxin does not raise the percentage
of cases of albuminuria. As regards vomiting,
the statistics give little information, as vomiting is usually
met with only in the very severe cases. This also holds
good of anuria. The number of cases of adenitis appears
to be distinctly reduced by the use of antitoxin, as the
percentage of cases falls as the injections of antitoxin are
pushed. The use of antitoxin has also had a perceptible
effect in diminishing the cases of nephritis, and it certainly
has not aggravated the kidney complications of
diphtheria. There can be no doubt that in cases treated
with antitoxin there is a greater percentage of cases in
which joint-pains occur than in cases not so treated;
these, however, are transitory, and are probably the
result of some slight change in the blood set up by the
action of the serum itself, and not by the antitoxic substance
in the serum. The number of primary abscesses
has undoubtedly been reduced by the use of antitoxin.
It may also be accepted that antitoxic serum has some
effect in temporarily raising the temperature, but only
during the periods of joint-pains and serum rashes; all
these, however, are of comparatively slight importance
as compared with the effect the antitoxin has in diminishing
the percentage mortality and alleviating the more
severe symptoms.
"It is of importance to observe that amongst the cases
of paralysis following diphtheria the death-rate (32 per
cent.) was actually higher amongst those not injected
with antitoxin than amongst those where antitoxin was
used (30.5 per cent.), although the former paralyses must
be looked upon as being the result of a comparatively
mild attack of the disease. From this it is evident that,
when once paralysis supervenes in these cases, it is quite
as fatal in its effects as in the cases (usually those of a
more severe type) where antitoxin has been given. Antitoxin
cannot cure the degeneration of the nerve, but it
can neutralise the diphtheria toxin, and so put a stop to
the advance of the degenerative changes due to its action.
In 1896, when, of course, antitoxin was given much more
freely, the percentage of deaths in the non-injected cases
where paralysis had come on fell to 18.4.
"Antitoxin rashes occur at a comparatively late stage
of the disease. They cannot be looked upon as in any
way dangerous, although the secondary rise of temperature,
and the irritation of the skin which usually accompany
their presence are very undesirable complications,
and may retard somewhat the convalescence of nervous
and irritable patients.
"Antitoxin appears to diminish the liability of the lungs
to inflammatory change in severe attacks of diphtheria."
Now let us take another point of view. If anybody
really doubts whether the antitoxin did really save these
lives in the hospitals of the Metropolitan Asylums
Board, what answer has he got to the following table?
It is published in the Board's Report for 1904, and
was drawn up by Dr. MacCombie, Medical Superintendent
of the Brook Hospital. It shows the supreme
importance of giving the antitoxin at the very beginning
of the disease. The figures in brackets are the total
numbers of the cases in the eight years:—
Percentage Mortality according to Time of coming under
Treatment.
Day of
Disease. |
1897. |
1898. |
1899. |
1900. |
1901. |
1902. |
1903. |
1904. |
| (204) 1st |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
0.0 |
| (1278) 2nd |
5.4 |
5.0 |
3.8 |
3.6 |
4.1 |
4.6 |
4.2 |
5.43 |
| (1374) 3rd |
11.5 |
14.3 |
12.2 |
6.7 |
11.9 |
10.5 |
17.6 |
10.63 |
| (1086) 4th |
19.0 |
18.1 |
20.0 |
14.9 |
12.4 |
19.8 |
16.7 |
19.51 |
(1382) 5th
and after |
21.0 |
22.5 |
20.4 |
21.2 |
16.6 |
19.4 |
17.3 |
13.11 |
Here we see that in 1482 patients, who got the
antitoxin within forty-eight hours of the onset of the
disease, the mortality was 2-1/4 per cent. In 1278
patients, who did not get the antitoxin till the third
day, the mortality was 11-3/4 per cent. That is the
result of one day's delay over sending the child into
hospital.
Again, it is not only lives that are saved, but suffering
that is avoided. Just lately, at a meeting of the
Chelsea Clinical Society (May 1906), reference was
made to this point by Dr. Foord Caiger, Medical Superintendent
of the South-Western Hospital. "The
number of tracheotomies is less than half what it used
to be;" and again, "Instead of the spectacle of a
number of patients in great distress, with swollen necks
and stuffed-up noses, fretful and crying, such cases are
now quite the exception, and, in the few one does come
across, the condition lasts for a comparatively short
time." And again, "It was quite unusual (before
1895) for a nurse to care to stay very long in charge
of one of the diphtheria wards, because she found the
work so depressing. But nowadays the diphtheria
wards are perhaps the most popular in the hospital, a
fact which is mainly owing to the change in the general
aspect of the patients and the greatly reduced mortality."
(Clinical Journal, May 23, 1906.)
Before bacteriology, the cause of tetanus (lock-jaw) was
unknown, and men were free to imagine that it was
due to inflammation travelling up an injured nerve to
the central nervous system. This false and mischievous
theory was abolished by the experimental work of
Sternberg (1880), Carle and Rattone (1884), and
Nicolaier (1884), who proved, once and for all, that the
disease is an infection by a specific flagellate organism.
Their work was of the utmost difficulty, for many
reasons. First, because tetanus, in some tropical
countries, is so common that it may fairly be called
endemic; and many of these tropical cases, there being
no record of any external infection, had been taken as
evidence that the disease can occur "of itself." Of
this frequency of tetanus in tropical countries, Sir
Patrick Manson, in his book on Tropical Diseases (1898),
says:—
"Tetanus is an exceedingly common disease in some
tropical countries. In Western Africa, for example, a
large proportion of wounds, no matter how trifling as
wounds they may be, if they are fouled by earth or dirt,
result in tetanus. The French in Senegambia have
found this to their cost. A gentleman who had travelled
much in Congoland told me that certain tribes poison
their arrows by simply dipping the tips in a particular
kind of mud. A wound from these arrows is nearly sure
to cause tetanus. In many countries, so general and so
extensive is the distribution of the tetanus-bacillus that
trismus neonatorum (tetanus of newly-born infants) is a
principal cause of the excessive infant mortality."
Next, because the tetanus-bacillus has its natural
abode in the superficial layers of the soil: here it is
associated with a vast number of other organisms, so
that its identification and isolation were a work of
immeasurable complexity. What mixed company it
keeps, is shown by Houston's estimate of the number
of microbes per gramme in twenty-one samples of
different soils. This number ranged from 8326 in
virgin sand, and 475,282 in virgin peat, to 115,014,492
in the soil from the trench of a sewage-farm. In all rich
and well-manured soil the tetanus-bacillus may possibly
be present; but it was the work of years to dissociate
it from the myriads of organisms outnumbering it.
Next, because it cannot be got to grow in cultures
exposed to the air: its proper place is below the surface
of the soil, away from the air; it is "strictly anaërobic,"
and the attempts to cultivate it by ordinary methods
failed again and again. It had to be cultivated below
the surface of certain nutrient media, or in a special
atmosphere of nitrogen or hydrogen.
These and other difficulties for many years delayed
the final proof of the true pathology of tetanus. The
success of the work was mainly due to Nicolaier. He
started from the well-known fact that tetanus mostly
comes of wounds or scratches contaminated with
particles of earth—such mischances as the grinding of
dirt or gravel into the skin, or the tearing of it by a
splinter of wood or a rusty nail; as Dr. Poore says, in
his Milroy Lectures (1899), "Every child who falls on
the ground and gets an abrasion of the skin, all
tillers of the soil who get accidental wounds in the
course of duty, and every horse which 'breaks its
knees' by falling in the London streets, runs potentially
a risk of inoculation with tetanus." Nicolaier therefore
studied the various microbes of the soil, and made
inoculations of garden-mould under the skin of rabbits.
He was able, by these inoculations, to produce tetanus
in them; and the discharge from the points of inoculation,
put under the skin of other rabbits, produced the
disease again. He also identified the bacillus, and
cultivated it; but in these cultures it was mixed with
other organisms, and he failed to isolate it from them.
Carle and Rattone, and Rosenbach, were able to produce
tetanus in animals by inoculating them with discharge
from the wounds of patients attacked by the disease.
Finally, Kitasato, in 1889, found a way of obtaining
pure cultures of the bacillus. Beginning with impure
cultures such as Nicolaier had made, he kept these at a
temperature of 36° C. till the bacillus had spored; then,
by repeated exposures of the cultures to a temperature
of 80° C. for three-quarters of an hour at a time, he
killed-off all organisms except the spores of the tetanus-bacillus;
then he kept these in an atmosphere of
hydrogen, at a temperature of 20° C., and thus got
pure cultures.
Brieger, Fränkel, Cohen, Sidney Martin, Kanthack,
and others, have studied the chemical products of the
disease, have obtained them from cultures and from
infected tissues, and have been able with these toxins
to produce the disease in animals. As with the other
infective diseases, so with tetanus, there have been
two main lines of researches; the one, toward a fuller
knowledge of the chemical changes in the blood and in
the central nervous system; the other, toward a fuller
knowledge of the nature and ways of the bacillus, and
its method of invasion. Before any study of immunity
or immunisation, or of neutralisation of the toxins in
man by an antitoxin, came the study of the toxins
and of the bacillus. It was proved, by an immense
quantity of hard work, that the bacillus does not tend
to invade the blood, or to pass beyond the lymphatic
glands in the immediate neighbourhood of the site of
inoculation; that it stays in and about the wound, and
there multiplies, and from this site pours into the blood
the chemical products which cause the disease; and
that these chemical substances have a selective action
on certain nerve-cells in the brain and the spinal cord.
This is the bare outline of the facts; and no account
can be given here of the intricate problems of bacteriology
and animal chemistry that have been answered,
or are still waiting an answer. At least, it is evident
that the whole pathology of tetanus was found, proved,
and interpreted by the help of experiments on animals;
and that these alone did away with the old false
doctrine that the disease was due to rapid extension of
inflammation up a nerve to the brain.
In 1894 came the use of an antitoxin in cases of the
disease, and, in 1895, 42 cases were reported, with 27
recoveries. It cannot be said that any one of the
diverse preparations of tetanus-antitoxin, up to this
present time, has triumphed over the disease. Tetanus
is of all diseases the hardest to reckon with: the first
sign of it is the last stage of it; there is no warning,
nothing, it may be, but a healed scratch, till the central
nervous system is affected with sudden and rapidly
advancing degeneration of certain cells. These and
other difficulties have stood in the way of an antitoxin
treatment; and there is no less difficulty in estimating
the efficacy of that treatment. The recovery, under
antitoxin, of a "chronic" case cannot always or altogether
be attributed to the treatment; and in a very
acute case, antitoxin, like everything else, has but small
chance of success. Various reports on the antitoxin
treatment, published during 1897-1899, give the following
figures:—
| 26 cases, |
with 12 recoveries. |
| 98" |
57" |
| 36" |
25" |
| 22" |
11" |
| 51" |
36" |
| 10" |
7" |
Probably the paper by Dr. Lambert of New York,
in the Medical News, July 1900, gives fairly the general
opinion of the treatment, so far as the subcutaneous
administration of antitoxin is concerned:—
"The following cases of tetanus, treated with antitoxin,
comprise published and unpublished cases. We
have a total of 279 cases, with a mortality of 44.08 per
cent.: but of these we must rule out 17 cases—4 deaths
from intercurrent diseases, 8 deaths in cases in which
the antitoxin was given but a few hours before death,
and 5 recoveries in which antitoxin was not given until
after the twelfth day (as they probably would have recovered
without it). We have left 262 cases, with 151
recoveries, and 111 deaths, a mortality of 42.36 per cent.
Dividing the cases into acute and chronic, we have 124
acute cases, with 35 recoveries and 89 deaths, a mortality
of 71.77 per cent., and 138 chronic cases, with 116 recoveries
and 22 deaths, a mortality of 15.94 per cent. In
interpreting critically these statistics, we see that in acute
cases the mortality is but slightly reduced, being but 72
per cent. instead of 88 per cent. But, in the less acute
cases, there is a decided improvement, from 40 per cent.
to 16 per cent. Taking the statistics as a whole, there
is a distinct improvement in the mortality of tetanus since
the introduction of antitoxin."
It would be foreign to the present purpose to pursue
this matter further: for the other treatments, used by
Baccelli and by Krokiewicz, and the sub-dural use of
antitoxin, are also founded on experiments on animals;
and the same will be true of any better method that
shall be developed out of them.
The preventive use of the tetanus-antitoxin, for the
immunisation of human beings or of animals, has given
excellent results. Horses are very apt to be infected
by tetanus; and the antitoxin has been used in veterinary
practice, both for prevention and for cure. The
curative results are not, at present, very good. But, as
regards protection against the disease, there is evidence
that horses can be immunised against tetanus by the
antitoxin with almost mechanical accuracy. In some
parts of the world, the loss of horses by tetanus is
so common that their immunity is a very important
matter; and that the antitoxin does confer immunity
on them is shown by statistics from France and from
the United States:—
1. France.—"The results of Nocard's method of preventive
inoculations in veterinary practice are most
striking. Among 63 veterinarians, there have been inoculated
2737 animals with preventive doses of antitoxin,
and not a single case of tetanus developed; while during
the same period, in the same neighbourhoods, 259 cases
of tetanus developed in non-inoculated animals." (Med.
News, 7th July 1900.)
2. United States.—"Joseph MacFarland and E. M.
Ranck, in addition to a synopsis of the method of manufacture
of tetanus-antitoxin, give some facts of interest
and importance in regard to its use for prophylaxis
and treatment. The studies were made upon several
hundred horses used for the production of various immunised
serums in one of the large laboratories of the
United States. The horses, because of the constant
manipulations, frequently became infected with tetanus,
and in 1897 and 1898, when scrupulous cleanliness and
disinfection were the only precautions employed to prevent
the disease, the death-rate varied from 8 to 10 per
cent. During 1899 nearly two hundred horses were subjected
to systematic immunisation with tetanus-antitoxin;
and, in spite of otherwise similar conditions, the death-rate
descended to 1 per cent." (Medical Annual, 1901.)
The preventive use of the antitoxin has, of course, a
very limited range outside veterinary surgery. Tetanus,
thanks to the use of antiseptic or aseptic methods, not
only in hospital surgery but also in amateur and domestic
surgery, has become a very rare disease, except in
tropical countries. It is no longer a "hospital disease";
and, even in war, it no longer has anything like the
frequency that it had, for instance, in the War of the
Rebellion. A student may now go all his time at a
large hospital without seeing more than a very few
cases. But, now and again, attention is called to some
wholly unsuspected risk of the disease. For example,
certain cases of tetanus occurred in Dundee among
workers at the jute-mills there:—
"The last victim was a female worker in the jute-mill,
who, six days after a crushed and lacerated wound of the
foot, developed tetanus and died within twenty-four hours.
Some of the dust, taken from under the machine in which
the foot was crushed, was found to contain an unusually
large number of tetanus-bacilli. The source of the jute
used is India." (Medical News, August 1900.)
Again, at the Gebaer Anstalt at Prague, in 1899, an
outbreak of tetanus occurred, with several deaths; but
it was stopped when a preventive dose of the antitoxin
was given to the new patients on admission.
Again, an amazing number of deaths from tetanus,
in the United States, are due to wounds of the hands
with toy-pistols. It is said that after the Fourth of
July festivities in 1899, no less than 83 cases of tetanus
were reported, 26 of them in and around New York.
Almost all of them were due to gunshot wounds of the
hand with toy-pistols: the unclean wad of the cartridge,
made of refuse paper picked up in the streets,
penetrates deep into the tissues of the hand, taking the
germs of the disease with it, out of the reach of surgical
disinfection. These cases of tetanus in the United States
from toy-pistol wounds are so frequent, that immunisation
has been recommended for them. The Medical
News, 1st June 1901, has the following note:—"H. G.
Wells states that tetanus is endemic in Chicago, the
specific organism being present in the dirt of the streets.
Every Fourth of July an epidemic occurs, because these
bacilli are carried deeply into wounds before wads from
blank cartridges.... The writer thinks that such cases
should receive a prophylactic dose, say, 5 c.c. of tetanus-antitoxin,
as soon as possible after the wound is first
seen. It seems certain that if antitoxin prophylaxis
were adopted, there would be no further Fourth of July
epidemics, and this end would justify the means."
Again, a man might receive a lacerated wound under
conditions especially favourable to infection: he might
tear his hand in a stable where horses had died of
tetanus, or he might cut his finger while he was working
at the disease in a pathological laboratory, or he
might receive a poisoned arrow-wound out in Africa.
In any such emergency, he could safeguard his life
with a protective dose of antitoxin.
It remains to be added, that the modern study of
tetanus has brought into more general use the old rule
that the wounded tissues in a severe case of tetanus
should be at once excised. Before Nicolaier's work,
while the theory still survived that the disease was
due to ascending inflammation of a nerve, this rule was
neither enforced nor explained.
The results published during the last few years
(Medical Annual, 1905-1906) seem to show that the
antitoxin has neither gained nor lost ground as a
remedy. It is, of course, used in conjunction with all
other remedies. Perhaps, in a few years more, something
better will be discovered. And that discovery,
when it comes, will be, as it were, Nicolaier's gift. The
whole study of the disease goes back straight to the
rabbits inoculated in 1880-1884: neither is it possible
that the disease should be further studied, without the
help of bacteriology.
Pasteur's study of rabies began in 1880; and the date
of the first case treated—Joseph Meister, a shepherd-boy
of Alsace—is July 1885. The first part of the
work was spent in a prolonged search for the specific
microbe of rabies. It was not found: its existence is
a matter of inference, but not of observation.[24] In his
earlier inoculations, Pasteur made use of the saliva of
rabid animals; and M. Valléry-Radot tells the story,
how Pasteur took him on one of his expeditions:—
"The rabid beast was in this case a huge bull-dog,
foaming at the mouth and howling in his cage. All
attempts to induce the animal to bite, and so infect one
of the rabbits, failed. 'But we must,' said Pasteur,
'inoculate the rabbits with the saliva.' Accordingly a
noose was made and thrown, the dog secured and
dragged to the edge of the cage, and his jaws tied
together. Choking with rage, the eyes bloodshot, and
the body convulsed by a violent spasm, the animal was
stretched on a table, and kept motionless, while Pasteur,
leaning over his foaming head, sucked up into a narrow
glass tube some drops of the saliva."
But these inoculations of saliva sometimes failed to
produce the disease; and, when they succeeded, the
incubation-period was wholly uncertain: it might be
some months before the disease appeared. Thus
Pasteur was led to use, instead of the saliva, an
emulsion of the brain or spinal cord; because, as
Dr. Duboué had suggested, the central nervous system
is the chief seat, the locus electionis, of the virus of
rabies. But these inoculations also were not always successful,
nor did they give a definite incubation-period.
Therefore he followed with rabies the method that
he had followed with anthrax. As he had cultivated
the virus of anthrax, by putting it where its development
could be watched and controlled, so he must put
the virus of rabies in the place of its choice. It has
a selective action on the cells of the central nervous
system, a sort of affinity with them; they are, as it
were, the natural home of rabies, the proper nutrient
medium for the virus: therefore the virus must be
inoculated not under the skin, but under the skull.
These sub-dural inoculations were the turning-point
of Pasteur's discovery. The first inoculation was made
by M. Roux:—
"Next day, when I informed Pasteur that the intracranial
inoculation offered no difficulty, he was moved
with pity for the dog. 'Poor beast, his brain is doubtless
injured: he must be paralysed.' Without reply I
went down to the basement to fetch it, and let it come
into the laboratory. Pasteur did not like dogs, but when
he saw this one, full of life, inquisitively rummaging
about in all directions, he exhibited the greatest delight,
and lavished most charming words upon it."
Henceforth all uncertainty was at an end, and the
way was clear ahead: Pasteur had now to deal with
a virus that had a definite period of incubation, and a
suitable medium for development. The central nervous
system was to the virus of rabies what the test-tube
was to the virus of fowl-cholera or anthrax. As he
had controlled these diseases, had turned them this
way and that, attenuated and intensified them, so he
could control rabies. By transmitting it through a
series of rabbits, by sub-dural inoculation of each rabbit
with a minute quantity of nerve-tissue from the rabbit
that had died before it, he was able to intensify the
virus, to shorten its period of incubation, to fix it at
six days. Thus he obtained a virus of exact strength,
a definite standard of virulence, virus fixe: the next
rabbit inoculated would have the disease in six days,
neither more nor less.
As he was able to intensify the virus by transmission,
so he was able to attenuate it by gradual drying
of the tissues that contained it. The spinal cord, taken
from a rabbit that has died of rabies, slowly loses
virulence by simple drying. A cord dried for four days
is less virulent than one that has been dried for three,
and more virulent than one dried for five. A cord dried
for a fortnight has lost all virulence: even a large dose
of it will not produce the disease. By this method
of drying, Pasteur was enabled to obtain the virus in
all degrees of activity: he could always keep going
one or more series of cords, of known and exactly
graduated strengths, according to the length of time
they had been dried—ranging from absolute non-virulence
through every shade of virulence.
And, as with fowl-cholera and anthrax, so with
rabies; a virus which has been attenuated till it has
been rendered innocuous, can yet confer immunity
against its more virulent forms: just as vaccination can
protect against smallpox. A man, bitten by a rabid
animal, has at least some weeks of respite before the
disease can break out; and, during that time of respite,
he can be immunised against the disease, while it is
still dormant: he begins with a dose of virus attenuated
past all power of doing harm, and advances day by day
to more active doses, guarded each day by the dose of
the day before, till he has manufactured within himself
enough antitoxin to make him proof against any outbreak
of the disease.
The cords used for treatment are removed from the
bodies of the rabbits, by an aseptic method, and are cut
into lengths and hung in glass jars, with some chloride
of calcium in them, for drying. The jars are dated,
and then kept in glass cases in a dark room at a
constant temperature. To make sure that the cords
are aseptic, a small portion of each cord is sown on
nutrient jelly in a test-tube, and watched, to see that no
bacteria occur in the tube. For each injection, a
certain small quantity of cord is rubbed-up in sterilised
fluid; and these subcutaneous injections give no pain
or malaise worth considering.
Of course, the treatment is adjusted to the gravity of
the case. A bite through naked skin is more grave
than a bite through clothing; and bites on the head or
face, and wolf-bites, are worst of all. The number and
character of the scars are also taken into account. An
excellent description of the treatment, by a patient, was
published in the Birmingham Medical Review of January
1898. It gives the following tables of treatment:—
1. Ordinary Treatment.
Day of
Treatment. |
|
Days of Drying
of Cord. |
| 1 |
|
14 and 13 |
| 2 |
|
12 and 11 |
| 3 |
|
10 and 9 |
| 4 |
|
8 and 7 |
| 5 |
|
6 |
| 6 |
|
6 |
| 7 |
|
5 |
| 8 |
|
4 |
| 9 |
(1/2 dose) |
3 |
| 10 |
(full dose) |
5 |
| 11 |
|
5 |
| 12 |
|
4 |
| 13 |
|
4 |
| 14 |
(1/2 dose) |
3 |
| 15 |
(full dose) |
3 |
2. Cases of Moderate Gravity.
Same treatment, up to 13th day.
Day of
Treatment. |
|
Days of Drying
of Cord. |
| 14 |
|
3 |
| 15 |
|
5 |
| 16 |
|
4 |
| 17 |
(1/2 dose) |
3 |
| 18 |
(full dose) |
3 |
3. Grave Cases.
Same treatment, up to 10th day.
Day of
Treatment. |
|
Days of Drying
of Cord. |
| 11 |
|
4 |
| 12 |
|
3 |
| 13 |
|
5 |
| 14 |
|
5 |
| 15 |
|
4 |
| 16 |
|
4 |
| 17 |
(1/2 dose) |
3 |
| 18 |
(full dose) |
3 |
| 19 |
|
5 |
| 20 |
|
3 |
| 21 |
|
4 |
| 22 |
|
3 |
4. Very Grave Cases.
Same treatment as 3, and in addition.
Day of
Treatment. |
|
Days of Drying
of Cord. |
| 23 |
|
5 |
| 24 |
|
4 |
| 25 |
(1/2 dose) |
3 |
| 26 |
(full dose) |
3 |
Furious criticism, unbelief, and flagrant misstatement
of facts began at once, and lasted more than two years.
Of Pasteur's opponents, the chief was M. Peter, who
besought the Académie des Sciences, about once a week,
that they should close Pasteur's laboratory, because he
was not preventing hydrophobia but producing it. The
value of M. Peter's judgment may be estimated by what
he had said, a few years earlier, about bacteriology in
general—"I do not much believe in that invasion of
parasites which threatens us like an eleventh plague of
Egypt. After so many laborious researches, nothing
will be changed in medicine, there will only be a few
more microbes. M. Pasteur's excuse is that he is a
chemist, who has tried, out of a wish to be useful, to
reform medicine, to which he is a complete stranger."
