XIV Snake-Venom
The Report of the 1875 Commission said:—
“It is not possible for us to recommend that the Indian Government should be prohibited from pursuing its endeavours to discover an antidote for snake-bites; or that, without such an effort, your Majesty’s Indian subjects should be left to perish in large numbers annually from the effects of these poisons.”
Certainly it was not possible; and the numbers are large indeed. During 1897, 4227 persons were killed by wild animals in India, and 20,959 by snakes. (British Medical Journal, 5th November 1898.)
Sir Joseph Fayrer’s name must be put in the highest place of all those who have studied the venomous snakes of India.
Sewell, in 1887, showed that animals could be rendered immune, by repeated inoculation with minute quantities of rattlesnake-venom, to a dose seven times as large as would kill an unprotected animal. Kanthack, in 1891, immunised animals in the same way against cobra-venom. He also made experiments to ascertain whether the blood-serum of these animals acted as an antidote to the venom. Then came the work of Calmette, Fraser, Phisalix, Bertrand, Martin (Australia), Stephens, and Meyers. Professor Fraser’s observations on the antidotal properties of the bile are, of course, of the utmost importance; not only in preventive medicine, but also in physiology. The results obtained by Calmette are a good instance of the fineness and accuracy of the experimental method. It is to be noted that the animals were inoculated with a fine needle, not thrust into cages with snakes, as at zoological gardens; and that an animal thus poisoned has a painless death. The different venoms were measured in decimal milligrammes, and their potency was estimated according to the body-weight of the animal inoculated. As with tetanus, so with snake-venom, there must be a standard, or “unit of toxicity.”
“The following table gives the relative toxicity, for 1 kilogr. of rabbit, of the different venoms that I have tested. To denote this toxicity I use terms such as Behring, Roux, and Vaillard used for the toxin of tetanus, taking the number of grammes of animal killed by one gramme of toxin:—
| 1. | Venom of naja | 0.25 mgr. per kilogr. of rabbit. | |
| One gramme of this venom kills 4000 kilogrammes of rabbit; it has, therefore, an activity of | 4,000,000 | ||
| 2. | Venom of hoplocephalus | 0.29 mgr. | 3,450,000 |
| 3. | Venom of pseudechis | 1.25 mgr | 800,000 |
| 4. | Venom of pelias berus | 4.00 mgr | 250,000 |
“Of course, this estimation of virulence is not absolute; it varies considerably according to the species of animal tested. Thus the guinea-pig, and still more the rat, are extremely sensitive. For instance, 0.15 mgr. of viper-venom is enough to kill, in less than 12 hours, 500 grammes of guinea-pig; so that the activity of this venom with a guinea-pig is 3,333,000, but with a rabbit is not more than 650,000. With more resistant animals, the opposite result is obtained; about 10 mgr. of cobra-venom are necessary to kill a dog of 6.50 kilogrm. weight; but to kill the same weight of rabbit 1.65 mgr. is enough. Thus the virulence of this venom with the rabbit is 4,000,000; but with the dog not more than 650,000.”
By experiments in test-tubes, Calmette studied these venoms under the influences of heat and various chemical agents. He found how to attenuate their virulence, and how to diminish the local inflammation round the point of inoculation; and it was in the course of these test-tube experiments and inoculations that he discovered the value of calcium hypochlorite as a local application. Working, by various methods, with attenuated venoms, he was able to immunise animals:—
“I have come to immunise rabbits against quantities of venom that are truly colossal. I have got several, vaccinated more than a year ago, which take, without the least discomfort, so much as 40 mgr. of venom of naja tripudians at a single injection; that is to say, enough to kill 80 rabbits of 2 kilogr. weight, or 5 dogs.
“Five drops of serum from these rabbits wholly neutralise in vitro (in a glass test-tube) the toxicity of 1 mgr. of naja-venom.”
By 1894 he had found that the serum of an animal, thus immunised by graduated doses of one kind of venom, neutralised other kinds of venom:—
“If 1 mgr. of cobra-venom, or 4 mgr. of viper-venom, be mixed, in a test-tube, with a small quantity of serum from an immunised rabbit, and a fresh rabbit be inoculated with this mixture, it does not suffer any discomfort. It is not even necessary that the serum should come from an animal vaccinated against the same sort of venom as that in the mixture. The serum of a rabbit immunised against the venom of the cobra or the viper acts indifferently on all the venoms that I have tested.”
