Hydrophobia: An Account of M. Pasteur’s System (Chapter 1)

A SHORT DESCRIPTION OF HYDROPHOBIA FROM THE EARLIEST TIMES DOWN TO THE END OF 1880

Seven years ago, in 1880, rabies or hydrophobia had already been known, dreaded, and studied, in Europe, for more than 2,000 years. Countless authors had written upon it, beginning, so far we can ascertain, with Democritus in the fifth century B.C., down to and including many living men of mark. Yet all our knowledge of it could be summarised in a very few pages. The disease at first circumscribed, to all appearances, within a few limited geographical areas, had, with increasing facilities of intercommunication between nations, gradually spread to nearly every country of the globe, irrespective of latitude or longitude. 1 : raged, with varying intensity, at all seasons of the year, and often assumed the proportions of an epidemic. It. was occasionally met with in herbivorous animals : the ox, the horse, the sheep ; in swine and in birds more rarely ; commonest of all in the carnivora : the cat, the fox, the jackal, the wolf, and the dog. It always originated in the latter — in what manner, spontaneously or otherwise, was not and is not yet known — and spread from them by contact and direct inoculation, by a bite oftenest, to the herbivora and to man.

The poison deposited in the wound lay incubative for a period varying from a few days to several months, and possibly even to several years. Then, having silently crept up and invaded the nervous centres, it suddenly broke out into a train of terrific symptoms, uniformly terminating in death about the fourth day, by asphyxia or by syncope, sudden stoppage of the heart. During that long and hopeless agony the patient’s intellect kept clear and even brightened, and his affective sentiments became more vivid than ever, circumstances which all tended to add to the horror of the picture. Indeed, the very name of the scourge evoked in the popular mind in an unequalled degree the sombre image of fate, mysterious, awful, and inevitable.

Not all died who had been bitten by rabid animals, but only a certain varying proportion, as we shall see later on by quoting a few figures. Those who escaped death still had to live for years with a feeling as of the sword of Damocles ever hanging over their heads, an uncertainty of life which led not a few to commit suicide.

As in all similar cases, everything had been thought of and used as remedial agents. In particular shall we refer to blood-letting ad deliquiu to exposure to a high temperature and excessive sweating, to mercury (Daniel Johnson, 1829), curare, electricity and revulsion all along the spinal column. Unfortunately, however, in the vast majority of re- ported cases of so-called cure by those or other means the diagnosis is far from unimpeachable. But on the other hand there is no doubt as to the efficiency of the preventive treatment first pro- pounded by Celsus in the first century of our era, and than which none better had been devised up to our own day. He recommended, to sum up, the use, immediately after the bite, of free suction of the wound, then its thorough cauterisation by means of the hot iron. But seldom only could this treatment, in actual practice, be applied with sufficient boldness and thoroughness, or soon enough after the accident. And thus the percent- age of deaths still ran very high.

Police regulations also, by diminishing the total number of dogs in a country, and by enforcing the better supervision of those that remained, contributed efficiently to lessen the number of casualties, as evidenced in the cases of Germany and of the Scandinavian peninsula, where the number of deaths from hydrophobia has gradually gone down from year to year until it is at present only counted by units.

And yet, withal, small epidemics were ever and anon starting up afresh, and the malady retained intact all its old terrors. As the late Professor Bouley justly remarked, any positive knowledge we had gained in the general study of hydrophobia was limited to its causation, morbid anatomy, and history. The therapeutic phase had not dawned yet, and many thoughtful authors considered it as lying indefinitely beyond our reach. Experimental researches into the nature, the seat, and the proper- ties of the virus of rabies had often been under- taken, but had only yielded very scanty results.

Somewhere about the year 1870 they were resumed with increased accuracy, not uninfluenced certainly by the lessons already taught by Pasteur on the micro-organisms and their importance in pathology. Hallier, Klebs, and many others be- lieved they had found the microbe of rabies. More recently Fol, of Geneva, and Dowdeswell, of London, announced a similar discovery. But the question is still unsettled and the microbe to be isolated. Numerous experimenters, in every country, tried inoculative experiments, and accumulated interesting although too often contradictory facts. Paul Bert ascertained that the substance of the salivary glands was always virulent, as also, to a high degree, I bronchial mucus. Nocard, of Alfort, dialysed the pure saliva of rabid dogs, and showed that its solid elements were always virulent and reproduced the disease when injected into healthy animals, while the liquid portion, similarly injected, remained inactive.

