1884--1885
Amidst the various researches undertaken in his laboratory, one study
was placed by Pasteur above every other, one mystery constantly haunted
his mind--that of hydrophobia. When he was received at the Académie
Française, Renan, hoping to prove himself a prophet for once, said to
him: “Humanity will owe to you deliverance from a horrible disease and
also from a sad anomaly: I mean the distrust which we cannot help
mingling with the caresses of the animal in whom we see most of nature’s
smiling benevolence.”
The two first mad dogs brought into the laboratory were given to
Pasteur, in 1880, by M. Bourrel, an old army veterinary surgeon who had
long been trying to find a remedy for hydrophobia. He had invented a
preventive measure which consisted in filing down the teeth of dogs, so
that they should not bite into the skin; in 1874, he had written that
vivisection threw no light on that disease, the laws of which were
“impenetrable to science until now.” It now occurred to him that,
perhaps, the investigators in the laboratory of the Ecole Normale might
be more successful than he had been in his kennels in the Rue
Fontaine-au-Roi.
One of the two dogs he sent was suffering from what is called _dumb
madness_: his jaw hung, half opened and paralyzed, his tongue was
covered with foam, and his eyes full of wistful anguish; the other made
ferocious darts at anything held out to him, with a rabid fury in his
bloodshot eyes, and, in the hallucinations of his delirium, gave vent to
haunting, despairing howls.
Much confusion prevailed at that time regarding this disease, its seat,
its causes, and its remedy. Three things seemed positive: firstly, that
the rabic virus was contained in the saliva of the mad animals;
secondly, that it was communicated through bites; and thirdly, that the
period of incubation might vary from a few days to several months.
Clinical observation was reduced to complete impotence; perhaps
experiments might throw some light on the subject.
Bouley had affirmed in April, 1870, that the germ of the evil was
localized in the saliva, and a new fact had seemed to support this
theory. On December 10, 1880, Pasteur was advised by Professor
Lannelongue that a five-year-old child, bitten on the face a month
before, had just been admitted into the Hôpital Trousseau. The
unfortunate little patient presented all the characteristics of
hydrophobia: spasms, restlessness, shudders at the least breath of air,
an ardent thirst, accompanied with an absolute impossibility of
swallowing, convulsive movements, fits of furious rage--not one symptom
was absent. The child died after twenty-four hours of horrible
suffering--suffocated by the mucus which filled the mouth. Pasteur
gathered some of that mucus four hours after the child’s death, and
mixed it with water; he then inoculated this into some rabbits, which
died in less than thirty-six hours, and whose saliva, injected into
other rabbits, provoked an almost equally rapid death. Dr. Maurice
Raynaud, who had already declared that hydrophobia could be transmitted
to rabbits through the human saliva, and who had also caused the death
of some rabbits with the saliva of that same child, thought himself
justified in saying that those rabbits had died of hydrophobia.
Pasteur was slower in drawing conclusions. He had examined with a
microscope the blood of those rabbits which had died in the laboratory,
and had found in it a micro-organism; he had cultivated this organism in
veal broth, inoculated it into rabbits and dogs, and, its virulence
having manifested itself in these animals, their blood had been found to
contain that same microbe. “But,” added Pasteur at the meeting of the
Academy of Medicine (January 18, 1881), “I am absolutely ignorant of the
connection there may be between this new disease and hydrophobia.” It
was indeed a singular thing that the deadly issue of this disease should
occur so early, when the incubation period of hydrophobia is usually so
long. Was there not some unknown microbe associated with the rabic
saliva? This query was followed by experiments made with the saliva of
children who had died of ordinary diseases, and even with that of
healthy adults. Thuillier, following up and studying this saliva microbe
and its special virulence with his usual patience, soon applied to it
with success the method of attenuation by the oxygen in air. “What did
we want with a new disease?” said a good many people, and yet it was
making a stop forward to clear up this preliminary confusion. Pasteur,
in the course of a long and minute study of the saliva of mad dogs--in
which it was so generally admitted that the virulent principle of rabies
had its seat, that precautions against saliva were the only ones taken
at post-mortem examinations--discovered many other mistakes. If a
healthy dog’s saliva contains many microbes, licked up by the dog in
various kinds of dirt, what must be the condition of the mouth of a
rabid dog, springing upon everything he meets, to tear it and bite it?
The rabic virus is therefore associated with many other micro-organisms,
ready to play their part and puzzle experimentalists; abscesses, morbid
complications of all sorts, may intervene before the development of the
rabic virus. Hydrophobia might evidently be developed by the inoculation
of saliva, but it could not be confidently asserted that it would.
Pasteur had made endless efforts to inoculate rabies to rabbits solely
through the saliva of a mad dog; as soon as a case of hydrophobia
occurred in Bourrel’s kennels, a telegram informed the laboratory, and a
few rabbits were immediately taken round in a cab.
One day, Pasteur having wished to collect a little saliva from the jaws
of a rabid dog, so as to obtain it directly, two of Bourrel’s assistants
undertook to drag a mad bulldog, foaming at the mouth, from its cage;
they seized it by means of a lasso, and stretched it on a table. These
two men, thus associated with Pasteur in the same danger, with the same
calm heroism, held the struggling, ferocious animal down with their
powerful hands, whilst the scientist drew, by means of a glass tube held
between his lips, a few drops of the deadly saliva.
But the same uncertainty followed the inoculation of the saliva; the
incubation was so slow that weeks and months often elapsed whilst the
result of an experiment was being anxiously awaited. Evidently the
saliva was not a sure agent for experiments, and if more knowledge was
to be obtained, some other means had to be found of obtaining it.
