690 COLLECTED STUDIES IN IMMUNITY. 



that the arseno-receptor actually represents a distinct function 

 whose affinity can be systematically decreased step by step by immuni- 

 zation. Thus far we have obtained three degrees of affinity. Grade 

 I was produced by subjecting the parasites systematically to the 

 action of p-amidophenylarsinic acid and its acetyl combination. We 

 carried out this treatment ad maximum for years, until finally no 

 further increase in resistance was produced. The resistant strain 

 thus obtained proved to be resistant at the same time to a number 

 of other arsenicals, among them particularly, the p-oxycombination, 

 the combination with urea, and with benzyliden, and a number of 

 acid derivatives. 



In practical therapeutics in man and animals, it is, of course, 

 possible that arsenic-fast strains develop; and these, naturally, will 

 absolutely hinder therapeutic success. In animal experiments this 

 is a common occurrence. In view of this it is important to discover 

 substances able still to attack these resistant strains, substances able 

 to combine with their receptors. After long search we found alto- 

 gether three combinations, of which the most important is arseno- 

 phenylglycin. With the aid of this combination it is possible to heal 

 infections produced by the arsenic-fast strain I, which was described 

 above. This can only be explained by assuming that the arsenophenyl- 

 glycin lays hold on what is left of the arseno-receptor, somewhat as a 

 stump is grasped by a pair of pliers. The anchoring of this substance, 

 however, furnishes a possibility for still further increasing the arsenic- 

 resistance of the strain. After considerable effort we succeeded in 

 producing, out of arsenic strain I, a more resistant strain, arsenic 

 strain II, which was entirely unaffected by arsenophenylglycin. 



Plimmer has recently called attention to tartar emetic as a sub- 

 stance which kills trypanosomes, even in high dilutions. Tartar 

 emetic is the salt of an antimony combination, and antimony, it is 

 well known, is closely related to arsenic. On testing arsenic strain II 

 with tartar emetic, we found that the parasites were destroyed by 

 the tartar emetic. By treating arsenic strain II with arsenious 

 acid we were able to produce a still further increase in resistance, 

 so that arsenic strain III was resistant even against tartar emetic. 

 I want to call particular attention to the fact that this arsenic strain 

 III, produced only under the influence of arsenious acid, was re- 

 sistant to tartar emetic but not against arsenious acid. This can only 

 be explained by assuming that of all conceivable arsenicals, arsenious 

 acid is the one possessing the greatest affinity to the arsenic receptor, 