But it does not matter what was said twenty years
ago. In England, the Report of the 1886 Committee,
and the Mansion House meeting in July 1889, mark
the decline and fall of all intelligent opposition to the
work. Among so many thousand cases, during so
many years, it would be a miracle indeed if not a single
case had failed or gone amiss; but we are concerned
here with the thousands. Take, to begin with, four
reports from Athens, Palermo, Rio, and Paris. It is to
be noted that the patients, alike at Paris and at other
Institutes, are divided into three classes:—
"A. Bitten by animals proved to have been rabid by
the development of rabies in other animals inoculated
from them.
"B. Bitten by animals proved to have been rabid by
dissection of their bodies by veterinary surgeons.
"C. Bitten by animals suspected to have been rabid."
It is to be noted also, as a fact proved beyond doubt,
that the full benefit of the treatment is not obtained at
once; the highest degree of immunity is reached about
a fortnight after the discontinuance of the treatment.
Those few cases, therefore, where hydrophobia has
occurred, not only in spite of treatment, but within a
fortnight of the last day of treatment, are counted as
cases where the treatment came too late.
Finally, what was the risk from the bite of a rabid
animal, in the days before 1885? It is a matter of
guess-work. One writer, and one only, guessed it at
5 per cent.; another guessed it at 55, and a third came
to the safe conclusion that it was "somewhere between
these limits." Leblanc, who is probably the best
guide, put it at 16; and Pasteur himself put it between
15 and 20. But suppose it were only 10; that,
before Pasteur, out of every 100 men bitten by
rabid animals, 90 would escape and only 10 would
die of hydrophobia; then take this fact, that in one
year, at one Institute alone, there were 142 patients in
class A, bitten by animals that were proved, by the
unanswerable test of inoculation, to have been rabid;
and 1 death. And every year the same thing; and in
all the twelve years together, 2872 such cases (A) and
20 deaths—a mortality not of 10 per cent., but of less
than 1 per cent.
The Annales de l'Institut Pasteur, June 1898, contain
Dr. Pampoukis' report of three years' work at the
Hellenic Institute, from August 1894 to December
1897. During this period 797 cases were treated—590
male and 207 female. The animals that bit them
were—dogs, 732; cats, 34; wolf, 1; other animals,
13; and the 17 other patients had been exposed to
infection from the saliva of hydrophobic patients. Of
the 797 cases, 245 were of class A, 112 B, and 440 C.
"Among the 797 persons treated, there are 2
deaths, one in class B and the other in class C. Thus
the mortality has been 0.25 per cent. Besides these 2
who died of rabies there are 5 more, in whom the first
signs of rabies showed themselves in less than fifteen
days after the last inoculation.
"Finally, beside these 797 cases, there is 1 other
case, bitten by a wolf, in which the treatment failed.
If we reckon this last case in the statistics of mortality,
we have 3 deaths in 798 cases = 0.37 per cent.
"Beside these 798 cases treated at the Institute,
there have been others that have not undergone the
antirabic treatment, having trusted the assurances of
those who are called in Greece empirics. Among
these non-treated cases there are 40 who have died of
rabies."
The Annales for April 1896 give the report by
Dr. de Blasi and Dr. Russo-Travali of the work of the
Municipal Institute at Palermo during 8-1/2 years, from
March 1887 to December 1895. The number of cases
was 2221; in 1240 (class A), the animals were proved
to have been rabid by the result of inoculations; in 981,
there was reason to suspect rabies.
"Setting aside 5 patients who died during the course
of the treatment, and 5 others who died less than
fifteen days after the end of the treatment, we have had
to deplore only 9 failures = 0.4 per cent. Even if
we count against ourselves the 10 other cases, the
mortality is still only 0.85."
The Annales for August 1898 give Dr. Ferreira's
report of ten years' work (February 1888 to April
1898) at the Pasteur Institute at Rio. The number of
cases treated was 2647, of whom 1987 were male and
660 female. Beside these 2647 there were 1234 who
were not treated, because it was ascertained that they
were in no danger of rabies; 3 who were brought to
the Institute, already suffering from the disease; and
59 who refused treatment.
Of the 2647 persons treated, 10 had pricked their
hands at work in the laboratory, 3 had exposed chance
scratches on their hands to the saliva of rabid animals,
and 1 had been bitten by a rabid patient. Of the rest,
1886 had been bitten on the bare skin, and 747
through clothing.
In 236 cases the rabies of the animal had been
proved by inoculation. In 1173 it had been recognised
by the signs of the disease. In 1238 there was good
reason to suspect that the animal had been rabid.
Of the 2647 patients, in 30 cases the treatment was
stopped, because the animals were at last traced, after
treatment was begun, and were found not to be rabid.
In 65 cases the patients, after treatment was begun,
refused to go on with it, and 3 of them died of rabies.
In 6 cases rabies developed during treatment; 5 of
them had been very badly bitten about the head, and 1
did not come for treatment till the twenty-first day
after the bite, and was attacked by rabies two days
later. And 5 cases died of other maladies that had
nothing to do with rabies. Setting aside these 106
cases, there remain 2541 cases, with 20 deaths = 0.78
per cent. But, of these 20 deaths, 9 occurred within
fifteen days of the end of treatment, before protection
was fully established. If these 9 deaths be excluded,
the figures stand at 2532 cases, with 11 deaths = 0.43
per cent.
Dr. Pottevin's report on the work of the Pasteur
Institute (Paris) during 1897 (Annales, April 1898)
must be given word for word, without abbreviation.
I
During 1897, 1521 patients received the anti-treatment
at the Pasteur Institute: 8 died of rabies.
The notes of their cases will be found at the end of this
paper.
If we exclude 2 of these 8 cases—the cases of
Heniquet and Morin, where death occurred before it
was possible for the vaccinations to produce their effect—the
results of the vaccinations in 1897 are
| Patients treated |
1519 |
| Deaths |
6 |
| Mortality per cent. |
0.39 |
In the following table these figures are compared
with those of preceding years:—
| Year. |
Patients
treated. |
Deaths. |
Mortality
per cent. |
| 1886 |
2671 |
25 |
0.94 |
| 1887 |
1770 |
14 |
0.79 |
| 1888 |
1622 |
9 |
0.55 |
| 1889 |
1830 |
7 |
0.38 |
| 1890 |
1540 |
5 |
0.32 |
| 1891 |
1559 |
4 |
0.25 |
| 1892 |
1790 |
4 |
0.22 |
| 1893 |
1648 |
6 |
0.36 |
| 1894 |
1387 |
7 |
0.50 |
| 1895 |
1520 |
5 |
0.33 |
| 1896 |
1308 |
4 |
0.30 |
| 1897 |
1521 |
6 |
0.39 |
II
Patients treated at the Pasteur Institute are divided
into three classes, as follows:—
A. The rabies of the animal was proved by experiment,
by the development of rabies in animals inoculated
with its bulb (the upper end of the spinal cord).[25]
B. The rabies of the animal was proved by veterinary
examination (dissection of its body).
C. The animal was suspected of rabies.
We give here the patients treated in 1897, under
these three classes:—
Bites of the
Head. |
Bites on the
Hands. |
Bites of the
Limbs. |
Total. |
| |
P |
D |
M p |
P |
D |
M p |
P |
D |
M p |
P |
D |
M p |
| |
a |
e |
o e |
a |
e |
o e |
a |
e |
o e |
a |
e |
o e |
| |
t |
a |
r r |
t |
a |
r r |
t |
a |
r r |
t |
a |
r r |
| |
i |
t |
t |
i |
t |
t |
i |
t |
t |
i |
t |
t |
| |
e |
h |
a c |
e |
h |
a c |
e |
h |
a c |
e |
h |
a c |
| |
n |
s |
l e |
n |
s |
l e |
n |
s |
l e |
n |
s |
l e |
| |
t |
|
i n |
t |
|
i n |
t |
|
i n |
t |
|
i n |
| |
s |
|
t t |
s |
|
t t |
s |
|
t t |
s |
|
t t |
| |
. |
|
y . |
. |
|
y . |
. |
|
y . |
. |
|
y . |
| A |
15 |
0 |
0 |
81 |
0 |
0 |
46 |
1 |
2.1 |
142 |
1 |
0.7 |
| B |
106 |
0 |
0 |
539 |
4 |
0.74 |
273 |
1 |
0.4 |
918 |
5 |
0.65 |
| C |
30 |
0 |
0 |
244 |
0 |
0 |
187 |
0 |
0 |
461 |
0 |
0 |
| |
151 |
0 |
0 |
864 |
4 |
0.46 |
506 |
2 |
0.4 |
1521 |
6 |
0.39 |
The following tables, giving the results obtained
since the vaccinations were first used, show that the
gravity of the bites varies with their position on the
body, and that the mortality is always below 1 per
cent. among patients bitten by dogs undoubtedly
rabid:—
| |
Patients. |
Deaths. |
Mortality. |
|
Patients. |
Deaths. |
Mortality. |
| Bites of the Head |
1,759 |
21 |
1.1 |
A |
2,872 |
20 |
0.69 |
| Bites of the Hands |
11,118 |
53 |
0.47 |
B |
12,547 |
61 |
0.48 |
| Bites of the Limbs |
7,289 |
22 |
0.30 |
C |
4,747 |
15 |
0.31 |
| |
20,166 |
96 |
0.46 |
|
20,166 |
96 |
0.46 |
III
In regard to their nationality, the 1521 patients
treated at the Pasteur Institute in 1897 were as
follows:—
| Germany |
|
8 |
| England |
|
83 |
| Belgium |
|
14 |
| Egypt |
|
2 |
| United States |
|
1 |
| Greece |
|
1 |
| India |
|
33 |
| Switzerland |
|
33 |
That is, 175 foreigners and 1346 French.
IV
Notes of the eight cases where the treatment
failed:—
1. Camille Bourg, 26. Bitten 11th April; treated at the
Pasteur Institute, 13th to 30th April; died of rabies at the
Lariboisière Hospital, 26th May. Six penetrating bites
on the ball of the left thumb. The dog was examined
by M. Grenot, a veterinary surgeon at Paris, and the
dissection gave evidence of rabies. Another person
bitten and treated at the same time as Bourg is now
in good health.
2. Louis Fiquet, 23. Bitten 22nd April; treated at
the Pasteur Institute, 23rd April to 10th May; died of
rabies at the Necker Hospital, 4th June. Five bites,
two of them deep, round the right thumb. They had
been cauterised five hours after infliction. The dog
was examined by M. Caussé, a veterinary surgeon at
Boulogne, and the dissection gave evidence of rabies.
Another person bitten at the same time as Fiquet is now
in good health.
3. Annette Beaufort, 19. Licked on the hands, which
were chapped, on 15th April. The dog was killed next
day, examined, and declared to have been rabid by
M. Lachmann, a veterinary surgeon at Saint-Étienne.
Treated at the Pasteur Institute, 20th April to 7th May.
Died of rabies 14th October. Two other persons bitten
by the same dog and treated at the Pasteur Institute are
now in good health.
4. Julien Heniquet, 53. Bitten 11th March, by a dog
that M. Jenvresse, veterinary surgeon at Beaumont-sur-Oise,
declared after dissection to have been rabid. One
bite had torn the lower lip, the wound had been sutured;
three other wounds on the nose. The wounds had not
been cauterised. Treated at the Pasteur Institute, 18th
May to 5th June. First symptoms of rabies showed
themselves 4th June, before the treatment was finished;
died 7th June. As the disease had its onset during the
course of the inoculations, this case should be excluded
from the number of those who died of rabies after treatment.
5. Germain Segond, 7. Penetrating bite on the bare
right fore-arm, 23rd May. Cauterised an hour later
with a red-hot iron. Treated 26th May to 9th June;
died of rabies 22nd July. The dog's bulb had been sent
to the Pasteur Institute. A guinea-pig inoculated in the
eye 26th May was seized with rabies 10th September.
6. Suzanne Richard, 8. Bitten 12th June on the left
leg by a dog, found on dissection to have been rabid
by M. Touret, veterinary surgeon at Sannois. The bite,
penetrating 3 cm. long, had been sutured; it had been
made through a cotton stocking, and had been cauterised
in half-an-hour. Treated 13th to 30th June; died of
rabies 2nd August. (Notes from M. le Dr. Margny, at
Sannois.)
7. Joseph Vaudale, 33. Bitten on the left hand, 8th
August. Six penetrating bites on the back of the hand;
had not been cauterised. The dog was declared rabid by
M. Verraert, veterinary surgeon at Ostend. Treated at
the Pasteur Institute, 11th to 28th August; died of rabies
27th September.
8. Paul Morin, 38. Bitten 24th August on the left
cheek, a single bite, 2 cm. long; no cauterisation. The
dog was sent to the Alfort School, 25th August, and
found to be rabid. Treated at the Pasteur Institute,
26th August to 15th September. Died of rabies some
days after the end of treatment (three weeks after the
bite, says a note sent to us). The interval between the
end of the treatment and the onset of the disease being
less than fourteen days, Morin must not be counted in
the number of patients inoculated under conditions which
permit successful inoculation.
We hardly need follow the work of the remaining
years. The figures are as follows:—
| Year. |
Patients
treated. |
Deaths. |
Mortality
per cent. |
| 1898 |
1465 |
3 |
0.2 |
| 1899 |
1614 |
4 |
0.25 |
| 1900 |
1420 |
4 |
0.28 |
| 1901 |
1318 |
5 |
0.38 |
| 1902 |
1105 |
2 |
0.18 |
| 1903 |
628 |
2 |
0.32 |
| 1904 |
755 |
3 |
0.39 |
The falling off in the number of patients at the Paris
Institute is related to the establishment of similar Institutes
at Lyon, Marseilles, Bordeaux, Lille, and Montpellier.
But is it not possible that a patient, after treatment
at the Paris Institute, should die at home of rabies,
and his death not be notified to the Institute? The
answer is, that the Institute is very careful, so far as
possible, to keep in touch with its old patients. For
instance, in 1903, it recorded the case of a carpenter
in a Welsh village, who had died of rabies nearly
two years after treatment. And, of course, an Institute
patient, wherever he was, would be of interest to his
neighbours: and a death from rabies would excite attention,
and would hardly fail to be reported.
It is not impossible that some sort of intensive
modification of Pasteur's treatment may be found, not
for the prevention, but for the cure of hydrophobia;
and two successful cases of this kind have been reported
in the Annales of the Paris Institute. Apart
from this faint hope, the cure of hydrophobia is where
it was in the days of the "Tonquin medicine" and the
"Tanjore pills."
The study of cholera was the hardest of all the hard
labours of bacteriology; it took years of work in all
parts of the world, and the difficulty and disappointments
over it are past all telling. Koch's discovery of
the comma-bacillus (1883) raised a thousand questions
that were solved only by infinite patience, international
unity for science, and incessant research; and the
Hamburg epidemic (1892) marks the time when the
comma-bacillus was at last recognised as the cause of
cholera. A mere list of the men who did the work
would fill page after page; it was bacteriology in
excelsis, often dangerous,[26] and always laborious.
There is the same heroic note in the story of the
preventive treatment of cholera by Haffkine's method;
one of the men in whom Pasteur seems to live again.
He began in 1889, under Pasteur's guidance, to study
the immunisation of animals against the cholera-bacillus.
Other men, of course, were working on the same lines—Pfeiffer,
Brieger, Metchnikoff, Fischer, Gamaleïa,
Klein, Wassermann, and many more—and by 1892
the immunisation of animals was proved up to the hilt.
Then came the advance from animals to men, from
laboratories to Indian cities, villages, and cantonments;
and here the honour is Haffkine's, and his
alone. Ferran's inoculations (Spain, 1885) had failed.
Haffkine, having tested his method on himself and his
friends, went to India, with a commendatory letter
from the British Government:—
"Researches on cholera, with special reference to inoculation,
were undertaken and carried on in my laboratory,
in the Pasteur Institute in Paris, between 1889
and 1893. The experiments resulted in the elaboration
of the present method, which when tried on animals was
found to render them resistant against every form of
cholera-poisoning otherwise fatal to them.
"The physiological and pathological effect on man was
then studied on some sixty persons, mostly medical and
scientific men interested in the solution of the problem.
The effect was found to be harmless to health. The
next step was to transfer the operations to the East."
(Haffkine's Report to the Government of India, 1895.)
He reached Calcutta in March 1893, and at the
request of Mr. Hankin[27] was invited to Agra; here, in
April, he vaccinated over 900 persons, including many
English officers. From Agra to Aligarh; and from
Aligarh he was asked to more places than he could
visit. In 1895 his health failed, and no wonder; and
he came back to Europe for a short time:—
"My actual work in India lasted twenty-nine months,
between the beginning of April 1893 and the end of July
1895. During this period the anti-cholera vaccination
has been applied to 294 British officers, 3206 British
soldiers, 6629 native soldiers, 869 civil Europeans, 125
Eurasians, and 31,056 natives of India. The inoculated
people belonged to 98 localities in the North-West
Provinces and Oudh, in the Punjab, in Lower Bengal
and Behar, in the Brahmaputra Valley, and in Lower
Assam. No official pressure has been brought on the
population, and only those have been vaccinated who
could be induced to do so by free persuasion. In every
locality, efforts were made to apply the operation on
parts of large bodies of people living together under
identical conditions, in order to compare their resistance
in outbreaks of cholera with that of non-inoculated
people belonging to the same unit of population. This
object has been obtained in 64 British and native regiments,
in 9 gaols, in 45 tea-estates, in the fixed agricultural
population of the villages parallel to Hardwâr
pilgrim road, in the bustees of Calcutta, in a certain
number of boarding-schools, where the parents agreed
to the inoculation of their children, in orphanages, etc.
The vast majority of inoculated people lived thus under
direct observation of the sanitary and medical authorities
of India." (Haffkine, Lecture in London. British
Medical Journal, 21st Dec. 1895.)
Altogether, upwards of 70,000 injections on 42,179
people—without having to record a single instance of
mishap or accident of any description produced by our
vaccines. Consider the colossal difficulties of this new
treatment: the frequent running short of the vaccine,
preventing a second injection; the absolute necessity,
at first, of using very small doses of a weak vaccine,
lest one disaster should occur; the impossibility of
avoiding, now and again, some loss of strength in the
vaccine; the impossibility of knowing how long the
protection would last. Surely in all science there is
nothing to beat this first voyage of adventure single-handed
to fight the cholera in India.
Later than Haffkine's 1895 report, we have Dr.
Simpson's 1896 report: "Two Years of Anti-choleraic
Inoculations in Calcutta. W. J. Simpson, M.D.,
M.R.C.P., D.P.H., Health Officer, Calcutta." The date
of this report is 8th July 1896; and it gives not only
the Calcutta results, but all that are of any use for
exact judgment:[28] —
"The results of Calcutta are fully confirmed by those
obtained in other parts of India, wherever it was possible
to make all the necessary observations with precision,
and wherever the cases were sufficiently numerous to
show the effect of the inoculation.
"Outside Calcutta, since the commencement of the
inoculations in India in April 1893, opportunities for an
exact comparison of the respective powers of resistance
against cholera of inoculated and non-inoculated persons
presented themselves; (1) in Lucknow, in the East
Lancashire Regiment; (2) in Gaya, in the jail; (3) in
Cachar, among the tea-garden coolies; (4) in Margherita,
among coolies of the Assam-Burmah Railway Survey; (5)
in Durbhanga, in the jail; (6) in the coolie camp at Bilaspur;
(7) in Serampur, among the general population."
Here, then, in this 1896 report, are all the results
that give an answer to the question, What will happen
when cholera breaks out among a number of people
living under the same conditions, of whom some have
received preventive treatment, and the rest have been
left to Nature?
"The number of people inoculated during the period
under review was 7690; of these, 5853 are Hindus, 1476
Mahomedans, and 361 other classes.... Considering
that the system is a new one, that the inoculations are
purely voluntary, and everything connected with them
has to be explained before the confidence of the people
can be obtained, and considering how long new ideas are
in taking root among the general population—and in this
case it is not merely the acceptance of an idea, but such
faith in it as to consent to submit to an operation—the
number is certainly satisfactory for a beginning. The
present problem can be compared with the introduction of
vaccination against smallpox into Calcutta. It took 25
years before the number of vaccinations reached an
average of 2000; whereas the inoculations against
cholera have in two years nearly doubled that average.
This is a proof that, in spite of the difficulties which
every new movement naturally has to meet with, there
are large numbers of people anxious to avail themselves
of the protective effect of the inoculations.
"Although all sorts and conditions of individuals,
weak and strong, sickly and healthy, young and old, well
nourished and badly nourished, and often persons suffering
from chronic diseases, have been inoculated, in every
instance, without exception, the inoculations have proved
perfectly harmless.
"The investigations on the effect of the inoculation are
made exclusively in those houses in which cholera has
actually occurred, the object being to ascertain and
compare the incidence of cholera on the inoculated and
not inoculated in those houses in which inoculations
had been previously carried out. For this purpose,
affected houses in which inoculations have not been performed,
and inoculated houses in which cholera has not
appeared, are excluded."
Nature gave a demonstration in 77 houses. In one
house, and one only, all the household had been inoculated;
in 76, inoculated and non-inoculated were living
together; but of these 76 houses, 6 are excluded from
the table of results, because the inoculated in them were
so few—less than one-tenth of the household—that
their escape from cholera might be called chance. The
cholera came, and left behind it this fact:—
654 uninoculated individuals had 71 deaths
= 10.86 per cent.
402 inoculated in the same households had
12 deaths = 2.99 per cent.
If we add the 6 houses which Dr. Simpson excludes,
we find that in 77 houses there were 89 deaths from
cholera, 77 being among the uninoculated and 12
among the inoculated.
Moreover, of these 12 deaths, 5 occurred during
the first five days after inoculation—that is to say,
during the period in which the protective influence of
the vaccine was still incomplete. Then came a period of
more than a year, during which the uninoculated had 42
deaths, and the inoculated had one death. The remaining
6 of the 12 deaths occurred more than a year after
inoculation, and 5 of these 6 had received only one
inoculation of the weak vaccine that was used early in
1894.
Take a good instance that came at the very beginning
of the work:—
"A local epidemic took place around two tanks in
Kattal Began bustee, ward 19, occupied by about 200
people. In this bustee, about the end of March, 2 fatal
cases of cholera and 2 cases of choleraic diarrhœa
occurred. The outbreak led to the inoculation of 116
persons in the bustee out of the 200. Since then, 9 cases
of cholera, of which 7 were fatal, and 1 case of choleraic
diarrhœa have appeared in the bustee, and it is a very
extraordinary fact that all these 10 cases of cholera have
occurred exclusively among the uninoculated portion of
the inhabitants, which, as stated, forms the minority
in the bustee; while none of the inoculated have been
affected." (Cholera in Calcutta in 1894. W. J.
Simpson.)
The story of the outbreak of cholera in the East
Lancashire Regiment must be read carefully:—
"Rumour magnified the events connected with this
outbreak, and distorted the facts connected with the
inoculations; and as a result, the current of public
opinion, which had previously been in favour of inoculation,
set in strongly in the opposite direction. The
advocates of anti-choleraic inoculations were abused in
no particularly measured terms, and the inoculations
were held up to be the source of every possible evil
and danger ... of the most loathsome diseases, and of
every ill which man is heir to. The distrust engendered
by these misrepresentations and fulminations was, however,
only of a temporary nature; and when the exact
circumstances came to be known and understood, the
confidence created by the Calcutta experience began to be
considerably restored. Inoculations were performed in
May 1893, in the East Lancashire, Royal Irish, 16th
Lancers, 7th Bengal Infantry, 7th Bengal Cavalry, and
general populations in the Civil Lines. In 1894, cholera
appeared among the native population of Lucknow, in the
form of an epidemic distinguished by its extreme virulence,
patients succumbing in the course of a few hours.
It is stated that the epidemic was of a most malignant
type. In the latter part of July it entered the cantonments,
and attacked the East Lancashire, almost
exclusively confining its ravages to that regiment."
In the East Lancashire, 185 men were inoculated in
May 1893. From the statistical returns obtained from
the military authorities at Lucknow, it appears that at
the time of the outbreak, in July 1894, the strength of
the men, including those in hospital, was 773; and
of these, 133 had been inoculated, as recorded in the
inoculation register, and 640 had not been inoculated.
