124: Professor Thomas B. Fraser [March 20, 



substance (antivenene) against serpents' venom, it is instructive to 

 find that it is itself almost devoid of any physiological action, for 

 6ven very large quantities may be injected under the skin without 

 producing any other physiological reaction than a moderate degree of 

 irritation in the neighbourhood of the injection. How then are we 

 to explain the operation of this physiologically inert substance in 

 protecting an animal against even fifty times the minimum-lethal dose 

 of venom, or by a single administration of it, in saving an animal 

 from death after there has been introduced into its body more than 

 twice the quantity of venom that is required to kill it ? When an 

 answer has been attempted to be given to this question in discussions 

 in the wider field of the serum therapeutics which deals with the 

 toxines of diseases, the answer has been found either in the destruc- 

 tive power of phagocytes upon microbes and their toxines, or in the 

 theory that the toxine elaborates from the blood the antidotal anti- 

 toxine, which, whether thus originated or separately introduced into 

 the body, confers upon the body a resisting power which enables it 

 to oppose successfully the injurious action of the toxines. 



These answers cannot solve the problem in so far as snake venom 

 is concerned. Phagocytosis cannot, of course, operate in vitro in 

 solutions which are free from organised structures. Even when solu- 

 tions of venom and antivenene, mixed together in vitro, have been 

 inserted into the body, it is incredible that the increase in the quantity 

 of antivenene by the 1 /500th part of a cubic centimetre could cause 

 such an increased proliferation of leucocytes as to prevent a lethal 

 dose of venom from producing death, whereas a dose only the l/600th 

 part of a cubic centimetre smaller would be unable to do so. Further, 

 there is no observable increase of leucocytes when much more than 

 these infinitesimal quantities of antivenene have been administered to 

 an animal. 



In view of many of the facts that have to-night been stated, the 

 " resistance of tissues " theory is also untenable. It is opposed, for 

 instance, by the fact that so great a quantity of antivenene as • 42 c.c, 

 or nearly ^ of a cubic centimetre, per kilogramme is required to 

 prevent death when given thirty minutes before a lethal dose of 

 venom, whereas, for the same dose of venom, only -0004 c.c, or the 

 l/2500th part of a cubic centimetre, or nearly the 1/lOOOth part of 

 the former dose, is sufficient, when it is mixed with the venom before 

 administration, and in circumstances, therefore, which are much less 

 favourable for the production by the antivenene of this supposed 

 increase in the resistance of the tissues. 



As I have already pointed out, however, a chemical theory, 

 implying a reaction between antivenene and venom, which results 

 in a neutralisation of the toxic activities of the venom, is entirely 

 compatible with the observed facts. 



The experiments which I have described to-night indicate that, 

 with some limitations in the largest quantities, the greater the quantity 

 of venom that has been introduced into the body in the process of 



