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 Fran?aise, 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{391} 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 H?pital 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{392} 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.{393}
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{394} 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 an?sthesia. 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{395} 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{396} 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{397} 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{398} 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{399} 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{400} 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{401} 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 l............