the École Normale, a malady the name of which was not even known in
Paris, but which made great ravages in the country--namely, swine fever
(_rouget_). Here, again, it is a microbe which causes the disorder.
This microbe was first perceived by Thuillier, in a little commune of
the Département de Vienne, when examining the blood and humours of pigs
which had died of the fever. Experiments were at once set on foot in
the laboratory, with the view of proving that the microbe was really
the cause of the disease. The microbe was cultivated in a sterilised
infusion of veal. This cultivation was passed on to a succeeding one,
a small drop of the preceding cultivation being always taken for seed.
Inoculations from these last cultivations produced the fever in certain
breeds of pigs. The proof was thus given that the microbe was really
the origin of the disease.
Pasteur then, accompanied by Thuillier and a young assistant, M. Loir,
went, in his turn, to study the disease in the Department of Vaucluse.
He remained more than a month in the canton of Bollène, in the house
of a veterinary surgeon, M. Maucuer, who took him to all the pigsties
in the arrondissement. After having had recourse to the oxygen of
the air to attenuate the virulence of the microbe, Pasteur made some
experiments in vaccination. Some pigs which had been vaccinated
remained in the canton of Bollène, under the supervision of M. Maucuer,
the owners having pledged themselves to keep their vaccinated pigs
for at least a year. In the ensuing September, when swine fever
raged everywhere in the canton of Bollène and in the arrondissement
of Orange, not a single vaccinated pig was attacked. 'They are all
flourishing,' wrote M. Maucuer. An address of thanks was sent to
Pasteur by the municipal council of Bollène.
But, notwithstanding these happy results, the question of the
application of vaccines to different breeds requires still further
investigation, before the vaccination of pigs can become general.
Soon afterwards a method, different from that of the atmospheric
oxygen, for weakening the virulence of the fever virus, was tried in
the laboratory.
Pasteur had proved that viruses are not morbid entities, that they
can assume numerous forms, and especially physiological properties,
dependent on the medium in which they live and multiply. The virulence
belongs to living microscopic species, but is at the same time
essentially modifiable. It may be weakened or intensified, and each of
these states is capable of being made permanent by culture. A microbe
is virulent in an animal, when it has the power of swarming in the
body of that animal, after the manner of a parasite, and of producing,
by the renewal of its own life, disturbances which cause disease
and death. If this microbe has lived in any species of animal--that
is to say, if several times over it has passed from the body of one
individual into that of another of the same kind, without having been
subjected to any sensible exterior influence during its passage--we
may consider that the virulence of this parasite has reached a fixed
and maximum state for the individuals of that race. The splenic fever
parasite pertaining to sheep, for instance, varies little from one
subject to another or from one year to another in the same country;
this must be attributed, doubtless, to the fact that, in its successive
passages through the sheep, the habit of the parasite to live in sheep
has, so to speak, attained a definite state. It is thus with the virus
of the Jennerian vaccination. But the virulence of a virus which is
not at its maximum may be essentially modified by its passage into a
succession of individuals of the same race. It will be remembered how,
when Pasteur and his assistants wished to increase progressively the
virulence of the virus of chicken cholera and splenic fever, so as to
bring them at last to their maximum intensity, these viruses were first
inoculated into young subjects, and from them successively into older
ones.
'The Academy remembers, without doubt,' said Pasteur in a recent
communication, 'that, some time ago, we discovered a microbe virus
in the saliva of hydrophobia. This microbe, though very virulent for
rabbits, is shown to be harmless for adult guinea-pigs, but it kills
rapidly guinea-pigs only some hours or days old. In following out
this inoculation from young guinea-pigs, we have seen the virulence
increase, and easily arrive at the point of causing death to older
guinea-pigs. There was even at last a marked difference in the lesions.
The increase of virulence, by successive passages through individuals
of one race, was clearly shown.
'But the new and unexpected result that I wish to point out to the
Academy consists in this: that the microbe, after having increased its
virulence by successive passages through the bodies of guinea-pigs,
shows itself to be less virulent in relation to rabbits than it was
before.
