688 COLLECTED STUDIES IN IMMUNITY. 



Provided that the resistance thus produced is of maximum intensity, 

 such a strain is extremely useful in identifying new types of try- 

 panocidal agents. If, for example, a new substance is encountered 

 which is able to kill ordinary trypanosomes, we have merely to 

 test its action on this triple-fast strain in order to determine whether 

 the substance really represents a new type of trypanocidal agent. 

 If it does not, we shall find that treatment with this substance does 

 not cause the parasites to disappear; on the contrary they multiply. 

 If they disappear, however, we can conclude that the substance does 

 not correspond to any of the three types mentioned, but represents 

 a new type of trypanocidal agent. The triple-fast strain thus acts 

 as a kind of cribrum therapeuticum, by the aid of which it is possible 

 to recognize substances belonging together and to separate unrelated 

 substances. 



It was now necessary to determine in what manner this specific 

 drug resistance is brought about, and for this purpose I undertook 

 .a series of experiments with the atoxyl strain. In order to gain a clear 

 insight into the question it seemed advisable to study the behavior 

 of the arsenic-fast strains, also in a test tube, away from all disturb- 

 ances and complications of the animal organism. This method 

 very soon encountered a great obstacle, for it was found that the 

 drug mostly used therapeutically, namely, atoxyl (paramidophenyl- 

 arsinic acid), does not exert the least destructive action on try- 

 panosomes in test-tube experiments. Even solutions containing 

 several per cent, of the substance proved insufficient for this pur- 

 pose. This phenomenon was all the more remarkable because in 

 the human body, according to Koch, injections of 0.5 g. atoxyl 

 suffice to cause the disappearance of the parasites within a few hours. 

 In this case, therefore, destruction is effected in a concentration 

 of 1 to 120,000. 



We are here dealing with a phenomenon which is usually spoken 

 of as "indirect action." It was not difficult for rne to discover the 

 reason for this peculiar behavior, as I had for years busied myself 

 with reducing power of the animal organism. We know that in 

 the body arsenic acid is transformed into arsenious acid; that 

 cacodylic acid is reduced to the ill-smelling cacodyl. It was natural, 

 therefore, to think first of reductions. In atoxyl, paramidophenyl- 

 arsinic acid, the arsenic is pentavalent, whereas in the two products 

 obtained from atoxyl by reduction the arsenic is trivalent. In 

 this way we obtained two different products: 1. The monomo- 