Magendie and Renault had both tried experimenting with rabic blood, but
with no results, and Paul Bert had been equally unsuccessful. Pasteur
tried in his turn, but also in vain. “We must try other experiments,” he
said, with his usual indefatigable perseverance.
As the number of cases observed became larger, he felt a growing
conviction that hydrophobia has its seat in the nervous system, and
particularly in the medulla oblongata. “The propagation of the virus in
a rabid dog’s nervous system can almost be observed in its every stage,”
writes M. Roux, Pasteur’s daily associate in these researches, which he
afterwards made the subject of his thesis. “The anguish and fury due to
the excitation of the grey cortex of the brain are followed by an
alteration of the voice and a difficulty in deglutition. The medulla
oblongata and the nerves starting from it are attacked in their turn;
finally, the spinal cord itself becomes invaded and paralysis closes the
scene.”
As long as the virus has not reached the nervous centres, it may sojourn
for weeks or months in some point of the body; this explains the
slowness of certain incubations, and the fortunate escapes after some
bites from rabid dogs. The _a priori_ supposition that the virus attacks
the nervous centres went very far back; it had served as a basis to a
theory enunciated by Dr. Duboué (of Pau), who had, however, not
supported it by any experiments. On the contrary, when M. Galtier, a
professor at the Lyons Veterinary School, had attempted experiments in
that direction, he had to inform the Academy of Medicine, in January,
1881, that he had only ascertained the existence of virus in rabid dogs
in the lingual glands and in the bucco-pharyngeal mucous membrane. “More
than ten times, and always unsuccessfully, have I inoculated the product
obtained by pressure of the cerebral substances of the cerebellum or of
the medulla oblongata of rabid dogs.”
Pasteur was about to prove that it was possible to succeed by operating
in a special manner, according to a rigorous technique, unknown in other
laboratories. When the post-mortem examination of a mad dog had revealed
no characteristic lesion, the brain was uncovered, and the surface of
the medulla oblongata scalded with a glass stick, so as to destroy any
external dust or dirt. Then, with a long tube, previously put through a
flame, a particle of the substance was drawn and deposited in a glass
just taken from a stove heated up to 200° C., and mixed with a little
water or sterilized broth by means of a glass agitator, also previously
put through a flame. The syringe used for inoculation on the rabbit or
dog (lying ready on the operating board) had been purified in boiling
water.
Most of the animals who received this inoculation under the skin
succumbed to hydrophobia; that virulent matter was therefore more
successful than the saliva, which was a great result obtained.
“The seat of the rabic virus,” wrote Pasteur, “is therefore not in the
saliva only: the brain contains it in a degree of virulence at least
equal to that of the saliva of rabid animals.” But, to Pasteur’s eyes,
this was but a preliminary step on the long road which stretched before
him; it was necessary that all the inoculated animals should contract
hydrophobia, and the period of incubation had to be shortened.
* * * * *
It was then that it occurred to Pasteur to inoculate the rabic virus
directly on the surface of a dog’s brain. He thought that, by placing
the virus from the beginning in its true medium, hydrophobia would more
surely supervene and the incubation might be shorter. The experiment was
attempted: a dog under chloroform was fixed to the operating board, and
a small, round portion of the cranium removed by means of a trephine (a
surgical instrument somewhat similar to a fret-saw); the tough fibrous
membrane called the dura-mater, being thus exposed, was then injected
with a small quantity of the prepared virus, which lay in readiness in a
Pravaz syringe. The wound was washed with carbolic and the skin stitched
together, the whole thing lasting but a few minutes. The dog, on
returning to consciousness, seemed quite the same as usual. But, after
fourteen days, hydrophobia appeared: rabid fury, characteristic howls,
the tearing up and devouring of his bed, delirious hallucination, and
finally, paralysis and death.
A method was therefore found by which rabies was contracted surely and
swiftly. Trephinings were again performed on chloroformed
animals--Pasteur had a great horror of useless sufferings, and always
insisted on anæsthesia. In every case, characteristic hydrophobia
occurred after inoculation on the brain. The main lines of this
complicated question were beginning to be traceable; but other obstacles
were in the way. Pasteur could not apply the method he had hitherto
used, _i.e._ to isolate, and then to cultivate in an artificial medium,
the microbe of hydrophobia, for he failed in detecting this microbe. Yet
its existence admitted of no doubt; perhaps it was beyond the limits of
human sight. “Since this unknown being is living,” thought Pasteur, “we
must cultivate it; failing an artificial medium, let us try the brain
of living rabbits; it would indeed be an experimental feat!”
As soon as a trephined and inoculated rabbit died paralyzed, a little of
his rabic medulla was inoculated to another; each inoculation succeeded
another, and the time of incubation became shorter and shorter, until,
after a hundred uninterrupted inoculations, it came to be reduced to
seven days. But the virus, having reached this degree, the virulence of
which was found to be greater than that of the virus of dogs made rabid
by an accidental bite, now became fixed; Pasteur had mastered it. He
could now predict the exact time when death should occur in each of the
inoculated animals; his predictions were verified with surprising
accuracy.