'In these new conditions, it gives to the rabbit a disease which is
spontaneously curable; and, moreover, having once gone through the
malady, the animal becomes refractory in regard to the microbe which
is deadly to rabbits. From this arises the all-important consequence,
that the habit of living in one species (the guinea-pig) at a definite
corresponding degree of virulence, can change this virulence in
relation to another species (the rabbit), so much diminishing its
effects as to cause it to become a vaccine for this latter species.
'The importance of this result cannot fail to be perceived by everyone,
for it contains the secret of a new method of attenuation, which can be
applied to some of the most virulent viruses. We will give an example
and an application of it.
'If a pigeon be inoculated in the pectoral muscle with the microbe of
swine fever, the pigeon dies in an interval of six or eight days, after
having shown the apparent exterior symptoms of fowl cholera.
'When a second pigeon is inoculated with the blood of the first, a
third with that of the second, and so on in succession, the microbe
acclimatises itself to the pigeon. The symptoms of forming itself into
a ball, and of somnolence, which are the habitual characteristics of
the disease, appear in a much shorter time than with the first pigeons
of the series. Death likewise comes on more rapidly. Finally, the blood
of the last pigeons exhibits much more virulence in the pig than even
the most infectious products of a pig that has died of what is called
spontaneous fever.
'The passage of the swine fever microbe through rabbits leads to quite
a different result. Rabbits inoculated with the infectious products of
a pig that has died of the fever, or with the cultivations of them, are
always made ill and most frequently die.
'When the virus is inoculated from rabbit to rabbit, the microbe
acclimatises itself to the rabbit. All the animals die, and death
comes in a very few days. The cultures of the blood of these rabbits
in sterilised media become progressively easy and more abundant. The
microbe itself changes its aspect somewhat, grows rather larger than
in the pig, and appears in the form of an 8, without the filiform
lengthening out characteristic of certain other cultures.'
'When pigs are inoculated with the blood of the last rabbits, and the
results compared with those obtained from the first of the series, it
is found that the virulence has been progressively diminishing from the
first rabbit to the following ones. Very soon the blood of the rabbits
ceases to cause death in the pigs, though it renders them ill. On
recovery they are proof against the deadly swine fever.'
III.
But in the midst of these investigations undertaken by Pasteur, there
is one which is paramount over all the others, one on which for three
years all his efforts, as well as those of his pupils, have been
concentrated, and this is Hydrophobia. Mysterious in its incubation,
alarming in its symptoms, Pasteur's attention had for a long time
been drawn to it, when in 1880 he finally attacked it. Besides the
attraction which an obscure problem had for him, he felt that if he
succeeded in discovering the probably microbean etiology of such a
disease, he would carry all minds with him into the current of these
new ideas. He had been very often struck, if not with the opposition,
at least with the prudent and circumspect reserve, shown in the
examination of his doctrine, by a considerable number of physicians
who, possessed by the idea that the moral element could cause
modifications in the symptoms and development of a malady in man, are
not disposed to recognise the least assimilation between human diseases
and those of the animal species. No doubt the emotional qualities,
grave family cares, the terror of approaching death, the dread of the
great unknown, may modify the course of the evil in man, may aggravate
it, even hasten it; but, whilst recognising--for never was there a man
more a creature of sentiment than he--what there is of deep truth in
this opinion, Pasteur could not help thinking that the first origin,
the cause of every contagious malady, is physiologically the same in
the two groups, and that our bodies, notwithstanding our superior moral
qualities, are exposed to the same dangers, to the same disorders, as
the bodies of animals.
To overcome these resistances, it was necessary, as in the great
experiments on splenic fever, to attack a disease common both to
men and animals--one in which experimentation, the only, but great,
strength of Pasteur, was supreme. Hydrophobia offered these conditions.
