846 CHEMOTHERAPY 



parasitotropic than organotropic. If a given chemical agent shows a 

 greater affinity for the albumins of the body-juices and for the cells than 

 it does for the protoplasm of the microparasites, that is, if it is more 

 organotropic than parasitotropic, it is evident that it is not suitable 

 for therapeutic purposes, especially if, at the same time, the toxic dose 

 for the host should be smaller than that for the microorganism. 



The object of chemotherapeutic research is, therefore, to discover chem- 

 icals that have a greater parasitotropic than organotropic activity, and the 

 greater the difference between these, the more valuable do the substances be- 

 come. 



There is only one way of determining these values, and that is by 

 animal experimentation. Rats, mice, guinea-pigs, rabbits, and fowls 

 have been most generally employed for this purpose, and most work so 

 far has been done with protozoan parasites, such as the organism of 

 chicken spirilloses, the spirillum of recurrent fever, various trypano- 

 somes, and the spirochete of syphilis. These were selected because 

 they are readily found in the blood or in lesions, and are rapidly patho- 

 genic. 



As a result of the study of several hundreds of different products by 

 Ehrlich and his collaborators and by many other noted investigators, it 

 was found that there are, after all, comparatively few that exert a para- 

 sitotropic effect in animals; these are, however, well characterized chem- 

 ically, and have been classified into three main groups : 



1. The group of arsenical compounds arsenious acid (arsenic tri- 

 oxid), atoxyl, arsacetin, arsenophenylglycin, dioxydiamido-arsenobenzol 

 dichlorhydrate (popularly known as "606," or salvarsan), and various 

 antimony compounds. 



2. Certain azo-dyes of the benzidin group, for example, trypan red, 

 trypan blue, and trypan violet. 



3. The group of basic triphenylmethane dyes, such as parafuchsin, 

 methyl-violet, pyronin, and others. 



Newly discovered drugs are administered in increasing amounts 

 to experimental animals until the toxic dose (dosis lethalis), the tolerated 

 dose (dosis tolerata), and the curative or sterilizing dose (dosis curativa 

 or sterilisana) have been determined. 



While chance may succeed in giving us a drug fulfilling the require- 

 ments, so far it has had little influence, and it is difficult to realize the 

 tremendous amount of work done by Ehrlich and the members of his 

 institute before salvarsan was discovered. The following table illus- 

 trates the relation of the tolerated to the curative doses of a few chem- 