The following table shows the total number of attacks
and deaths in not inoculated and inoculated:—
| |
Attacks. |
Deaths. |
| |
Per cent. |
Per cent. |
| Non-inoculated, 640 |
120 = 18.75 |
79 = 12.34 |
| Inoculated, 133 |
18 = 13.53 |
13 = 9.7 |
The men were moved into camp; but this movement
seemed only to make things worse: "the epidemic in
the camp appears to have been twice as severe as in
the cantonment."[29]
Lucknow came so early in the work of inoculation,
that weak vaccines were used in small doses. The
cholera, when it broke out, was "of a most malignant
type, senior medical officers of long experience in the
country stating that such a virulent cholera had not
been seen by them for very many years past." More
than a year had elapsed between the inoculations and
the outbreak of the cholera. It is no wonder that the
regiment was not well protected:—
"The small amount of protection which the inoculations
afforded in this case may have depended on the mild
effects which the injections produced on the men at the
time of the operation in 1893, in comparison with the
severity of the epidemic which attacked the regiment. It
is recorded in the Lucknow Inoculation Registers that
only in two men, out of the 185 inoculated in 1893, a
marked febrile reaction was obtained; in 77 individuals
the vaccinal fever was only slight, while in 66 there was
no reaction: an effect which was due to the weakness of
the vaccines procurable at that period of work, and to
the small doses used. The influence of the vaccines was
possibly further reduced, at the time of the epidemic,
by a lapse of fourteen to fifteen months." (Haffkine,
1895 Report.)
On 9th July 1894, an outbreak of cholera occurred
in the Gaya jail, and by 18th June there had been
6 cases and 5 deaths. On that day and the next day,
215 prisoners were inoculated. The average number
of the prisoners during the outbreak was 207 inoculated,
and 202 not inoculated. Surgeon-Major Macrae, superintendent
of the jail, reports:—
"The inoculations being purely voluntary, no selection
of prisoners was possible, but all classes of the jail
were represented—male and female, old and young,
habituals and less frequent offenders, strong and weakly,
convalescent and even hospital patients sent their representatives;
no difference of any kind was made between
inoculated and non-inoculated; they were under
absolutely identical conditions as regards food, water,
accommodation, etc., in fact in every possible respect."
Of course, the best results could hardly be obtained,
because the cholera was already at work: it took about
ten days for the 1894 vaccine to produce its full effect;
and two inoculations were generally made, one five days
after the other. This gradual action of the vaccine is
well shown in Dr. Simpson's table:—
| |
Non-Inoculated,
202 |
Inoculated,
207 |
| Cases. |
Deaths. |
Cases. |
Deaths. |
| During 5 days after 1st |
7 |
5 |
5 |
4 |
| inoculation |
|
|
|
|
| During 3 days after 2nd |
5 |
3 |
3 |
1 |
| inoculation |
|
|
|
|
| After 3 days after 2nd |
8 |
2 |
0 |
0 |
| inoculation |
|
|
|
|
Haffkine's comment on these figures must be noted
here:—
"In the Gaya jail, the inoculations were for the first
time applied in a prevalent epidemic, and very weak doses
of a relatively weak vaccine were used.... Far higher
results have been obtained by an application of stronger
doses. In the bustees situated round the tanks in Calcutta,
where cholera exists in a permanent state, the
disease occurred in 36 houses with inoculated people.
In each of these houses there was one part of the family
inoculated and another not. The observations were
continued for 459 days, with the following results:—
During the first period of 5 days, subsequent to the
inoculation with first vaccine, cholera occurred in 8
houses.
75 non-inoculated had 5 cases, with 3 deaths.
52 inoculated had 3 cases, with 3 deaths.
During the second period of 5 days, subsequent to the
second inoculation, cholera occurred in 2 houses.
8 non-inoculated had 2 cases, with 2 deaths.
17 inoculated had no cases.
After the 10 days necessary for the preventive treatment
had expired, and up to the 459th day, the disease visited
26 houses.
263 non-inoculated had 38 cases, with 34 deaths.
137 inoculated had 1 case, with 1 death, in a child
that had not been brought up for the second
inoculation."
For a good instance of lives saved even during an
outbreak, take the Assam-Burmah Railway coolies:—
"Three hundred and fifty
[30] Khassia Hill coolies had
been collected for the survey party of the Assam-Burmah
Railway, and put under the escort of a detachment of
Goorkhas, when cholera broke out amongst them. The
largest part of the coolies immediately submitted to the
preventive inoculation, the rest remained uninoculated.
The result was that among the not-inoculated minority
there were 34 cases, with 30 deaths; whereas the inoculated
had 4 fatal cases." (Haffkine, 1895, Lecture in
London.)
The figures in this instance are small: but Surgeon-Captain
E. Harold Brown's report is very pleasant
reading. Cholera broke out in the jail on 31st March
1896, and by 9th April there had been 8 cases. Next
day, 172 prisoners were moved into camp 12 miles
away; and 53 were left behind, the sick in the jail
hospital, the patients in the cholera huts, with their
attendants, the old and infirm, and a few cooks and
sweepers. That day, 3 cases occurred in the camp,
and 1 in the jail; and on the 11th, at 2 and 4 a.m.,
2 more cases were reported in camp. At 7.30 a.m.,
Haffkine and Dr. Green came to the camp:—
"The prisoners were spoken to on the subject, and
seemed to be pleased with the idea, the word tika (inoculation),
which was familiar to them from its association
with smallpox, appearing to appeal to them. They were
accordingly arranged in four rows facing the tent, in front
of which Dr. Haffkine was about to commence operations.
I was the first subject to be inoculated; and after me the
jailor, assistant jailor, hospital assistant, and three warders.
The first prisoner in the front rank was next brought up
and submitted cheerfully; after which, every alternate
man was taken, so that no selection of cases was made,
until one-half of the total number were inoculated. Those
who had not been inoculated were far from pleased at
having been passed over; and, to our surprise, they rose
almost to a man, and begged to be inoculated; nor
were they satisfied when told that the medicine was
exhausted."
The dose administered on this occasion (11th April
1896) was stronger than the Gaya jail dose (18th July
1894): it acted in a few hours, and the reaction was
well marked.
"There were fresh cases of cholera that day at 12
(noon), 6, 7, and 7.30 p.m., and at midnight, all in
those who had not been inoculated, and all terminating
fatally, despite the greatest care and the most prompt
and assiduous treatment. On the 12th two further cases
occurred, both among the uninoculated, and both died;
there being thus eight cases in succession, all from the
men who were not inoculated, and all proving fatal."
The inoculations were made at 7.30 A.M. Surgeon-Captain
Brown had pain within half-an-hour, and fever
in three hours, with temperature 104°, but this was
probably due to the fact that I was not able to rest. The
prisoners, of course, went to bed: they all reacted
before 4 P.M., but did not have so much trouble over
it. The last case was on the 15th. The outbreak
was a bad type of cholera; out of 30 cases 24 died,
some of them in 1-1/2 to 4 hours. "To summarise the
combined results of the camp and the jail, we find that
of a daily average of 99 non-inoculated there were 11
cases, all fatal = 11.11 per cent.; of 110 inoculated there
were 5 cases, with 3 deaths = 2.73 per cent."
Here again the figures are small, but worth noting.
In a coolie camp at Bilaspur (Central Provinces) 100
non-inoculated had 5 deaths, and 150 inoculated had
1 death. In Serampur, among the general population,
51 non-inoculated had 5 cases and 3 deaths, and 42
inoculated had 2 cases and 1 death.
This series of inoculations was begun in February
1895, for the protection of the coolies on various tea-estates.
The results are excellent, and deal with large
numbers.[31] The latest report from Dr. Arthur Powell,
the Medical Officer, is quoted in Dr. Simpson's 1896
report:—
At Kalain—
1079 not inoculated had 50 cases, with 30 deaths.
1250 inoculated—3 cases, with 2 deaths.[32]
At Kalaincherra—
685 not inoculated had 10 cases, with 7 deaths.
155 inoculated—no cases.
At Degubber—
254 not inoculated had 12 cases, with 10 deaths.
407 inoculated—5 cases, all recovered.
At Duna—
121 not inoculated had 4 cases, with 2 deaths.
29 inoculated—no cases.
At Sandura—
454 not inoculated had 2 cases, with 1 death.
51 inoculated—2 cases, with 1 death.
At Karkuri—
198 not inoculated had 15 cases, with 9 deaths.
443 inoculated—3 cases, with 1 death.
At Craig Park—
185 not inoculated had 1 fatal case.
46 inoculated—no cases.
Total.
Not inoculated, 2976, with 94 cases and 60 deaths.
Inoculated, 2381, with 13 cases and 4 deaths.
To the preceding instances, which are rather old
now, must be added the following more recent report,
from the Indian Medical Gazette, September 1901:—
"We are glad to see, from a paragraph in the Report
of the Sanitary Commissioner for Bengal (Major H. J.
Dyson, I.M.S., F.R.C.S.), that an increased number of
anti-cholera inoculations were performed during the year
1900. Assistant-Surgeon G. C. Mukerjee, who was in
charge of this work, reports that in the Puralia Coolie
Depot no less than 13,291 persons were inoculated
against cholera, including over 1000 children. All these
cases of inoculation were among labour emigrants proceeding
to the tea-gardens of Assam and Cachar. The
employers of labour are beginning to realise the value
of cholera inoculation. It is unfortunately not always
easy, or even possible, to follow up the after-history of
persons inoculated; but Major Dyson has quoted a table,
received from the Superintendent of Emigration, which
shows the number of cases among the inoculated and the
non-inoculated at Goalundo. From this table, it is seen
that out of 1527 non-inoculated coolies, who passed
through Goalundo, 33, or 2.09 per cent., got cholera;
whereas of 873 inoculated coolies, only 2, or 0.2 per
cent., were attacked by the disease; that is, the unprotected
suffered about ten times as much as the inoculated.
Assistant-Surgeon Mukerjee also reports that during his
cold-weather tour he passed through some villages in the
Manbhum district, in which he had practised inoculation
the previous year: and, though there had been epidemics
of cholera in them, the inoculated persons escaped. They
came to him in numbers, stating that they owed their
safety to the inoculation."
Of course, the preventive treatment touches points
only here and there on the map of India, with its
300,000,000 people. Probably it will never become
so general in India as vaccination. Cholera in India
recalls what Ambroise Paré, more than 400 years ago,
wrote of the plague, "Here in Paris it is always with
us." But, wherever preventive inoculation has been
done, there it has done good.
The Medical Annual for 1905 contains an account of
some preventive inoculations recently made during an
epidemic in Japan. Among the inoculated, the attack-rate
was much lower than among the uninoculated;
and the mortality was 45.5 per cent., as against 75
per cent.
Another most important result of the discovery of
the cholera bacillus is its use in diagnosis. For
example, if a case of suspected cholera is landed at a
British port, the sanitary authority at once takes steps
to ascertain whether the specific microbe is present;
and, according to the answer given by bacteriology,
either allows the patient to proceed on his journey, or
adopts measures of isolation to prevent the spread of
the disease to others. Thus, thanks to the insular
position of Great Britain, this dreadful disease has
for many years been prevented from invading her
population.
The bacillus pestis was discovered by Kitasato and
Yersin, working independently, in 1894. Yersin's discovery
was made at Hong Kong, whither the French
Government had sent him to study plague: an excellent
account of his work is given in the Annales de
l'Institut Pasteur, September 1894. The first experiments
in preventive inoculation, in animals, were made
by Yersin, Calmette, and Borrel, working conjointly, in
1895. They found that it was possible to confer on
animals a certain degree of immunity, by the hypodermic
injection of dead cultures of the bacillus. These
experiments were made on rabbits and guinea-pigs.
Haffkine's fluid was first used on man in January
1897. It is a bouillon containing no living bacilli, and
nothing offensive to the religious beliefs of India.[33] He
proved its efficacy on rabbits; and then, on 10th
January 1897, inoculated himself with a large dose,
four times as strong as the subsequent standard dose.
A few days later, Lieut.-Col. Hatch, Principal of the
Grant Medical College, Bombay, and other members of
the College Staff, were inoculated. These first inoculations
were described by Haffkine in a lecture (1901) at
Poona:—
"In a short time, a number of the most authoritative
physicians in Bombay, European and native, official
medical officers and private practitioners, submitted
themselves for inoculation. It is a matter of gratification
to me to be able to quote, among these authorities,
the Head of the Medical Service of the Presidency,
Surgeon-General Bainbridge, who not only got himself
inoculated, but inoculated also the members of his family.
Previous to that, Surgeon-General Harvey, the able
Director-General of the Indian Medical Service, submitted
himself to inoculation in 1893 against cholera;
and, in 1898, against plague. It was the example of
these gentlemen, whose competence in the matter of
health could not be disputed, that encouraged thousands
of people, rich and poor, in Bombay and elsewhere, to
come forward for inoculation. Thus his Excellency the
Viceroy thought it right to tell you here, in Poona, that
previous to his starting for the plague-stricken districts
he and his staff had also undergone the prophylactic
inoculation. In due course, mothers brought their children
to be protected by the new 'vaccination.'"
Within a few months, 8142 persons in or near
Bombay were inoculated. It was not possible, in
Bombay, during the rush of plague-work, to follow
up every one of these 8142 persons. But there is
reason to believe, making some allowance for oversights,
that only 18 = 0.2 per cent. of them, were attacked
during the epidemic; that, of these 18, only 2 died:
and that these 2 died within twenty-four hours of inoculation,
i.e., had the plague in them already at the
time of inoculation.
And, with regard to a small group of the inoculated,
there are the following more definite facts. This group
lived outside Bombay, across the harbour, in a village
called Mora. The population of Mora, at the time of
the epidemic, was estimated at less than 1000. Out
of this number 429 were inoculated; which, if the
population be reckoned at 1000 exactly, left 571 uninoculated.
Among the 429 inoculated, there were 7
cases of plague, with no deaths: among the uninoculated
there were 26 cases, with 24 deaths.
Just a week after Haffkine had informed the Indian
Government that he had tested his fluid on himself,
plague broke out in the Byculla House of Correction,
Bombay, on 23rd January 1897. Between the 23rd
and the afternoon of the 30th, there were 14 cases,
with 7 deaths. On the afternoon of the 30th, 152
prisoners were inoculated, and 172 were left uninoculated.
The outbreak ceased on 7th February. The
figures, as corrected by the Plague Commission, are,
among the inoculated, 1 case, which recovered; among
the uninoculated, 7 cases, with 2 deaths.
For a full and severe examination of the reports,
statistics, and other evidence concerning this and other
outbreaks in which preventive inoculations were made,
the Report (1901) of the Indian Plague Commission must
be studied. The Commissioners, Professor T. R. Fraser,
Mr. J. P. Hewett, Professor (now Sir) A. E. Wright,
Mr. A. Cumine, Dr. Ruffer, and Mr. C. J. Hallifax,
Secretary, travelled and took evidence in India from
November 1898 to March 1899: during which time
they held 70 sittings and examined 260 witnesses,
some at great length. The evidence and the report
are published in five large volumes. The report, 540
pages in all, deals exhaustively with the whole subject.
It represents the very least—what might almost be
called the very worst—that can be said of Haffkine's
fluid: and, of course, it reads rather differently from
the reports of the men who, with their lives in their
hands, and worked almost past endurance, fought
plague themselves. The following paragraphs give,
so far as possible, the bare facts of various outbreaks
of the disease in 1897-99, in which Haffkine's fluid
was used.
Plague broke out in Daman, a town in Portuguese
territory, north of Bombay, and in constant communication
with Bombay by sea, in March 1897. By the
end of the month, when a Government cordon was
placed round the town, about 2000 out of 10,900 had
fled. The outbreak reached its height in mid-April,
and was practically over by the end of May. Inoculations
were begun on 26th March. The total
population on that day (2000 having gone out, and
670 having died of plague) is estimated at 8230.
Of these, 2197 were inoculated, and 6033 were left
uninoculated. Among the inoculated there were 36
deaths = 1.6 per cent.; among the uninoculated 1482
deaths = 24.6 per cent.
The Commissioners criticise these figures severely,
and do not accept them as exact. But they admit the
evidence as to the results of inoculation among the
Parsee community of Daman. Of this community, 306
in number, 277 were inoculated, and only 29 were
left uninoculated. Among the inoculated there was 1
death = 0.36 per cent.: among the uninoculated there
were 4 deaths = 13.8 per cent.
They admit, also, the house-to-house investigations
made by Major Lyons, I.M.S., President of the Bombay
Government Plague Committee. At the end of May,
he visited 89 houses, in 62 of which both inoculated
and uninoculated were living together. He found that
out of 382 inoculated, 36 had died = 9.4 per cent.;
out of 123 uninoculated, 38 had died = 30.9 per cent.
Plague attacked Lanauli, a small hill-station and
railway depot, during April to September 1897. The
entire population was estimated at about 2000. Inoculations
were begun on 24th July in two wards of
the town, and a daily house-to-house inspection was
instituted. The figures reported, on the basis of
the average daily strength of the two groups, are as
follows:—
Inoculated, 323, with 14 cases, of which 7 died
= 2 per cent.
Uninoculated, 377, with 78 cases, of which 57 died
= 15 per cent.
The Commissioners criticise the method on which
these figures are based, and do not accept them as
accurate. But they agree that inoculation "exerted
a distinct preventive effect"; and they admit Major
Baker's evidence—"In the place where inoculation
had been made use of, the town was thriving and
full of people; and the other part of the town was absolutely
empty. One side had plague, and the other
had none."
The figures here were obtained under especially
favourable circumstances; and the Commissioners have,
practically, no fault to find with their accuracy. The
following account is by Surgeon-Major Bannerman,
Superintendent of the Plague Research Laboratory,
Bombay:—
"Plague broke out in Kirki, in the artillery cantonment,
situated four miles from Poona; and the followers of the
four batteries stationed there suffered severely. These
men were living with their families in lines on a sloping
plain, under military discipline, and in circumstances
far superior in a sanitary sense to those of the average
villager. When the disease appeared, the lines were
isolated, so that none could enter or leave without the
knowledge of the military. A special hospital was erected
close by, where all sick persons were sent as they were
discovered by the search parties of European artillerymen,
who visited each house thrice daily. It is therefore probable
that all cases of plague were promptly discovered
and removed to hospital: and in each case the usual disinfection
was thoroughly and systematically carried out.
Yet, in spite of all this, it was found that, in those not
protected by inoculation, 1 out of every 6 of the population
was attacked, and 2 out of every 3 attacked died.
The epidemic was, therefore, a severe one. The population
of the lines numbered 1530; and, out of these, 671
volunteered for inoculation. At the close of the epidemic,
the plague-hospital admission and discharge book was
examined, and compared with the register of those inoculated,
when the following result was got. The population
operated on being under military discipline, and
confined to their lines, makes the accuracy of the figures
undoubted:—
Inoculated, 671, with 32 cases, of which 17 died
= 2.5 per cent.
Uninoculated, 859, with 143 cases, of which 98 died
= 11.4 per cent.
"Here, then, is seen a body of people divided into
two groups by the fact that one had undergone inoculation
and the other not, but differing in no other way,
reacting towards plague in such a markedly different
manner that the conclusion is forced on one, that the
inoculation must be the cause. Seeing the absolute
similarity of conditions, the 671 inoculated should have
had proportionately 112 cases and 77 deaths, if they had
remained as susceptible to the disease as their uninoculated
brothers, sisters, parents, wives, husbands, children; but,
instead of that, they had only 32 cases and 17 deaths.
This death-rate would doubtless have been still further
reduced, but for the fact that a very much weakened
vaccine had to be used, owing to the demand having got
beyond the resources of the laboratory at that time."
In Belgaum, a town of Southern India with a normal
population of about 30,700, two outbreaks of plague
occurred in quick succession. The first outbreak lasted
from November 1897 to May 1898; the second,
from July 1898 to January 1899. During the two
epidemics, 2466 persons were inoculated. Of these,
it was reported that only 61 (or 62) had been attacked,
of whom 33 died = 1.34 per cent. But these figures,
in the judgment of the Commission, cannot be accepted
as even approximately correct. There are, however,
two groups of these Belgaum cases, one of which the
Commission admits as substantially accurate, and the
other as absolutely accurate. These groups are,
(1) the Army cases; (2) the cases reported by Major
Forman, R.A.M.C., Senior Medical Officer of the
Station.
(1) The Army Cases.-These cases occurred in the
26th Madras Infantry, which was living in lines close
to the cantonment and the city. The first case of
plague in the regiment was on 12th November 1897.
Ten days later, the regiment was moved out into camp.
Inoculation was begun, by Surgeon-Major Bannerman,
on 23rd December, up to which time there had been,
among the regiment and its families and followers, 78
cases, with 49 deaths. The following account of the
inoculations is given by Surgeon-Major Bannerman:—
"No difficulty was experienced in persuading the men
to consent to inoculation, when it was explained to them
that they would be free to return to their houses in the
lines after being operated on. General Rolland was the
first to be operated on, and his example, combined with
that of the officer commanding, and their medical officer,
who were all operated on in front of the men, sufficed to
convince the Sepoys of the harmlessness of the operation:
and the only difficulty that then remained was to perform
the operation fast enough.... The community was,
practically, completely inoculated by the end of the year.
The total operated on was 1665, out of a population of
1746 living in the lines at that date. The 81 not operated
on were infants, women far advanced in pregnancy, and
the sick in hospital chiefly, though one solitary Sepoy
has, up to the present time, refused to submit to
operation."
From this time onward to the end of the first
epidemic, though the disease was at its height in
January in the neighbouring city and cantonment,
and though the men were allowed to go freely to
these places after inoculation, only 2 out of the 1665
were attacked, and both recovered.
When the second epidemic came, in July 1898, the
troops, families, and followers, were reinoculated at their
own request, 1801 in all. "Practically no one was left
in the lines unprotected by inoculation." From this
time onward to the end of the second epidemic, though
it was much more severe than the first, only 12 cases
occurred. In the first epidemic, before inoculation, 78
cases occurred, and 2 after it: in the second, and much
more severe, epidemic, though the sanitary measures adopted
in both epidemics were similar, only 12 cases occurred.
"It would hardly appear to be open to doubt," says
the Commission, "that the practical immunity of
the regiment, during the second outbreak, was due
to inoculation."
(2) Major Forman's evidence before the Commission
is very striking, though the figures are small. The
following abstract of it is given in the Report of the
Commission:—
"The groups of persons, concerning whom Major
Forman gave us evidence, were his private servants, and
the hospital attendants of the Belgaum Station Hospital
with their wives and children. He inoculated these
groups when plague first broke out in the town, and
was able to keep in touch with them continuously after
that time. Regarding the first group, he says, bringing
down their history to 3rd March 1899, 'Of my private
servants there were in all, including their wives and
children, 28 people inoculated. There have been no
cases of plague, and no deaths up to date. There were
3 uninoculated. One was a child of 9 years of age,
whose father refused to allow it to be inoculated. It died
of plague 12 days after the other people were inoculated.
The other 2 cases that were not inoculated were not so
distinctly under my own observation. One was a sweeper
employed in the cantonment, and sleeping in my compound:
he, I am told, died of plague some months afterwards.
The other was my water-carrier: he threw
himself into a well: I was informed that he had buboes
and fever, and ran away to escape segregation. Of the
28 inoculated, none died of plague: and of 3 uninoculated,
2 are said to have died of plague, and 1 undoubtedly
died of plague.'"
"Regarding the second group of which he gave us
particulars, Major Forman said that, out of 90 hospital
servants, 87 were inoculated. Of the inoculated persons,
1 died from fever and endocarditis, and 1 died of plague.
Excepting these two, the rest of the inoculated were alive
and well in March 1899. Only 3 persons remained
uninoculated. Of these, one was not operated upon,
because she had recently been delivered; another was
not operated upon, because she was pregnant; and the
third was a boy of 16 years of age, whose father refused
to let him be inoculated. The boy died of plague, two
months after the inoculation of the rest of the hospital
servants had been done. One of the two uninoculated
women died of plague two days after the boy, she having
been in attendance upon him. The other uninoculated
woman remained well."
Plague broke out in this jail on the last day of 1897,
and 3 prisoners died. Next day, 1st January 1898,
all the prisoners were paraded, and all were willing to
be inoculated. But it was decided to divide them into
two equal groups, and inoculate one group. There
were 402 altogether: 2, when their turn came, refused
to be inoculated: thus 199 were inoculated, and
203 were left uninoculated. No distinction was made
between the two groups: "They had the same food
and drink, the same hours of work and rest, and the
same accommodation." The plague did not come
wholly to an end till March. The figures, since the
inmates of a jail are a shifting population, are based on
the average daily number of each group: this was 147
for the inoculated, and 127 for the uninoculated. The
figures are:—
| Average Daily Number. |
Cases. |
Deaths. |
| Inoculated |
147 |
3 |
0 |
| Uninoculated |
127 |
9 |
5 |
The Commission draw attention to "the important
fact that, during the whole period of the outbreak, the
number of attacks among the inoculated was only one-third
of the number among the uninoculated; and that
the disease among the inoculated was remarkably mild,
resembling mumps more than plague, though the cases
among the uninoculated were of average severity."