Brown- Sequard and Duboue insisted on the importance of the nervous element in hydrophobia, and the former calls it ‘an ascending neuritis.’ Magendie had already discovered that dogs could be rendered refractory to rabies as produced by dog-bites. He got a first mad dog to bite a second healthy one ; this in turn when mad a third one, and so on. The periods of incubation became longer and longer, and the fourth or fifth dog failed to take the disease. That interesting fact remained useless and was soon completely forgotten. Galtier, of Lyons, confirmed by Bouchard and others, showed that the lymphatic fluid was constantly virulent ; the blood had long before been proved to be innocuous when injected into animals. The same author reproduced the malady in rabbits by inserting small pieces of the brain and medulla of rabid dogs under their skin. He for the first time studied hydrophobia in the rabbit, and found that : ‘ The rabbit in which rabies is developing itself remains quiet and low-spirited, often sleepy, more rarely agitated and frightened by the slightest sound. From the very outset there is well-marked weakness, sometimes localised in the first instance to the lumbar region, the hind limbs, and even the cervical region ; soon it creeps and invades the whole body, and then it is gradually replaced by paralysis. All the movements of the animal are difficult, irregular, ill-defined, and soon become quite impossible. It walks in a sort of crawling way, the fore-limbs dragging the hind ones, which have become quite helpless. After the first few hours it is almost always possible to notice a series of contractions, sudden, convulsive, and frequent, in the limbs, the trunk, the cervical region, the muscles of mastication ; in many cases there is also present an unceasing chewing movement. A General sensibility is gradually dulled and is some- times quite lost, so that it becomes possible to thrust a pin into the animal without giving rise to any reaction on its part. Sight is lost or perverted, the eye becomes gradually less and less sensitive, the conjunctiva is congested, and the cornea, the aqueous and vitreous humours, dull and cloudy. Some of the animals groan and utter loud cries of distress if suddenly displaced or taken up by the ears or legs.

‘ The sense of taste appears to be also perverted, for they are seen swallowing fragments of straw and of fecal matter, and to lick the floor of their cage.

‘ As a rule they do not try to bite. In one case, however, the animal had a tendency to do so, in particular when worried. There is an abundant flow of saliva. Thirst and hunger have disappeared, or, when the subject tries still to drink or to eat, there soon supervenes a moment when deglutition is quite impossible.

‘ The circulation of the blood is irregular and the pulse beats from 109 to 200 a minute.

‘ The urine is scanty or is only expelled at the time of death, so that the bladder is found after death to be at times full, at other times empty.’ He concludes :

1. Dog-madness can be transferred to the rabbit, which thus becomes a convenient and safe reagent enabling us to find out the virulence or non-viru- lence of various fluids taken from rabid animals. I have often used it hi that capacity for the study of the different sorts of saliva (parotidean, sub- maxillary, &c.) and of a number of other liquids taken from rabid dogs, sheep, and rabbits.
2. Rabbit-madness can be transferred to other animals of the same species ; but I cannot as yet say whether the rabies-virus of the rabbit is equall} 7 virulent with that of the dog.
3. The predominating symptoms of rabies in the rabbit are of the paralytic and convulsive types.
4. The rabbit can survive from a few hours to one, two, three, and even four days, after the symptoms of rabies have clearly manifested them- selves.

‘ 5. Not only is the rabbit susceptible of taking rabies and of surviving a certain time after the malady has broken out, but it is also a constant fact, judging from my experiments, that the period of incubation is shorter in this animal than in any other one ; and this, I repeat, makes of it a most valuable reagent, enabling us to ascertain the viru- lence of this or that liquid.’