Pasteur was not yet satisfied with the immense progress marked by
infallible inoculation and the shortened incubation; he now wished to
decrease the degrees of virulence--when the attenuation of the virus was
once conquered, it might be hoped that dogs could be made refractory to
rabies. Pasteur abstracted a fragment of the medulla from a rabbit which
had just died of rabies after an inoculation of the fixed virus; this
fragment was suspended by a thread in a sterilized phial, the air in
which was kept dry by some pieces of caustic potash lying at the bottom
of the vessel and which was closed by a cotton-wool plug to prevent the
entrance of atmospheric dusts. The temperature of the room where this
desiccation took place was maintained at 23° C. As the medulla gradually
became dry, its virulence decreased, until, at the end of fourteen days,
it had become absolutely extinguished. This now inactive medulla was
crushed and mixed with pure water, and injected under the skin of some
dogs. The next day they were inoculated with medulla which had been
desiccating for thirteen days, and so on, using increased virulence
until the medulla was used of a rabbit dead the same day. These dogs
might now be bitten by rabid dogs given them as companions for a few
minutes, or submitted to the intracranial inoculations of the deadly
virus: they resisted both.
Having at last obtained this refractory condition, Pasteur was anxious
that his results should be verified by a Commission. The Minister of
Public Instruction acceded to this desire, and a Commission was
constituted in May, 1884, composed of Messrs. Béclard, Dean of the
Faculty of Medicine, Paul Bert, Bouley, Villemin, Vulpian, and
Tisserand, Director of the Agriculture Office. The Commission
immediately set to work; a rabid dog having succumbed at Alfort on June
1, its carcase was brought to the laboratory of the Ecole Normale, and a
fragment of the medulla oblongata was mixed with some sterilized broth.
Two dogs, declared by Pasteur to be refractory to rabies, were
trephined, and a few drops of the liquid injected into their brains; two
other dogs and two rabbits received inoculations at the same time, with
the same liquid and in precisely the same manner.
Bouley was taking notes for a report to be presented to the Minister:
“M. Pasteur tells us that, considering the nature of the rabic virus
used, the rabbits and the two new dogs will develop rabies within twelve
or fifteen days, and that the two refractory dogs will not develop it at
all, however long they may be detained under observation.”
On May 29, Mme. Pasteur wrote to her children:
“The Commission on rabies met to-day and elected M. Bouley as chairman.
Nothing is settled as to commencing experiments. Your father is absorbed
in his thoughts, talks little, sleeps little, rises at dawn, and, in one
word, continues the life I began with him this day thirty-five years
ago.”
On June 3, Bourrel sent word that he had a rabid dog in the kennels of
the Rue Fontaine-au-Roi; a refractory dog and a new dog were immediately
submitted to numerous bites; the latter was violently bitten on the head
in several places. The rabid dog, still living the next day and still
able to bite, was given two more dogs, one of which was refractory; this
dog, and the refractory dog bitten on the 3rd, were allowed to receive
the first bites, the Commission having thought that perhaps the saliva
might then be more abundant and more dangerous.
On June 6, the rabid dog having died, the Commission proceeded to
inoculate the medulla of the animal into six more dogs, by means of
trephining. Three of those dogs were refractory, the three others were
fresh from the kennels; there were also two rabbits.
On the 10th, Bourrel telegraphed the arrival of another rabid dog, and
the same operations were gone through.
“This rabid, furious dog,” wrote Pasteur to his son-in-law, “had spent
the night lying on his master’s bed; his appearance had been suspicious
for a day or two. On the morning of the 10th, his voice became
rabietic, and his master, who had heard the bark of a rabid dog twenty
years ago, was seized with terror, and brought the dog to M. Bourrel,
who found that he was indeed in the biting stage of rabies. Fortunately
a lingering fidelity had prevented him from attacking his master....
“This morning the rabic condition is beginning to appear on one of the
new dogs trephined on June 1, at the same time as two refractory dogs.
Let us hope that the other new dog will also develop it and that the two
refractory ones will resist.”
At the same time that the Commission examined this dog which developed
rabies within the exact time indicated by Pasteur, the two rabbits on
whom inoculation had been performed at the same time were found to
present the first symptoms of rabic paralysis. “This paralysis,” noted
Bouley, “is revealed by great weakness of the limbs, particularly of the
hind quarters; the least shock knocks them over and they experience
great difficulty in getting up again.” The second new dog on whom
inoculation had been performed on June 1 was now also rabid; the
refractory dogs were in perfect health.
During the whole of June, Pasteur found time to keep his daughter and
son-in-law informed of the progress of events. “Keep my letters,” he
wrote, “they are almost like copies of the notes taken on the
experiments.”
Towards the end of the month, dozens of dogs were submitted to
control-experiments which were continued until August. The dogs which
Pasteur declared to be refractory underwent all the various tests made
with rabic virus; bites, injections into the veins, trephining,
everything was tried before Pasteur would decide to call them
vaccinated. On June 17, Bourrel sent word that the new dog bitten on
June 3 was becoming rabic; the members of the Commission went to the Rue
Fontaine-au-Roi. The period of incubation had only lasted fourteen days,
a fact attributed by Bouley to the bites having been chiefly about the
head. The dog was destroying his kennel and biting his chain
ferociously. More new dogs developed rabies the following days. Nineteen
new dogs had been experimented upon: three died out of six bitten by a
rabid dog, six out of eight after intravenous inoculation, and five out
of five after subdural inoculation. Bouley thought that a few more
cases might occur, the period of incubation after bites being so
extremely irregular.
Bouley’s report was sent to the Minister of Public Instruction at the
beginning of August. “We submit to you to-day,” he wrote, “this report
on the first series of experiments that we have just witnessed, in order
that M. Pasteur may refer to it in the paper which he proposes to read
at the Copenhagen International Scientific Congress on these magnificent
results, which devolve so much credit on French Science and which give
it a fresh claim to the world’s gratitude.”
The Commission wished that a large kennel yard might be built, in order
that the duration of immunity in protected dogs might be timed, and that
other great problem solved, viz., whether it would be possible, through
the inoculation of attenuated virus, to defy the virus from bites.
