TETANUS TOXIN E. 121 



incubation it is assumed that the true poison is produced during 

 this period, and that until then there is no action. This compli- 

 cated view is not necessary, for the mode of action of the poison 

 is at least as satisfactorily accounted for by the slow action of 

 the toxophore groups and by the different degrees of slowness in 

 the distribution of the poison in the nerve tracks as found by 

 MEYER and RANSOM (vide supra}. A further point against their 

 view is that the period of incubation becomes shorter in pro- 

 portion to the amount of toxine introduced into the animal, 

 although, as is the case with every toxine, there is a limit to this 

 reduction of the incubation period by larger doses. 



Again, the complicated behaviour of the incubation period in 

 the case of the frog, which has been brought forward as a special 

 argument in support of this view can be explained more simply. 

 H.. was able to prove that on warming the animal 



. 



there was at first only a very rapid and firm combination of the 

 toxine, but no poisoning. If the frog, after being kept at 32 C. 

 for twenty-four hours, was then again placed in the ice chest, 

 it remained permanently well, although if again exposed to a 

 temperature of 32 C. it died after an incubation period that was 

 shortened by twenty-four hours, notwithstanding the injection of 

 enormous quantities of antitoxine. If, as COURMONT and DOYON 

 assume, a secondary change in the poison were produced by the 

 warming, the frog would not remain permanently well even in 

 the ice chest. The heat has here only promoted the formation 

 of an extremely stable combination, and this requires further 

 warming before it causes death by the action of the toxophore 

 group. The fact that after combination has taken place the 

 antitoxine is more or less completely ineffective has been put 

 forward as of special significance in support of the theory of 

 the secondary poison, but in my opinion this is far from being 

 the case. The predominance of the antitoxine circulating in the 

 blood over the toxine, which it prevents from combining with 

 the central nervous system is solely due to the fact that it does 

 so circulate in the blood and thus immediately seizes upon the 

 toxine when introduced into the circulatory system and mechani- 

 cally wards it off from the threatened tissues, and not to its 

 possessing any greater affinity for the toxine. It has but little 

 power of breaking up the combination between the nerve cell 

 and the toxine when once formed, and it does so only by mass 

 action when very large doses of antitoxine have been used. 

 It is thus obvious that the antitoxine must be ineffective if 

 introduced some time after the poisoning, and much more so 

 when only applied after the appearance of the symptoms, and 



