32 TOXINES AND ANTITOXINES. 



as that the action of definite doses of ricine upon the blood was 

 invariably exactly neutralised by corresponding doses of anti- 

 ricine. The action of other hsemolysines, such as snake poison 

 (KANTHACK), eel's blood (KOSSEL), and tetanolysine (EHRLICH). 

 <fec., can be counteracted by similar means. 



Direct relationships between toxine and antitoxine were thus 

 established. But these might still depend upon a direct destruc- 

 tion of the poison by the antidote. The facts, however, showed 

 that this was not the case, but that there was a simple combina- 

 tion of the two constituents. 



In particular, the fact that it is possible, when this compound 

 has only been formed a short time, to break it up in such a way 

 that the original toxic activity is restored, has afforded the 

 strongest support to the theory that there is a loose form of 

 combination. CALMETTE was the first to demonstrate this fact 

 with certainty in the case of the animal toxine, snake poison, the 

 antitoxine of which is much more unstable than the toxine. 



It has also been found by WASSERMANN that the antitoxine of 

 B. pyocyaneus (q.v.) is much more readily destroyed than the 

 toxine, so that we are justified in assuming that there is also a 

 simple combination in the case of bacterial toxines. 



The gist of these experiments was that a neutral mixture of 

 toxine with antitoxine required a large proportion of the original 

 toxic capacity on being heated, owing to the fact that the anti- 

 toxine, being the more readily attacked constituent of the loose 

 combination, was destroyed by the higher temperature. The 

 two components, however, must only have been mixed a short 

 time, since otherwise it was no longer possible to separate the 

 compound. A process of diffusion can also be used to separate 

 the two components in the case of snake poison, the toxine of 

 which is much more diffusible than the antitoxine (MARTIN and 

 CHERRY) (cf. Snake Poison). 



On the other hand, similar experiments with diphtheria poison have 

 proved unsuccessful (DziERZGOWSKi 1 ). Now, here the conditions are quite 

 different. In the first place, as EHRLICH has shown, the combination is 

 exceedingly stable. But, apart from that, the toxine in this case is the 

 more destructible, so that on heating the mixture it is not the toxine but 

 the free antitoxine that ought to be regenerated. The reason why this 

 does not happen is manifest a priori; for in the change that takes place 

 in the toxine on heating the poison does not disappear, but is only trans- 



1 Dzierzgowski, " Zur Frage liber die Beziehungen zwischen dem anti- 

 diphth. Heilserumu. d. Diphtherietoxin," Arch. Internal. dePharmacodyn., 

 v., 1, 1898. Cf. Marenghi, " Ueber d. gegens. Wirkg. antidiphth. Serums 

 und des Diphth. -Toxins," Centralbl.f. Bakt., xxii., 520, 1897. 