By the Minister’s request, the Commission investigated the Meudon woods
in search of a favourable site; an excellent place was found in the
lower part of the Park, away from dwelling houses, easy to enclose and
presumably in no one’s way. But, when the inhabitants of Meudon heard of
this project, they protested vehemently, evidently terrified at the
thought of rabid dogs, however securely bound, in their peaceful
neighbourhood.
Another piece of ground was then suggested to Pasteur, near St. Cloud,
in the Park of Villeneuve l’Etang. Originally a State domain, this
property had been put up for sale, but had found no buyer, not being
suitable for parcelling out in small lots; the Bill was withdrawn which
allowed of its sale and the greater part of the domain was devoted by
the Ministry to Pasteur’s and his assistants’ experiments on the
prophylaxis of contagious diseases.
Pasteur, his mind full of ideas, started for the International Medical
Congress, which was now to take place at Copenhagen. Sixteen hundred
members arranged to attend, and nearly all of them found on arriving
that they were to be entertained in the houses of private individuals.
The Danes carry hospitality to the most generous excess; several of them
had been learning French for the last three years, the better to
entertain the French delegates. Pasteur’s son, then secretary of the
French Legation at Copenhagen, had often spoken to his father with
appreciative admiration of those Northerners, who hide deep enthusiasm
under apparent calmness, almost coldness.
The opening meeting took place on August 10 in the large hall of the
Palace of Industry; the King and Queen of Denmark and the King and Queen
of Greece were present at that impressive gathering. The President,
Professor Panum, welcomed the foreign members in the name of his
country; he proclaimed the neutrality of Science, adding that the three
official languages to be used during the Congress would be French,
English, and German. His own speech was entirely in French, “the
language which least divides us,” he said, “and which we are accustomed
to look upon as the most courteous in the world.”
The former president of the London Congress, Sir James Paget, emphasized
the scientific consequences of those triennial meetings, showing that,
thanks to them, nations may calculate the march of progress.
Virchow, in the name of Germany, developed the same idea.
Pasteur, representing France, showed again as he had done at Milan in
1878, in London in 1881, at Geneva in 1882, and quite recently in
Edinburgh, how much the scientist and the patriot were one in him.
“In the name of France,” said he, “I thank M. le Président for his words
of welcome.... By our presence in this Congress, we affirm the
neutrality of Science ... Science is of no country.... But if Science
has no country, the scientist must keep in mind all that may work
towards the glory of his country. In every great scientist will be found
a great patriot. The thought of adding to the greatness of his country
sustains him in his long efforts, and throws him into the difficult but
glorious scientific enterprises which bring about real and durable
conquests. Humanity then profits by those labours coming from various
directions....”
At the end of the meeting Pasteur was presented to the King. The Queen
of Denmark and the Queen of Greece, regardless of etiquette, walked
towards him, “a signal proof,” wrote a French contemporary, “of the
esteem in which our illustrious countryman is held at the Danish Court.”
Five general meetings were to give some of the scientists an opportunity
of expounding their views on subjects of universal interest. Pasteur was
asked to read the first paper; his audience consisted, besides the
members of the Congress, of many other men interested in scientific
things, who had come to hear him describe the steps by which he had made
such secure progress in the arduous question of hydrophobia. He began by
a declaration of war against the prejudice by which so many people
believe that rabies can occur spontaneously. Whatever the pathological,
physiological, or other conditions may be under which a dog or another
animal is placed, rabies never appears if the animal has not been bitten
or licked by another rabid animal; this is so truly the case that
hydrophobia is unknown in certain countries. In order to preserve a
whole land from the disease, it is sufficient that a law should, as in
Australia, compel every imported dog to be in quarantine for several
months; he would then, if bitten by a mad dog before his departure, have
ample time to die before infecting other animals. Norway and Lapland are
equally free from rabies, a few good prophylactic measures being
sufficient to avert the scourge.
It will be objected that there must have been a first rabid dog
originally. “That,” said Pasteur, “is a problem which cannot be solved
in the present state of knowledge, for it partakes of the great and
unknown mystery of the origin of life.”
The audience followed with an impassioned curiosity the history of the
stages followed by Pasteur on the road to his great discovery: the
preliminary experiments, the demonstration of the fact that the rabic
virus invades the nervous centres, the culture of the virus within
living animals, the attenuation of the rabic virus when passed from dogs
to monkeys, and simultaneously with this graduated attenuation, a
converse process by successive passages from rabbit to rabbit, the
possibility of obtaining in this way all the degrees of virulence, and
finally the acquired certainty of having obtained a preventive vaccine
against canine hydrophobia.
“Enthusiastic applause,” wrote the reporter of the _Journal des Débats_,
“greeted the conclusion of the indefatigable worker.”
In the course of one of the excursions arranged for the members of the
Congress, Pasteur had the pleasure of seeing his methods applied on a
large scale, not as in Italy to the progress of sericiculture, but to
that of the manufacture of beer. J. C. Jacobsen, a Danish citizen, whose
name was celebrated in the whole of Europe by his munificent donations
to science, had founded in 1847 the Carlsberg Brewery, now one of the
most important in the world; at least 200,000 hectolitres were now
produced every year by the Carlsberg Brewery and the Ny Carlsberg branch
of it, which was under the direction of Jacobsen’s son.
In 1879, Jacobsen, who was unknown to Pasteur, wrote to him, “I should
be very much obliged if you would allow me to order from M. Paul Dubois,
one of the great artists who do France so much credit, a marble bust of
yourself, which I desire to place in the Carlsberg laboratory in token
of the services rendered to chemistry, physiology, and beer-manufacture,
by your studies on fermentation, a foundation to all future progress in
the brewer’s trade.” Paul Dubois’ bust is a masterpiece: it is most
characteristic of Pasteur--the deep thoughtful far-away look in his
eyes, a somewhat stern expression on his powerful features.
