VI Rabies
Pasteur’s study of rabies began in 1880; and the date of the first case treated—Joseph Meister, a shepherd-boy of Alsace—is July 1885. The first part of the work was spent in a prolonged search for the specific microbe of rabies. It was not found: its existence is a matter of inference, but not of observation.24 In his earlier inoculations, Pasteur made use of the saliva of rabid animals; and M. Valléry-Radot tells the story, how Pasteur took him on one of his expeditions:—
“The rabid beast was in this case a huge bull-dog, foaming at the mouth and howling in his cage. All attempts to induce the animal to bite, and so infect one of the rabbits, failed. ‘But we must,’ said Pasteur, ‘inoculate the rabbits with the saliva.’ Accordingly a noose was made and thrown, the dog secured and dragged to the edge of the cage, and his jaws tied together. Choking with rage, the eyes bloodshot, and the body convulsed by a violent spasm, the animal was stretched on a table, and kept motionless, while Pasteur, leaning over his foaming head, sucked up into a narrow glass tube some drops of the saliva.”
But these inoculations of saliva sometimes failed to produce the disease; and, when they succeeded, the incubation-period was wholly uncertain: it might be some months before the disease appeared. Thus Pasteur was led to use, instead of the saliva, an emulsion of the brain or spinal cord; because, as Dr. Duboué had suggested, the central nervous system is the chief seat, the locus electionis, of the virus of rabies. But these inoculations also were not always successful, nor did they give a definite incubation-period.
Therefore he followed with rabies the method that he had followed with anthrax. As he had cultivated the virus of anthrax, by putting it where its development could be watched and controlled, so he must put the virus of rabies in the place of its choice. It has a selective action on the cells of the central nervous system, a sort of affinity with them; they are, as it were, the natural home of rabies, the proper nutrient medium for the virus: therefore the virus must be inoculated not under the skin, but under the skull.
These sub-dural inoculations were the turning-point of Pasteur’s discovery. The first inoculation was made by M. Roux:—
“Next day, when I informed Pasteur that the intracranial inoculation offered no difficulty, he was moved with pity for the dog. ‘Poor beast, his brain is doubtless injured: he must be paralysed.’ Without reply I went down to the basement to fetch it, and let it come into the laboratory. Pasteur did not like dogs, but when he saw this one, full of life, inquisitively rummaging about in all directions, he exhibited the greatest delight, and lavished most charming words upon it.”
Henceforth all uncertainty was at an end, and the way was clear ahead: Pasteur had now to deal with a virus that had a definite period of incubation, and a suitable medium for development. The central nervous system was to the virus of rabies what the test-tube was to the virus of fowl-cholera or anthrax. As he had controlled these diseases, had turned them this way and that, attenuated and intensified them, so he could control rabies. By transmitting it through a series of rabbits, by sub-dural inoculation of each rabbit with a minute quantity of nerve-tissue from the rabbit that had died before it, he was able to intensify the virus, to shorten its period of incubation, to fix it at six days. Thus he obtained a virus of exact strength, a definite standard of virulence, virus fixe: the next rabbit inoculated would have the disease in six days, neither more nor less.
As he was able to intensify the virus by transmission, so he was able to attenuate it by gradual drying of the tissues that contained it. The spinal cord, taken from a rabbit that has died of rabies, slowly loses virulence by simple drying. A cord dried for four days is less virulent than one that has been dried for three, and more virulent than one dried for five. A cord dried for a fortnight has lost all virulence: even a large dose of it will not produce the disease. By this method of drying, Pasteur was enabled to obtain the virus in all degrees of activity: he could always keep going one or more series of cords, of known and exactly graduated strengths, according to the length of time they had been dried—ranging from absolute non-virulence through every shade of virulence.
And, as with fowl-cholera and anthrax, so with rabies; a virus which has been attenuated till it has been rendered innocuous, can yet confer immunity against its more virulent forms: just as vaccination can protect against smallpox. A man, bitten by a rabid animal, has at least some weeks of respite before the disease can break out; and, during that time of respite, he can be immunised against the disease, while it is still dormant: he begins with a dose of virus attenuated past all power of doing harm, and advances day by day to more active doses, guarded each day by the dose of the day before, till he has manufactured within himself enough antitoxin to make him proof against any outbreak of the disease.
