386 ANNUAL REPORT SMITHSONIAN INSTITUTION, 1946 
Some years ago at the University of California there was a cele- 
bration commemorating the three hundredth anniversary of the intro- 
duction of quinine, in the form of Peruvian or Jesuit’s bark, into 
medicine. On that occasion the late Dr. William H. Welch said that 
the introduction of this drug into medicine was as important as the 
whole concept of infectious disease because prior to its discovery all 
forms of treatment were directed either to purging, to sweating, or 
to causing increased urination in the patients in the hope of expelling 
evil humors. 
Modern chemotherapy had its beginnings in the work of Paul 
Ehrlich, at the turn of the present century. This diligent investigator 
devised the technique of synthesizing many new drugs of slightly 
varying chemical formulas and testing each experimentally. He 
began by studying the effects of drugs in destroying a unicellular 
organism, a trypanosome which had just been discovered to be the 
cause of a disease of horses and which could be transmitted for experi- 
mental study in mice. When, not long after, the cause of syphilis was 
revealed, he was prepared to attack the spirochete in the same way. 
The story of Ehrlich’s epoch-making contribution is one of incredible 
tenacity. It was his six hundred and sixth arsenical compound, sal- 
varsan, which had the desired effect. 
Ehrlich’s object was to sterilize the body of the parasites without 
injuring the body tissues. He sought to do this by giving the experi- 
mental animal or the patient a substance which could be taken inter- 
nally, and thus his purpose differed from that of Lister who proposed 
to destroy bacteria which might have reached an external wound, or 
that of the “aseptic” school which tried to prevent access of bacteria 
to a wound. Ehrlich’s task proved to be a difficult one, for neither 
“606” nor his later compound “14” accomplished such internal steriliza- 
tion without sometimes causing grave injury to the patient. Never- 
theless these agents have proved to be extremely effective for the treat- 
ment of syphilis and the risks involved have been far surpassed by 
the results accomplished. 
It was not until more than two decades later that another compound 
was found equal in importance to the organic arsenicals produced by 
Ehrlich. It is significant that the methods used for the discovery of 
the new drug were essentially the same as those devised by him. As 
long ago as 1915 two American workers (4) studied the bactericidal 
properties of a large series of azo dyes including several sulfonamide 
compounds. They limited their observations to the action of the dyes 
upon bacteria in the test tube and they did not study the effect of these 
dyes in animals. It remained, therefore, for Dr. Gerhard Domagk, 
at the I. G. Farbenindustrie in Germany, to discover an effective 
chemotherapeutic agent against hemolytic streptococcus infection in 
mice. 