He then quotes twenty-five cases of exp mental rabies in the rabbit giving an average in- cubation of eighteen days ; also an experiment with salicylic acid, proving that that substaiic quite inefficient — used by the hypodermic way— in preventing the development of the disease ; ami finally, he states that the saliva taken from a live mad dog, and kept mixed with water, was still virulent after twenty-four, and even thirty-six hours. “We may now give a short list of the main signs by which it is possible to make the diagnosis of rabies in the dog. The disease shows itself in one of two forms : —

1. Furious or delirious madness; by far the commonest.
2. Dumb madness. In the furious form note :(a) A change in the usual ways and habits of the animal. He becomes dull and voiceless, crouch is down in dark and quiet corners. He tries to sleep but is often disturbed in his sleep as if by painful dreams and delusions; he rises and walks about, then lies down again. He is in a continuous state of restlessness and agitation. In some cases he is not agitated, but sleepy and careless of whatever is going on near him. If disturbed, he growls and shows no inclination to stir.In either case he still obeys the voice of his master and has no tendency to bite yet.

   The agitation increases. In his kennel he piles up the straw, lays his chest on it, then rises in anger and scatters the litter about. In apartments he tears and tosses the cushions, carpets, &c. Oc- casionally there is a manifestation of intense and unwonted attachment to some other animal, or to the people of the household ; or he is seen constantly to lick cold objects (Delabere-Blaine). He is haunted by visions and hallucinations, he barks, snaps, and growls at imaginary beings (Youatt). But still he knows and obeys the voice of his master and has no tendency to bite him. Nevertheless, his saliva is already virulent, and his caresses dangerous. The saliva is virulent eight days, and possibly longer, before the disease is plainly evident.

   Often, too, even in this early stage, dogs will bite a stick thrust at them. So also will they often bite people when worried but slightly.

   (b) The mad dog has no horror of or repulsion for water. On the contrary, at all periods of the malady he drinks eagerly or tries to drink. When he fails to swallow the water it is only owing to spasmodic contraction of his throat.

   The appetite may be at first and for a short time increased. But very soon it diminishes and is quite lost and replaced by marked disgust for all kinds of ordinary food and a thorough perversion of the sense of taste. He tears everything that he meets, carpets, trees, grass, and swallows fragments of anything, including his own excreta, urine, earth, bits of straw, chips of wood, anything. As a con- sequence of this there is not unfrequently present a certain quantity of blood in the vomited matter, vomiting being a common phenomenon at this stage.

   The saliva of the mad dog is not usually over-abun- dant, and may even be quite normal in quantity.

   (c) The bark of the mad dog is quite character- istic, and is never forgotten when it has been heard once. Bouley says of it : ‘ Instead of bursting out with its usual sonority and of being made up of a succession of notes equal in duration and in in- tensity, it is hoarse, veiled, lower in tone, and after a first full-mouthed bark there follows immediately a succession of five, six, or eight howls coming far back from the throat and during which the jaws are never completely closed, as they are ordinarily after each bark.’ It is not unlike the voice of dogs chasing a hare ; it is something intermediate between a bark and a howl, made up of the two, with something more added, strange and sinister.

   (d) The sight of another dog at once and almost invariably puts the mad dog in a fit of passion. This is, therefore, an easy and valuable test method. The same effect is produced by the sight of a dog on all rabid animals, to whatever species they belong, including the sheep. Man alone perhaps constitutes an exception to the rule.

   Renault quotes the case of a horse rendered rabid by inoculation from a sheep. This animal when shown a dog remained careless, but when a sheep — a healthy one — was brought in, he grew quite furious and tore it to pieces. This case stands solitary. This symptom has, of course, most value in the case of clogs which are naturally tame and non-aggressive in disposition.

   The mad dog is analgesic, i.e., his general sensi- bility is blunted to a considerable degree. He now seems to feel only the very intensest pains. He no longer expresses pain by the usual nasal sound or the sharp cry which is so familiar. He can be beaten, pricked, and even slightly burnt, without stirring and without uttering any sound at all. If severely burnt he moves to another place, hut still remains mute although the face becomes expressive of pain. This fact explains the cases in winch dogs which were later on ascertained to be mad were seen to bite and tear at their own limbs and bodies.

   There is often present a certain degree of hyper- esthesia at the seat of the bite, if the dog has been bitten by a rabid animal, shown by his constant rubbing, licking, or biting of the part, the leg, the ear, on which, on examination, there is found nothing capable of explaining the facts observed, except, perhaps, a small cicatrix. The same phenomenon is often met with in other animals and in man, shortly before the onset of the disease.

