248 CHEMOTHERAPY 



A strain which has been rendered resistant to trypan-red and 

 which is also fast to trypan-blue and violet, is thus non-resistant 

 to arsenic and to the triphenylmethane dyes, while one which has 

 been rendered arsenic-fast, is resistant only to this, and not to the 

 trypan-dyes and the triphenylmethanes, etc. This fastness, it was 

 then ascertained, remained a constant character through innumerable 

 generations, so long in fact as the organism multiplies by direct 

 division, while it is lost in the descendants of sexual reproduction. 



The attempt to explain the development of such drug-fast stains, 

 as I have just said, led Ehrlich to assume the existence of chemo- 

 ieceptors. Since arsanil itself is non-toxic, while its reduction pro- 

 ducts are capable of killing trypanosomes in high dilution, it follows 

 that the trivalent arsenical radicle which is in combination with the 

 benzoyl radicle must in some manner be anchored to the trypano- 

 somes; and as the toxic effect of the arsanil is lost in the so-called 

 arsenic fast stains, the conclusion suggests itself that the untreated 

 parasite must possess a definite group or receptor with which the 

 arsenical group can unite, and which is capable of undergoing a 

 certain modification, in consequence of which its affinity for the 

 preparation in question is lost, or at least diminished. In the absence 

 of such a combining group it would be very difficult to explain why 

 the treated strain should be arsenic resistant, and the non-treated 

 arsenic susceptible. 



Drug " Fastness." In a former chapter we have seen that a certain 

 type of immunity results from the occurrence of receptoric atrophy, 

 and Ehrlich has shown that during the process of serum immunization, 

 trypanosomes may develop a serum-fastness which is of this character; 

 where, in other words, those nutriceptors of the parasite, which are 

 continuously occupied by a corresponding antibody furnished by 

 the host (the rat for example), disappear or are replaced by receptors 

 of a different structure, through which the nutrition of the cell can 

 again be carried on. In studying the nature of drug fastness, 

 Ehrlich then ascertained that this is not dependent on atrophy of 

 the corresponding receptors, but upon a modification in their 

 structure, as is evidenced by the fact that by changing the structure 

 of the arsenical product, for example, this may still be forced upon 

 the parasite, so to speak, and lead to its destruction. 



The recognition of this possibility is, of course, of the greatest 

 importance, as it shows the lines along which such parasiticidal 