Again, it was Dr. Lannelongue who introduced Pasteur to his first
case of hydrophobia. On December 10, 1880, a child of five years old,
who had been bitten in the face a month previously, was dying in the
Trousseau Hospital. Devoured at the time by a raging thirst, and
seized with a horror for all liquids, he approached with his lips the
spout of a closed coffee pot, then suddenly started back--the throat
contracted--a prey to such fury that he insulted the nursing sister who
was attending on him. He was at the same time attacked by aerophobia
to a prodigious degree. At a certain moment, the heel of one of his
feet protruded from the bed. An assistant blew on it. The child had not
seen the assistant, and the breath of air was so light as to be almost
imperceptible. The poor child flew into a rage, and a violent spasm
seized him in the throat. The next day delirium began, a frightful
delirium. The frothy matters which filled his throat suffocated him.
Four hours after his death, the mucus from the palate of the child
was collected. It was diluted with a little water, and two rabbits
were inoculated under the skin of the abdomen. The rabbits perished
in less than thirty-six hours. The saliva of these dead rabbits also
transmitted the disease to fresh rabbits. Did it not seem as if one
had got hold of an inoculation of hydrophobia? Such was in fact the
conclusion of Dr. Maurice Raynaud, who, having been informed, at the
same time as Pasteur, of the illness of the child, had made, on his own
account, some experiments on rabbits. His rabbits were dead. Already
a year previously M. Maurice Raynaud had announced the transmission,
by the saliva, of rabies from man to rabbits. 'We are, then, in the
presence of a new fact of this kind,' he said, 'and we really believe,
until a proof to the contrary is given us, that these latter rabbits
died of hydrophobia.'
With his habitual prudence, and trusting more to the results of
experiment than to medical observation alone, Pasteur was not in a
hurry to form such positive conclusions. He began by doing what Dr.
Maurice Raynaud had neglected to do. He examined with the microscope
the tissues and the blood of the rabbits inoculated in the laboratory;
he discovered, both in those that were dead, and in those which were
on the point of death, the presence of a special microbe, easily
cultivable in a pure state and of which the successive cultures caused
the death of other rabbits. Invariably, the same microbe appeared in
the blood. As one or two days sufficed to cause death, hydrophobia
could not have had time to make its appearance. Pasteur, moreover,
found this same microbe in the saliva of children who had died of
common maladies, and even in the normal saliva of healthy adults.
It was a new microbe, causing a disease unknown up to that time. To
Pasteur it seemed, in the case of the experiments made with the mucus
from the child's palate, to be simply an accompaniment of the rabic
virus.
* * * * *
This microbe of the saliva is very easily cultivated in sterile
infusions--that of veal, for example--and successive cultures can be
made in the usual way. The virulence continues. Could the virulence
be attenuated, asked Pasteur, by the action of the oxygen of the air?
This would, by a new example, go to establish the generalisation of the
method of attenuation by oxygen. The attempt succeeded. When care is
taken, as with the attenuation of the fowl cholera contagium, not to
allow more than some hours' interval to elapse between one cultivation
and the succeeding one, the virulence of the successive cultivations
of the microbe of the saliva is preserved in some sort indefinitely.
In other words, if it be arranged that the cultures succeed each other
every twelve hours, the rabbits inoculated from the last cultures die
as quickly as those inoculated from the first. Thuillier had had the
patience to make, in this manner, eighty cultures in contact with
air, and eighty cultures in a vacuum; the microbe of the saliva being
both aerobic and anaerobic. The eightieth culture killed as quickly
as the first. But by allowing the successive cultures to remain for
some time in contact with the air, before passing from one culture to
the following one, the virulence of the cultures becomes enfeebled.
Thus, then, as in fowl cholera, attenuated cultures of the microbe can
be obtained. Unlike what happens with cholera, however, the cultures
of the microbe of the saliva, exposed to the contact of air, perish
very quickly. Two or three days of keeping suffice for the parent
cultivation to lose all virulence. The seed, taken in any quantity from
it, does not fertilise a new cultivation. But, before perishing, this
culture passes through very different degrees of progressively weakened
virulence, and it is easy with these cultivations to render rabbits ill
without causing their death. Once cured, they resist all inoculation
which would be mortal for others. The oxygen of the air is manifestly
the transformer of this virulent virus into vaccine virus; for, if the
virulent blood or cultivations remain inclosed in their tubes, sealed
from all entrance of the air, they retain not only for some hours, but
for months, their life and their original virulence.