   The sexual instincts also are greatly excited and increased.

   (e) Confirmed Rabies. — In a few cases the animal remains tame and unaggressive to the end, but as a rule he is in a state of delirious rage about which there can be no mistake as to its significance.

   He bites and tears at everything thrown at him if he is chained or in a cage. He attacks furiously all animals that come within reach, later on man also, more rarely his own master. The pupils arc dilated and the whole face bears an expression of terrible fierceness. Whilst biting and tearing he is always silent, unlike the non-rabid dog who fights and barks all at once. He always, in preference, attacks animals rather than man. He often leaves home and wanders far away. From a distance he shows nothing peculiar, has his ordinary gait, and his tail instead of being held between the legs, as so often asserted, is kept high and wagging.

   Later on, when tired, he walks with a tottering- gait, the head low, the tongue hanging out of the mouth, covered with blood and dust, and the tail falling helpless. His sight, as well as his other senses, is now dulled, and he is much less dangerous. Still he can bite, however, and is to be dreaded. After wandering about for a few hours, or it may be days, he often comes home again. At last, on the fifth day or thereabout, emaciated and worn out by repeated attacks of rightful fury and the want of food, paralysed in the hind-quarters, he dies from sheer exhaustion and asphyxia.

Dumb-madness. — Inoculations of this form of madness often reproduce the disease in its furious form, and vice versa, showing that the two are only different manifestations of one and the same malady. The stages a, b, c, are very much the same as in the furious type, perhaps less marked. Then, (d, e), the voice is quite lost, and even in the first stages it is more exclusively a howl, with no admixture of the hark. The mouth is constantly gaping, owing to the paralysis of the lower jaw ; the eyes open, without expression, constantly fixed in the same direction. The predominant symptoms are muscular weakness and cerebral depression. The animal is constantly lying down or sleepy, has neither the will nor the power to bite. His saliva is quite as virulent as in the other form.

In the immense majority of cases hydrophobia in the dog ends fatally ; a few exceptional cases are, however, on record when the disease, spontaneously or under the influence of medical treatment — namely, submersion in cold water until asphyxia is nearly complete, bleeding, enemata — gradually dis- appeared and a cure was effected.

On post-mortem examination the main points of interest are the following : dark blue and almost black colour of the tongue and of the whole mucous membrane of the mouth. In the stomach sonic discoloration of the lining membrane, presence often of a black liquid, like coffee dregs ; presence also of a collection of heterogeneous materials not usually swallowed by healthy dogs : hairs, straw, wood, coal, ashes, bits of carpeting, earth, &c. Blaine, Youatt, and others note this last sign in almost every case ; Bruckmiiller, of Vienna, only in fifty- four per cent, of his observations.

Congestion of the lungs, of the central nervous system (Bruckmiiller), extreme retraction of the bladder, are frequent but by no means constant or characteristic phenomena. The duration of incubation is less than two months in more than eighty per cent, of the cases ; very seldom longer than six months ; eleven months in one case related by Youatt.

In the cat many of the symptoms of rabies forcibly recall to mind those we have already noted in the dog. It will therefore not be necessary to refer to them in detail, and it will be enough to add that this animal, like the wolf, very generally directs his attacks to the head and face. Wounds on those regions are particularly dangerous, as pointed out by all statistics.

The general precautionary measures best cal- culated to diminish the number of hydrophobic animals and to increase the security of the public from that terrible disease, are thus summed up by Bouley : —

1. Declaration to the authorities, by the pro- prietor, of any distemper in his animals, which can in any way be suspected of being rabies.
2. Immediate locking up of such animals, by the proprietor himself.
3. Destruction by the police of all rabid animals, and of all others bitten by such.
4. Compulsory locking up, under police super- vision, and for a period of time not less than eight months, of all animals suspected of having been bitten by a rabid animal. Immediate destruction is always to be preferred, however.
5. All dogs constantly to wear round their neck a collar with their police number and the name and address of the proprietor.
6. All dogs left free to wander about, to wear an efficient muzzle.
7. All dogs to be stopped which do not fulfil the preceding two conditions.
8. Destruction of all dogs so stopped, after the lapse of a certain time, if not claimed. Such animals ought never to be sold or bought.
9. Male animals to be taxed more heavily than females.
10. Blunting of the teeth, so as to render the bites less virulent, like those of herbivorous animals whose teeth oftenest simply crush the tissues and do not penetrate them. (Bourrel).