Actuated, like his father, by a feeling of gratitude, the younger
Jacobsen had placed a bronze reproduction of this bust in a niche in the
wall of the brewery, at the entrance of the Pasteur Street, leading to
Ny Carlsberg.
This visit to the brewery was an object lesson to the members of the
Congress, who were magnificently entertained by Jacobsen and his son; no
better demonstration was ever made of the services which industry may
receive from science. In the great laboratory, the physiologist Hansen
had succeeded in finding differences in yeast; he had just separated
from each other three kinds of yeast, each producing beer with a
different flavour.
The French scientists were delighted with the practical sense and
delicate feelings of the Danish people. Though they had gone through
bitter trials in 1864, though France, England, and Russia had
countenanced the unrighteous invasion, in the face of the old treaties
which guaranteed to Denmark the possession of Schleswig, the diminished
and impoverished nation had not given vent to barren recriminations or
declamatory protests. Proudly and silently sorrowing, the Danes had
preserved their respect for the past, faith in justice and the cult of
their great men. It is a strange thing that Shakespeare should have
chosen that land of good sense and well-balanced reason for the
surroundings of his mysterious hero, of all men the most haunted by the
maddening enigma of destiny.
Elsinore is but a short distance from Copenhagen, and no member of the
Congress, especially among the English section, could have made up his
mind to leave Denmark without visiting Hamlet’s home.
A Transport Company organized the visit to Elsinore for a day when the
Congress had arranged to have a complete holiday. Five steamers, gay
with flags, were provided for the thousand medical men and their
families, and accomplished the two hours’ crossing to Elsinore on a
lovely, clear day, with an absolutely calm sea. The scientific tourists
landed at the foot of the old Kronborg Castle, ready for the lunch which
was served out to them and which proved barely sufficient for their
appetites; there was not quite enough bread for the Frenchmen,
proverbially bread-eaters, and the water, running a little short, had to
be supplemented with champagne.
Some of the visitors returned from a neighbouring wood, where they had
been to see the stones of the supposed tomb of Hamlet, disappointed at
having looked in vain for Ophelia’s stream and for the willow tree which
heard her sing her last song, her hands full of flowers. Evidently this
place was but an imaginary scenery given by Shakespeare to the drama
which stands like a point of interrogation before the mystery of human
life; but his life-giving art has for ever made of Elsinore the place
where Hamlet lived and suffered.
Pasteur, to whom the Danish character, in its strength and simplicity,
proved singularly attractive, remained in Copenhagen for some time after
the Congress was over. He had much pleasure in visiting the Thorwaldsen
Museum. Copenhagen, after showering honours on the great artist during
his lifetime, has continued to worship him after his death. Every
statue, every plaster cast, is preserved in that Museum with
extraordinary care. Thorwaldsen himself lies in the midst of his
works--his simple stone grave, covered with graceful ivy, is in one of
the courtyards of the Museum.
* * * * *
Pasteur went on to Arbois from Copenhagen. The laboratory he had built
there not being large enough to take in rabid dogs, he dictated from his
study the experiments to be carried out in Paris; his carefully kept
notebooks enabled him to know exactly how things were going on. His
nephew, Adrien Loir, now a curator in the laboratory of Rue d’Ulm, had
gladly given up his holidays and remained in Paris with the faithful
Eugène Viala. This excellent assistant had come to Paris from Alais in
1871, at the request of Pasteur, who knew his family. Viala was then
only twelve years old and could barely read and write. Pasteur sent him
to an evening school and himself helped him with his studies; the boy
was very intelligent and willing to learn. He became most useful to
Pasteur, who, in 1885, was glad to let him undertake a great deal of the
laboratory work, under the guidance of M. Roux; he was ultimately
entrusted with all the trephining operations on dogs, rabbits, and
guinea-pigs.
The letters written to him by Pasteur in 1884 show the exact point
reached at that moment by the investigations on hydrophobia. Many people
already thought those studies advanced enough to allow the method of
treatment to be applied to man.
Pasteur wrote to Viala on September 19, “Tell M. Adrien (Loir) to send
the following telegram: ‘Surgeon Symonds, Oxford, England. Operation on
man still impossible. No possibility at present of sending attenuated
virus.’ See MM. Bourrel and Béraud, procure a dog which has died of
street-rabies, and use its medulla to inoculate a new monkey, two
guinea-pigs and two rabbits.... I am afraid Nocard’s dog cannot have
been rabid; even if you were sure that he was, you had better try those
tests again.
“Since M. Bourrel says he has several mad dogs at present, you might
take two couple of new dogs to his kennels; when he has a good biting
dog, he can have a pair of our dogs bitten, after which you will treat
one of them so as to make him refractory (carefully taking note of the
time elapsed between the bites and the beginning of the treatment). Mind
you keep notes of every new experiment undertaken, and write to me every
other day at least.”
Pasteur pondered on the means of extinguishing hydrophobia or of merely
diminishing its frequency. Could dogs be vaccinated? There are 100,000
dogs in Paris, about 2,500,000 more in the provinces: vaccination
necessitates several preventive inoculations; innumerable kennels would
have to be built for the purpose, to say nothing of the expense of
keeping the dogs and of providing a trained staff capable of performing
the difficult and dangerous operations. And, as M. Nocard truly
remarked, where were rabbits to be found in sufficient number for the
vaccine emulsions?
