CHEMOTHERAPY 125 



This is possibly due to differing reactioiLs of the host 

 to the absolution or excretion of the di'ug. A further 

 possibihty may be the possession by different hosts of 

 different amounts of substances inhibiting the drug, as 

 illustrated by the fact that rats can be protected against 

 streptococcal infections by pantoyltaurine, whilst mice, 

 which normally have a higher concentration of panto- 

 thenic acid in their blood, are not (see p. 149). 



The development of chemotherapy can be regarded 

 as commencing in 1867 with Lister's use of phenol as an 

 antiseptic in surgery, although knowledge existed much 

 earlier of such traditional remedies as mercury and 

 iodides for sjrphilis, cinchona bark for malaria and 

 ipecacuanha for amoebic dysentery and although, many 

 years before the causes of the diseases themselves had 

 been elucidated, the active principle of cinchona bark 

 was shown to be quinine, and ipecacuanha was known 

 to act in virtue of the alkaloid, emetine, which it 

 contained. 



Progress in chemotherapy was greatly hampered in 

 the early days by lack of in vitro methods of testing 

 drugs. Such methods could not be developed until 

 methods of culture of the test organisms were available. 

 Trypanosome infections in rats and mice were originally 

 used for testing drugs against such diseases as sleeping 

 sickness. In untreated animals the parasites progres- 

 sively multiply in the blood stream and death results in a 

 few days. An adequate dose of an effective compound 

 leads to permanent elimination of the parasite from the 

 blood stream, more or less rapidly depending on the 

 drug. In 1930 a method was devised for maintaining 

 tr5rpanosomes alive in vitro for about twenty-four hours 

 and has been of great use in investigating trypanocidal 

 drugs. The study of amoebecides was greatly facilitated 

 by Dobell and Laidlaw's in vitro method of culturing 

 amoeba such as Entamoeba histolytica which causes 

 amoebic dysentery. 