In 1894 he had prepared enough serum for the treatment to be tried by his own countrymen practising in some of the French colonies. In April 1895, he gave the following account of his work:—
“I have immunised two asses, one having received 220 mgr. of naja-venom from 25th September to 31st December 1894, and the other 160 mgr. from 15th October to 31st December. The serum of the first of these two animals has now reached this point, that half a cubic centimetre destroys the toxicity of 1 mgr. of naja-venom. Four cubic centimetres of this serum, injected four hours before the inoculation of a dose of venom enough to kill twice over, preserve the animal in every case. It is also therapeutic, under the conditions that I have already defined; that is to say, if you first inoculate a rabbit with such a dose of venom as kills the control-animals in three hours, and then, an hour after injecting the venom, inject under the skin of the abdomen 4 to 5 cubic centimetres of serum, recovery is the rule. When you interfere later than this the results are uncertain; and in all my experiments the delay of an hour and a half is the most that I have been able to reach.
“This antivenomous serum of asses has these same antitoxic properties with all kinds of snake-venom; it is equally active in vitro, preventive, and therapeutic, with the venoms of cerastes, of trigonocephalus, of crotalus, and of four kinds of Australian snakes that Mr. MacGarvie Smith has sent to M. Roux. I am still injecting these two animals with venom, and I hope to give to their serum at last a much greater antitoxic power.”
In 1896 four successful cases of this treatment in the human subject were reported in the British Medical Journal. In 1898 Calmette made the following statement of his results:—
“It is now nearly two years since the use of my antivenomous serum was introduced in India, in Algeria, in Egypt, on the West Coast of Africa, in America, in the West Indies, Antilles, &c. It has been very often used for men and domestic animals (dogs, horses, oxen), and up to now none of those that have received an injection of serum have succumbed.... A great number of observations have been communicated to me, and not one of them refers to a case of failure.” (British Medical Journal, 14th May 1898.)
Good accounts of Fraser’s and Calmette’s work are given by Dr. Stone in the Boston Medical and Surgical Journal, 7th April 1898, and by Staff-Surgeon Andrews, R.N., in the British Medical Journal, 9th September 1899. For other cases see the Pioneer, 10th August 1899, the Lancet, 25th November 1899, and the British Medical Journal, 23rd December 1899. In one of these cases, recorded by Dr. Rennie, the patient was, literally, at the point of death, but recovered after the serum had been injected. Two cases have also been recorded of cobra-bite during work in the laboratory: both of them recovered after injection. “Every Government or private dispensary,” says Surgeon Beveridge, “should be supplied with antivenene, which is certainly the best remedy for snake-bite available.” The cases are few at present; but it does not appear that the treatment has failed in any case; and, with a new remedy of this kind, it is fairly certain that failures would be published.
From all these instances in physiology, pathology, bacteriology, and therapeutics, we come to consider the Act relating to experiments on animals in the United Kingdom. Many subjects have been left out; among them, the work of the last few years on the suprarenal glands and adrenalin, and Dr. William Hunter’s admirable work on pernicious anæmia. No attempt has been made to describe the researches of experts in many countries into the nature of malignant disease, or to guess what may come of the discovery that mice can be immunised against that form of cancer which occurs in mice and is inoculable from mouse to mouse. Nothing has been said of the discovery that the African sleeping-sickness is due to a blood-parasite carried by flies from man to man. Nothing has been said about those discoveries in bacteriology that have not yet been applied to practice, or of the many inventions of medical and surgical practice that owe only an indirect debt to experiments on animals. Artificial respiration, the transfusion of saline fluid, the hypodermic administration of drugs, the use of oxygen for inhalation, the torsion of arteries, the grafting of skin, the transplantation of bone, the absorbable ligature, the diagnostic and therapeutic uses of electricity, the rational employment of blood-letting—all these good methods have been left out of the list; only some facts have been presented, those that mark most clearly the advance of knowledge and of practice, and stand up even above the rest of the work. There they will stand, when we are all dead and gone: and by them, as by landmarks, all further advance will be guided.