PRINCIPLES OF CHEMOTHERAPY 241 



of the parasites are destroyed, but some remain alive. This number 

 may be so small that for several days the blood may seem sterile, but 

 then the remaining trypanosomes multiply and a relapse occurs. The 

 same fuchsin preparation is again injected and now, one may attain 

 a complete cure if the dose this time is sufficiently large; but if not a 

 relapse sets in. 



Thus the treatment is continued. If, however, the relapses are 

 numerous and the same curative agent is repeatedly employed, a 

 state is reached in which the fuchsin no longer has any beneficial influence 

 whatever. The trypanosomes have become immunized or acclimated to 

 fuchsin, in other words, have become "fuchsin-fast." 



To prove that it is the trypanosomes that have acquired a new characteristic and 

 not that the organism of the mouse had become altered in its susceptibility, one may 

 infect for the first time another mouse with this " f uchsin-f ast " strain, and here again 

 this dye will have no effect at all. The artificially attained resistance toward fuchsin 

 remains as a permanent characteristic of this particular strain of trypanosomes, even 

 though transplanted from mouse to mouse for years. It disappears, however, if 

 the parasites are allowed to increase by a sexual cycle of development which is 

 possible for example in the rat louse Hematopinus spinolosus. 



This fuchsin-fast character has not at the same time altered the 

 susceptibility of the trypanosomes toward any of the trypanocidal 

 agents of the second or third group as trypan red or atoxyl. Just as 

 guinea-pigs immunized against cholera may succumb to infection by the 

 typhoid bacillus, so also may trypanosomes, which have become inert to 

 fuchsin, be attacked by trypan red or atoxyl. Furthermore the acquired 

 resistance of the protozoa to the action of these various chemicals is just as 

 specific as is the immunity of an animal toward bacteria. 



Group reactions play a role in chemotherapy just as they do in im- 

 munity; the individual vaccinated against cow pox becomes immune 

 toward small-pox; the strain of trypanosomes which has become resistant 

 toward trypan red can no longer be affected by trypan blue. 



Ehrlich's conception that it is necessary for substances to be taken up by the 

 parasites before they can be acted upon destructively is concisely expressed by him: 

 " Corpora non agunt nisi fixata." In terms of the side chain theory, the protoplasm 

 groups which have a specific affinity for the chemical radicles are known as chemocep- 

 tors. Accordingly, the trypanosomes may be said to possess three distinctly different 

 chemoceptors, one directed against fuchsin, one against benzopurpurin and another 

 against atoxyl. 



While the early chemotherapeutic studies with the aniline dyes 

 were mainly of theoretical interest, the arsenic derivatives soon claimed 

 their position of practical importance. 



In 1902 Laveran and Mesnil discovered that arsenous acid could 



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