Optional vaccination did not seem more practicable; it could only be
worked on a very restricted scale and was therefore of very little use
in a general way.
The main question was the possibility of preventing hydrophobia from
occurring in a human being, previously bitten by a rabid dog.
The Emperor of Brazil, who took the greatest interest in the doings of
the Ecole Normale laboratory, having written to Pasteur asking when the
preventive treatment could be applied to man, Pasteur answered as
follows--
“_September 22._
“SIRE--Baron Itajuba, the Minister for Brazil, has handed me the letter
which Your Majesty has done me the honour of writing on August 21. The
Academy welcomed with unanimous sympathy your tribute to the memory of
our illustrious colleague, M. Dumas; it will listen with similar
pleasure to the words of regret which you desire me to express on the
subject of M. Wurtz’s premature death.
“Your Majesty is kind enough to mention my studies on hydrophobia; they
are making good and uninterrupted progress. I consider, however, that it
will take me nearly two years more to bring them to a happy issue....
“What I want to do is to obtain prophylaxis of rabies _after_ bites.
“Until now I have not dared to attempt anything on men, in spite of my
own confidence in the result and the numerous opportunities afforded to
me since my last reading at the Academy of Sciences. I fear too much
that a failure might compromise the future, and I want first to
accumulate successful cases on animals. Things in that direction are
going very well indeed; I already have several examples of dogs made
refractory after a rabietic bite. I take two dogs, cause them both to be
bitten by a mad dog; I vaccinate the one and leave the other without any
treatment: the latter dies and the first remains perfectly well.
“But even when I shall have multiplied examples of the prophylaxis of
rabies in dogs, I think my hand will tremble when I go on to Mankind. It
is here that the high and powerful initiative of the head of a State
might intervene for the good of humanity. If I were a King, an Emperor,
or even the President of a Republic, this is how I should exercise my
right of pardoning criminals condemned to death. I should invite the
counsel of a condemned man, on the eve of the day fixed for his
execution, to choose between certain death and an experiment which would
consist in several preventive inoculations of rabic virus, in order to
make the subject’s constitution refractory to rabies. If he survived
this experiment--and I am convinced that he would--his life would be
saved and his punishment commuted to a lifelong surveillance, as a
guarantee towards that society which had condemned him.
“All condemned men would accept these conditions, death being their only
terror.
“This brings me to the question of cholera, of which Your Majesty also
has the kindness to speak to me. Neither Dr. Koch nor Drs. Straus and
Roux have succeeded in giving cholera to animals, and therefore great
uncertainty prevails regarding the bacillus to which Dr. Koch attributes
the causation of cholera. It ought to be possible to try and communicate
cholera to criminals condemned to death, by the injection of cultures of
that bacillus. When the disease declared itself, a test could be made of
the remedies which are counselled as apparently most efficacious.
“I attach so much importance to these measures, that, if Your Majesty
shared my views, I should willingly come to Rio Janeiro, notwithstanding
my age and the state of my health, in order to undertake such studies on
the prophylaxis of hydrophobia and the contagion of cholera and its
remedies.
“I am, with profound respect, Your Majesty’s humble and obedient
servant.”
In other times, the right of pardon could be exercised in the form of a
chance of life offered to a criminal lending himself to an experiment.
Louis XVI, having admired a fire balloon rising above Versailles,
thought of proposing to two condemned men that they should attempt to go
up in one. But Pilâtre des Roziers, whose ambition it was to be the
first aëronaut, was indignant at the thought that “vile criminals should
be the first to rise up in the air.” He won his cause, and in November,
1783, he organized an ascent at the Muette which lasted twenty minutes.
In England, in the eighteenth century, before Jenner’s discovery,
successful attempts had been made at the direct inoculation of
small-pox. In some historical and medical _Researches on Vaccine_,
published in 1803, Husson relates that the King of England, wishing to
have the members of his family inoculated, began by having the method
tried on six criminals condemned to death; they were all saved, and the
Royal Family submitted to inoculation.
There is undoubtedly a beautiful aspect of that idea of utilizing the
fate of a criminal for the cause of Humanity. But in our modern laws no
such liberty is left to Justice, which has no power to invent new
punishments, or to enter into a bargain with a condemned criminal.
Before his departure from Arbois, Pasteur encountered fresh and
unforeseen obstacles. The successful opposition of the inhabitants of
Meudon had inspired those of St. Cloud, Ville d’Avray, Vaucresson,
Marnes, and Garches with the idea of resisting in their turn the
installation of Pasteur’s kennels at Villeneuve l’Etang. People spoke of
public danger, of children exposed to meet ferocious rabid dogs
wandering loose about the park, of popular Sundays spoilt, picnickers
disturbed, etc., etc.
A former pupil of Pasteur’s at the Strasburg Faculty, M. Christen, now a
Town Councillor at Vaucresson, warned Pasteur of all this excitement,
adding that he personally was ready to do his best to calm the terrors
of his townspeople.
Pasteur answered, thanking him for his efforts. “...I shall be back in
Paris on October 24, and on the morning of the twenty-fifth and
following days I shall be pleased to see any one desiring information on
the subject.... But you may at once assure your frightened neighbours,
Sir, that there will be no mad dogs at Villeneuve l’Etang, but only dogs
made refractory to rabies. Not having enough room in my laboratory, I am
actually obliged to quarter on various veterinary surgeons those dogs,
which I should like to enclose in covered kennels, quite safely secured,
you may be sure.”
Pasteur, writing about this to his son, could not help saying, “Months
of fine weather have been wasted! This will keep my plans back almost a
year.”
