The life of Pasteur

by René Vallery-Radot

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.