In man hydrophobia assumes the same two forms as in the dog — viz. the delirious and the paralytic, the former being by far the commoner of the two.

The delirious form can be subdivided into three stages :

(a) Melancholia. — Towards the end of the period of incubation the patient, whether he is aware of the impending danger or not, child or adult, becomes sad, taciturn, shuns all society. He suffers constantly from the intensest headache, and at night his sleep is disturbed by terrible dreams of very varied character. There are occasionally some itching or even painful sensations at the seat of the bite. This period is not always present, and seldom lasts more than four or five days. There is now also, in some cases, an irresistible impulse to walk or to run. In such exceptional cases of mus- cular excitement there is also found occasionally a state of mental irritability instead of the usual melancholy.

(b) Excitement. Hydrophobia proper. — The breathing becomes difficult, laboured. Inspiration is cut up by frequent sighs. Gradually all the muscles receiving their nervous supply from the medulla oblongata (the part of the nervous axis wherein the brain and spinal cord become connected) become implicated, and there are produci I the peculiar spasmodic contractions of the pharynx and larynx. General hyperesthesia (or increased activity) of all the senses, horror of water and of all bright objects, of the lightest draught of air, of the slightest sound or smell, Convulsive fits. On the second or third day there supervenes the frequent symptom of ‘ sputation,’ — the mouth, at first dry, now becomes moist and watery, filled with frothy mucus. There are frequent hallucinations of sight, of hearing. The voice is hoarse, convulsive, spa – modic, and may simulate the bark or howl of a dog. During the convulsive attacks the patient often hurts and bruises himself, and has still the tendency to run away from home. These attacks may alter- nate with fits of melancholia and manifestations of great despondency. The temperature rises, us in tetanus, and may still increase for one hour after death (Peter) ; up to 43° C. (Joffroy).

(c) Paralysis of all the senses, and finally of the intellect also, and death from exhaustion and paralysis of the respiratory and circulatory centres.

Hydrophobia in man can be confounded with hysteria, tetanus, epilepsy, delirium tremens, and certain forms of acute mania. It has sometimes been identified with uraemia or blood-poisoning from kidney disease. It will be enough, in order to avoid confusion with the last-named affection, to remember that in hydrophobia the temperature rises as death approaches ; in uraemia it always goes down below the normal. The type of the convulsions, the mental disorder, and the abnormalities of general and special sensibility, are very different in the two.

The paralytic form of rabies in man is much less common than the one just described. Never- theless, in the second number of the ‘ Annales de l’lnstitut Pasteur,’ Dr. Gamaleia, of Odessa, from whom is borrowed this description, publishes an account of about thirty such cases. He finds that they are generally the result of deep and multiple bites :

‘ Onset by a strong fever, general malaise and aching, headache and vomiting, as in all acute in- fectious diseases. Such an onset is very frequent also in cases of ordinary rabies. In all the patients whose temperatures were taken, there was found, at a certain period of the malady, a high degree of fever.

‘ Then come a train of localised pains, generally in the limbs bitten, and girdle pains at different heights of the vertebral column. These localised premonitory pains are rare in the lower limbs (Brouardel) .

‘ Next supervene a degree of numbness of the senses, fibrillar contractions, ataxy, paresis, and then paralysis more or less complete of the muscles first implicated. General sensibility remains intact, or, if it disappear, it does so very much later.

‘ Then the paralysis spreads, preceded or accom- panied by sharp pain in the muscles invaded ; the remaining limbs, the trunk, the rectum, and bladder, the face, the tongue, the eyes, are all paralysed. So also, sooner or later, and more or less completely, the respiratory centre, the implication of which brings about a marked change in the inspiratory phase of the patient’s breathing, and, as a corollary, some difficulty in swallowing liquids (the so-called great symptom of hydrophobia, or horror of water, being a result much more of the imagination of the patient and of the medical man, than of the rabies virus).

‘ When well-marked, this respiratory lesion is the cause of dyspnceic convulsions in the muscles which are not yet paralysed. Then, frequently, return of the breathing to the normal, but spread of the paralysis to the heart and death by syncope.