* * * * *
But though these results were as new as they were unexpected, and
though one cause of confusion in the study of this terrible problem was
removed, yet these first researches were not marked by any progress in
the etiology of hydrophobia. The question remained wholly unsolved.
Impatient with the length of time required for the incubation of the
disease, and with the obligation of waiting whole months for the result
of an experiment, when the subject demanded such numerous ones, Pasteur
began to seek some means of producing hydrophobia with certainty and
of making it appear more rapidly. Notwithstanding the assertion of a
professor of the veterinary school at Lyons that the saliva of the
rabid dog alone contained the virus of the disease, and that he had
failed in every attempt to inoculate, whether with the substance of the
brain or with the spinal marrow of rabid dogs; Pasteur, with due care
as to purity, introduced under the skin of some rabbits and some dogs,
divers parts of the brain of a dog which had died in a rabid state.
Hydrophobia declared itself in both dogs and rabbits, with a duration
of incubation about equal to that which followed the ordinary bite of a
dog. Although it was necessary still to submit to this long uncertainty
with regard to the incubation, one great result was obtained:
hydrophobia _could_ be inoculated with other matter than saliva.
Not only is the saliva always impure, containing a saliva microbe,
which is endowed with a special virulence of its own, but it presents
other inconveniences. It is necessary, in these researches, to have a
supply of material constantly at hand. Now, the saliva loses its rabic
virulence in twenty-four hours. The existence of the rabic virulence
in the brain substance placed, on the contrary, at the disposal of the
experimenter, an abundance of the virus, in a state of great purity and
capable of long preservation.
* * * * *
The idea then occurred to Pasteur and his assistants, to inoculate
the virulent rabic matter in its pure state under the _dura mater_
on the surface of the brain of a dog. Why not carry the virus, said
Pasteur, directly to the place of its activity and development? After
having trepanned the skull of a chloroformed dog, a little bit of the
medulla of an animal which had died of hydrophobia was deposited on
the surface of the brain. As soon as the influence of the chloroform
was dissipated, the dog recovered its healthy appearance. It ate its
food that same evening. But after some days the symptoms of hydrophobia
appeared. The animal became dejected and restless; it tossed its
litter about, refused all nourishment. A doleful, sharp howling was
the first indication of the rabic voice, which is but one long cry
of suffering and appeal, mingled with barkings from hallucinations.
The stomach became depraved; the dog swallowed hay and straw. It soon
grew furious, agitated with violent convulsions; finally, after a last
fit, it died. During all this time there was great rejoicing in the
laboratory. They were at last in possession of a method for singularly
shortening the period of incubation, and for communicating the disease
with certainty. The experiments were multiplied; all the dogs which
were trepanned, and which received on the surface of the brain a
little of the medulla of the rabid animal, succumbed to the disease,
with very rare exceptions, within a period of twenty days. Did not the
method pursued demonstrate, among other things, that hydrophobia is a
disease of the brain; that the seat of the rabic virus, far from being
exclusively in the saliva, belongs, above all, to the cerebral matter?
Other results, in addition to this one, were not slow in revealing
themselves. It was established that not only the brain, but the spinal
marrow, along its whole length, may be rabic, and that the nerves
themselves throughout their whole system, from the centre to the
periphery, may contain the virus of hydrophobia. If there exists a
microbe of hydrophobia, its medium of cultivation in the body is, _par
excellence_, the brain, the spinal marrow, and the nerves. It was also
established that there were localisations of virus in certain parts
of the mucous system, and that the very considerable differences of
rabic symptoms which exist in different cases of hydrophobia, must be
sought for in this fact. At the moment of death the medulla oblongata
is always rabic. Finally, it was established that hydrophobia could be
given (and almost as rapidly as by trepanning) by inoculating rabic
nervous matter into the circulation of the blood by a vein.