The cords used for treatment are removed from the bodies of the rabbits, by an aseptic method, and are cut into lengths and hung in glass jars, with some chloride of calcium in them, for drying. The jars are dated, and then kept in glass cases in a dark room at a constant temperature. To make sure that the cords are aseptic, a small portion of each cord is sown on nutrient jelly in a test-tube, and watched, to see that no bacteria occur in the tube. For each injection, a certain small quantity of cord is rubbed-up in sterilised fluid; and these subcutaneous injections give no pain or malaise worth considering.
Of course, the treatment is adjusted to the gravity of the case. A bite through naked skin is more grave than a bite through clothing; and bites on the head or face, and wolf-bites, are worst of all. The number and character of the scars are also taken into account. An excellent description of the treatment, by a patient, was published in the Birmingham Medical Review of January 1898. It gives the following tables of treatment:—
1. Ordinary Treatment.
| Day of Treatment. | Days of Drying of Cord. | |
| 1 | 14 and 13 | |
| 2 | 12 and 11 | |
| 3 | 10 and 9 | |
| 4 | 8 and 7 | |
| 5 | 6 | |
| 6 | 6 | |
| 7 | 5 | |
| 8 | 4 | |
| 9 | (1/2 dose) | 3 |
| 10 | (full dose) | 5 |
| 11 | 5 | |
| 12 | 4 | |
| 13 | 4 | |
| 14 | (1/2 dose) | 3 |
| 15 | (full dose) | 3 |
2. Cases of Moderate Gravity.
Same treatment, up to 13th day.
| Day of Treatment. | Days of Drying of Cord. | |
| 14 | 3 | |
| 15 | 5 | |
| 16 | 4 | |
| 17 | (1/2 dose) | 3 |
| 18 | (full dose) | 3 |
3. Grave Cases.
Same treatment, up to 10th day.
| Day of Treatment. | Days of Drying of Cord. | |
| 11 | 4 | |
| 12 | 3 | |
| 13 | 5 | |
| 14 | 5 | |
| 15 | 4 | |
| 16 | 4 | |
| 17 | (1/2 dose) | 3 |
| 18 | (full dose) | 3 |
| 19 | 5 | |
| 20 | 3 | |
| 21 | 4 | |
| 22 | 3 |
4. Very Grave Cases.
Same treatment as 3, and in addition.
| Day of Treatment. | Days of Drying of Cord. | |
| 23 | 5 | |
| 24 | 4 | |
| 25 | (1/2 dose) | 3 |
| 26 | (full dose) | 3 |
Furious criticism, unbelief, and flagrant misstatement of facts began at once, and lasted more than two years. Of Pasteur’s opponents, the chief was M. Peter, who besought the Académie des Sciences, about once a week, that they should close Pasteur’s laboratory, because he was not preventing hydrophobia but producing it. The value of M. Peter’s judgment may be estimated by what he had said, a few years earlier, about bacteriology in general—“I do not much believe in that invasion of parasites which threatens us like an eleventh plague of Egypt. After so many laborious researches, nothing will be changed in medicine, there will only be a few more microbes. M. Pasteur’s excuse is that he is a chemist, who has tried, out of a wish to be useful, to reform medicine, to which he is a complete stranger.”
But it does not matter what was said twenty years ago. In England, the Report of the 1886 Committee, and the Mansion House meeting in July 1889, mark the decline and fall of all intelligent opposition to the work. Among so many thousand cases, during so many years, it would be a miracle indeed if not a single case had failed or gone amiss; but we are concerned here with the thousands. Take, to begin with, four reports from Athens, Palermo, Rio, and Paris. It is to be noted that the patients, alike at Paris and at other Institutes, are divided into three classes:—
“A. Bitten by animals proved to have been rabid by the development of rabies in other animals inoculated from them.
“B. Bitten by animals proved to have been rabid by dissection of their bodies by veterinary surgeons.
“C. Bitten by animals suspected to have been rabid.”
It is to be noted also, as a fact proved beyond doubt, that the full benefit of the treatment is not obtained at once; the highest degree of immunity is reached about a fortnight after the discontinuance of the treatment. Those few cases, therefore, where hydrophobia has occurred, not only in spite of treatment, but within a fortnight of the last day of treatment, are counted as cases where the treatment came too late.