‘ This form of rabies has a duration of seven days and a half on an average.

The same author concludes that the virus, from the study of the symptoms detailed, can only spread by the nerves, from the periphery or ex- ternal surfaces to the centre. He also insists on the necessity of giving up the old notion of incura- bility of rabies when once developed, although he does not himself quote any authentic case of re- covery, his main argument being based on the fact that rabies is not so common or so severe in its symptoms in man as in the dog, and yet there are on record cases of undoubted recovery in the latter animal. The medical man ‘ ought to cease aiding on the virus by morphia ; he ought, on the contrary, to help the nervous system in its struggle against the all-invading virus, to assist the organism in bear- ing up against the momentary arrest of the vital functions (e.g. by artificial respiration).’ In that train of reasoning hypodermic injections of strych- nine might at any rate be tried.

On post-mortem examination the lesions of main interest are found to lie in the central nervous system. The nerve-cells are cloudy and granular ; general congestion of the nerve-centres, the blood- vessels being dilated and ruptured here and there, giving rise to small haemorrhages ; miliary abscesses throughout the substance of the medulla oblongata, more sparsely in that of the brain and cord; foci of finely granular matter infiltrating the normal nervous element, the peri-vascular lymph spaces and the walls of the blood-vessels which are com- pressed and assume a moniliform or beaded aspect ; hyaline thrombi or blood-clots form in their interior at the level of those compressed points, the whole giving the appearance of a nodule or small tubercle in the interior of which Klebs thought he had dis- covered the specific micrococcus.

Ross, of Manchester, finds that the lesions are most marked around the central canal, but the anterior and posterior horns and the grey matter throughout is largely implicated also, mainly so perhaps. The same author draws attention to this interesting fact, that in tetanus and rabies the lesions are very similar, but that in the former case they are chiefly spinal, in the latter cerebral, in their main localisations (?). The ganglia of the sympathetic system and the nerve-roots show the same lesions as the brain and cord. The nen and in particular those of the part bitten, those rising from the medulla : the vagi, the glossopharyngeal, the hypoglossal, the spinal accessory, the phrenic, have been found red and hypera?mic, swollen, and the seat of minute foci of haemorrhage ; ] the myelin is diffluent, fragmented, and in many nerve fibres the axis cylinder has altogether disappeared. (Wagner, Krukenberg, Cheadle.)

The lungs are red and congested, here and there the seat of small haemorrhages, filled with frothy mucus formed at the time of death, for there were no auscultation signs of its presence during life. Very generally also some interstitial and subpleural emphysema. Those pulmonary lesions, just like the liquid venous-black state of the blood, seem to be the result of the terminal asphyxia (Brouardel) .

Note also in some cases : haemorrhages in the muscular tissue of the heart ; parenchymatous nephritis ; congestion and swelling of the lymphatic glands, with the terminal leucocythaemia ; softness of the spleen and liver, the latter being in a state of fatty degeneration — all those forcibly remind one of the lesions found in other well-known in- fectious diseases, variola, scarlatina, septicaemia.

Incubation in Man. — Professor Brouardel quotes several trustworthy statistics, and in particular one in which, out of 170 cases, rabies showed itself within the first three months in 147 cases; and a second one in which 73 times out of 97 cases the disc- declared itself within the same period. He concludes : ‘ Babies supervenes oftenest in the course of the second month after infection ; rarely after the third month, quite exceptionally after the sixth month.’ The more numerous the bites, and the greater their gravity, the earlier do the symptoms appear. They manifest themselves earlier also in children than in old people.

From statistics drawn by Tardieu, Bouley, and the French Committee of Hygiene or Board of Health, as well as those published by medical men, the same author finds that after efficient and early cauterisation the death-rate amounts to 30 per cent. of the cases, rising to 80 per cent, in the cases where there was no cauterisation at all or where it was insufficient or tardy. The actual figures are slightly above those here mentioned. Efficient cau- terisation is that effected by means of the hot iron, concentrated sulphuric, nitric, or carbolic arid, or the chloride of antimony and the acid nitrate of mercury, and applied less than one hour after the accident. Before applying the caustic it is often advisable to open up the wound well and 26 HYDROPHOBIA freely by means of a knife. Occasionally ampu- tation of a finger or of a limb will have to be considered.