Little by little, in spite of the opposition which burst out now and
again, calm was again re-established. French good sense and appreciation
of great things got the better of the struggle; in January, 1885,
Pasteur was able to go to Villeneuve l’Etang to superintend the
arrangements. The old stables were turned into an immense kennel, paved
with asphalte. A wide passage went from one end to the other, on each
side of which accommodation for sixty dogs was arranged behind a double
barrier of wire netting.
The subject of hydrophobia goes back to the remotest antiquity; one of
Homer’s warriors calls Hector a mad dog. The supposed allusions to it to
be found in Hippocrates are of the vaguest, but Aristotle is quite
explicit when speaking of canine rabies and of its transmission from one
animal to the other through bites. He gives expression, however, to the
singular opinion that man is not subject to it. More than three hundred
years later we come to Celsus, who describes this disease, unknown or
unnoticed until then. “The patient,” said Celsus, “is tortured at the
same time by thirst and by an invincible repulsion towards water.” He
counselled cauterization of the wound with a red-hot iron and also with
various caustics and corrosives.
Pliny the Elder, a worthy precursor of village quacks, recommended the
livers of mad dogs as a cure; it was not a successful one. Galen, who
opposed this, had a no less singular recipe, a compound of cray-fish
eyes. Later, the shrine of St. Hubert in Belgium was credited with
miraculous cures; this superstition is still extant.
Sea bathing, unknown in France until the reign of Louis XIV, became a
fashionable cure for hydrophobia, Dieppe sands being supposed to offer
wonderful curing properties.
In 1780 a prize was offered for the best method of treating hydrophobia,
and won by a pamphlet entitled _Dissertation sur la Rage_, written by a
surgeon-major of the name of Le Roux.
This very sensible treatise concluded by recommending cauterization, now
long forgotten, instead of the various quack remedies which had so long
been in vogue, and the use of butter of antimony.
Le Roux did not allude in his paper to certain tenacious and cruel
prejudices, which had caused several hydrophobic persons, or persons
merely suspected of hydroprobia, to be killed like wild beasts, shot,
poisoned, strangled, or suffocated.
It was supposed in some places that hydrophobia could be transmitted
through the mere contact of the saliva or even by the breath of the
victims; people who had been bitten were in terror of what might be done
to them. A girl, bitten by a mad dog and taken to the Hôtel Dieu
Hospital on May 8, 1780, begged that she might not be suffocated!
Those dreadful occurrences must have been only too frequent, for, in
1810, a philosopher asked the Government to enact a Bill in the
following terms: “It is forbidden, under pain of death, to strangle,
suffocate, bleed to death, or in any other way murder individuals
suffering from rabies, hydrophobia, or any disease causing fits,
convulsions, furious and dangerous madness; all necessary precautions
against them being taken by families or public authorities.”
In 1819, newspapers related the death of an unfortunate hydrophobe,
smothered between two mattresses; it was said à propos of this murder
that “it is the doctor’s duty to repeat that this disease cannot be
transmitted from man to man, and that there is therefore no danger in
nursing hydrophobia patients.” Though old and fantastic remedies were
still in vogue in remote country places, cauterization was the most
frequently employed; if the wounds were somewhat deep, it was
recommended to use long, sharp and pointed needles, and to push them
well in, even if the wound was on the face.
One of Pasteur’s childish recollections (it happened in October, 1831)
was the impression of terror produced throughout the Jura by the advent
of a rabid wolf who went biting men and beasts on his way. Pasteur had
seen an Arboisian of the name of Nicole being cauterized with a red-hot
iron at the smithy near his father’s house. The persons who had been
bitten on the hands and head succumbed to hydrophobia, some of them
amidst horrible sufferings; there were eight victims in the immediate
neighbourhood. Nicole was saved. For years the whole region remained in
dread of that mad wolf.
The long period of incubation encouraged people to hope that some
preventive means might be found, instead of the painful operation of
cauterization; some doctors attempted inoculating another poison, a
viper’s venom for instance, to neutralize the rabic virus--needless to
say with fatal results. In 1852 a reward was promised by the Government
to the finder of a remedy against hydrophobia; all the old quackeries
came to light again, even Galen’s remedy of cray-fish eyes!
Bouchardat, who had to report to the Academy on these remedies,
considered them of no value whatever; his conclusion was that
cauterization was the only prophylactic treatment of hydrophobia.
Such was also Bouley’s opinion, eighteen years later, when he wrote that
the object to keep in view was the quickest possible destruction of the
tissues touched by rabietic saliva. Failing an iron heated to a light
red heat, or the sprinkling of gunpowder over the wound and setting a
match to it, he recommended caustics, such as nitric acid, sulphuric
acid, hydrochloric acid, potassa fusa, butter of antimony, corrosive
sublimate, and nitrate of silver.
Thus, after centuries had passed, and numberless remedies had been
tried, no progress had been made, and nothing better had been found than
cauterization, as indicated by Celsus in the first century.
* * * * *
As to the origin of rabies, it remained unknown and was erroneously
attributed to divers causes. Spontaneity was still believed in. Bouley
himself did not absolutely reject the idea of it, for he said in 1870:
“In the immense majority of cases, this disease proceeds from contagion;
out of 1,000 rabid dogs, 999 at least owe their condition to inoculation
by a bite.”
Pasteur was anxious to uproot this fallacy, as also another very serious
error, vigorously opposed by Bouley, by M. Nocard, and by another
veterinary surgeon in a _Manual on Rabies_, published in 1882, and still
as tenacious as most prejudices, viz., that the word hydrophobia is
synonymous with rabies. The rabid dog is _not_ hydrophobe, he does _not_
abhor water. The word is applicable to rabid human beings, but is false
concerning rabid dogs.