According to Surgeon-Major Bannerman, the hospital
authorities were doubtful whether these three cases
among the inoculated were plague at all.
The figures for Undhera are very valuable: "The
conditions," says Surgeon-Major Bannerman, "approached
very nearly the strictness of a laboratory
experiment." Even the Commissioners are enthusiastic
here.
Undhera is an agricultural village, 6 miles from
Baroda. Plague broke out in it, in January 1898. A
careful census was taken, and showed a population of
1029. By 12th February there had been 76 deaths.
On that day the village was visited by Mr. Haffkine,
Surgeon-Major Bannerman, and other experts, and 513
persons were inoculated:—By reference to the census
papers, the whole of the inhabitants were called out, house
by house, and the half of each household inoculated. In
this way, an endeavour was made to inoculate half the
men, half the women, and half the children in each family,
and to arrange that a fairly equal proportion of the sickly-looking
should be placed in each division. The plague
lasted 42 days after the inoculations, and affected 28
families. On 4th April a house-to-house investigation
was made by Mr. Haffkine, Surgeon-General Harvey,
Surgeon-Major Bannerman, and Captain Dyson. The
figures are as follows:—
Population on
12th February. |
|
|
Cases. |
Deaths. |
Mortality. |
| 1029-76=953 |
Inoculated, |
513 |
8 |
3 |
0.6 per cent. |
| |
Uninoculated, |
440 |
28 |
27 |
6.0 per cent. |
Thus, out of 28 families, where the protected and
the unprotected lived and ate and slept together, the
protected, 71, had 3 deaths; and the unprotected, 64,
had 27. The percentage of attacks was four times
higher among the unprotected; the percentage of
deaths was ten times higher.
The head of this community, H.H. Sir Sultan Shah,
Aga Khan, K.C.I.E., opened a private station for the
inoculation of the community in March 1897, and again
in December of that year. He was himself inoculated
three times, and many of the community so often as
five times. The work of inoculation went on daily, and
by 20th April 1898 the number of persons inoculated
or reinoculated was 5184. The whole community,
according to a careful census taken at the beginning
of 1898, numbered 9350; but, since many families
had fled to avoid the infection, this number is too low.
The Commissioners guess 9770: Haffkine, to the disadvantage
of his own statistics, guesses so high as
13,330. The number of the inoculated or reinoculated
shifted, of course, as the work went on: their
average daily number during the four months of plague,
January to April 1898, was 3814.
During these four months, the number of deaths
from all causes in the whole community was 184.
According to the average mortality of the community
in times of no plague, the deaths from all causes during
four months would be 102. It may fairly be assumed
that the extra deaths, 82, were due to plague: and,
indeed, 64 plague-deaths were either acknowledged by
the relatives, or certified by the burial-books of the
community. Of these 82 deaths, 3 occurred among the
inoculated or reinoculated, and 77 among the uninoculated.
The Commissioners find fault with these figures:
"Nevertheless, quite apart from the statistics put before
us, which we think inaccurate, we do not doubt that
inoculations had a good effect, especially as much
weight must be allowed to the opinion of a community
so intelligent as that of the Khojas."
This, the greatest and most amazing of all instances
of preventive plague-work, was done in a town of
50,000 persons. The following report, by Surgeon-Captain
Leumann, was forwarded to the Plague Commissioners
by Mr. E. K. Cappel, Collector of Dhárwár,
with this comment:—
"The town of Hubli—a mercantile town of over 50,000
inhabitants—was attacked by plague in an epidemic form
at the commencement of the monsoon rains. The average
rainfall between April and October amounts to more than
28 inches. Under these circumstances, although a large
and weather-proof health camp had been prepared for
emergencies, complete evacuation of the infected townsite
was impossible; and the attempt to effect it would
have led to the severest hardships and to the immediate
spread of the disease into surrounding villages and districts.
It was for this reason that the determination was
formed to make a bold and comprehensive experiment
with the prophylactic, and not on any à priori grounds.
If this experiment had failed, the results, judged by the
actual mortality among the uninoculated, would have
been appalling. All possible sanitary measures in the
shape of disinfection, unroofing of houses, and segregation,
were applied concurrently with inoculation, as Government
are already aware; but the rate of mortality among
those who held back from inoculation rose at one time to a
height which, I believe, has never been approached elsewhere....
"However, the experiment, in the hands of Dr. Leumann,
did not fail, and it has afforded a demonstration
of success which is of Imperial importance. Many thousands
of lives have undoubtedly been saved, and at the
present moment the plague mortality is merely sporadic,
and Hubli is steadily regaining its normal population and
trade, though surrounded by infected villages."
The Hubli report must be put at full length, for
the vivid picture it gives of plague in India, and of
the difficulties besetting the magnificent work of the
Indian Medical Service. It is a story that Mr. Kipling
ought to write. And it is to be noted that Surgeon-Captain
Leumann, who saved Hubli, recognised the
extreme importance of other methods than inoculation—disinfection,
isolation of cases, evacuation of infected
districts. He says:—
"While paying the highest tribute to the value of
Mr. Haffkine's inoculation method, which I claim, here
in Hubli, to have put to perhaps the severest test to
which it has yet been subjected, I am of the opinion that
individual protection is, on however great a scale conducted,
of less importance to that of general protection
and hygiene (considering each method separately, that
is to say), for it seems to me more radical, if not more
rational, to eradicate a disease than to leave it to pursue
its course and only protect people against its ravages."
Sanitation, therefore, was Dr. Leumann's faith. Now
for his works:—
"I first started inoculation here on 11th May....
When I began my inoculations, I operated first of all on
some European or native gentlemen in front of a crowd of
poor and low-caste people, whom I had gathered together
in the worst-affected area, and they were thus soon induced
to ask for inoculation themselves.... They have
presented themselves, by the hundred, at all times of
the day, before myself and others, for the purpose of
being inoculated.[34] ... I have never experienced the
slightest difficulty in inoculating Mussulmanis or any
other purdáh women in Hubli.... The very men who,
in March last, created a disturbance in Hubli, were
not only the first and the most willing to undergo inoculation,
but also to bring their wives and families to
my hospital, or to invite me to their homes to inoculate
them.
"Inoculated persons holding certificates of double
inoculation have, at my special wish and order, been
left in their homes throughout this epidemic; only their
clothes, house, and property being disinfected on the
occurrence of a plague case or death in their house. As
the vast majority of plague cases have never been notified
before death in Hubli (nor, in my experience of nearly
two years, elsewhere, if native supervision be largely
resorted to), it will readily be understood that the majority
of the inoculated have actually been living in the same
house, or even room, with a plague case (often of the
pneumonic type, whose terrible power of spreading the
disease was first shown by Professor Childe, I.M.S.,
of Bombay) during the whole of the time that case was
living, probably attending on the patient, breathing the
same stuffy air, and, perhaps, sharing the same blanket;
and I attach at the end of this report a long series of
cases where such conditions have occurred, the non-inoculated
dying of plague, and the inoculated escaping,
almost to a man.
"Various critics on my work, not knowing what the
actual facts were and are, have at different times asserted
that the inoculated inhabitants of Hubli left the town in
larger numbers than the non-inoculated. Exactly the
reverse was the case. The British officers on plague
duty here, and all the Divisional Superintendents, invariably
replied (officially and in writing when so required)
that the non-inoculated left Hubli in far greater
numbers and proportion than the inoculated; and my
own observations entirely bear out this statement.
"It has been urged that those who received inoculation
were of a class or classes better protected than others
against plague by reason of their habits, the food they
eat, the houses they live in, etc. In reply, I unhesitatingly
state that if there be but one town in India where
that line of argument will not hold good, it certainly is
Hubli; for not only were the poorer, dirtier, lower-caste
people the first to be persuaded to receive inoculation, but
I made it my personal and special duty to work amongst
them. My first few thousand inoculations were almost
entirely amongst the lowest and poorest of the people.
The Brahmins are, perhaps, of all castes, supposed to
be the most cleanly in their houses, habits, etc., yet the
Brahmins of Hubli (who at first, imagining themselves
immune, were the foremost and greatest perverters of
the truth concerning its efficacy, and the last to apply for
the protection inoculation affords), simply inundated the
various inoculation centres, as soon as plague began to
spread in their midst, clamouring for the very method of
which they had only lately tried to prevent others from
availing themselves.
"Unfortunately, the average native, educated or not,
appears to have the very greatest aversion to notifying
any case of sickness—plague or other—and hence, in my
opinion, it becomes more necessary than ever to protect
the people by inoculation, since they will not help to protect
themselves by the foremost and simplest of sanitary
and hygienic measures.[35] With so few police (and those
none too good) to help one; an inadequate British Staff;
with so much reliance placed in Native Superintendents
and Supervisors, and a Municipality so bankrupt that it
could not apparently afford to buy enough blankets out
of its own funds for the patients in the Plague Hospitals—the
work of segregation, house-to-house inspection,
etc., became, from a medical point of view, absurdly insufficient.
"The total number of inoculations performed in Hubli,
both on actual inhabitants and on people from outside
(villages) between 11th May and 27th September, amounts
to some 78,000 altogether."
I
| Dates. |
Census of
Hubli. |
Non-
Inoculated. |
Inoculated. |
Plague-deaths
among: |
Non-
Inoculated. |
Inocu-
lated. |
Five weeks
from May 11 |
Fell from
50,000 to |
|
|
|
|
| to June 14 |
47,427 |
44,573 |
2,854 |
47 |
1 |
| Week ending: |
|
|
|
|
|
| June 21 |
47,082 |
41,494 |
5,588 |
22 |
3 |
| June 28 |
47,485 |
39,042 |
8,443 |
29 |
1 |
| July 5 |
46,537 |
36,020 |
10,517 |
55 |
6 |
| July 12 |
46,518 |
33,255 |
13,263 |
34 |
6 |
| July 19 |
45,240 |
29,716 |
15,524 |
82 |
7 |
| July 26 |
43,809 |
24,112 |
19,697 |
100 |
15 |
| Aug. 2 |
43,707 |
21,031 |
22,676 |
140 |
16 |
| Aug. 9 |
42,768 |
15,584 |
27,184 |
272 |
19 |
| Aug. 16 |
40,441 |
10,685 |
29,756 |
386 |
61 |
| Aug. 23 |
39,400 |
6,367 |
33,033 |
371 |
41 |
| Aug. 30 |
38,210 |
4,094 |
34,116 |
328 |
28 |
| Sept. 6 |
38,382 |
2,731 |
35,469 |
227 |
34 |
| Sept. 13 |
38,408 |
1,116 |
37,292 |
138 |
47 |
| Sept. 20 |
39,142 |
937 |
38,205 |
106 |
55 |
| Sept. 27 |
39,315 |
603 |
38,712 |
58 |
20 |
II
| Dates. |
Plague death-rate.
Comparison per 1000
between |
Percentage reduction
of Plague death-rate
in favour of the
Inoculated. |
Non-
Inoculated. |
Inoculated. |
Five weeks
from May 11 |
|
|
|
|
| to June 14 |
1.022 |
.350 |
Over |
65 per cent. |
| |
|
|
|
|
| Week ending: |
|
|
|
|
| June 21 |
.530 |
.527 |
About |
1 per cent. |
| June 28 |
.742 |
.118 |
Nearly |
85 per cent. |
| July 5 |
1.524 |
.570 |
About |
63 per cent. |
| July 12 |
1.022 |
.452 |
Nearly |
56 per cent. |
| July 19 |
2.793 |
.450 |
|
84 per cent. |
| July 26 |
4.147 |
.761 |
|
82 per cent. |
| Aug. 2 |
6.656 |
.705 |
|
89 per cent. |
| Aug. 9 |
17.325 |
.698 |
Over |
96 per cent. |
| Aug. 16 |
33.694 |
2.083 |
|
94 per cent. |
| Aug. 23 |
57.011 |
1.241 |
|
98 per cent. |
| Aug. 30 |
80.116 |
.820 |
|
98 per cent. |
| Sept. 6 |
83.112 |
.958 |
|
99 per cent. |
| Sept. 13 |
112.903 |
1.260 |
Over |
99 per cent. |
| Sept. 20 |
113.127 |
1.439 |
Over |
99 per cent. |
| Sept. 27 |
96.185 |
.517 |
Over |
99 per cent. |
"It appears that if the 47,427 inhabitants had remained, as they
did—in their town, without running away by rail or otherwise, or
without camping out in a mass—and if no inoculation had been
resorted to—they would have lost 24,899 souls, or a little over half
of their number. The official records show that this has actually
occurred, during the present terrible outbreak, in a number of large
villages, of 2000 inhabitants and over, in the Hubli taluka and elsewhere
in the Dhárwár District, where no inoculation was done,
and no camping-out was possible on account of the wet weather."
(Haffkine's commentary on Dr. Leumann's report.)
That is the story of Hubli; and, as it stands, it is
almost incredible. The Commissioners, by very strict
inquiry, reduced it to credibility without robbing it of
glory. The inquiry brought out more instances of the
immeasurable difficulty of the work. Natives who
wished to avoid inoculation would escape through the
back door at the sight of a plague officer: bribery,
personation, sale or transfer of certificates of inoculation,
concealment of cases and of deaths, were all
practised by those who wished not to be inoculated,
or to get the privileges of the inoculated without
inoculation, or to save their infected houses from being
disinfected and unroofed. Again, with the people dying
like flies, and many of them bearing no mark of identification,
and with the medical officers overworked past
human endurance, the wonder is, not that the statistics
were faulty, but that there are any statistics at all.
Certainly, the Commission is well within the mark in
saying, "It is quite clear that a very large number of
lives must have been saved in Hubli by inoculations
during the whole course of the epidemic there. Moreover,
we may note that an arithmetical estimate is not the
only criterion by which we can appreciate the value of inoculations.
And in Hubli their value is approved by the consensus
of opinions of officers who have seen probably far
more of this process and its results in practice than any
other persons in India, and who, having every facility
for forming a sound judgment as to its effect where
plague was really virulent, are satisfied as to its great
value."
Finally, as at Daman so at Hubli, there are lesser
groups of statistics, of that kind which is approved by
the consensus of opinions of officers. These are, (1)
Lieutenant Keelan's house-to-house investigation;
(2) the Southern Mahratta Spinning Mills; (3) the
Southern Mahratta Railway employés.
1. Lieutenant Keelan made a house-to-house visitation
of 200 houses, in each of which there were protected
and unprotected persons living together, and
in each of which there had been one or more cases
of plague. The figures for 69 of these houses are
appended to Captain Leumann's report. They are as
follows:—
| |
Inmates. |
Cases. |
Deaths. |
Mortality. |
| Inoculated |
336 |
11 |
4 |
1.19 |
| Uninoculated |
144 |
84 |
80 |
55 |
These 69 houses were selected: there was nothing
unfair in the method of selection, still, they were
"good houses"; they are not, therefore, exact for
statistics; but, as the Commissioners say, they are
"of interest as quite special examples of successful
inoculation."
2. In the Southern Mahratta Spinning and Weaving
Company's Mills, a careful record of inoculation was
kept and checked by the manager. The number of
the workpeople at the time when inoculation was begun,
21st June, was 1173. At the end of the epidemic the
figures were:—
| |
|
Deaths. |
Mortality per
cent. |
| Inoculated twice |
1040 |
22 |
2.11 |
| Inoculated once |
58 |
8 |
13.79 |
| Uninoculated |
75 |
20 |
26.66 |
Here, again, the figures have not a statistical value:
"We are not informed whether the inoculations were
performed simultaneously; or at what stage of the
outbreak the average strength of the inoculated was
reached." All the same, what Major Bannerman says
of them is true—The experience in this company's mill at
Hubli should be an object lesson to all mill-owners in
plague-stricken towns.
3. The figures for the Southern Mahratta Railway
are given by Major Bannerman in his "Statistics"
(1900): they are not mentioned in the Report of the
Plague Commission. They are of great value, because
the daily shifting of the numbers was recorded as the
work of inoculation went on, and the date of each case
of plague was also noted. Major Bannerman gives the
following account:—
"The railway employés were living in barracks, and
in the railway yard, apart from the general population of
Hubli town. They were under close daily inspection by
English officials, who formed a committee for this purpose,
with Dr. Chenai as their medical adviser. The
results may therefore be regarded as accurate in a high
degree, the numbers dealt with not being excessive, and
the supervision strict."
The figures, based on the average numbers in each
group, are as follows:—
| |
|
Cases. |
Deaths. |
Mortality per
cent. |
| Twice Inoculated |
990 |
6 |
1 |
0.1 |
| Once Inoculated |
270 |
5 |
1 |
0.3 |
| Uninoculated |
760 |
35 |
21 |
2.7 |
These eight instances must suffice: many must be
left out—among them, Dhárwár and Gadag, where Miss
Corthorn, M.B., did work as splendid as Leumann's
work at Hubli; and Mr. Anderson's work in the Ahmednagar
villages; and many more. These plague-reports
are to be read, not for their record of heroic zeal and
resourcefulness, but only as one more example of many
thousand lives saved by a method learned from experiments
on animals.
But, of course, there is not, and perhaps there never
will be, a national acceptance and adoption of this
method through the length and breadth of India. It
does not work miracles; it is an uncomfortable process
to submit to; privileges must be offered with it, or the
native will often prefer to take his chance; the protection
is of uncertain duration; all sorts of lies are
told about it, partly by anti-vivisectionist writers,
partly by native political agitators, partly by the
hakims. For instance, at a meeting of hakims at
Masti, Lahore, on 11th April 1898, the following resolutions
were passed:—
"That in the opinion of this meeting the bubonic
plague is not a contagious disease. It originates from
poisoned air, and this poison is created in the air on
account of atmospherical germs and the excess of terrestrial
humidities.
"That this meeting, having carefully considered the
Resolution of the Punjab Government (11th January
1898), is of opinion that the rules embodied in that
Resolution (isolation, disinfection, etc.), are unnecessary
under the principles of Unani medical science."
And among statements to be made to the Plague
Commissioners was the following, from a native practitioner
in Bombay (April 1899):—
"I do not think the plague was imported in Bombay
from Hong Kong or anywhere else. I attribute three
sources of causes of outbreaks of plague in Bombay:
(a) The predisposing cause was the Bombay Municipality;
(b) The exciting cause was the Nature herself;
(c) The aggravating cause was the Plague Committee."
All these difficulties were well stated by Surgeon-General
Harvey, Director-General of the Indian Medical
Service, at the discussion on Haffkine's discourse before
the Royal Society, June 1899:—
"The people of England should consider the difficulties
attending the work of a bacteriologist in India.... He
had no doubt as to the value of the inoculations. At
Undhera he carefully examined the results of the experiment,
and, as far as he could judge, there was no
possibility of error. The results in that experiment were
such as to be 90 per cent. in favour of the inoculated
against the uninoculated. The natives of India were,
however, a strange people, and it was difficult to prophesy
how they would act. In Calcutta, the mention of inoculations
had driven in hot haste from the city 300,000
people, many of whom afterwards returned and were
inoculated; while at Hubli he had seen the inhabitants
come in their thousands to be inoculated and pay for
the inoculations. The medical officer in charge at Hubli
had performed about 80,000 inoculations, and had only
observed some 12 abscesses. He thought that 12
abscesses only, in 80,000 inoculations, showed good
results. But, after all, what were the numbers of inoculations
performed to the 300,000,000 inhabitants of
India? He felt that even if every one consented to be
inoculated it was impossible to provide the vaccine or the
medical officers for such a demand. It was accordingly
to sanitary improvements that he looked with the most
confidence to protect India against the plague."
Therefore, now and for many years to come, preventive
inoculation must fall into line with the other
world-wide ways of fighting plague—quarantine, notification,
isolation, all sanitary measures, destruction of rats—le
rat, le génie de la peste—evacuation of infected
towns, disinfection or unroofing of infected houses.
Happily, this is just what it does. That admirable
paper, the Indian Medical Gazette (September 1901),
has put this fact very simply: "No one ever imagined
that inoculation was the only means of fighting plague.
Its great value consists in its immediate application.
To sanitate, ventilate, and practically rebuild a town or
village takes time; and in the meantime thousands
die." For sudden outbursts of plague—since rats are
one chief source of infection, and notification is fundamentally
abhorrent to native custom, and evacuation
may ruin trade, or spread infection, or be impossible
by reason of the rains—since "East is East, and West
is West"—it is not always possible to provide, for an
Indian village smitten by plague, the excellent arrangements
of the Western world. In all such cases, and
in all cases of epidemic plague within narrow limits,
as in jails, barracks, mills, and the like centres of
human life; and in all inner communities, such as the
Parsee community at Daman, or the Jewish community
at Aden—by every test of this kind, the saving power
of preventive inoculation has been proved, again and
again, past all doubt. As for those larger death-traps,
Hubli, Dhárwár, and the rest of them, here, though
the statistics are inexact, we have the word of the
men and women themselves who stood between the
dead and the living, and the plague was stayed. Such
faults as there were, in 1899, in the treatment—the
contamination of this or that stock of the fluid,
and the inadequate method of standardisation—have
been duly noted by the Commission. The rush for
the fluid in 1899 may be estimated from the following
paragraphs:—
(i.) Paris. "The preparation of anti-plague serum is
being rapidly proceeded with; up to the present time
the Institute has supplied it, in response to all the very
numerous requests which have come from Portugal,
Spain, Italy, and Turkey, without encroaching on the
reserve kept in readiness for Paris and the departments."
(Lancet, 16th September 1899.)
(ii.) India. "The spread of plague westward to Spain
and Portugal seems to have excited more or less general
alarm, and I hear that an unprecedented demand has
suddenly arisen for the plague prophylactic fluid. The
Government of India have been asked the cost of supplying
from 50,000 to 100,000 doses, and the earliest date
at which this quantity could be despatched. It is also
desired to know if in case of need 50,000 doses a week
could be sent to London. Russia desires to obtain a
considerable stock for Port Arthur. Italy has been
making inquiries for home use; and also Portugal, in
order to inoculate at Mozambique. The present laboratory
is at Government House, Parel, Bombay, and has
only recently been fitted up by the Government of India.
About 10,000 doses a day can be turned out, but it is
thought that still further enlargements will be required
if the demand should increase beyond this amount."
(Lancet, 23rd September 1899.)
It would take too long for the present purpose to
consider what has been done, not only for the prevention
of plague, but also for its cure by a serum
treatment. The results obtained by this treatment in
India have not been very good; but Yersin and others
report better results in other countries. Good results
are reported from Amoy (1896), Nhatrang (1898),
Oporto (1899), and Buenos Ayres (1899-1900). In
Glasgow, the prophylactic use of Yersin's serum seems
to have done excellent service: the success of its
curative use was not very striking. The curative
results at Nhatrang (Yersin, Annales de l'Institut
Pasteur, March 1899) are notable. Nhatrang is an
Annamese fishing-village; and the plague, when it was
left to itself, killed every case that it got:—
"La peste s'est montrée excessivement meurtrière chez
les Annamites. Sur 72 cas de peste, 39 personnes chez
lesquelles la maladie a évolué normalement, ou qui n'ont
été traités que par des médecins indigènes, sont mortes
sans exception. Les 33 autres cas ont pu être traités
par le sérum, quelquefois dans de bonnes conditions, mais
le plus souvent quelques heures seulement avant la mort.
Malgré cela, nous avons obtenu 19 guérisons et 14 décès,
ce qui fait une mortalité de 42 per cent., chez les traités.
Ainsi, d'une part, 100 pour 100 de mortalité chez les non-traités;
de l'autre, 42 per cent. chez les malades qui ont
reçu du sérum. Ces chiffres confirment les résultats que
j'avais obtenu en Chine en 1896."
A long review of this curative treatment, fairly hopeful
but nothing more, is given in the Report of the
Plague Commission, vol. v., pp. 269-320. The Commissioners
are of opinion that it ought not yet to be
extended, as a general measure, over all the districts
affected with plague; and that there is need of more
work in bacteriology before it can be thus extended.
"We desire to record our opinion that, though the
method of serum-therapy, as applied to plague, has not
been crowned with a therapeutic success in any way
comparable to that obtained by the application of the
serum method to the treatment of diphtheria, none the
less the method of serum-therapy is in plague, as in other
infectious diseases, the only method which holds forth a
prospect of ultimate success."