Under the age of twenty, 31 per cent, of persons bitten die of hydrophobia ; the proportion rises to 62 per cent, above that age.

For wolf bites, Renault finds that, out of 254 individuals bitten, 164 died of hydrophobia, that is, about two-thirds. Dr. du Mesnil having collected accounts of over 800 cases of bites by mad wolves, found a death-rate from hydrophobia of 65 per cent.

For bites by mad dogs Renault gives the per- centage of deaths as being one-third of the total number bitten. Statistics based on 383 cases collected by Bouley between 1862 and 1868, and by the Comite d’Hygiene from that date up to 1872 give a death-rate of 47 per cent. (180 out of 383).

Faber, in the kingdom of Wurtemberg, finds only 28 deaths out of 145 people bitten — i.e. 20 per cent. Some Viennese statistics give a death-rate of 11 per cent. ; another counts 25 deaths for 125 cases. In Austria, in 1860, out of 115 persons bitten, 25 took hydrophobia— i.e. 22 per cent. Leblanc notes only five deaths out of 36 cases where the biting dogs had been diagnosed rabid at the Alfort Veterinary School — 15 per cent. In all those cases we are unfortunately not told how late after the accidents the tables were drawn up. If Bouley”s figures seem to be perhaps too high, pos- sibly because certain cases not followed by death 1 were not reported, some of the other statistics, on the other hand, seem to remain below the truth.

The Comité d’Hygiène give the following figures for the years 1862-72:

Those figures do not give an exact expression of facts, but they are still of great use in indicating very fairly in what direction the truth lies.

Mr. Alfred Poland puts down the death-rate as being 1 in 4 — i.e. 25 percent. ; Dr. and Mr. Gamgee sayit varies from 5 to 55 per cent. Professor Gown 3, in Quain’s ‘ Dictionary of Medicine,’ says : ‘ When no preventive measures are adopted, at least halt, perhaps two-thirds, of persons bitten escape. The immunity may be due partly to the bites being inflicted through clothes ; partly to individual in- susceptibility which has been found to exist in animals as well as in man.’ These statements agree perfectly with those of the French authors.

As to the time of the year when rabies is commonest, it is sufficiently pointed out in the following table, published by Dr. Pasca, of Milan (1865) :—

Such was the state, very briefly summarised, of our knowledge of hydrophobia, when in December 1880 M. Pasteur’s attention was called by M. Lannelongue to the case of a little girl who was dying of that disease in his ward at the Hopital Sainte-Eugénie.

M. Pasteur had now for many years been devoting his whole energies to the investigation of maladies confined almost exclusively to animals, and with what extraordinary amount of success most people have heard. They formed a necessary stepping- stone to the study of the more complex problems of human diseases, for they left more scope for free experimentation and the acquisition thereby of great familiarity with such questions. The two classes of diseases, moreover, not unfrequently merge into one, being simply propagated from animal to man, and more or less modified in the latter. Experimentation, ingenious and critical, and an intuition of things, a manner of scientific conscience, developed to an unusual degree and suggesting the right choice out of many possible ones, added to which great perseverance and un- shaken faith in results thus patiently come to, such are the main elements of M. Pasteur’s strength.

A new era was now dawning in the history of hydrophobia, and more was done for it in the next few years than had been realised in the previous ages. Light was thrown upon many obscure points of its natural history; but, most important of all, the possibility of its prophylactic treatment in man. based on results already secured in animals in the analogous cases of splenic fever, the fowl-cholera, the swine-plague, and other maladies, was now announced for the first time. This early announcement was soon justified, and shown to lie not on Impossible but probable, from the resultsof numerous experiments on dogs and other animals. In 1885 it was actually applied to the human subject. But we must not anticipate.

Those results were published in a series of communications made to the Académie cles Sciences. They are so concise that we can do no better than translate them, only aiming in our rendering at being as faithful to the original as possible. We shall next give a detailed account of all we saw and learnt at the two laboratories of Rue d’Ulm and Rue Vauquelin, during our stay of many months at those two places, summing up with the statistics of all cases treated by the new method, and a few general remarks.