Finally, what was the risk from the bite of a rabid animal, in the days before 1885? It is a matter of guess-work. One writer, and one only, guessed it at 5 per cent.; another guessed it at 55, and a third came to the safe conclusion that it was “somewhere between these limits.” Leblanc, who is probably the best guide, put it at 16; and Pasteur himself put it between 15 and 20. But suppose it were only 10; that, before Pasteur, out of every 100 men bitten by rabid animals, 90 would escape and only 10 would die of hydrophobia; then take this fact, that in one year, at one Institute alone, there were 142 patients in class A, bitten by animals that were proved, by the unanswerable test of inoculation, to have been rabid; and 1 death. And every year the same thing; and in all the twelve years together, 2872 such cases (A) and 20 deaths—a mortality not of 10 per cent., but of less than 1 per cent.
1. Athens
The Annales de l’Institut Pasteur, June 1898, contain Dr. Pampoukis’ report of three years’ work at the Hellenic Institute, from August 1894 to December 1897. During this period 797 cases were treated—590 male and 207 female. The animals that bit them were—dogs, 732; cats, 34; wolf, 1; other animals, 13; and the 17 other patients had been exposed to infection from the saliva of hydrophobic patients. Of the 797 cases, 245 were of class A, 112 B, and 440 C.
“Among the 797 persons treated, there are 2 deaths, one in class B and the other in class C. Thus the mortality has been 0.25 per cent. Besides these 2 who died of rabies there are 5 more, in whom the first signs of rabies showed themselves in less than fifteen days after the last inoculation.
“Finally, beside these 797 cases, there is 1 other case, bitten by a wolf, in which the treatment failed. If we reckon this last case in the statistics of mortality, we have 3 deaths in 798 cases = 0.37 per cent.
“Beside these 798 cases treated at the Institute, there have been others that have not undergone the antirabic treatment, having trusted the assurances of those who are called in Greece empirics. Among these non-treated cases there are 40 who have died of rabies.”
2. Palermo
The Annales for April 1896 give the report by Dr. de Blasi and Dr. Russo-Travali of the work of the Municipal Institute at Palermo during 8-1/2 years, from March 1887 to December 1895. The number of cases was 2221; in 1240 (class A), the animals were proved to have been rabid by the result of inoculations; in 981, there was reason to suspect rabies.
“Setting aside 5 patients who died during the course of the treatment, and 5 others who died less than fifteen days after the end of the treatment, we have had to deplore only 9 failures = 0.4 per cent. Even if we count against ourselves the 10 other cases, the mortality is still only 0.85.”
3. Rio de Janeiro
The Annales for August 1898 give Dr. Ferreira’s report of ten years’ work (February 1888 to April 1898) at the Pasteur Institute at Rio. The number of cases treated was 2647, of whom 1987 were male and 660 female. Beside these 2647 there were 1234 who were not treated, because it was ascertained that they were in no danger of rabies; 3 who were brought to the Institute, already suffering from the disease; and 59 who refused treatment.
Of the 2647 persons treated, 10 had pricked their hands at work in the laboratory, 3 had exposed chance scratches on their hands to the saliva of rabid animals, and 1 had been bitten by a rabid patient. Of the rest, 1886 had been bitten on the bare skin, and 747 through clothing.
In 236 cases the rabies of the animal had been proved by inoculation. In 1173 it had been recognised by the signs of the disease. In 1238 there was good reason to suspect that the animal had been rabid.
Of the 2647 patients, in 30 cases the treatment was stopped, because the animals were at last traced, after treatment was begun, and were found not to be rabid. In 65 cases the patients, after treatment was begun, refused to go on with it, and 3 of them died of rabies. In 6 cases rabies developed during treatment; 5 of them had been very badly bitten about the head, and 1 did not come for treatment till the twenty-first day after the bite, and was attacked by rabies two days later. And 5 cases died of other maladies that had nothing to do with rabies. Setting aside these 106 cases, there remain 2541 cases, with 20 deaths = 0.78 per cent. But, of these 20 deaths, 9 occurred within fifteen days of the end of treatment, before protection was fully established. If these 9 deaths be excluded, the figures stand at 2532 cases, with 11 deaths = 0.43 per cent.
4. Paris
Dr. Pottevin’s report on the work of the Pasteur Institute (Paris) during 1897 (Annales, April 1898) must be given word for word, without abbreviation.
I
During 1897, 1521 patients received the anti-treatment at the Pasteur Institute: 8 died of rabies. The notes of their cases will be found at the end of this paper.