It is a strange contrast, between this opinion and
the statements made by the opponents of all experiments
on animals. Some of these statements will be
found in Part IV. of this book. Happily for the world,
no amount of foul language can hinder the good work;
and, when we talk of Empire-building, and of deeds that
win the Empire, we must reckon bacteriology among
them: as Lord Curzon did, in his speech at Calcutta,
March 3, 1899—What is this medical science we bring
to you? It is built on the bed-rock of pure irrefutable
science; it is a boon which is offered to all, rich and poor,
Hindu and Mohammedan, woman and man.
The names of Klebs, Eberth, and Koch, are associated
with the discovery, in 1880-81, of the bacillus of
enteric fever, bacillus typhosus; and it was obtained in
pure culture by Gaffky in 1884. It has been studied
from every point of view, in man and in animals; in
the blood, tissues, and excretions; in earth, air, water,
milk, and food; in its distribution, methods of growth,
and chemical products. Especially, the study of its
chemical products has been directed toward (1) immunisation
against the disease, (2) bacteriological diagnosis
of the disease at an early stage.
The date of the first protective inoculations against
typhoid is July to August 1896: they were made at
Netley Hospital, by Professor Wright and Surgeon-Major
Semple. The first inoculations in Germany,
made by Pfeiffer and Kolle, were published two months
later. The story of these famous Netley inoculations
is told in the British Medical Journal, 30th January
1897. Eighteen men offered themselves—
"A good deal of fever was developed in all cases, and
sleep was a good deal disturbed. These constitutional
symptoms had to a great extent passed away by the
morning, and laboratory work went on without interruption....
With two exceptions, all these vaccinations
were performed upon Medical Officers of the Army or
Indian Medical Services, or upon Surgeons on Probation
who were preparing to enter those services."
Good luck attend all eighteen of them, and immunity
against typhoid, wherever they are. The doses
that they received were estimated in proportion to the
dose that would kill a guinea-pig of 350-400 grammes
weight; and the protective fluid contained no living
bacilli:—
"The advantages which are associated with the use of
such 'dead vaccines' are, first, that there is absolutely
no risk of producing actual typhoid fever by our inoculations;
secondly, that the vaccines may be handled and
distributed through the post without incurring any risk
of disseminating the germs of the disease; thirdly, that
dead vaccines are probably less subject to undergo alterations
in their strength than living vaccines."
The first use of the vaccine during an outbreak of
typhoid was in October 1897, at the Kent County
Lunatic Asylum. The treatment was offered to any of
the working staff who desired it:—
"All the medical staff, and a number of attendants,
accepted the offer. Not one of those vaccinated—84 in
number—contracted typhoid fever: while of those unvaccinated
and living under similar conditions, 16 were
attacked. This is a significant fact, though it should
in fairness be stated that the water was boiled after a
certain date, and other precautions were taken, so that
the vaccination cannot be said to be altogether responsible
for the immunity. Still, the figures are striking."
(Lancet, 19th March 1898; see also Dr. Tew's paper, in
Public Health, April 1898.)
Certainly, they are striking; so is the story of the
eight young subalterns on the Khartoum expedition, of
whom six were vaccinated, and two took their chance.
The six escaped typhoid, the two were attacked by it,
and one died. But these figures are too small to be of
much value.
The first anti-typhoid inoculations on a large scale
were made among British troops in India (Bangalore,
Rawal Pindi, Lucknow), when the Plague Commission,
of which Professor Wright was a member, was in
India, November 1898 to March 1899. These inoculations
were voluntary, at private cost, and without
official sanction; though the original proposal for them,
in 1897, had come from the Indian Government.
Pending official sanction, they were stopped. Then,
on 25th May 1899, the Indian Government made
application to the Secretary of State for India that
they should be sanctioned, and should be made at the
public cost. The application is as follows:—
"The annual admissions per mille for enteric fever
amongst British troops in India have risen from 18.5 in
1890 to 32.4 in 1897, while the death-rate has increased
from 4.01 to 9.01; and we are of opinion that every
practicable means should be tried to guard against the
ravages made by this disease. The anti-typhoid inoculations
have been, we believe, on a sufficiently large scale
to show the actual value of the treatment, while the
results appear to afford satisfactory proof that the inoculations,
when properly carried out, afford an immunity
equal to or greater than that obtained by a person who
has undergone an attack of the disease; further, the
operation is one which does not cause any risk to health.
In these circumstances, we are very strongly of opinion
that a more extended trial should be made of the treatment;
and we trust that your Lordship will permit us to
approve the inoculation, at the public expense, of all
British officers and soldiers who may voluntarily submit
themselves to the operation."
On 1st August, the Secretary of State for India
announced in Parliament that this treatment, at the
public expense, had been sanctioned.
On 20th January 1900, Professor Wright published
in the British Medical Journal an account of these
1898-99 inoculations in India. "They were undertaken
under conditions which were very far from ideal.
In particular, there is reason to suppose that the results
obtained may have been unfavourably influenced by a
weakening of the vaccine, brought about by repeated
re-sterilisation." In no case was reinoculation done.
The statistics were compiled from information furnished
by officers of the Royal Army Medical Corps actually in
charge of troops in the various stations; and were supplemented
by reports received from the commanding
officers of the various inoculated regiments. They are
as follows:—
Numbers under
Observation. |
|
Cases. |
Deaths. |
Percentage
of Cases. |
Percentage
of Deaths. |
| Inoculated |
2835 |
27 |
5 |
0.95 |
0.2 |
| Uninoculated |
8460 |
213 |
23 |
2.5 |
0.34 |
If the inoculated had been attacked equally with the
uninoculated throughout the period of observation, they
would have had 71 cases instead of 27.
These inoculations belong to the early part of 1899.
During the rest of the year, inoculations were made in
India, Egypt, and Malta: the results are given in an
appendix to the Report of the Royal Army Medical
Department, 1899. (See British Medical Journal, 21st
September 1901.) The great majority of the troops
tabulated were in India. Of the troops stationed at
Malta, 61 were inoculated, 2456 not inoculated; among
the former there were no cases, among the latter there
were 17 cases and 5 deaths. In Egypt, of 4835
troops, 461 were inoculated; among these there were
no cases, among the uninoculated there were 30 cases
and 7 deaths. In India, of 30,353 troops, 4502 were
inoculated, leaving 25,851 not inoculated; among the
inoculated there were 44 cases and 9 deaths, among
the non-inoculated 657 cases and 146 deaths. Taking
the Indian statistics, and estimating percentage to
strength, we find, amongst the inoculated, admissions
0.98, deaths 0.2; amongst the non-inoculated, admissions
2.5, deaths 0.56. The cases which occurred
amongst the inoculated men were in the majority of
instances of a mild character. Taking Malta, Egypt,
and India together, it appears that the inoculated, if
they had suffered equally with the non-inoculated,
would have had 108 cases and 24 deaths, instead of
44 cases and 9 deaths.
At the end of 1899, this treatment, only just out of
the hands of science, was suddenly demanded for the
protection of a huge army at war in a country saturated
with typhoid. Still, the South African results, and
other results during 1899 to 1901, show a good
balance of lives saved. The following paragraphs give
all results published from the beginning of 1900 to
May 1902. They are put in order of publication.
Doubtless a few other reports have been overlooked in
compilation; but the list includes all that were easily
accessible.
1. Manchester, England. The British Medical Journal,
28th April 1900, contains a note by Dr. Marsden,
Medical Superintendent of the Monsall Fever Hospital,
Manchester, on the inoculation of 14 out of 22 nurses
engaged in nursing typhoid patients. Of the remaining
8, 4 had already had typhoid. The inoculations were
made in October 1899. The following table shows the
subsequent freedom from typhoid of the nursing staff:—
| Year. |
Number of
Typhoid Patients. |
Cases among
Nursing Staff. |
| 1895 |
229 |
3 |
| 1896 |
238 |
3 |
| 1897 |
302 |
4 |
| 1898 |
426 |
8 |
| To end of September 1899 |
163 |
5 |
| From October 1899 to March 1900 |
146 |
0 |
2. Ladysmith, South Africa. The Lancet, 14th July
1900, contains a short note by Professor Wright, on
the distribution of typhoid among the officers and men
of the military garrison, during the siege of Ladysmith.
The figures are as follows:—
| |
Number. |
No. of
Cases. |
Proportion
of Cases. |
No. of
Deaths. |
Proportion
of Deaths. |
Case-
mortality. |
| Not inoculated |
10,529 |
1489 |
1 in 7.07 |
329 |
1 in 32 |
1 in 4.52 |
| Inoculated |
1,705 |
35 |
1 in 48.7 |
8 |
1 in 213 |
1 in 4.4 |
The wide difference between the two groups, as
regards the incidence of the disease, is well marked;
but the case-mortality is practically the same in each
group. (The statistics of the General Hospital, Ladysmith,
also tell in favour of the preventive treatment:
see Surgeon-Major Westcott's letter, British Medical
Journal, 20th July 1901, in answer to Dr. Melville's
letter, British Medical Journal, 20th April 1901.)
3. The Portland Hospital: Modder River and Bloemfontein.
The British Medical Journal, 10th November
1900, contains an account by Dr. Tooth of the cases
of typhoid in this hospital. Concerning the preventive
treatment, he says: "The experience of my colleague
Dr. Calverley and myself may be of interest, though we
fear that the numbers are too few for safe generalisation.
"Personnel of the Portland Hospital. We take first
the relation of disease and inoculation among the
personnel of the hospital. Twenty-four non-commissioned
officers, orderlies, and servants of the Portland
Hospital, and 4 of the medical staff, were inoculated
on the voyage out. All these showed the local symptoms
at the time; that is, pain, stiffness, and local
erythema; 17 also presented well-marked constitutional
symptoms—general feeling of illness, fever, and headache.
Of the orderlies, 9 had enteric fever subsequently.
Two had refused inoculation, and both of
these had the disease very severely; in fact one died.
Of the inoculated cases, 5 had the disease lightly, and
2 fairly severely. One of the sisters had the disease
rather severely, and she had not been inoculated.
"Officers and men admitted to the Portland Hospital.
We had under treatment at the Portland Hospital 231
cases of enteric fever, most of which came under our
care at Bloemfontein. We have not included in these
figures a number of patients who came in convalescent
for a short time only, and on their way to the base, and
who would therefore appear in the admission and discharge
book of the hospital. If we did so, of course
our percentages would be lower. Of these 231
patients, 53 had been inoculated at home or on the
voyage out, and of them 3 died, making a percentage
of deaths among the inoculated of 5.6 per cent.; 178
had not been inoculated, of whom 25 died; that is, a
mortality among the non-inoculated of 14 per cent.
The general mortality in enteric fever with us was 28
deaths out of 231 cases; that is, 12.1 per cent., which
seems to compare favourably with the experience of the
London hospitals.
"It is interesting to record our experience among
the officers taken separately. Thirty-three officers were
admitted with enteric fever; 21 had been inoculated;
that is, 63.6 per cent.; a much larger percentage than
among the men. Only one of these officers died, and
he had not been inoculated.
"These figures are small, but such as they are they
are significant, and they dispose us to look with favour
upon inoculation. So also does our clinical experience
with our patients, for among the inoculated the disease
seemed to run a milder course."
4. No. 9 General Hospital, Bloemfontein. The Medical
Chronicle for January 1901 contains an account, by
Dr. J. W. Smith, of the work of this hospital. He says:
"The general impression amongst the medical officers
in our hospital was that a single inoculation probably
did not confer an immunity lasting very long—the
lapse of time differing in individuals—and also that
there was a tendency in the cases of enteric in inoculated
patients to abort at the end of ten or fourteen
days. I should say, however, that a very considerable
number of our detachment who had been inoculated
suffered from enteric, of whom 4 at least died. Of the
medical staff, the only member of the junior staff who
had not been inoculated died of enteric."
5. Scottish National Red Cross Hospital, Kroonstadt.
The British Medical Journal, 12th January 1901,
contains an account of the work of this hospital by
Surgeon-Colonel Cayley, Officer in Charge. He says:
"The first section of the hospital, consisting of 61
persons—officers, nursing sisters, and establishment—left
Southampton on 21st April 1900. During the
voyage out, all except 4 were inoculated twice, at an
interval of about ten days; 2 were inoculated once;
and 2 (who had had typhoid) were not inoculated.
Immediately we reached the Cape, the hospital was
sent up to Kroonstadt in the Orange River Colony, and
remained there as a stationary hospital till the middle
of October. During this period there were always
many cases of enteric under treatment in hospital.
Further, some of the medical officers and student
orderlies had charge of the Kroonstadt Hotel temporary
hospital, which was crowded up with enteric cases; and
the nursing sisters, for three weeks, did duty in the
military hospitals at Bloemfontein in May and June,
when enteric fever was at its worst. There was not a
single case of enteric among the personnel of this first
section of the hospital.
"The second section of the hospital—medical officers,
nurses, and establishment, 82 in all—left Southampton
in May 1900. On board ship nearly all of them were
inoculated, but many of them only once. The material
for inoculation had been on board for some time, and
was not so fresh as in the first instance. Of this
second section, 1 nurse had enteric at Kroonstadt.
She was the only one, out of a total of 36 nurses, who
suffered from enteric; and she was the only nurse who
was not inoculated, excepting the 2 who were protected
by a previous attack of enteric. A third section of the
hospital, consisting of 4 medical officers and 16 nurses,
went out in July; they were all inoculated, and none of
them had enteric.
"Of the second section, 5 orderlies had enteric fever
at Kroonstadt, of whom 2 died. Of these 5, there
were 2 inoculated (once) and 3 non-inoculated. Of the
2 who died, 1 had been once inoculated, the other had
not been inoculated."
6. Meerut, India. The British Medical Journal, 9th
February 1901, gives a short note by Professor Wright
on inoculations in the 15th Hussars. He says:
"Through the kindness of Lieutenant-General Sir
George Luck, commanding the Bengal Army, I am
permitted to publish the following officially compiled
statistics, dealing with the effects of anti-typhoid inoculations
in the case of the 15th Hussars:—
From 22nd October 1899 to 22nd October 1900.
| |
Strength. |
Inoculated. |
Cases. |
Deaths. |
Not
Inoculated. |
Cases. |
Deaths. |
| Officers |
22 |
19 |
0 |
0 |
3 |
0 |
0 |
| N.C.O. and Men |
481 |
317 |
2 |
1 |
164 |
11 |
6 |
| Women |
36 |
24 |
0 |
0 |
12 |
0 |
0 |
It would thus appear that the incidence of enteric in the
inoculated was represented by 0.55 per cent., and the
mortality by 0.27 per cent.; while the incidence in
the uninoculated was 6.14 per cent., and the death-rate
3.35 per cent."
If the inoculated had suffered equally with the uninoculated,
they would have had 22 cases with 11 deaths,
instead of 2 cases with 1 death.
7. The Edinburgh Hospital, South Africa. The Scottish
Medical and Surgical Journal, March 1901, contains
an account of the work of the Edinburgh Hospital, by
Dr. Francis Boyd. Of the staff, 58 were inoculated
(27 once, and 31 twice). Among these 58, there were
9 cases of typhoid fever, with I death, in a patient
who had old mitral disease. "Our experience has been
that, while inoculation appears to modify the disease,
completely modified attacks are met with in the uninoculated.
Again, very severe attacks, with complications
and relapse, occur in those who have been
inoculated. One cannot from this conclude that inoculation
has been valueless, for had not the patient
been inoculated, the attack might have been still more
severe."
8. Egypt and Cyprus. The British Medical Journal,
4th May 1901, gives a short note by Professor Wright
on inoculations during 1901 in Egypt and Cyprus. He
says: "I am indebted to the kindness of Colonel W. J.
Fawcett, R.A.M.C., Principal Medical Officer in Egypt,
for the following statistics dealing with the incidence
of enteric fever, and the mortality from the disease,
for the year 1900, in the inoculated and uninoculated
among the British troops in Egypt and Cyprus:—
| |
Average Annual
Strength. |
Cases. |
Deaths. |
Percentage
of Cases. |
Percentage
of Deaths. |
| Uninoculated |
2669 |
68 |
10 |
2.50 |
0.40 |
| Inoculated |
720 |
1 |
1 |
0.14 |
0.14 |
These figures testify to a nineteen-fold reduction in the
number of attacks of enteric fever, and to a threefold
reduction in the number of deaths from that disease,
among the inoculated.... The only case which occurred
among the inoculated was that of a patient
admitted to hospital on the thirty-third day after inoculation.
It would seem that the disease was in this
case contracted before anything in the nature of protection
had been established by the inoculation."
9. Imperial Yeomanry Hospital, Pretoria. Dr. Rolleston,
Consulting Physician to this hospital, writes in
the British Medical Journal, 5th October 1901: "Among
the personnel of the hospital (17 medical officers, 50
nursing sisters, 83 orderlies, etc.), total, 150, there
were 22 cases of enteric fever, or an incidence of 14.6
per cent. Of the 150, 35 were inoculated, and of
these, 6, or 17 per cent., suffered from enteric; while,
of 115 non-inoculated members of the personnel, 16, or
13.9 per cent., suffered from enteric fever; the percentage
is therefore higher among the inoculated.
There were 2 deaths, both in non-inoculated patients.
In 100 cases of enteric fever among non-commissioned
officers and men, taken mainly from convalescent
patients, only 8 had been previously inoculated; there
were 3 fatal cases, all among non-inoculated patients.
Among 42 officers who had enteric, no fewer than 19
had been previously inoculated; 6 of these 19 cases
were severe in character, but none were fatal; of the
23 non-inoculated cases, 7 were severe, and of these 7,
3 ended fatally. The interval between inoculation and
the subsequent incidence of enteric fever varied between
one and twenty-one months, but in only four instances
was the interval less than six months. The average
interval between inoculation and the onset of enteric
fever in these 19 cases was thirty-eight weeks.
"As far as these scanty figures go, they point to the
conclusion (1) that anti-typhoid inoculation does not
absolutely protect against a future attack of typhoid
fever; (2) that when enteric occurs in an inoculated
person, there is, as a rule, an interval of about six
months; (3) that inoculation protects against a fatal
termination to the disease."
10. Richmond Asylum, Dublin. The British Medical
Journal, 26th October 1901, contains a note by Professor
Wright on an outbreak of typhoid in this asylum
during August to December 1900. Inoculations were
begun on 6th September, by Dr. Cullinan, and by 30th
November 511 persons were inoculated. After careful
criticism of all doubtful cases, Professor Wright gives
the following figures:—
Comparative Incidence of Typhoid Fever in Inoculated and Non-Inoculated,
calculated upon the average strength of the representative
groups during the period intervening between the
commencement of the inoculations and the termination of the
epidemic.
| |
Average
Strength. |
Cases. |
Deaths. |
Percentage
of Cases. |
Percentage
of Deaths. |
| Uninoculated |
298 |
30(-1?) |
4 |
10.1 |
1.3 |
| Inoculated |
339 |
5(+1?) |
1 |
1.3 |
0.3 |
"It may be noted," he says, "that the result is in
conformity with that of all the statistical returns of
anti-typhoid inoculation which have reached me."
11. Deelfontein. The Lancet, 18th January 1902,
contains a paper by Dr. Washbourn and Dr. Andrew
Elliot, on 262 cases of typhoid fever in the Imperial
Yeomanry Hospital at Deelfontein during the year
March 1900 to March 1901. (See Dr. Washbourn's
earlier letter, Brit. Med. Jour., 16th June 1900.) They
say: "In 211 of our cases, it was definitely recorded
whether the patient had been inoculated or not: 186
of these cases had not been inoculated, with 20 deaths,
or a mortality of 10.7 per cent.; 25 had been inoculated,
with 4 deaths, or a mortality of 16 per cent. The
mortality was thus higher among the inoculated than
among the non-inoculated." Of the personnel of the
hospital, there were 59 inoculated, with 4 cases, and
25 not inoculated, with 4 cases.
12. Winburg. The Lancet, 5th April 1902, contains
a short note by Professor Wright, on the 5th
Battalion, Manchester Regiment. He says: "In view
of the dearth of statistics bearing on the incidence of
typhoid fever in South Africa in inoculated and uninoculated
persons respectively, the following, for which
I am indebted to Lieutenant J. W. West, R.A.M.C.,
Winburg, Orange River Colony, may not be entirely
without interest. The statistics here in question give
the results obtained in the case of the 5th Battalion,
Manchester Regiment, for the six months which have
elapsed since their landing in South Africa. The
figures, which relate to a total strength of 747 men
and officers under observation, are as follows:—
| |
Number. |
Cases. |
Deaths. |
Percentage
of Cases. |
Percentage
of Deaths. |
| Uninoculated |
547 |
23 |
7 |
4.2 |
1 in 3.3 |
| Inoculated |
200 |
3 |
0 |
1.5 |
0 |
"The three attacks in the inoculated are reported
to have been of exceptionally mild type, contrasting
in a striking manner with the severe attacks which
occurred in the uninoculated. At the time of sending
in the report, some of the uninoculated patients were
'not yet out of danger.'"
Certainly, these instances show a good balance of
lives saved, not only under the adverse conditions of
the war, but also in Egypt, India, and the United
Kingdom. But the bacteriological work on typhoid
fever has been directed also to the working out of a
very different problem: and that is the method of
diagnosis which is called "Widal's reaction." The
practical uses of this reaction are of the utmost importance.
It is the outcome of work in different parts of
the world—by Wright and Semple and Durham in England,
Chantemesse and Widal in France, Pfeiffer and
Kolle and Grüber in Germany, and many more. The
first systematic study of it was made by Durham and
Pfeiffer; and Widal's name is especially associated
with the application of their work to the uses of practice.
Admirable accounts of the whole subject are
given by Dr. Cabot in his book, The Serum-Diagnosis
of Disease (Longmans, 1899), and by Mr. Foulerton
in the Middlesex Hospital Journal, October 1899 and
July 1901.
Widal's reaction is surely one of the fairy tales of
science. The bacteriologist works not with anything
so gross as a drop of blood, but with a drop of blood
fifty or more times diluted; one drop of this dilution is
enough for his purpose. Take, for instance, an obscure
case suspected to be typhoid fever: a drop of blood
taken from the finger is diluted fifty or more times, that
the perfect delicacy of the test may be ensured; a drop
of this dilution is mixed with a drop of nutrient fluid
containing living typhoid bacilli, and a drop of this
mixture of blood and bacilli is watched under the
microscope:—
"The motility of the bacilli is instantaneously or
very quickly arrested, and in a few minutes the bacilli
begin to aggregate together into clumps, and by the end
of the half-hour there will be very few isolated bacilli
visible. In less marked cases, the motility of the bacilli
does not cease for some minutes; while in the least
marked ones the motility of the bacilli may never be
completely arrested, but they are always more or less
sluggish, while clumping ought to be quite distinct by
the end of the half-hour."
The result of this clumping is also plainly visible
to the naked eye, by the subsidence of the agglutinated
bacteria to the bottom of the containing vessel: and
thus an easy practical mode of diagnosis is afforded
by it.
As with typhoid, so with Malta fever, cholera, and
some other infective diseases. And the unimaginable
fineness of this reaction goes far beyond the time of
the disease. Months, even years, after recovery from
typhoid, a fiftieth part of a drop of the blood will still
give Widal's reaction: and it has been obtained in an
infant whose mother had typhoid before it was born.
A drop of dried blood, from a case suspected to be
typhoid, may be sent a hundred miles by post to be
tested; and typhoid, like diphtheria, may now be submitted
to the judgment of an expert far away, and the
answer telegraphed back. It would be difficult to exaggerate
the practical importance of this reaction for
the early diagnosis of cases of typhoid fever, especially
those cases that appear, at the onset, not severe.
The specific organism of Malta fever (Mediterranean
fever), the bacillus Melitensis, was discovered in 1887 by
Surgeon-Major David Bruce, of the Army Medical Staff.
Its nature and action were proved by the inoculation of
monkeys. The use of Widal's reaction is of great value
in this disease:—
"The diagnosis of Malta fever from typhoid is, of
course, a highly important practical matter. It is exceedingly
difficult in the early stages." (Manson, loc.
cit.)