In presence of such facts it is easy to account for what takes place in
the case of a bite from a mad dog. The circulation of the blood carries
the virus to the surface of the brain, or to the surface of the spinal
marrow; there it houses itself in particular spots, and, little by
little, invades the nervous matter. This last would be progressively
attacked throughout, if death from the medulla oblongata did not almost
always supervene before the propagation of the virus can become general.
The saliva glands are often rabic, doubtless because the virus oozes
into them, little by little, from the nerves which enter these glands.
Thus may the presence of this virus be explained in the saliva of mad
dogs, where, at all times since the disease was first known, it has
been found to exist. When the first point attacked by the virus is the
spinal marrow, or certain portions of it, a general paralysis often
precedes death. In this case the howling and biting symptoms are for
the most part absent, and the dog continues to be caressing until it
dies.
In a thesis written by M. Roux, Pasteur's laboratory assistant, last
July, we read the following:--'If we examine with care a little of
the pulp taken freshly from the brain of a rabid animal, and compare
it with the same substance from the brain of a healthy animal, it is
difficult to distinguish any difference between the two. In the rabic
pulp, however, besides the granulations which are found in profusion
in the healthy pulp, there seem to exist little grains of extreme
minuteness, almost imperceptible even with the strongest microscopes.
In the cephalo-rachidic liquid so limpid in appearance, it is possible
with great attention to detect similar little grains. Can this be the
microbe of hydrophobia? Some do not hesitate to affirm that it is.
For ourselves, as long as the cultivation of the microbe outside of
the organism has not been effected, and that hydrophobia has not been
communicated by means of artificial cultures, we shall abstain from
expressing a definite opinion on the subject.'
But the grand problem in regard to hydrophobia is, not so much the
isolation of the microbe, as the finding of a means of preventing this
frightful disease.
* * * * *
Even now the experiments are in full swing. Biting dogs and bitten
dogs fill the laboratory. Without reckoning the hundreds of mad dogs
that have died in the laboratory during the last three years, there
never occurs a case of hydrophobia in Paris of which Pasteur is not
informed. Not long ago a veterinary surgeon telegraphed to him, 'Attack
at its height in poodle-dog and bull-dog. Come.' Pasteur invited me
to accompany him, and we started, carrying six rabbits with us in a
basket. The two dogs were rabid to the last degree. The bull dog
especially, an enormous creature, howled and foamed in its cage. A
bar of iron was held out to him: he threw himself upon it, and there
was great difficulty in drawing it away from his bloody fangs. One
of the rabbits was then brought near to the cage, and its drooping
ear was allowed to pass through the bars. But, notwithstanding this
provocation, the dog flung himself down at the bottom of his cage and
refused to bite.
Two youths then threw a cord with a slip loop over the dog, as a lasso
is thrown. The animal was caught and drawn to the edge of the cage.
There they managed to get hold of him and to secure his jaws; and the
dog, suffocating with fury, his eyes bloodshot, and his body convulsed
with a violent spasm, was extended upon a table and held motionless,
while Pasteur, leaning over his foaming head, at the distance of a
finger's length, sucked up into a narrow tube some drops of the saliva.
In the basement of the veterinary surgeon's house, witnessing this
formidable _tête-à-tête_, I thought Pasteur grander than I had ever
thought him before.
* * * * *
TRANSCRIBER'S NOTES:
Footnotes have been moved to the end of each chapter and renumbered
consecutively through the document.
Footnotes 7 and 8 are [enclosed in brackets] in the original, and this
has been preserved.
Italic text is denoted by _underscores_.
Punctuation has been standardized.
Variations in spelling and hyphenation were retained as they appear in
the original publication, except as noted below.
Changes have been made as follows:
Ecole changed to École in several places (École Normale)
Page ix: ETUDIES changed to STUDIES (STUDIES ON WINE)
Page 48: buding changed to budding (multiplication by budding,)
Page 166: nett changed to net (villa a net profit)
Page 219: pebrine changed to pébrine (pébrine and flacherie, also)
Page 258 earth worms changed to earth-worms (by the earth-worms.)
Page 260: resistent changed to resistant (more resistant to the)