If we exclude 2 of these 8 cases—the cases of Heniquet and Morin, where death occurred before it was possible for the vaccinations to produce their effect—the results of the vaccinations in 1897 are
| Patients treated | 1519 |
| Deaths | 6 |
| Mortality per cent. | 0.39 |
In the following table these figures are compared with those of preceding years:—
| Year. | Patients treated. | Deaths. | Mortality per cent. |
|---|---|---|---|
| 1886 | 2671 | 25 | 0.94 |
| 1887 | 1770 | 14 | 0.79 |
| 1888 | 1622 | 9 | 0.55 |
| 1889 | 1830 | 7 | 0.38 |
| 1890 | 1540 | 5 | 0.32 |
| 1891 | 1559 | 4 | 0.25 |
| 1892 | 1790 | 4 | 0.22 |
| 1893 | 1648 | 6 | 0.36 |
| 1894 | 1387 | 7 | 0.50 |
| 1895 | 1520 | 5 | 0.33 |
| 1896 | 1308 | 4 | 0.30 |
| 1897 | 1521 | 6 | 0.39 |
II
Patients treated at the Pasteur Institute are divided into three classes, as follows:—
A. The rabies of the animal was proved by experiment, by the development of rabies in animals inoculated with its bulb (the upper end of the spinal cord).25
B. The rabies of the animal was proved by veterinary examination (dissection of its body).
C. The animal was suspected of rabies.
We give here the patients treated in 1897, under these three classes:—
| Bites of the Head. | Bites on the Hands. | Bites of the Limbs. | Total. | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P | D | M p | P | D | M p | P | D | M p | P | D | M p | |
| a | e | o e | a | e | o e | a | e | o e | a | e | o e | |
| t | a | r r | t | a | r r | t | a | r r | t | a | r r | |
| i | t | t | i | t | t | i | t | t | i | t | t | |
| e | h | a c | e | h | a c | e | h | a c | e | h | a c | |
| n | s | l e | n | s | l e | n | s | l e | n | s | l e | |
| t | i n | t | i n | t | i n | t | i n | |||||
| s | t t | s | t t | s | t t | s | t t | |||||
| . | y. | . | y. | . | y. | . | y. | |||||
| A | 15 | 0 | 0 | 81 | 0 | 0 | 46 | 1 | 2.1 | 142 | 1 | 0.7 |
| B | 106 | 0 | 0 | 539 | 4 | 0.74 | 273 | 1 | 0.4 | 918 | 5 | 0.65 |
| C | 30 | 0 | 0 | 244 | 0 | 0 | 187 | 0 | 0 | 461 | 0 | 0 |
| 151 | 0 | 0 | 864 | 4 | 0.46 | 506 | 2 | 0.4 | 1521 | 6 | 0.39 | |
The following tables, giving the results obtained since the vaccinations were first used, show that the gravity of the bites varies with their position on the body, and that the mortality is always below 1 per cent. among patients bitten by dogs undoubtedly rabid:—
| Patients. | Deaths. | Mortality. | Patients. | Deaths. | Mortality. | ||
|---|---|---|---|---|---|---|---|
| Bites of the Head | 1,759 | 21 | 1.1 | A | 2,872 | 20 | 0.69 |
| Bites of the Hands | 11,118 | 53 | 0.47 | B | 12,547 | 61 | 0.48 |
| Bites of the Limbs | 7,289 | 22 | 0.30 | C | 4,747 | 15 | 0.31 |
| 20,166 | 96 | 0.46 | 20,166 | 96 | 0.46 |
III
In regard to their nationality, the 1521 patients treated at the Pasteur Institute in 1897 were as follows:—
| Germany | 8 | |
| England | 83 | |
| Belgium | 14 | |
| Egypt | 2 | |
| United States | 1 | |
| Greece | 1 | |
| India | 33 | |
| Switzerland | 33 |
That is, 175 foreigners and 1346 French.
IV
Notes of the eight cases where the treatment failed:—
1. Camille Bourg, 26. Bitten 11th April; treated at the Pasteur Institute, 13th to 30th April; died of rabies at the Lariboisière Hospital, 26th May. Six penetrating bites on the ball of the left thumb. The dog was examined by M. Grenot, a veterinary surgeon at Paris, and the dissection gave evidence of rabies. Another person bitten and treated at the same time as Bourg is now in good health.