As with typhoid, so with Malta fever, Netley led the
way to the discovery of an immunising serum. In the
course of the work, one of the discoverers was by accident
infected with the disease:—
"He was indisposed when he went to Maidstone to
undertake anti-typhoid vaccination, and after fighting
against his illness for some days, he was obliged to
return to Netley on 9th October. Examination of blood-serum
(Widal's reaction) showed that he was suffering
from Malta fever. It appears that he had scratched his
hand with a hypodermic needle on 17th September,
when immunising a horse for the preparation of serum-protective
against Malta fever; and his blood, when
examined, had a typical reaction on the micrococcus of
Malta fever in 1000-fold dilution. The horse, which has
been immunised for Malta fever for the last eight months,
was immediately bled, and we are informed that the
patient has now had two injections, each of 30 cub. cm.
of the serum. He is doing well, and it is hoped that the
attack has been cut short." (British Medical Journal,
16th October 1897.)
About fifty cases had up to September 1899 been
treated at Netley "with marked benefit: whereas they
found that all drug-treatment failed, the antitoxin treatment
had been generally successful."[36] A good instance
of the value of the serum-treatment of Malta fever is
published in the Lancet, 15th April 1899. For a later
account of this treatment and of its efficacy, see the
Philadelphia Medical Journal, 24th November 1900.
Another point is noted by Sir Patrick Manson, in his
recent Lane Lectures (Constable, 1905). "For some
time back," he says, "a commission of experts, working
under the direction of the Royal Society, has been
studying this disease in Malta. The commission has
accumulated much detailed information; but the most
important observation it has published is the fact that
a large percentage of the goats in Malta are infected
with Micrococcus melitensis, and that the milk of the
infected goats contains the bacterium. May not this
account for the great prevalence of Mediterranean fever
there and in other places having perhaps a similar milk-supply?"
Within the last few years, it has been proved that the
mosquito is an intermediate host, between man and
man, of malaria, yellow fever, and filariasis (elephantiasis).[37]
Just as the grosser parasites, the tapeworms,
must alternate between man and certain animals, and
cannot otherwise go through their own life-changes and
reproduce their kind, so the micro-parasites that are the
cause of malaria alternate between man and the mosquito,
having the mosquito as an intermediate host.
These organisms, once they get into the mosquito, pick
out certain structures, and there carry out a definite
cyclical phase of their lives, whereby their progeny
make their way into the stylets of the mosquito, and so
get back to man, who is their "definite host." Thus,
malaria is not, strictly speaking, a disease of man; it is
one phase in man of micro-organisms that have another
phase in mosquitoes. So also with filariasis; the
filariæ in man, their ova, and their embryo-worms, are
one phase of filariasis; and the embryo-worms in certain
structures of the mosquito are another phase. The
plasmodium malariæ and the filaria are instances of a law
of animal life that holds good also of plant life:—
"All plants and animals possess parasites, and thousands
of different species of parasites have been closely
studied by science; we therefore know much about their
general ways of life. As a rule, a particular species of
parasite can live only in the particular species of animal
in which, by the evolution of ages, it has acquired the
power of living. It is therefore not enough for the parasites
of an individual animal—say a man—to be able to
multiply within that individual, but they must also make
arrangements, so to speak, for their progeny to enter into
and infect other individuals of the same species. They
cannot live for ever in one individual; they must spread
in some way or other to other individuals.
"The shifts made by parasites to meet this requirement
of their nature are many and various, and constitute
one of the wonders of nature. Some scatter their spores
and eggs broadcast in the soil, water, or air, as it were
in the hope that some of them will alight by accident on
a plant or animal suitable for their future growth. Many
parasites employ, in various ways, a second species of
animal as a go-between. Thus, some tapeworms, and
the worms which cause trichinosis, spend a part of their
lives in the flesh of swine, and transfer themselves to
human beings when the latter eat this flesh. To complete
the cycle, the parasites return to swine from human
offal; so that they propagate alternately from men to
swine, and from swine to men. The blood-parasites
which cause the deadly tsetse-fly disease among cattle in
South Africa are transferred from one ox to another on
the proboscis of the ox-biting or tsetse-fly. The progeny
of the flukes of sheep enter a kind of snail, which spreads
the parasites upon grass. The progeny of the guinea-worm
of man enter a water-flea. The progeny of the
parasites which cause Texas cattle-fever, and which are
very like the malarial parasites, live in cattle-ticks, and
are transferred by the young of these ticks into healthy
cattle." (Ross, Malarial Fever, 1902.)
The plasmodium malariæ was discovered by Laveran
in 1880, in the blood of malarial patients. For many
years his work stopped there, because it was impossible
to find the plasmodium in animals: "the difficulties
surrounding the subject were so great that this discovery
seemed to be almost hopeless." In 1894, Sir
Patrick Manson—who had proved mosquitoes to be
the intermediate host in the case of the parasitic nematode
filaria—suggested, as a working theory of malaria,
that the plasmodium was carried by mosquitoes. This
belief, not itself new, he made current coin. He observed
that there is a flagellate form of the plasmodium,
which only comes into existence after the blood has
left the body: and he suggested that the flagella might
develop in the mosquito as an intermediate host, a
halfway-house between man and man. Then, in 1895,
Ross set to work in India, keeping and feeding vast
numbers of mosquitoes on malarial blood; and for two
years without any conclusive result. About this time
came MacCallum's observations, at the Johns Hopkins
University, on a parasitic organism, halteridium, closely
allied to the plasmodium malariæ; he showed that the
flagella of the halteridium are organs of impregnation,
having observed that the non-flagellated form, which
he regarded as the female, after receiving one of the
flagella, changed shape, and became motile. In August
1897, Ross found bodies, containing pigment like that
of the malarial parasite, in the outer coat of the stomach
of one kind of mosquito, the grey or dapple-winged
mosquito, Anopheles maculipennis, that had been fed on
malarial blood. In February 1898, he was put on
special duty under the Sanitary Commissioner with the
Government of India, to study malaria, and started
work again in Calcutta:—
"Arriving there at a non-fever season, he took up
the study of what may be called 'bird malaria.' In
birds, two parasites have become well known—(1) the
halteridium, (2) the proteosoma of Labbé. Both have
flagellated forms, and both are closely allied to the plasmodium
malariæ. Using grey mosquitoes and proteosoma-infected
birds, Ross showed by a large number of
observations that it was only from blood containing the
proteosoma that pigmented cells in the grey mosquito
could be got; therefore that this cell is derived from the
proteosoma, and is an evolutionary stage of that parasite.
Next, Ross proceeded to find out its exact location, and
found that it lay among the muscular fibres of the wall
of the mosquito's stomach. It grows large (40-70 micro-millimetres)
and protrudes from the external surface of
the stomach, which under the microscope appears as if
covered with minute warts." (Manson, at Edinburgh
meeting of British Medical Association, 1898.)
These pigmented spherical cells give issue to innumerable
swarms of spindle-shaped bodies, "germinal
rods"; and in infected mosquitoes Ross found these
rods, in the glands that communicate with the proboscis.
Thus the evidence was complete, that the plasmodium
malariæ, like many other parasites, has a special intermediate
host for its intermediate stage of development;
and that this host is the dapple-winged mosquito. It
is impossible to over-estimate the infinite delicacy and
difficulty of Ross's work; for instance, in his "Abstract
of Recent Experiments with Grey Mosquitoes,"
he says that "out of 245 grey mosquitoes fed on birds
with proteosoma, 178, or 72 per cent., contained pigmented
cells; out of 249 fed on blood containing
halteridium, immature proteosoma, &c., not one contained
a single pigmented cell." Another time (April
1898) he counted these pigment-cells under the microscope:—
"Ten mosquitoes fed on the sparrow with numerous
proteosoma contained 1009 pigmented cells, or an average
of 101 each. Ten mosquitoes fed on the sparrow with
moderate proteosoma contained 292 pigmented cells, or
an average of 29 each. The mosquitoes fed on the
sparrow with no proteosoma contained no pigmented
cells."
Finally, he completed the circle of development by
infecting healthy sparrows by causing mosquitoes to
bite them.
In 1899, there went out a German Commission to
German East Africa, a Royal Society's Commission to
British Central Africa, and an expedition from the
Liverpool School of Tropical Medicine; in 1900,
another German Commission, this time to the East
Indies, and another expedition from the Liverpool
School; by July 1901, the Liverpool School was
organising its seventh expedition. Italy, of course, has
given infinite study to the disease:—
"It has been decided that, in addition to the stations
of observation and experiment in the provinces of Rome,
Milan, Cremona, Mantua, Gercara, Foggia, Lecce, others
shall be established in the provinces of Udine, Verona,
Vicenza, Padua, Ravenna, Pisa, Basilicata, and Syracuse.
Besides epidemiological researches, applications on a
large scale will be made of preventive measures for the
protection of the agricultural population against the
scourge. Another extensive experiment on the prophylaxis
of malaria will be made on the Emilian littoral.
Moreover, in all the malarious regions of the Italian
peninsula the provincial and communal administrations
and many private persons will co-operate in the application
of preventive measures. From all this it may be
gathered that during the summer and autumn the war
against malaria will be carried on in Italy with great
vigour and thoroughness." (British Medical Journal,
6th July 1901.)
In India, the work started in 1900 by the Royal
Society Commissioners, and by the Nagpur Conference,
has been widely extended; especially by such researches
as those of Major Buchanan, I.M.S., Superintendent of
the Central Jail, Nagpur. The following paragraph,
from the report of the Sanitary Commissioner with the
Government of India, refers to Major Buchanan's
published work, Malarial Fevers and Malarial Parasites
in India:—
"A remarkable note is struck at the outset, in the
acknowledgment made, by the author, of the capable
assistance rendered in these researches by several of his
Burmese prisoners, whom he trained to the use of the
microscope, and who soon became expert in detecting
and distinguishing the various kinds of parasites....
Besides a systematic clinical account of the different
forms of fever and the associated parasites, which is
the first attempt of the kind in India, there are a
summary of the facts showing the relation of the
seasonal prevalence of Anopheles to the incidence of
attacks; experiments exhibiting the protective effects of
mosquito-curtains; inoculation-experiments; researches
on the blood-parasites of birds; and many other
points.... Nor can we pause to notice the many
attempts now being made by health officers and others
to pursue the methods of prophylaxis indicated; these
efforts are necessarily in the tentative stage, but, so far,
and especially where carried out in connection with small
communities and institutions, they are giving promise of
gratifying success."
The famous experiment made by Dr. Sambon and
Dr. Low in 1900, must be recalled here:—
"Dr. Luigi Sambon and Dr. G. C. Low, both connected
with the London School of Tropical Medicine,
volunteered to live from June till October, that is to say,
through what may be called the height of the malaria
season, in a part of the Campagna near Ostia, which is
so infested by the disease that no one who spends a
night there under ordinary conditions escapes the effect
of the poison. Dr. Sambon, Dr. Low, Signor Terzi, and
their servants, have now exposed themselves to the
pestilential influence of this valley of the shadow of
death for over two months. They live in a mosquito-proof
hut; they take no quinine or other drug which
might be regarded as prophylactic. Not one of the experimenting
party has the least sign of infection.[38] ...
"What for practical purposes may be regarded as an
experiment of the same kind is being conducted in West
Africa. Dr. Elliot, a member of the Liverpool expedition
sent to Nigeria some time ago to investigate the subject
of malarial fever, has recently returned to this country.
He reports that the members of the expedition have been
perfectly well, although they have spent four months in
some of the most malarious spots. They lived practically
amongst marshes and other places hitherto supposed to
be the most deadly. They have not kept the fever off
by the use of quinine, and they attribute their immunity
to the careful use of mosquito-nets at night." (British
Medical Journal, 22nd September 1900.)
A similar "experiment," of the utmost importance,
was made in 1900 by Professor Grassi. It concerned
the workmen and their families along the Battipaglia-Reggio
railway, 104 in all, including 33 children.
The great majority of them had suffered from malaria
in the preceding year; and only 11, including 4
children, had never suffered from it. Pending the
arrival of the malarial season, quinine was given to
all who needed it. The first Anopheles with its
salivary glands infected was found on 14th June.
Twelve days later came a case of malaria outside the
"zone of experiment," in a person who had never had
malaria before. The twelve days correspond to the
incubation-period after infection. Anopheles having
come, and the malarial season with him, the experiment
was begun. The houses were carefully protected
with wire netting, chimneys and all; the siesta was
taken under wire netting; the workmen, if they were
out in the evening or at night, wore veils and gloves;
and Anopheles was to be killed wherever he was found.
Quinine was altogether given up and forbidden, except
for three workmen who had escaped or evaded its use
before June, and had, indeed, never before been treated
with quinine; one of them, moreover, had been sleeping
outside the zone of experiment in July. Except these
three, all the 104 and their doctors remained absolutely
free from malaria up to 16th September, the date of
Professor Grassi's report:—
"Rightly to estimate the value of these facts, it is
necessary briefly to describe the surroundings of the
protected area. Towards the north, coming from Battipaglia,
three railway cottages are situated, at a distance
of 1, 2, and 3 kilometres respectively. The 25 inhabitants
of these cottages, although they were put under the tonic
and quinine treatment in the non-malarial season, all
without exception were taken ill with malarial fevers, in
many cases obstinate."
Experiments of voluntary exposure to bite from an
infected mosquito were made at or about this time, in
London, New York, Italy, and India. The London
"consignment" of mosquitoes had been allowed to bite
a malaria-patient in Rome. The experiment had to be
very carefully planned:—
"To have sent mosquitoes infected with malignant
tertian parasites might have endangered the life of the
subject of the experiment; and quartan-infected insects
might have conferred a type of disease which, though not
endangering life, is extremely difficult to eradicate. The
cases, therefore, on which the experimental insects were
fed had to be examples of pure benign tertian—a type of
case not readily met with in Rome during the height of
the malarial season; the absolute purity of the infection
could be ascertained only by repeated and careful microscopic
examination of the blood of the patient." (British
Medical Journal, 29th September 1900.)
The mosquitoes were forwarded, through the British
Embassy in Rome, to the London School of Tropical
Medicine. The two brave gentlemen who let themselves
be bitten by some thirty of the mosquitoes were
in due time attacked by malaria, and the tertian forms
of the parasite were found in their blood. Nine months
later, one of them had a relapse, and the parasite was
again found in his blood.
It is not possible to sum up the wealth of work on
malaria published in 1900-1901. Good accounts of it
are in the Transactions of the Section of Tropical
Diseases, at the Annual Meeting of the British Medical
Association (Cheltenham, 1901), and in the Thompson
Yates Laboratories Reports, vol. iii., pt. 2, 1901.
Everything had to be studied: not only the nature
and action of the plasmodium in all its phases, but also
the whole natural history and habits of the Anopheles
of different countries; and, above all, the incidence of
the disease on natives and on Europeans in China,
India, and Africa. All that can be done here is to try
to indicate the principal lines followed in the present
world-wide campaign against malaria. The following
paragraphs are taken mostly from the accounts given
by Dr. Christophers and Dr. Annett, in the Thompson
Yates Laboratories Report, 1901:—
1. Elimination of the Infection at its Source. This is
the method employed with success by Professor Koch
in New Guinea, viz., to search out all cases of malaria
(the concealed ones in particular), and to render them
harmless by curing them with quinine. At Stephansort,
by thus hunting up all infected cases, and as it were,
sterilising them by the systematic administration of
quinine, he was able to achieve a great reduction of
the disease in the next malarial season, even under
adverse conditions. He says, in his report to the
German Government: "The results of our experiment,
which has lasted nearly six months, have been so uniform
and unequivocal that they cannot be regarded as
accidental. We may assume that it is directly owing
to the measures we have adopted that malaria here has,
in a comparatively short time, almost disappeared."
This method, of course, is applicable only in small
communities; and, within these limits, it may become
one of the most valuable of all methods, being, like
the quality of mercy, a blessing both to him who gives
and to him who taketh. But it cannot be practised
on a vast scale. This difficulty is well put by Sir
William MacGregor, K.C.M.G., Governor of Lagos,
West Africa:—
"In all probability, the day will come before long,
when newly-appointed officers for places like Lagos will
have to undergo a test as to whether they can tolerate
quinine or not. A man that cannot, or a man that will
not, take quinine, should not be sent to or remain in a
malarial country, as he will be doing so at the risk of his
own life, and to the danger of others.... The great
difficulty is how to extend this treatment beyond the
service, more particularly to the uneducated masses of
the natives. It is simply impossible to protect the whole
population by quinine administered as a prophylactic.
In the first place, the great mass of natives would not
take the medicine; and, in the second place, the Government
could not afford to pay for the 70 tons of quinine
a year that would be required to give even a daily grain
dose to each of 3,000,000 of people."
2. Segregation of Europeans from Natives. This
method is strongly advocated by the members of the
Nigeria Expedition of the Liverpool School (1900).
The distance of removal to half a mile is considered
sufficient: "Considerable evidence has now been accumulated
to prove that the distance which is traversed
by a mosquito is never very great, and extremely rarely
reaches so much as half a mile." The arguments in
favour of this method of "segregation" are of so great
interest that they must be put here at some length.
The drawback is that the method cannot be followed
everywhere to its logical issue without some risk of
giving offence, of seeming to abandon the native, of
damaging commerce, and so forth. But, short of this,
much might be done for the protection of Europeans in
Africa:—
"This method is a corollary of the discovery that native
children in Africa practically all contain the malaria
parasite, and are the source from which Europeans
derive malaria. Koch showed in New Guinea that in
most places infection was very prevalent in native
children, so much so that in some villages 100 per
cent. of those examined contained parasites. He also
showed that, as the children increased in age, immunity
was produced, so that in the case of adults a marked
immunity was present, and malarial infection was absent.
The Malaria Commission showed, independently, that
a condition of universal infection existed among the
children of tropical Africa, associated with an immunity
of the adults. This infection in children had many remarkable
characteristics. The children were in apparent
health, but often contained large numbers of parasites,
and a small proportion only of the children failed to
show some degree of infection.... The Liverpool
School Expedition found a similar condition of a
ffairs in
all parts of Nigeria visited by them.
"With a knowledge of the ubiquity of native malaria,
the method of infection of Europeans becomes abundantly
clear. The reputed unhealthiness or healthiness of
stations is seen at once to be dependent on the proximity
or non-proximity of native huts. The attack of malaria
after a tour up-country, the malaria at military stations
like Prah-su, the abundance of malaria on railways, are
all explicable when the extraordinary condition of universal
native infection is appreciated. It is evident that,
could Europeans avoid the close proximity of native huts,
they would do away with a very obvious and great source
of infection.... When it is understood that each of
these huts certainly contains many children with parasites
in their blood, and also scores or hundreds of
Anopheles to carry the infection, then the frequency with
which Europeans suffer from malaria is scarcely to be
wondered at.... The accompanying plan is that of
a new railway settlement on the Sierra Leone Railway.
Miles of land free from huts exist along the line, but the
close neighbourhood of native huts has been selected.
At the time of building of these quarters, it lay in the
power of the engineers to have a malaria-free settlement;
instead of which, by the non-observance of a simple fact,
the station is most malarious: in this particular instance,
much ingenuity has been shown in providing each set of
European quarters with plenty of malarial infection. In
towns only is there any difficulty in carrying out the
principle of segregation. In two instances, however, this
has been carried out in towns, with the result that the
segregated communities of Europeans are notoriously the
most healthy on the West Coast. Even when no scheme
of complete segregation can be carried out, the principle
should always be borne in mind, and, whenever opportunity
offers, huts should be removed, and European
houses built in the open.... It is almost universally
the rule in West Africa to find European houses built
round by native quarters, a practice which long experience
in India has taught Europeans to avoid carefully.
At Old Calabar, many of the factories are almost surrounded,
except in front, by native habitations; similarly,
at Egwanga, the small native town is built by the side and
back of one of the factories. Also at the Niger Company's
factory at Lokoja, the native houses are very close up
to the Company's boundary railings. Akassa engineers'
quarters may be, again, mentioned as an example where
the engineering artisans, chiefly natives of Lagos, Accra,
and Sierra Leone, are housed with their families alongside
the European house. A large proportion of these
native children were found by us to contain malarial
parasites. Similarly also at Asaba, the proximity of the
barracks of the Hausa soldiers, who have their wives and
children with them, is a dangerous menace to the officers
at the Force House.
"Examples of the opposite condition of affairs might
also be given. For instance, at Old Calabar, the Government
offices and Consulate, Vice-Consulate, and medical
house, are comparatively free from malarial fever; it
having been established that the natives shall not build
on the European side of the creek separating the two
slopes on which the native town and European quarters
are built. This creek is at a distance of about half a
mile from the houses mentioned."
It is plain, from these and other instances given by
the members of the Nigeria Expedition, that a modified
sort of "segregation" can be effected in many places,
without any injury either to native feelings, or to
politics, or to commerce; and that by such segregation
the risk of malaria among Europeans in Africa
would be diminished.
3. Protection against Anopheles. Manson, in his
Tropical Diseases (1905), says, "The question is often
asked, Is there any other way by which malaria can be
contracted than through a mosquito-bite? For many
reasons, I believe not. It is difficult to prove a negative;
but, so far, there is no observation capable of
bearing investigation that would lead us to suppose
that malaria can be acquired, under natural conditions,
except by mosquito-bite," All authorities are agreed
that, practically, the fight against malaria and the fight
against Anopheles are one and the same thing; and the
experiments by Sambon, Low, and Grassi, show what
can be done, in this war against the mosquito, by way
of defence. But what is practicable in Italy might not
be generally practicable on the West African coast; as
Sir William MacGregor says of Lagos:—
"It is not likely that in a place like Lagos as good
results can be obtained from the use of mosquito-proof
netting as in Italy. One great objection to it here is the
serious and highly disagreeable way it checks ventilation.
This is a difficulty that cannot be fully brought
home to one in a cold climate. But, in a low-lying, hot,
and moist locality like Lagos, it comes to be a choice of
evils, to sit inside the netting stewed and suffocated, or
to be worried and poisoned by mosquitoes outside. The
netting is hardly a feasible remedy as regards native
houses. It is not possible to protect even European
quarters completely by it. Few officers or others are so
occupied that they could spend the day in a mosquito-proof
room. Certain it is that any man that suffers
from the singular delusion that mosquitoes bite only
during the night, would have a speedy cure by spending
a few days, or even a few hours, in Lagos. Operations
here (September 1901) are being limited to supplying
one mosquito-proof room to the quarters of each officer.
In this he will be able to spend the evening free from
mosquitoes if he chooses to do so. The European wards
of the hospital are similarly protected."
The European in Africa, as Ross says, is generally
neglectful of his health; and the "unhealthiness" of
the African coast is to some extent due to the life that
men lead there:—
"Let us compare the habits of a European in a business-house
in Calcutta with the habits of a European in
West Africa. In Calcutta he sleeps under a punkah or
mosquito-net, or both; he dresses and breakfasts under
a punkah; in the evening he takes vigorous exercise,
and he dines under a punkah. He wears the lightest
possible clothing, he lives in a solid, cool, airy house, and
he obtains very good food; once in five or six years, he
returns to Europe for leave.... In Africa, the houses
are frequently very bad; in Freetown, for instance, they
are the same as the houses of natives, and are mingled
with them. The Anglo-African seems to imagine that
he can live in the tropics in the same manner as he
lives in England. He seldom uses a punkah, except
perhaps for an hour at dinner-time, and, not seldom,
he neglects even the mosquito-net. The food is often,
or generally, execrable. Owing to the frequent absence
of gymkhanas and clubs, the exile obtains little suitable
exercise."
But whatever risks the old resident may choose to
take, the newcomer can at least use a proper and
efficient mosquito-net at night, and avoid sleeping in a
native house, and protect himself in these and the like
ways against malaria.
4. The keeping down of Anopheles. The breeding
places of Anopheles are ponds, swamps, and puddles,
roadside ditches, tanks, and cisterns, old disused canoes,
and the like collections of stagnant water: also the
smaller receptacles that are more generally occupied by
Culex, such as broken bottles, old tins, pots, and calabashes,
and barrels, whatever will hold water—all the
débris and broken rubbish round huts or houses. In
all these places, Anopheles' eggs or larvæ are found;
and, with practice, it is easy to detect them. Of
course, it is not easy to wage war against the adult
mosquito: the work is, Venienti occurrere morbo, to
organise gangs of workmen, or of prison labour, and
"mosquito brigades"; to clear the ground of cartloads
of old biscuit-tins, broken gin-bottles, and other dust-heap
things, in and around the place; to cover-in the
cisterns, rain-barrels, and wells; to clean pools and
duck-ponds of weed, and stock them with minnows;
to put a film of kerosene to the puddles, or sweep them
out, or fill them up and turf them over; everywhere,
to drain, and level, and clean-up the surface soil; and
everywhere, by these and the like methods, to break
the cycle of the life of the plasmodium malariæ:—
"Draining and cultivation where the land will repay the
expenditure, permanent and complete flooding where it
will not, and such flooding is possible; proper paving of
unhealthy towns, and the filling-in of stagnant, swampy
pools; these—in other words, all measures calculated to
keep down mosquitoes—are the more important things
to be striven for in attempting the sanitation of malarious
districts. In England, in Holland, in France, in Algeria,
in America, and in many other places, enormous tracts
of country, which formerly were useless and pestilential,
have been rendered healthy and productive by such
means." (Manson.)
