CHEMOTHERAPY IN BACTERIAL DISEASES 883 



should be made to train or adapt a race of the particular microparasite 

 under study to survive and multiply in the tissues of an animal easily 

 obtained and handled, so that the abundance of experimental material 

 needed in chemotherapeutic studies on a large scale may be available. 

 In addition to this, as stated, an effort, should be made as far as possible 

 to reproduce in the experimental animals lesions similar to those found 

 in man. For example, the effect of a drug in the blood of a rabbit or 

 white mouse in a pneumococcus bacteremia must be different from that 

 in the exudate of a consolidated lung in pneumonia of man. 



The Role of Bactericidal Tests in the Living Animal in Bacterial 

 Chemotherapy. In chemotherapeutic studies on syphilis experience has 

 shown that a trypanosome may be used, as Trypanosoma equiperdum, 

 or a spirochete other than Spirochseta pallida, as S. gallinarum, to deter- 

 mine the parasitotropic effect of new compounds as they are produced; 

 because those compounds showing marked effects on these micropara- 

 sites, as, for example, arsenobenzol, also produce a profound effect on S. 

 pallida in human and experimental syphilis. It remains to be determined, 

 however, whether similar conditions hold true in the chemotherapy of 

 bacterial infections; that is, whether a compound showing a high bacteri- 

 cidal effect in vitro, or even in vivo, on one microorganism, as Bacillus 

 typhosus or the pneumococcus, will show a similar effect on the micro- 

 organisms of other diseases, as tuberculosis or anterior poliomyelitis. 

 Suffice it to say that the ultimate value of any drug can be determined 

 only by tests in the lower animals; first to determine toxicity, and then 

 therapeutic value. If these tests show a low toxicity and a promising 

 therapeutic effect the court of last resort is the use of the compound in 

 the treatment of man. 



The Role of Bactericidal Tests in Vitro in Bacterial Chemotherapy 

 In chemotherapeutic studies on bacterial infections experiments in vitro 

 may be said to have a positive value in preliminary orientation in the 

 development of leads and the study of new compounds as they are pro- 

 duced. Experimental data at hand tend to show that substances pos- 

 sessing a high bactericidal activity in vitro, and particularly in a men- 

 struum of fresh sterile serum, are more likely to exert an inhibitory effect in 

 vivo; for example, Morgenroth's drug, optochin (ethylhydrocuprein) and 

 its hydrochlorid, exert a very high bactericidal action on the pneumococcus 

 in vitro, and are likewise effective to some extent in vivo; other cinchona 

 derivatives, including certain salts of quinin, possessing more or less 

 bactericidal value in vitro are likewise effective to a certain degree in 

 vivo. 1 Arsenobenzol has been found to possess the highest parasitotropic 

 1 Jour. Infect. Dis., 1917, 20, 81. 



