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.