442 ANNUAL REPORT SMITHSONIAN INSTITUTION, 194 5 



have been ineffectual against many conditions and in particular against 

 diseases caused by protozoa. 



CHEMICALS IN THERAPY 



The application of chemical agents to the combatting of disease, 

 of course, is no new development. To a degree, chemicals had been 

 included in the armamentarium of the "medicine man" since time 

 immemorial. The magnifiicent charlatan, Paracelsus, was the first 

 real exponent of chemicals in therapy. Little was contributed to this 

 field of medical science for hundreds of years, until the discovery of 

 the alkaloid, quinine, in cinchona early in the last century by the 

 pharmacists Pelletier and Caventou, and the isolation of emetine 

 from ipecac. These substances were the first chemical agents effective 

 against the plasmodium of malaria and against amebic dysentery. 

 They represented the beginnings of "chemotherapy," differing from 

 "chemicals in therapy." 



CHEMOTHERAPY 



Chemotherapy had its true beginning in 1870, when the Frenchman 

 Laveran traveled to Africa in search of a chemical substance which 

 would prove of value in the treatment of trypanosomal diseases such 

 as malaria and sleeping sickness. Choosing arsenic from among the 

 heavy metals, Laveran successfully developed the arsanilates, and 

 for his biochemical discoveries was the recipient of the 1903 Nobel 

 prize. Ehrlich and Robert Koch went further in his researches. From 

 their work came salvarsan and neoarsphenamine. These were the 

 first potent agents against the protozoan disease, syphilis. 



Other than the discovery of the arsenicals there were no striking 

 advances in chemotherapy until Hoerlein's researches in 1910, in the 

 use of certain sulfonamide-substituted azo dyes. Even he failed to 

 recognize the value of his discovery. 



THERAPEUTIC INDEX 



It must be remembered that the value of a chemotherapeutic agent 

 against disease is determined by what is known as the therapeutic 

 index. Pharmaceutical research workers use the mathematical ratio 

 of "high killing power on bacteria or protozoa causing disease" as the 

 numerator of a fraction, the denominator of which is "low toxicity or 

 killing power on animals and patients." Thus many chemicals would 

 be effective against pneumococci of pneumonia or in combatting the 

 organisms causing some other disease, but at the same time they would 

 probably kill the patient. The higher the killing power against micro- 

 organisms and the lower the toxicity, the better the drug. 



