Nothing, moreover, is easier than to train animals vaccinated against cobra-venom to tolerate strong doses of the venoms of Lachesis, Vipera russellii, Crotalus, Hoplocephalus, or Pseudechis. In a few months we succeed in obtaining serums very active against these different venoms.
Utilising the horse as producer of antitoxin, I have prepared by this method polyvalent serums capable of preventing the local action of Viperine venoms, and of suppressing in vitro their coagulant and proteolytic effects upon the blood.
Unfortunately, great as has been the kindness of the many persons who have most obligingly given me their assistance in the course of the fifteen years during which I have studied this question, I have found it impossible to procure sufficient quantities of venoms of various origins to furnish each country with the polyvalent serums corresponding to its particular needs. I have therefore been obliged to confine myself to preparing for the most part antineurotoxins, which I have been able to do, thanks to the abundant provision of Cobra- and Bungarus-venoms, for which I am indebted to the liberality of the Government of the French Settlements in India, and to that of my pupils and friends who are at the present time in charge of the Colonial Laboratories of Indo-China. Moreover, the recent foundation of the Serum-Therapic Institutes of Bombay and Kasauli, Sydney, São-Paulo, and Philadelphia, to-day renders it very easy for each country to provide itself with antivenomous serum, either specific or polyvalent. Other institutes will doubtless be established for the purpose of extending the benefits of a method, the efficacy of which is sufficiently evident for its adoption to be incumbent upon all those who are concerned with safeguarding human existence.
CHAPTER XIV.
NEUTRALISATION OF VENOM BY ANTITOXIN.
It is difficult, in the present state of our knowledge on the subject of toxins and antitoxins, to determine the precise nature of the reactions that are produced in the living organism as the result of serum injected for the purpose of preventing the toxic action of venom.
I maintained, some years ago,[100] that the phenomenon in this case was a purely physiological one, which I considered to be proved by the fact that, if we mix in vitro, in determinate proportions, venom and antivenomous serum, and if we heat this mixture at 68° C. for half an hour, the injection of the heated mixture kills animals as if they were inoculated with venom alone, although with a considerable retardation. I concluded from this that, in all probability, antitoxic serum does not modify the toxin with which it is mixed, but that it confines itself to displaying a parallel and opposite action by preventing the noxious effects. I therefore supposed that no chemical combination is produced between these two substances, or, at least, that the combination effected is very unstable.
My experiments were subsequently repeated by Martin and Cherry,[101] who showed that the results as stated above were perfectly correct when the mixture of venom and antitoxin was heated less than ten minutes after it had been made, but that, if the heating did not take place until twenty or thirty minutes later, the toxicity of the venom no longer reappeared.
On the other hand, the admirable researches of Kyes and Sachs, and subsequently those of Morgenroth, pursued under the direction of Ehrlich at the Laboratory of Experimental Therapy at Frankfort, have proved the readiness of venom to enter into chemical combination with certain elements of normal serums, in particular with lecithin, a combination which results in the formation of hæmolysing and non-toxic lecithides, the neurotoxin being left free.
It therefore seemed impossible to deny the existence of a chemical reaction between the venom and the serum, which was until quite recently considered as proved. We shall see presently that this is not the case. But let us first endeavour to determine the laws that govern the neutralisation of variable quantities of venom by antivenomous serum.
If, in a series of test-tubes, we bring the same quantity of cobra-venom (e.g., 0·00005 gramme, a dose which is invariably lethal to the mouse in two hours) into contact with progressively increasing quantities of an antivenomous serum (e.g., 0·01 c.c., 0·02 c.c., &c., up to 0·1 c.c.), and, after thirty minutes of contact, inject these different mixtures subcutaneously into a series of mice, we find that all those that have received the mixtures containing less than 0·05 c.c. of serum succumb after variable intervals, while all the rest survive. It is evident that, under these conditions, the serum experimented upon has shown itself capable of neutralising in vitro, in a dose of 0·05 c.c., 5 centimilligrammes of venom.