882 CHEMOTHERAPY 



are markedly bacteriotropic or protozootropic in general constitutes an 

 important advance, the ultimate aim, as stated, should be the synthesis 

 of a strictly monotropic substance. It is suggested that further studies 

 with arsenobenzol, tending to increase its parasitotropic effect on spiro- 

 chetes alone and Treponema pallidum in particular, will still further 

 increase the therapeutic efficacy of this drug. 



"Leads" in Chemotherapeutic Research. In the present state of our 

 knowledge of chemotherapy chance or accidental discovery must play 

 an important role in the discovery of a "lead." Substances are to be 

 selected or prepared on as systematic a basis as possible, and tried out by 

 actual experiment; those yielding encouraging results are then subjected 

 to various systematic modifications with experimental trial of the new 

 compounds. In this manner chemotherapeutic research proves to be 

 costly and laborious, as amply demonstrated by the prolonged and 

 costly series of experiments directed by Ehrlich, which resulted in the 

 discovery of arsenobenzol. 



In the discovery of leads and the study of new compounds animal 

 experiments are of primary importance, not only because these are the 

 sole means of determining the organotropic or toxic effects of the com- 

 pounds, but because they are the sole means of determining the actual 

 parasitotropic or therapeutic effects. In conducting these experiments 

 it is necessary to select a protozoon or bacterium that yields a uniform 

 infection of the animals of not too severe a character, and to reproduce 

 as far as possible the same lesions in the animals as are found in man. 

 The test microparasite should either produce definite lesions easy of 

 detection and study or cause the death of the animal in a given period 

 of time. For studies in bacterial chemotherapy virulent cultures of 

 the pneumococcus are admirably adapted to work with mice and rabbits; 

 in studies of protozoa Trypanosoma equiperdum or T. brucei is valu- 

 able, the white rat being used as host. 



These experiments, however, are likely to prove costly, and, as in the 

 ase of tuberculosis, it may be many weeks or months before results can 

 be determined. Furthermore, special animals, such as monkeys or the 

 higher apes, may be necessary for the determination of the parasitotropic 

 effect of a substance, as in the case of anterior poliomyelitis and syphilis, 

 in which the particular microparasites fail entirely to infect such animals 

 as rabbits, guinea-pigs, and rats, or, at least, fail to do so with sufficient 

 uniformity. In chemotherapeutic studies in syphilis the rabbit may be 

 employed, although the infection usually pursues in this animal a brief 

 course tending to spontaneous recovery. For these reasons an effort 