And, short of such great enterprises as Government
works of drainage, much has already been done, in
many African towns, and in India, by the work of a
few men and women: not only by practical sanitary
improvements, but by insistent teaching and lecturing.
For the admirable results recently obtained in Ismailia,
Algeria, Formosa, and the Malay States, see the Medical
Annual, 1905 and 1906.[39]
Before leaving the subject of malaria, it must be
added that the discovery and study of the parasite
which causes it have cleared up the mystery of the
specific action of quinine upon the disease. It operates
simply by its germicidal effect upon the microbe. But,
beyond this, we have now a clue which we never had
before to guide us to the most advantageous manner of
administering the drug.
The specific organism of malaria may become active
again and again in the blood, causing relapses twenty
years or more after the original infection. The specific
organism of yellow fever expends itself at once, in one
acute attack; and, if the patient recovers, he is thenceforth
more or less immune against infection. That the
inoculation of the disease, by the application of a single
mosquito recently contaminated, is calculated to produce
a mild or abortive attack less dangerous than the average
attack among the non-acclimatised, was known to Finlay,
and was confirmed in 1899 by the Army Commission
of the United States.
Of the mortality of the disease, Sir Patrick Manson,
in 1900, wrote as follows:—
"It is better for women and children than for men;
better for old residents than for newcomers; worst of all
for the intemperate. According to a table of 293 carefully
observed cases given by Sternberg, the mean mortality
in the whole 293 cases was 27.7 per cent. This may be
taken as a fairly representative mortality in yellow fever
among the unacclimatised, something between 25 and 30
per cent., although in some epidemics it has risen as high
as 50 or even 80 per cent. of those attacked.... Some
of these epidemic visitations bring a heavy death-bill;
thus, in New Orleans, in 1853, 7970 people died of
yellow fever; in 1867, 3093; in Rio, in 1850, it claimed
4160 victims; in 1852, 1943; and in 1886, 1397. In
Havana, the annual mortality from this cause ranges
from 500 to 1600 or over."
The earlier attempts to reproduce the disease, by
inoculation with its products, failed altogether:—
"In 1816, Dr. Chervin, of Point-à-Pitre (Antilles),
drank repeatedly large quantities of black vomit without
feeling the least disturbance. Some years before,
other North American colleagues, Doctors Potter, Firth,
Catteral, and Parker, did everything possible to inoculate
themselves with yellow fever. After having uselessly
attempted experiments on animals, they experimented
on themselves, inoculating the black matter at the very
moment in which the moribund patient rejected it, placing
this matter in their eyes, or in wounds made in their
arms, injecting it more than twenty times in various parts
of their body ... in short, devising every sort of daring
means for experimentally transmitting yellow fever. All
these experiments were without result, and in the United
States during many years it was believed that this terrible
malady was non-contagious." (British Medical Journal,
3rd July, 1897.)
The history of the subject, from 1812 to 1880,
is given by Dr. Finlay of Havana, in the New York
Medical Record (9th February 1901). In 1880, two
very important reports on the disease were published;
one by a Havana Commission of the National Board of
Health of the United States, the other by the United
States Navy Department. They tended to show that
yellow fever is a "germ-disease"; that it is not wind-borne;
and that there may be some change, outside
the body of the patient, whereby the virulence of the
active principle of the disease is heightened. From
these reports, Dr. Finlay advanced his doctrine that
the mosquito receives and transmits the germs of the
disease:—
"It was upon the above line of reasoning (in these
reports), that I conceived the idea that the yellow-fever
germ must be conveyed from the patient to the non-immunes
by inoculation, a process which could be performed
in nature only through the agency of some stinging
insect whose biological conditions must be identical with
those which were known to favour the transmissibility of
the disease."
In 1881 he inoculated himself and six soldiers with
infected mosquitoes, and obtained, as he had calculated,
mild attacks and subsequent immunity. During the
years 1881-1900 he inoculated by this method 104
persons:—
"In these inoculations, be it remembered, my principal
object was rather to avoid than to seek the development
of a severe attack; in point of fact, only seventeen showed
any appreciable pathogenic effects after their inoculation.
I felt sure, however, that severe or fatal result
might follow an inoculation either with several mosquitoes
contaminated from severe cases of the disease, or from a
single insect applied several days or weeks after its contamination,
having come to this last conclusion in view
of the facts connected with the Anne Marie, and the
epidemic of Saint Nazaire."
Dr. Finlay's discovery that the mosquito can convey
yellow fever, and that the germ of the disease is more
virulent after a prolonged sojourning in the mosquito,
was proved beyond all question by the work of 1889-1901.
But, so far as immunisation is concerned, few
people would submit themselves to be bitten by an infected
mosquito, even with perfect assurance that the
germs contained in it were of a low degree of virulence:
the urgent need, therefore, was for an immunising serum.
In 1896, at Flores, Sanarelli discovered the bacillus
icteroides; and by October 1897, he had prepared an
immunising serum which was able to give a considerable
amount of protection to animals.[40] Next year
(Annales de l'Institut Pasteur, May 1898) came the
news that he had advanced against yellow fever with
its own weapons—Premières expériences sur l'emploi du
sérum curatif et préventif de la fièvre jaune. Of the first
8 cases (Rio de Janeiro), 4 recovered. Then came the
22 cases at San Carlos do Pinhal, in Saint-Paul au
Brésil (January 1898), with 16 recoveries, and only 6
deaths. And it is to be noted that he submitted his
method of treatment to the utmost test that was possible;
he chose the bad cases, and the country where
the fever was most fatal:—
"Chaque cas était choisi de commun accord entre
nous, dans le but de mettre bien en évidence l'action
thérapeutique du sérum, mettant toujours de côté tous les
cas qui se présentaient avec des symptômes vagues ou
attenuès ou en forme légère ou fruste. On ne conservait
donc que des cas oû, d'après la violence des phénomènes
d'invasion, on devait considérer comme très peu probable
une crise spontanée de la maladie...."
Furthermore, Sanarelli was able to show the preventive
value of the serum. At the end of February
1898, yellow fever broke out in the jail at San
Carlos:—
"La première victime fut un condamné, qui vivait
avec tous les autres dans une salle oû les conditions
hygiéniques étaient assez mauvaises. Le lendemain, la
sentinelle, qui était en rapport continuel avec la salle des
condamnés, tombait malade. Quelques jours après, un
autre condamné suivait le sort du premier, et bientôt un
quatrième cas, mortel aussi, finit par signaler la prison
comme un nouveau foyer d'infection qui venait s'allumer
au centre d'un quartier de la ville encore resté indemne.
"Si on avait abandonné la chose à elle-même, on
aurait vu se produire le même spectacle qu'avaient
fourni, dans les conditions identiques, pendant les dernières
épidémies, les prisons de Rio-Claro, de Limeira,
et d'autres villes de l'État de Saint-Paul."
Every prisoner, except one who had already had the
fever, was therefore given the preventive treatment.
At once the outbreak stopped; no more cases occurred,
though only a weak serum was used, though the state
of the prison and its occupants was unhealthy, though
the fever, two months later, was still raging round the
prison, in the town.
In October 1900, the United States Commission on
Yellow Fever published a preliminary report on 11
cases of mosquito-inoculation. Of these, the majority
gave a negative result, and were found susceptible to
infection, at a later date, from the blood of a yellow-fever
patient. Two gave a positive result. In the
course of these experiments, Dr. Lazear, a member of
the Commission, died of the disease. In February
1901, and again in July, the Commission published
further reports, emphasising the fact that the mosquito
conveys the disease, and denying that the disease can
be conveyed in clothing, bedding, and so forth:—
"Our observations appear to demonstrate that the
parasite of this disease must undergo a definite cycle of
development in the body of the mosquito before the latter
is capable of conveying infection. This period would
seem to be not less than twelve days.
"We also consider the question of house infection, and
are able to show that this infection is due to the presence
of mosquitoes that have previously bitten yellow-fever
patients; and that the danger of contracting the disease
may be avoided in the case of non-immune individuals
who sleep in this building, by the use of a wire screen.
"We also demonstrate, by observations made at this
camp (Fort Lazear), that clothes and bedding contaminated
by contact with yellow-fever cases, or by the
excreta of these cases, is absolutely without effect in
conveying the disease."
In February 1901, Dr. H. E. Durham published an
abstract of an interim report of the Liverpool School
Yellow Fever Commission. He and Dr. Walter Myers,
the two Commissioners, had both of them been attacked
by the disease, and Dr. Myers had died of it. The
report gives evidence that the disease is due to a bacillus
which is not the bacillus icteroides; and it does not
wholly favour the earlier report (1900) of the American
Commission. A later Commission to New Orleans,
September 1901 to January 1902, reported an extensive
series of investigations, which seem rather to
support the belief that the bacillus icteroides is the cause
of the disease. Later still, this belief is again denied;
and, as in rabies, so in yellow fever, the good work has
gone on without waiting for the identity of this or that
micro-organism.
Immunisation, by the direct use of an infected
mosquito, may be compared with the old custom of
inoculation against smallpox. The use of Sanarelli's
serum-treatment has not gone far. There remains for
consideration the method of keeping down infection by
keeping down Culex.
Three reports, in 1901-1902, come from Dr. Guitéras
(Havana), Surgeon-Major Gorgas, chief sanitary officer
(Havana), and the Commission at New Orleans. Dr.
Guitéras reports that 6 cases of yellow fever (inoculation)
were treated in a large "mosquito-proof" building,
which also contained cases of other diseases. No
prophylaxis was enforced, save the exclusion of mosquitoes;
non-immunes visited the yellow fever cases,
non-immunes nursed them, and most of the attendants
and labourers about the place were non-immunes; but
not a single case of infection occurred. The New
Orleans Commission reports that, of 200 cisterns, &c.,
examined in the city for the presence of larvæ, the larva
of Culex (Stegomyia) predominated in more than 60 per
cent.
The report of Surgeon-Major Gorgas is very pleasant
reading. For two centuries, Cuba had been cursed
with yellow fever; then, after the war with Spain,
America took it over:—
"The army took charge of the health department of
Havana, when deaths (from all causes) were occurring at
the rate of 21,252 per year. It gives it up, with deaths
occurring at the rate of 5720 per year. It took charge,
with smallpox endemic for years. It gives it up, with
not a case having occurred in the city for over eighteen
months. It took charge, with yellow fever endemic for
two centuries—the relentless foe of every foreigner
who came within Havana's borders, which he could not
escape, and from whose attack he well knew every fourth
man must die. The army has stamped out this disease
in its greatest stronghold."
Make fair allowance for the wide variation, from year
to year, of the number of yellow fever cases in any
town within the geographical belt of the disease; admit
that a town may, in the course of nature, have many
hundred cases in one year, and only half a dozen in
another year. Again, make fair allowance for all other
good influences of the American occupation of Cuba,
beside those that were concerned with the stamping out
of Culex; admit that the general death-rate of Havana,
in the last February of Spanish rule (1898), was 82.32
per thousand, and in February 1901, was 19.32. Still,
there is an example here, in the 1901 work in Havana,
for the world to follow, wherever yellow fever exists.
The following abstract of Surgeon-Major Gorgas' results
was published in the Practitioner, May 1902, by Professor
Hewlett, one of the foremost of English bacteriologists:—
"Commencing in February 1901, orders were issued
that every suspected case of yellow fever should be
screened with wire gauze at the public expense, so as to
render the room or rooms mosquito-proof. All mosquitoes
in the infected house and in contiguous houses were destroyed.
After the middle of February, 100 men were
employed in carrying out the destruction of the mosquito-larvæ
in their breeding places, putting oil in the cesspools
of all houses, clearing the streams, draining pools, and
oiling the larger bodies of water. Up to June, quarantine
was enforced, together with disinfection of the house and
fomites. After that, however, rigid quarantine of the
patient was stopped, and disinfection of fabrics and
clothing ceased. It was merely required that the patient
should be reported, his house placarded and screened, and
a guard placed over each case to report how general sick-room
sanitation was carried out, to see that the screen-door
communicating with the screened part of the house
was kept properly closed, and to see that communication
with the sick-room was not too free, four or five non-immunes
only being allowed in. By the end of September,
the last focus of the disease had been got rid of,
and since then, up to the beginning of January, there has
not been a single case. Whereas, for the years since
1889, from 1st April to 1st December, yellow fever
caused an average of 410.54 deaths, with a maximum of
1175 for 1896, and a minimum of 79 for 1899, it caused
in 1901 5 deaths only. In the months of October and
November, when the disease has hitherto been exceedingly
rife in Havana, there has not been a single case. For the
first time in 150 years, Havana has been free from yellow
fever."
Sir Patrick Manson, lecturing in America, last year,
on tropical diseases, summed up the work as follows:—
"Time will not permit—what to you is probably quite
unnecessary—the recapitulation of the story of the
labours of Reed and his coadjutors. I cannot pass on,
however, to what I have to say in connection with this
work without a word of admiration for the insight, the
energy, the skill, the courage, and withal the modesty and
simplicity of the leader of that remarkable band of workers.
If any man deserved a monument to his memory, it was
Reed. If any band of men deserve recognition at the
hands of their countrymen, it is Reed's colleagues.
"The principal outcome of the labours of these men
has been the demonstration, first, that the ultra-microscopic
germ of yellow fever is present in the blood of the
patient during the first three days of the disease. Second,
that the first step in the passage of the germ from the
sick to the sound is made, under natural conditions, in
the stegomyia mosquito. And third, that after about
twelve days and upwards in stegomyia, the yellow fever
germ, when implanted by the said mosquito into another
human host, is capable of reproduction, so that at the end
of a further period of about three days it has established
itself throughout the blood, is causing the violent reaction,
the clinical manifestations of which we call yellow
fever, and is once more in a condition to re-enter the
mosquito.
"These are great etiological facts. They are of
supreme practical and scientific value. Acting on them,
the United States sanitary authorities expelled yellow
fever from Havana. Acting on them, they should be
able in the future to protect the United States themselves
from such terrible visitations as in the past have swept
through some of your cities."
These same lectures contain an admirable account of
the life-history of Filaria. It is not necessary here to
describe the loathsome deformities which occur in the
later stages of filariasis. These deformities (elephantiasis,
Barbadoes leg), which may attain colossal size, are
due to the blocking of the lymphatic vessels with filarial
worms. Cases of the disease are hardly ever seen in
this country; but it is very frequent in some parts of
the tropics. In the endemic areas, says Manson, 10 per
cent. is not an uncommon proportion of the population to be
found affected with filariasis. Thirty and even 50 per cent.
may be affected. In many of the Pacific Islands—the
Samoa group for instance—I believe that even this proportion
is exceeded.
That Culex (fatigans) can carry the parasite, has
been proved past all doubt. Neither does anybody
doubt, that the keeping down of this mosquito would
keep down filariasis. A report of great interest, from
Barbadoes, was published in the British Medical Journal
for 14th June 1902. It is written by Dr. Low, whose
experiment on himself in the Campagna has already
been noted in this chapter. Dr. Low reports that there
is no indigenous malaria in the island, and that neither
he nor Mr. Lefroy could find a single Anopheles larva,
though they hunted diligently in the swamps and other
likely places. But filariasis is terribly common, and so
is Culex fatigans. Dr. Low examined the night-blood
of 600 cases of all kinds in the General Hospital, the
Central Almshouse, and elsewhere, and found the
filaria-embryos in no less than 76 = 12.66 per cent.
He caught and dissected a hundred mosquitoes (Culex
fatigans) from the wards and corridors of the General
Hospital, and found that no less than 23 of them were
infected. If it were not for Culex, and for men's indifference
and apathy, filariasis could be kept down all
over the island:—
"There is a perfect water supply, and people can get
their water fresh from the standpipes at their doors.
Old wells ought to be filled up; no water-barrels or tubs
should be allowed, or, if kept, they should be emptied
every week or so. Tanks and collections of water in
gardens should all be periodically treated with kerosene,
or be furnished with closely-fitting covers to prevent
mosquitoes getting in. These methods are simple and
inexpensive, and each householder should see that they
are applied in his garden and grounds. The difficulty
begins when one has to take into account the inability of
the negro to grasp anything of a hygienic nature. The
only way to get over this, would be a system of sanitary
inspection by a few competent men. For individual
prophylaxis, mosquito-nets ought always to be used;
but many, even educated people, still persist in sleeping
without them; of course, nothing in this line can be
expected of the native population.
"If such means were adopted for Barbadoes, the
presence of filarial disease, which at present is quite
alarming, could easily, with little trouble and expense, be
greatly diminished, and thus save much suffering, as well
as loss of time, hideous deformity, and doubtless in not a
few instances loss of life."
Thus, in a few years, from experiments on mosquitoes,
sparrows, and men, has come the present plan of campaign
against malaria, yellow fever, and filariasis; that
is, against Anopheles and Culex. He who would know
what is being done to check these diseases in Italy,
India, China, Africa, and America, must read Prof.
Ross' Malarial Fever, its Cause, Prevention, and Treatment
(1902), and Mosquito Brigades, and how to organise them
(1902). There has been nothing like it since Pasteur
died. Far and wide, from Staten Island to Cuba, from
Hong Kong to Lagos, the work of keeping down the
larvæ of Anopheles and Culex is going on. Henceforth
we have to reckon not with a nameless something, but with
a definite parasite, whose conditions of life are known.
Before all things, we must shut off the sources of the infection.
For centuries, men had believed in exhalations
and miasmata lying all over the land: and, behold, the
agents of malaria are in the puddles round a man's
house, and the agents of yellow fever are in the water-butt
and the broken bottles and old sardine-tins.
Science has given the word, and now there are Anopheles
brigades and Culex brigades set going; labourers
with brooms and rubbish-carts, sweeping out the stagnant
pools, draining the surface soil, and carrying off the odd
receptacles that serve to hold mosquito eggs and larvæ.
The job, like all sanitary jobs, must be steady, year in,
year out: it must be limited to infected places, a whole
continent cannot be treated. But there the work is,
and will grow; and saves, by unskilled labour, and at
a trivial expense, those "non-acclimatised" lives that
have hitherto been thrown away as recklessly as the
larvæ that are now swept out of the puddles and ditches
round African settlements.
The foregoing chapters are concerned with bacteriology
alone, and with those curative or preventive methods of
treatment that have come out of inoculation-experiments
on animals. The lives that are saved, or safeguarded,
by these methods, even in one year, must be many
thousands in each country of the civilised world. And,
beside human lives, there is the protection of sheep
and cattle against anthrax, swine against rouget, horses
against tetanus, cattle against rinderpest. In Cape
Colony alone, so far back as 1899, about half a million
cattle had received preventive treatment against rinderpest;
and the sum total of human and animal lives
saved or safeguarded, in all parts of the world, must
be reckoned in millions by this time.
The present chapter, and the next two chapters, are
concerned with methods that have come out of experiments
on animals, but not out of bacteriology.
It is plain that the grosser parasites of the human
body, tapeworms and the like, could not be explained
or understood without the help of feeding-experiments
on animals. By this method, and by this alone, their
life-history was discovered. They were known to
Aristotle and to Hippocrates; but nothing was understood
about them. They were never studied, for this
among other reasons, that men believed in spontaneous
generation; and the presence of lower forms of life
inside human bodies was attributed to the fault of the
patient, or the work of the devil. Then, at last, Redi
(1712), and Swammerdam (1752) in his Bibel der
Natur, struck at the doctrine of spontaneous generation,
saying that it did not apply to insects; and in 1781
Pallas boldly declared that the internal parasites of
man came out of eggs, like insects, and not "of themselves."
It would be a good theme for an essay—The
paralysing effect, on medicine and surgery, of the
doctrine of spontaneous generation. Rudolphi (1808)
and Bremser (1819) opposed Pallas; and von Siebold
(1835) and Eschricht (1837) supported him. Then
came the great students of this part of biology—Cobbold,
Busk, Davaine, van Beneden, Leuckart,
Küchenmeister. In 1842, Steenstrup had discovered,
in certain insects, the alternation of generations; in
1852, Küchenmeister proved that the generations of
internal parasites are similarly alternate. By feeding
carnivorous animals with "measly" meat, he produced
tapeworms in them; and by feeding herbivorous
animals with the ova of tapeworms, he made their
muscles "measly."
The feeding of animals was the only possible way
to understand the bewildering transformations and
transmigrations of the thirty or more entozoa to which
flesh is heir. This chapter of pathology makes up in
tragedy what it lacks in romance; for these animal
parasites have killed whole hosts of people. Take,
for instance, the trichina spiralis, a minute worm discovered
in 1835 encysted in countless numbers in the
muscles of the human body; it was studied by
Virchow, Leuckart, and others, by feeding-experiments
on animals, and was proved to come from infected
half-cooked ham and pork, and to make its way from
the alimentary canal all over the body. The name of
trichiniasis or trichina-fever was given to the acute
illness that came of the sudden dissemination of these
myriad parasites into the tissues. Trichiniasis had
killed hundreds of people by a most painful death;
outbreaks of it, in Germany and elsewhere, had swept
through villages like cholera or plague: then Leuckart
and Virchow traced it to its source, and it was stopped
there—Above all things, we must shut off the sources of
the infection—the butchers' shops were kept under
sanitary inspection, people were warned against half-cooked
ham and pork, and there was an end of it.
Or take hydatid disease, which occurs in all parts
of the world, and in some countries (Australia, Iceland)
is terribly common. The nature of this disease—that
it is an animal parasite transmissible between
men and dogs—was proved by feeding-experiments on
animals. In Iceland, where men and dogs live crowded
together in huts, there is an appalling number of deaths
from hydatid disease; Leuckart, in 1863, of it:—
"At present, almost the sixth part of all the inhabitants
annually dying in Iceland fall victims to the echinococcus
epidemic."
Before Küchenmeister's experiments in 1852, there
was no general knowledge of the exact pathology of
entozoic disease. The advance was not made by the
experimental method alone; other things helped: but
among them was neither clinical experience, nor what
Sir Charles Bell called "the observation of the just
facts of anatomy and of natural motions."
Beside the entozoa, there are also vegetable parasites.
Of these, the most important is the streptothrix
actinomyces, the cause of actinomycosis in man and
cattle. Israel, in 1877, gave the first accurate account
of it in man; and Böllinger, the same year, studied
it in cattle. Ponfick, in 1882, recognised the identity
of the disease in man and animals. In 1885, Israel
published the collected records of 37 cases in man,
tabulated according to the site of the primary infection.
Boström, about this time, made cultures of the fungus:
but all the earlier attempts at inoculation failed; and
it was not till 1891 that Wolff and Israel published
their successful inoculations, and thus completed the
evidence that actinomycosis is a parasitic infection, a
growth of vegetable threads and spores, transmissible
between men and animals, and able to keep its vitality
outside its host; so that men who are employed with
cattle, or have the habit of chewing straws or ears of
corn, incur some slight risk of infection. Before 1877,
the disease was hardly suspected in man, and was not
understood in cattle.
On 4th October 1873, Sir William Gull read a short
paper before the Clinical Society of London, "On a
Cretinoid State supervening in Adult Life in Women."
This famous first account of myxœdema was based on
five cases: it is less than five pages long, it does not
suggest a name for the disease, and it says nothing
about the thyroid gland. Four years later (23rd
October 1877), Dr. Ord read a paper before the
Medico-Chirurgical Society of London, "On Myxœdema;
a term proposed to be applied to an essential
condition in the 'Cretinoid' Affection occasionally
observed in Middle-aged Women." His work had
begun so far back as 1861; and in this 1877 paper
he gave not only clinical observations, but also pathological
and chemical facts; and he noted, as one among
many changes, wasting of the thyroid gland. He also
pointed out the close resemblance between cases of
myxœdema and cases of sporadic cretinism.
In 1882, Reverdin stated before the Medical Society
of Geneva that signs like those of myxœdema had been
observed in some cases of removal of the thyroid gland
on account of disease (goître). In April 1883, Kocher
of Berne read a paper on this subject, before the
Congress of German Surgeons; but he attributed
this myxœdema after removal of the gland (cachexia
strumipriva) not directly to the loss of thyroid-tissue,
but rather to some sort of interference with free
respiration, due to operation. On 23rd November,
Sir Felix Semon brought the subject again before the
Clinical Society; and on 14th December 1883, the
Society appointed a Committee of Investigation to
study the whole question.
