884 CHEMOTHERAPY 



activity on Trypanosoma equiperdum in vitro of a number of substances 

 tested, 1 and, as well known, this drug exerts the best therapeutic or 

 parasitotropic effects in vivo. Unfortunately, however, other substances 

 that are highly bactericidal in vitro, as the mercurials, also possess a 

 high degree of toxicity for the living animal, and all efforts of the chemo- 

 therapeutist have so far failed to lower materially the toxicity of these 

 compounds. 



Since the time of the earliest discoveries in bacteriology and of 

 bactericides substances highly bactericidal in the test-tube have been 

 known to fail to exert any appreciable influence in vivo when given in 

 safe doses. This lack of effect may be due to the high organotropic or 

 toxic effect of the substance on the body cells in general or on a particular 

 group of cells of vital centers, precluding the use of a bactericidal quan- 

 tity; to insolubility and difficulty of administration; to rapid union with 

 the proteins of the body and the formation of inert compounds; to rapid 

 elimination; to failure to reach the microorganism in a lesion, and to 

 still other causes. Of these possibilities, the first mentioned is of primary 

 importance; but the method and manner of attack of the bactericidal 

 drugs on the protoplasm of cells, aside from coagulation, is almost un- 

 known. Nevertheless, it is possible by systematic modification of the 

 molecule through addition, removal, or substitution of certain atom 

 groups, to produce in some instances a sufficient lowering of toxicity 

 to give an available therapeutic agent. The demonstration of this fact 

 constitutes the great triumph of Ehrlich and opens a fascinating field 

 of research to chemist and biologist. 



It is highly probable that experimental studies tending to increase 

 the monotropism of a drug in vitro and particularly in a menstruum of 

 serum will prove of value in chemotherapeutic work. For example, 

 ethylhydrocuprein, which shows the highest selective action upon the 

 pneumococcus in vitro, likewise proves mos btactericidal in vivo. Simi- 

 lar facts may be proved in the future in connection with the micropara- 

 sites of tuberculosis and of typhoid fever, staphylococci, and other 

 infective bacteria. 



On the other hand, a substance failing to exert parasitotropic action 

 either in vitro or in vivo may still prove of value as a basis of composition, 

 and offer a valuable lead in chemotherapeutic research. For example, 

 arsenic in the form of the trioxid has no appreciable effect on Trypano- 

 soma equiperdum in vivo and but slight effect in vitro, 2 and yet it forms 

 the basis of arsenobenzol, which is so highly parasitotropic both in vitro 

 and in vivo. 



1 Jour. Infect. Dis., 1917, 20, 10. 2 Jour. Infect. Dis., 1917, 20, 10. 