Many people in the country, constantly seeing Pasteur’s name associated
with the word rabies, fancied that he was a consulting veterinary
surgeon, and pestered him with letters full of questions. What was to be
done to a dog whose manner seemed strange, though there was no evidence
of a suspicious bite? Should he be shot? “No,” answered Pasteur, “shut
him up securely, and he will soon die if he is really mad.” Some dog
owners hesitated to destroy a dog manifestly bitten by a mad dog. “It is
such a good dog!” “The law is absolute,” answered Pasteur; “every dog
bitten by a mad dog must be destroyed at once.” And it irritated him
that village mayors should close their eyes to the non-observance of the
law, and thus contribute to a recrudescence of rabies.
Pasteur wasted his precious time answering all those letters. On March
28, 1885, he wrote to his friend Jules Vercel--
“Alas! we shall not be able to go to Arbois for Easter; I shall be busy
for some time settling down, or rather settling my dogs down at
Villeneuve l’Etang. I also have some new experiments on rabies on hand
which will take some months. I am demonstrating this year that dogs can
be vaccinated, or made refractory to rabies _after_ they have been
bitten by mad dogs.
“I have not yet dared to treat human beings after bites from rabid dogs;
but the time is not far off, and I am much inclined to begin by
myself--inoculating myself with rabies, and then arresting the
consequences; for I am beginning to feel very sure of my results.”
Pasteur gave more details three days later, in a letter to his son, then
Secretary of the French Embassy at the Quirinal--
“The experiments before the Rabies Commission were resumed on March 10;
they are now being carried out, and the Commission has already held six
sittings; the seventh will take place to-day.
“As I only submit to it results which I look upon as acquired, this
gives me a surplus of work to do; for those control experiments are
added to those I am now carrying out. For I am continuing my researches,
trying to discover new principles, and hardening myself by habit and by
increased conviction in order to attempt preventive inoculations on man
after a bite.
“The Commission’s experiments have led to no result so far, for, as you
know, weeks have to pass before any results occur. But no untoward
incident has occurred up to now; and if all continues equally well, the
Commission’s second report will be as favorable as that of last year,
which left nothing to be desired.
“I am equally satisfied with my new experiments in this difficult study.
Perhaps practical application on a large scale may not be far off....”
In May, everything at Villeneuve l’Etang was ready for the reception of
sixty dogs. Fifty of them, already made refractory to bites or rabic
inoculation, were successively accommodated in the immense kennel, where
each had his cell and his experiment number. They had been made
refractory by being inoculated with fragments of medulla, which had hung
for a fortnight in a phial, and of which the virulence was extinguished,
after which further inoculations had been made, gradually increasing in
virulence until the highest degree of it had again been reached.
All those dogs, which were to be periodically taken back to Paris for
inoculations or bite tests, in order to see what was the duration of
the immunity conferred, were stray dogs picked up by the police. They
were of various breeds, and showed every variety of character, some of
them gentle and affectionate, others vicious and growling, some
confiding, some shrinking, as if the recollection of chloroform and the
laboratory was disagreeable to them. They showed some natural impatience
of their enforced captivity, only interrupted by a short daily run. One
of them, however, was promoted to the post of house-dog, and loosened
every night; he excited much envy among his congeners. The dogs were
very well cared for by a retired _gendarme_, an excellent man of the
name of Pernin.
A lover of animals might have drawn an interesting contrast between the
fate of those laboratory dogs, living and dying for the good of
humanity, and that of the dogs buried in the neighbouring dogs’ cemetery
at Bagatelle, founded by Sir Richard Wallace, the great English
philanthropist. Here lay toy dogs, lap dogs, drawing-room dogs,
cherished and coddled during their useless lives, and luxuriously buried
after their useless deaths, while the dead bodies of the others went to
the knacker’s yard.
Rabbit hutches and guinea-pig cages leaned against the dogs’ palace.
Pasteur, having seen to the comfort of his animals, now thought of
himself; it was frequently necessary that he should come to spend two or
three days at Villeneuve l’Etang. The official architect thought of
repairing part of the little palace of Villeneuve, which was in a very
bad state of decay. But Pasteur preferred to have some rooms near the
stables put into repair, which had formerly been used for
non-commissioned officers of the Cent Gardes; there was less to do to
them, and the position was convenient. The roof, windows, and doors were
renovated, and some cheap paper hung on the walls inside. “This is
certainly not luxurious!” exclaimed an astonished millionaire, who came
to see Pasteur one day on his way to his own splendid villa at Marly.
On May 29 Pasteur wrote to his son--
“I thought I should have done with rabies by the end of April; I must
postpone my hopes till the end of July. Yet I have not remained
stationary; but, in these difficult studies, one is far from the goal as
long as the last word, the last decisive proof is not acquired. What I
aspire to is the possibility of treating a man after a bite with no fear
of accidents.
“I have never had so many subjects of experiment on hand--sixty dogs at
Villeneuve l’Etang, forty at Rollin, ten at Frégis’, fifteen at
Bourrel’s, and I deplore having no more kennels at my disposal.
“What do you say of the Rue Pasteur in the large city of Lille? The news
has given me very great pleasure.”
What Pasteur briefly called “Rollin” in this letter was the former
_Lycée Rollin_, the old buildings of which had been transformed into
outhouses for his laboratory. Large cages had been set up in the old
courtyard, and the place was like a farm, with its population of hens,
rabbits, and guinea-pigs.
Two series of experiments were being carried out on those 125 dogs. The
first consisted in making dogs refractory to rabies by preventive
inoculations; the second in preventing the onset of rabies in dogs
bitten or subjected to inoculation.