Their report, 215 pages long, with tabulated records
of 119 cases of myxœdema, was published in 1888. It
is a monument of good work, historical, clinical, pathological,
chemical, and experimental. Twenty years ago,
the purpose of the thyroid gland was unknown: a few
experiments had been made on it, by Sir Astley Cooper
and others, and had failed; and Claude Bernard, in his
Physiologie Opératoire (published in 1879, soon after his
death), makes it clear that nothing was known in his
time about it. He is emphasising the fact that anatomy
cannot make the discoveries of physiology:—
"The descriptive anatomy, and the microscopic characters,
of the thyroid gland, the facts about its blood-vessels
and its lymphatics—are not all these as well known in
the thyroid gland as in other organs? Is not the same
thing true of the thymus gland, and the suprarenal
capsules? Yet we know absolutely nothing about the
functions of these organs—we have not so much as an
idea what use and importance they may possess—because
experiments have told us nothing about them; and anatomy,
left to itself, is absolutely silent on the subject."
Therefore, in 1882-83, things stood at this point—that
the removal of a diseased thyroid gland had been
followed, in some cases, by a train of symptoms such as
Sir William Gull had recorded in 1873. Would the
same symptoms follow removal of the healthy gland?
The answer was given by Sir Victor Horsley's experiments,
begun in 1884. He was able, by removal of
the gland, to produce in monkeys a chronic myxœdema,
a cretinoid state, the facsimile of the disease in man:
the same symptoms, course, tissue-changes, the same
physical and mental hebetude, the same alterations of
the excretions, the temperature, and the voice. It was
now past doubt that myxœdema was due to want of
thyroid-tissue, and to that alone; and that "cachexia
strumipriva" was due to the loss, by operation, of such
remnants of the gland as had not been rendered useless
by disease.
The advance had still to be made from pathology to
treatment. Here, so far as England is concerned,
honour is again due to Sir Victor Horsley. On 8th
February 1890, he published the suggestion that
thyroid-tissue, from an animal just killed, should be
transplanted beneath the skin of a myxœdematous
patient:—
"The justification of this procedure rested on the remarkable
experiments of Schiff and von Eisselsberg. I
only became aware in April 1890, that this proposal had
been in fact forestalled in 1889 by Dr. Bircher, in Aarau.
(The date of Dr. Bircher's operation was 16th January
1889.) Kocher had tried to do the same thing in 1883,
but the graft was soon absorbed; but early in 1889 he
tried it again, in five cases, and one greatly improved."
The importance of this treatment, by transplantation
of living thyroid-tissue, must be judged by the fact
that in 1888 no practical use had yet been made of
the scientific work that had been done. The Clinical
Society's Report, published that year, gives but half a
page to treatment, of the old-fashioned sort; and not
a word of hope.
Then, at last, in 1891, came Dr. George Murray's
paper in the British Medical Journal, "Note on the
Treatment of Myxœdema by Hypodermic Injections of
an Extract of the Thyroid Gland of a Sheep." Later,
hypodermic injections of thyroid-extract gave way to
sandwiches, made with thyroid gland (Dr. Hector
Mackenzie, and Dr. Fox of Plymouth), and these in
their turn were eclipsed by tabloids.
It is a strange sequence, from 1873 onward: clinical
observation, post-mortem work, calamities of surgery,
experimental physiology, transplantation, hypodermic injections,
sandwiches, and tabloids. And far more has
been achieved than the cure of myxœdema. Even if
the discovery stopped here, it would still be a miracle
that little bottles of tabloids should bring men and
women back from myxœdema to what they were before
they became thick-witted, slow, changed almost past
recognition, drifting toward idiocy. But it does not
stop here. The same treatment has given good results
in countless cases of sporadic cretinism, restoring
growth of body and of mind to children that were
hopelessly imbecile. It is of great value also for
certain diseases of the skin. Moreover, physiology
has gained knowledge of the purpose of the thyroid
gland, and a clearer insight into the facts relating to
internal secretion.
Long after the Renaissance, the practice of medicine
was still under the influence of magic. Whatever
things were rare and precious were held to be good
against disease—gold, amber, coral, pearls, and the
dust of mummies; whatever took strange forms of
life—toads, earthworms, and the like; whatever looked
like the disease, after the doctrine of signatures—pulmonaria
for the lungs, because the spots on its leaves
were like tubercle, a kidney-shaped fruit for the
kidneys, a heart-shaped fruit for the heart, and yellow
carrots for the yellow jaundice. Among the drugs in
the 1618 Pharmacopœia are cranium humanum, mandibula
lucii, nidus hirundinum, sericum crudum, linum
vivum, and pilus salamandræ. In the Pharmacopœia
of 1667 are exuviæ serpentis, telæ aranearum, saliva
jejuni, cranium hominis violentâ morte extincti, and worse
obscenities.
Soon after the publication of this Pharmacopœia, on
14th February 1685, King Charles II. died; and in
the Library of the Society of Antiquaries there is a
manuscript account in Latin, by Dr. Scarbrugh, how
the case was treated. The King had sixteen physicians,
and nine consultations in five days; and to say "everything
was done that was possible" gives no idea of the
vigour of the treatment. Finally, the day he died, they
gave him, eleven of them in consultation—totus medicorum
chorus ab omni spe destitutus—they gave him, as
more generous cardiacs, the lapis Goæ, and the Bezoar-stone.
The lapis Goæ was a dust of topaz, jacinth,
sapphire, ruby, pearl, emerald, bezoar, coral, musk,
ambergris, and gold, all made into a pill and polished;
and the bezoar is a calculus found in the intestines of
herbivorous animals. Half a century later, the Pharmacopœia
of 1721 still included ants' eggs, teeth, lapis
nephriticus, and other horrors; and in the Pharmacopœia
of 1746, though the dust of Egyptian mummies
was ruled out, vipers and wood-lice were retained.
Certainly these "last enchantments of the Middle
Ages" were slow to depart. Clinical observation, anatomy,
and pathology, had all failed to bring about a
right understanding of the actions of drugs. It was
the physiologists, not the doctors, who first formulated
the exact use of drugs; it was Bichat, Magendie,
and Claude Bernard. That is the whole meaning of
Magendie's work on the upas-poison and on strychnine,
and Claude Bernard's work on curari and
digitalis. Of these four substances, two only are of
any use in practice; yet Magendie's study of strychnine[41]
was of immeasurable value, not so much
because it gave the doctors a "more generous
cardiac," though that was a great gift, but because
it revealed the selective action of drugs. Contrast his
account of strychnine with Ambroise Paré's story how
they tested the bezoar-stone on the thief instead of
hanging him; contrast Bernard's chapter on curari
with Dr. Scarbrugh's notes on the King's death, with
all the Crown jewels inside him: you are in two
different worlds. The selective action of drugs—the
affinity between strychnine and the central nerve-cells,
between curari and the terminal filaments of the motor
nerves—that was the revolutionary teaching of science:
and it came, not by experience, but by experiment.
Take Professor Fraser's address on "The Action
of Remedies, and the Experimental Method" at the
International Medical Congress in London, 1881:—
"The introduction of this method is due to Bichat;
and, by its subsequent application by Magendie, pharmacology
was originated as the science we now recognise.
Bichat represents a transition state, in which metaphysical
conceptions were mingled with the results of experience.
Magendie more clearly recognised the danger of adopting
theories, in the existing imperfections of knowledge; and
devoted himself to the supplementing of these imperfections
by experiments on living animals. The advantages
of such experiments he early illustrated by his
investigation on the upas-poison; and afterwards by a
research on the then newly-discovered alkaloid, strychnia....
He demonstrated the action of this substance upon
the spinal cord, by experiments upon the lower animals,
so thoroughly, that subsequent investigations have added
but little to his results."
Or take Professor Fraser's account of digitalis:—
"It was introduced as a remedy for dropsy; and, on
the applications which were made of it for the treatment
of that disease, a slowing action upon the cardiac movements
was observed, which led to its acquiring the reputation
of a cardiac sedative. Numerous observations
were made on man by the originators of its application,
by Dr. Sanders and many other physicians, in which
special attention was paid to its effects upon the circulation;
but no further light was thrown upon its remarkable
properties, with the unimportant exception that in
some cases it was found to excite the circulation. It
was not until the experimental method was applied in
its investigation, in the first instance by Claude Bernard,
and subsequently by Dybkowsky, Pelikan, Meyer, Boehm,
and Schmiedeberg, that the true action of digitalis upon the
circulation was discovered. It was shown that the effects
upon the circulation were not in any exact sense sedative,
but, on the contrary, stimulant and tonic, rendering the
action of the heart more powerful, and increasing the
tension in the blood-vessels. The indications for its use
in disease were thereby revolutionised, and at the same
time rendered more exact; and the striking benefits which
are now afforded by the use of this substance in most
(cardiac) diseases were made available to humanity."
Or take Sir T. Lauder Brunton's account of the
action of nitrite of amyl in angina pectoris:—
"The action of nitrite of amyl in causing flushing was
first observed by Guthrie, and Sir B. W. Richardson
recommended it as a remedy in spasmodic conditions,
from the power he thought it to possess of paralysing
motor nerves. In the spring of 1867 I had opportunities
of constantly observing a patient who suffered from
angina pectoris, and of obtaining from him numerous
sphygmographic tracings, both during the attack and
during the interval. These showed that during the
attack the pulse became quicker, the blood-pressure
rose, and the arterioles contracted.... It seemed probable
that the great rise in tension was the cause of the
pain, and it occurred to me that if it was possible to
diminish the tension by drugs instead of by bleeding,
the pain would be removed.
"I knew from unpublished experiments on animals by
Dr. A. Gamgee that nitrite of amyl had this power, and
therefore tried it on the patient. My expectations were
perfectly answered. The pain usually disappeared in
three-quarters of a minute after the inhalation began,
and at the same time the pulse became slower and much
fuller, and the tension diminished."
Of course it would be easy to lengthen out the list.
Aconite, adrenalin, belladonna, calcium chloride, colchicum,
cocain, chloral, ergot, morphia, salicylic acid,
strophanthus, the chief diuretics, the chief diaphoretics—all
these drugs, and many more, have been studied
and learned by experiments on animals. Then comes
the answer, that drugs act differently on animals and
on men. The few instances, that give a wise air to
this foolish answer, were known long ago to everybody:
they do not so much as touch the facts of daily
practice:—
"The action of drugs on man differs from that on the
lower animals chiefly in respect to the brain, which is
so much more greatly developed in man. Where the
structure of an organ or tissue is nearly the same in
man and in the lower animals, the action of drugs upon
it is similar. Thus we find that carbonic oxide, and
nitrites, produce similar changes in the blood of frogs,
dogs, and man, that curare paralyses the motor nerves,
alike in them all, and veratria exerts upon the muscles of
each its peculiar stimulant and paralysing action. Where
differences exist in the structure of the various organs,
we find, as we would naturally expect, differences in their
reaction to drugs. Thus the heart of the frog is simpler
than that of dogs or men, and less affected by the central
nervous system; we consequently find that while such a
drug as digitalis has a somewhat similar action upon the
hearts of frogs, dogs, and men, there are certain differences
between its effect upon the heart of a frog and on
that of mammals.
"Belladonna offers another example of apparent difference
in action—a considerable dose of belladonna will
produce almost no apparent effect upon a rabbit, while a
smaller dose in a dog or a man would cause the rapidity
of the pulse to be nearly doubled. Yet in all three—rabbits,
dogs, and men—belladonna paralyses the power
of the vagus over the heart. The difference is that in
rabbits the vagus normally exerts but little action on the
heart, and the effect of its paralysis is consequently slight
or hardly appreciable." (Professor Fraser.)
It would be strange indeed, if experts who work in
micromillimetres and decimal milligrammes, and study
the vanishing-point of microscopic structures, and
measure and ordain infinitesimal changes in invisible
organisms, were blind to such gross and palpable
differences as exist between men and pigeons in their
susceptibility to a dose of opium.
Anæsthetics must be reckoned among the drugs that
have been studied on animals: but, for the discovery of
them, men experimented on themselves. The first use
of nitrous oxide (laughing gas) in surgery was 11th
December 1844, when Horace Wells, of Connecticut,
had it administered to himself for the removal of a
tooth. The first use of ether was made by Dr. Long,
of Athens, Georgia; but he did not publish the case, or
follow up the work: and the honour of the discovery
of ether went to Morton, of Boston, who made repeated
experiments, both on animals and on himself. The
date when he first rendered himself absolutely unconscious
for seven or eight minutes, is 30th September
1846; and the first operation under ether was done on
16th October, in the Massachusetts General Hospital.
The first use of chloroform was 4th November 1847,
that famous evening when Simpson, George Keith, and
Matthews Duncan took it together. The whole history
of anæsthesia is to be found in the Practitioner, Oct. 1896.
It is sometimes said that the men who make experiments
on animals ought to make them on themselves.
But they do, hundreds of them, and suffer for it:
Heaven knows the list is long enough—the discoverers
of anæsthesia, Hunter, Garré, Koch, Klein, Moor, Haffkine,
Grassi, Bochefontaine, Quesada, Sanarelli, Pettenkofer—these
and hosts more, here or abroad, have done
it, as part of the day's work; and some—by accidental
infection, like Chabry and Villa, or by deliberate self-inoculation,
like Carrion—have been killed:—
"Dr. Angelo Knorr, Privat-docent in the Veterinary
School of Munich, died on 22nd February from acute
glanders, contracted in the course of an experimental
research on mallein. Helmann, the Russian investigator
who discovered mallein, himself fell a victim to accidental
inoculation of the glanders virus. Some time afterwards
another Russian, Protopopow, died of glanders contracted
in a French laboratory. An Austrian physician, Dr.
Koffman-Wellenhof, died of the same disease, contracted
in the Institute of Hygiene at Vienna. On 17th January
of the present year Dr. Guiseppe Bosso, of the University
of Turin, died of infection contracted in the course of
cultivations of tubercle-bacilli made in his laboratory.
Not long before, Dr Lola, assistant in the maternity
department of the Czech University Hospital of Prague,
died of tetanus caused by an experimental inoculation
made on himself. Some fourteen or fifteen years ago, a
medical student of Lima proved that 'verruga Peruana'
is an infectious disease by inoculating himself with it, an
act of scientific devotion which cost him his life.[42] Besides
those who have died, there are many who have only
escaped with their lives after long and painful illness.
Professor Kourloff contracted anthrax in a laboratory at
Munich, and was saved only by vigorous surgery. Dr.
Nicolas supplied, in his own person, the first example of
tetanus produced in man by inoculation of the pure toxin
of the bacillus of Nicolaier." (Brit. Med. Journal, 18th
March 1899.)
This list is seven years old now; it is twice the
length by this time. Typhoid, malaria, yellow fever,
have all taken toll of those who study them. It is a
long record of the men who fell ill, or died, or killed
themselves over their work; and the deaths of Barisch,
Dr. Müller, and Nurse Pecha, from plague at Vienna
(October 1898) are another instance that there is
danger in the constant handling of cultures. But these
deaths at Vienna were due to the great carelessness
of one man. In laboratories in all parts of the world
there are stored cultures of all sorts of organisms, yet
no harm comes of it. "More cases of infection occur
amongst young medical men attending fever cases,
whether in private practice or hospital wards, in a
single month, than have occurred in the whole of the
laboratories in the world since they were established."
(British Medical Journal, 29th October 1898.) Outside
the laboratory, outside the fever hospitals, the risk is
something less than a negligible quantity:—
"Apart from plague and cholera, in all the big laboratories
studies are uninterruptedly pursued, from one end
of the year to the other, upon anthrax, glanders, influenza,
Malta fever, various tropical diseases which do not exist
at all or are rare in the countries where they are being
studied. The laboratories in question are situated in the
largest and most important towns of their respective
countries; and, within those towns, very often in the
most fashionable or most populous centres.... On no
occasion was there even a suspicion aroused of an
epidemic having been produced by any of the above-mentioned
institutes, or by those tens of thousands of
operations against cholera performed in India." (Haffkine,
Madras Mail, 8th December 1898.)
The Report of the 1875 Commission said:—
"It is not possible for us to recommend that the
Indian Government should be prohibited from pursuing
its endeavours to discover an antidote for snake-bites;
or that, without such an effort, your Majesty's Indian
subjects should be left to perish in large numbers annually
from the effects of these poisons."
Certainly it was not possible; and the numbers are
large indeed. During 1897, 4227 persons were killed
by wild animals in India, and 20,959 by snakes.
(British Medical Journal, 5th November 1898.)
Sir Joseph Fayrer's name must be put in the highest
place of all those who have studied the venomous snakes
of India.
Sewell, in 1887, showed that animals could be
rendered immune, by repeated inoculation with minute
quantities of rattlesnake-venom, to a dose seven times
as large as would kill an unprotected animal. Kanthack,
in 1891, immunised animals in the same way
against cobra-venom. He also made experiments to
ascertain whether the blood-serum of these animals
acted as an antidote to the venom. Then came the
work of Calmette, Fraser, Phisalix, Bertrand, Martin
(Australia), Stephens, and Meyers. Professor Fraser's
observations on the antidotal properties of the bile are,
of course, of the utmost importance; not only in preventive
medicine, but also in physiology. The results
obtained by Calmette are a good instance of the fineness
and accuracy of the experimental method. It is
to be noted that the animals were inoculated with a
fine needle, not thrust into cages with snakes, as at
zoological gardens; and that an animal thus poisoned
has a painless death. The different venoms were
measured in decimal milligrammes, and their potency
was estimated according to the body-weight of the
animal inoculated. As with tetanus, so with snake-venom,
there must be a standard, or "unit of toxicity."
"The following table gives the relative toxicity, for
1 kilogr. of rabbit, of the different venoms that I have
tested. To denote this toxicity I use terms such as
Behring, Roux, and Vaillard used for the toxin of
tetanus, taking the number of grammes of animal killed
by one gramme of toxin:—
| 1. |
Venom of naja |
0.25 mgr. per kilogr.
of rabbit. |
|
| |
One gramme of this venom kills 4000 kilogrammes
of rabbit; it has, therefore, an activity of |
|
4,000,000 |
| 2. |
Venom of hoplocephalus |
0.29 mgr. |
3,450,000 |
| 3. |
Venom of pseudechis |
1.25 mgr |
800,000 |
| 4. |
Venom of pelias berus |
4.00 mgr |
250,000 |
"Of course, this estimation of virulence is not absolute;
it varies considerably according to the species of
animal tested. Thus the guinea-pig, and still more the
rat, are extremely sensitive. For instance, 0.15 mgr. of
viper-venom is enough to kill, in less than 12 hours, 500
grammes of guinea-pig; so that the activity of this venom
with a guinea-pig is 3,333,000, but with a rabbit is not
more than 650,000. With more resistant animals, the
opposite result is obtained; about 10 mgr. of cobra-venom
are necessary to kill a dog of 6.50 kilogrm. weight; but
to kill the same weight of rabbit 1.65 mgr. is enough.
Thus the virulence of this venom with the rabbit is
4,000,000; but with the dog not more than 650,000."
By experiments in test-tubes, Calmette studied these
venoms under the influences of heat and various chemical
agents. He found how to attenuate their virulence,
and how to diminish the local inflammation round the
point of inoculation; and it was in the course of these
test-tube experiments and inoculations that he discovered
the value of calcium hypochlorite as a local
application. Working, by various methods, with attenuated
venoms, he was able to immunise animals:—
"I have come to immunise rabbits against quantities
of venom that are truly colossal. I have got several,
vaccinated more than a year ago, which take, without the
least discomfort, so much as 40 mgr. of venom of naja
tripudians at a single injection; that is to say, enough to
kill 80 rabbits of 2 kilogr. weight, or 5 dogs.
"Five drops of serum from these rabbits wholly neutralise
in vitro (in a glass test-tube) the toxicity of 1 mgr.
of naja-venom."
By 1894 he had found that the serum of an animal,
thus immunised by graduated doses of one kind of venom,
neutralised other kinds of venom:—
"If 1 mgr. of cobra-venom, or 4 mgr. of viper-venom,
be mixed, in a test-tube, with a small quantity of serum
from an immunised rabbit, and a fresh rabbit be inoculated
with this mixture, it does not suffer any discomfort.
It is not even necessary that the serum should come from
an animal vaccinated against the same sort of venom as
that in the mixture. The serum of a rabbit immunised
against the venom of the cobra or the viper acts indifferently
on all the venoms that I have tested."
In 1894 he had prepared enough serum for the
treatment to be tried by his own countrymen practising
in some of the French colonies. In April 1895,
he gave the following account of his work:—
"I have immunised two asses, one having received
220 mgr. of naja-venom from 25th September to 31st
December 1894, and the other 160 mgr. from 15th
October to 31st December. The serum of the first of
these two animals has now reached this point, that
half a cubic centimetre destroys the toxicity of 1 mgr.
of naja-venom. Four cubic centimetres of this serum,
injected four hours before the inoculation of a dose of
venom enough to kill twice over, preserve the animal
in every case. It is also therapeutic, under the conditions
that I have already defined; that is to say, if you
first inoculate a rabbit with such a dose of venom as kills
the control-animals in three hours, and then, an hour after
injecting the venom, inject under the skin of the abdomen
4 to 5 cubic centimetres of serum, recovery is the rule.
When you interfere later than this the results are uncertain;
and in all my experiments the delay of an hour
and a half is the most that I have been able to reach.
"This antivenomous serum of asses has these same
antitoxic properties with all kinds of snake-venom; it is
equally active in vitro, preventive, and therapeutic, with
the venoms of cerastes, of
trigonocephalus, of crotalus, and
of four kinds of Australian snakes that Mr. MacGarvie
Smith has sent to M. Roux. I am still injecting these
two animals with venom, and I hope to give to their
serum at last a much greater antitoxic power."
In 1896 four successful cases of this treatment in
the human subject were reported in the British Medical
Journal. In 1898 Calmette made the following statement
of his results:—
"It is now nearly two years since the use of my antivenomous
serum was introduced in India, in Algeria, in
Egypt, on the West Coast of Africa, in America, in the
West Indies, Antilles, &c. It has been very often used
for men and domestic animals (dogs, horses, oxen), and
up to now none of those that have received an injection
of serum have succumbed.... A great number of
observations have been communicated to me, and not one
of them refers to a case of failure." (British Medical
Journal, 14th May 1898.)
Good accounts of Fraser's and Calmette's work are
given by Dr. Stone in the Boston Medical and Surgical
Journal, 7th April 1898, and by Staff-Surgeon Andrews,
R.N., in the British Medical Journal, 9th September
1899. For other cases see the Pioneer, 10th August
1899, the Lancet, 25th November 1899, and the British
Medical Journal, 23rd December 1899. In one of these
cases, recorded by Dr. Rennie, the patient was, literally,
at the point of death, but recovered after the serum had
been injected. Two cases have also been recorded of
cobra-bite during work in the laboratory: both of them
recovered after injection. "Every Government or
private dispensary," says Surgeon Beveridge, "should
be supplied with antivenene, which is certainly the best
remedy for snake-bite available." The cases are few
at present; but it does not appear that the treatment
has failed in any case; and, with a new remedy of this
kind, it is fairly certain that failures would be published.
From all these instances in physiology, pathology,
bacteriology, and therapeutics, we come to consider the
Act relating to experiments on animals in the United
Kingdom. Many subjects have been left out; among
them, the work of the last few years on the suprarenal
glands and adrenalin, and Dr. William Hunter's admirable
work on pernicious anæmia. No attempt has been
made to describe the researches of experts in many
countries into the nature of malignant disease, or to
guess what may come of the discovery that mice can
be immunised against that form of cancer which occurs
in mice and is inoculable from mouse to mouse. Nothing
has been said of the discovery that the African sleeping-sickness
is due to a blood-parasite carried by flies from
man to man. Nothing has been said about those discoveries
in bacteriology that have not yet been applied
to practice, or of the many inventions of medical and
surgical practice that owe only an indirect debt to experiments
on animals. Artificial respiration, the transfusion
of saline fluid, the hypodermic administration of drugs,
the use of oxygen for inhalation, the torsion of arteries,
the grafting of skin, the transplantation of bone, the
absorbable ligature, the diagnostic and therapeutic uses
of electricity, the rational employment of blood-letting—all
these good methods have been left out of the list;
only some facts have been presented, those that mark
most clearly the advance of knowledge and of practice,
and stand up even above the rest of the work. There
they will stand, when we are all dead and gone: and
by them, as by landmarks, all further advance will be
guided.
