which an opportunity is afforded for administering the anti-toxin. Before, however, passing on to the investigations which have culminated in the production of a specific antidote for this terrible toxin, there are a few more details which Calmette has furnished as to its character which are of interest. Serpent venom is characterised not only by its intensely virulent properties, but also by the tenacity with which it retains them under diverse. circumstances. Thus it may be stored up for a whole year, and yet at the end of that time be as active as ever; and even after several years, although its toxic powers are somewhat reduced, it still retains them to a very appreciable extent.

Unlike the bacterial toxins, this venom toxin can stand exposure to considerable temperatures without injury to its activity, and that of the cobra only suffers after it has been submitted to 98° Centigrade for twenty minutes. Sensitiveness to temperature varies, however, with the snake from which the venom is derived. Thus the venom of the so-called "tiger-snake" of Australia will stand being exposed for ten minutes to from 100° to 102° degrees Centigrade, and its virulence only disappears when this temperature has been applied for twenty minutes. The venom of the "black snake," another Australian variety, loses its toxicity at a temperature of between 99° and 100° Centi

grade; whilst an exposure to only 80° Centigrade for ten minutes is sufficient in the case of viper venom, according to Messrs. Phisalix and Bertrand, to profoundly modify its lethal action. A continuous exposure for a fortnight to a temperature of 38° Centigrade does not affect cobra venom in the least; but if during that same time it has been placed in the sunshine, it entirely loses all its lethal properties. Thus, a pigeon was inoculated with about thirty drops of venom which had been exposed to the sun's rays for fourteen days, and it survived; whilst another pigeon was inoculated with a little over six drops of similar venom which had been kept during this time in the dark, and it died in a quarter of an hour.

All these elaborate researches as to the character of serpent venom were essential to enable the next step to be taken in the elaboration of the antidote. Before this great achievement could be accomplished it was necessary to first succeed in artificially immunising animals against the effects of this powerful toxin, so that the serum of such animals could be applied for the protection and cure of other animals from the effects of snakebites.

It may be readily conceived that the task of artificially rendering animals immune from snake poison was not an easy one, for the process

depends upon training the animal to gradually withstand larger and larger doses of the venom; and considering the intensely toxic character of the substance which had to be handled, the danger was ever present of the animal succumbing to venom poison before its serum had acquired the requisite pitch of protective power to render it of service as an anti-toxin. Dr. Calmette tells us that he carried out a very large number of experiments before he met with success. But it is not necessary here to discuss his various efforts; suffice it to say that at length his labours were rewarded, and the following extract from one of his memoirs describes the methods which he adopted for this purpose:

"The best method of procedure for the purpose of vaccinating large animals destined to produce antivenomous serum consists in injecting them from the outset with gradually increasing quantities of the venom of the cobra mixed with diminishing quantities of a onein-sixty solution of hypochlorite of lime.* The condition and the variations in the weights of the animals are carefully followed, in order that the injections may be made less frequently if the animals do not thrive well. Quan

* More recently the snake venom employed by Dr. Calmette for the immunisation of his horses consists of a mixture of colubrine and viperine poisons, the former making up about 80 per cent. of the mixture. A solution of this mixture is heated at about 73° C. for half an hour and then filtered, and injected into horses.

tities of stronger and stronger venom are in turn injected, first considerably diluted, and then more concentrated; and when the animals have already acquired a sufficiently perfect immunity, the venoms derived from as large a number of different species of snakes as possible are injected. The duration of the treatment is of considerable length-at least fifteen months-before the serum is sufficiently active to be used for the purposes of treatment."

An immense number of animals have been vaccinated by this method at the Pasteur Institute at Lille, where Dr. Calmette is now director; and in one of his memoirs we are told that they have horses there which have yielded during a period of eighteen months serum extremely active against venom. These horses receive in a single inoculation, without suffering the least inconvenience, doses of venom sufficient to kill fifty horses fresh to the treatment.

Large quantities of this serum have been forwarded from the Lille Institute to various parts of the world where venomous serpents are most frequently met with, and already important evidence has been collected as to its efficacy in cases of human beings bitten by dangerous reptiles. So impressed with its importance are Indian medical authorities, that its preparation has been included in the work which the new great bacteriological institute at Agra is carrying on.

The importance of the production in situ of this anti-venomous serum has been recently demonstrated by the experiments which have been conducted in the Plague Research Laboratory, Bombay, by Mr. Lamb and his colleagues, on the keeping properties of such serums in India. From the careful investigations which have been made on this subject, these gentlemen state that anti-venomous serum undergoes a progressive and fairly rapid deterioration when stored in hot climates, and that this deterioration is greater and more rapid the higher the mean temperature to which it is subjected.

The protective potency of this horse-serum may be gathered from the fact that it suffices to inject a rabbit, for example, with a quantity amounting to about one two-hundred-thousandth of its weight to ensure the latter acquiring complete immunity from a dose of venom capable of otherwise killing it in twelve hours.

The rapidity with which it acts is also extremely remarkable. Thus, if a rabbit receive two cubic centimetres (about fifty drops) of anti-venomous serum in the marginal vein of one of its ears, it will suffer with absolute impunity an injection of venom into the marginal vein of the other ear capable of killing it under ordinary circumstances in a quarter of an hour. Its curative powers are