2. Louis Fiquet, 23. Bitten 22nd April; treated at the Pasteur Institute, 23rd April to 10th May; died of rabies at the Necker Hospital, 4th June. Five bites, two of them deep, round the right thumb. They had been cauterised five hours after infliction. The dog was examined by M. Caussé, a veterinary surgeon at Boulogne, and the dissection gave evidence of rabies. Another person bitten at the same time as Fiquet is now in good health.
3. Annette Beaufort, 19. Licked on the hands, which were chapped, on 15th April. The dog was killed next day, examined, and declared to have been rabid by M. Lachmann, a veterinary surgeon at Saint-Étienne. Treated at the Pasteur Institute, 20th April to 7th May. Died of rabies 14th October. Two other persons bitten by the same dog and treated at the Pasteur Institute are now in good health.
4. Julien Heniquet, 53. Bitten 11th March, by a dog that M. Jenvresse, veterinary surgeon at Beaumont-sur-Oise, declared after dissection to have been rabid. One bite had torn the lower lip, the wound had been sutured; three other wounds on the nose. The wounds had not been cauterised. Treated at the Pasteur Institute, 18th May to 5th June. First symptoms of rabies showed themselves 4th June, before the treatment was finished; died 7th June. As the disease had its onset during the course of the inoculations, this case should be excluded from the number of those who died of rabies after treatment.
5. Germain Segond, 7. Penetrating bite on the bare right fore-arm, 23rd May. Cauterised an hour later with a red-hot iron. Treated 26th May to 9th June; died of rabies 22nd July. The dog’s bulb had been sent to the Pasteur Institute. A guinea-pig inoculated in the eye 26th May was seized with rabies 10th September.
6. Suzanne Richard, 8. Bitten 12th June on the left leg by a dog, found on dissection to have been rabid by M. Touret, veterinary surgeon at Sannois. The bite, penetrating 3 cm. long, had been sutured; it had been made through a cotton stocking, and had been cauterised in half-an-hour. Treated 13th to 30th June; died of rabies 2nd August. (Notes from M. le Dr. Margny, at Sannois.)
7. Joseph Vaudale, 33. Bitten on the left hand, 8th August. Six penetrating bites on the back of the hand; had not been cauterised. The dog was declared rabid by M. Verraert, veterinary surgeon at Ostend. Treated at the Pasteur Institute, 11th to 28th August; died of rabies 27th September.
8. Paul Morin, 38. Bitten 24th August on the left cheek, a single bite, 2 cm. long; no cauterisation. The dog was sent to the Alfort School, 25th August, and found to be rabid. Treated at the Pasteur Institute, 26th August to 15th September. Died of rabies some days after the end of treatment (three weeks after the bite, says a note sent to us). The interval between the end of the treatment and the onset of the disease being less than fourteen days, Morin must not be counted in the number of patients inoculated under conditions which permit successful inoculation.
We hardly need follow the work of the remaining years. The figures are as follows:—
| Year. | Patients treated. | Deaths. | Mortality per cent. |
|---|---|---|---|
| 1898 | 1465 | 3 | 0.2 |
| 1899 | 1614 | 4 | 0.25 |
| 1900 | 1420 | 4 | 0.28 |
| 1901 | 1318 | 5 | 0.38 |
| 1902 | 1105 | 2 | 0.18 |
| 1903 | 628 | 2 | 0.32 |
| 1904 | 755 | 3 | 0.39 |
The falling off in the number of patients at the Paris Institute is related to the establishment of similar Institutes at Lyon, Marseilles, Bordeaux, Lille, and Montpellier. But is it not possible that a patient, after treatment at the Paris Institute, should die at home of rabies, and his death not be notified to the Institute? The answer is, that the Institute is very careful, so far as possible, to keep in touch with its old patients. For instance, in 1903, it recorded the case of a carpenter in a Welsh village, who had died of rabies nearly two years after treatment. And, of course, an Institute patient, wherever he was, would be of interest to his neighbours: and a death from rabies would excite attention, and would hardly fail to be reported.
It is not impossible that some sort of intensive modification of Pasteur’s treatment may be found, not for the prevention, but for the cure of hydrophobia; and two successful cases of this kind have been reported in the Annales of the Paris Institute. Apart from this faint hope, the cure of hydrophobia is where it was in the days of the “Tonquin medicine” and the “Tanjore pills.”