CHEMOTHERAPY 123 



a substance which is more harmful tu the parasite 

 than to the surrounding cells and tissues can be applied 

 directly, as did Lister when he used phenol to combat 

 sepsis in surgery, or as is done when flav^ines are used 

 for surface staphylococcal infections, or sulphonamides 

 are dredged into wounds. When the infection is deep 

 seated or general the chemotherapeutic agent must 

 circulate in the blood or lymph in order to reach the 

 organisms and then the body as a whole is subject to the 

 actions of the drug which may be toxic. Moreover, the 

 substance is liable to be excreted or destroyed or in- 

 activated by fixation in the tissues with lowering of the 

 effective concentration. The difficulty is even greater 

 if the organisms are situated in avascular tissue or 

 necrotic areas or inside cells where direct access of the 

 drug carried in the blood is not possible. 



Although a substance may be highly lethal to bacteria 

 in vitro it does not follow that it will be a good chemo- 

 therapeutic agent. Thus Koch, as long ago as 1881, 

 showed that amounts of mercuric chloride many times 

 the in vitro lethal dose when injected into guinea-pigs 

 had no effect on anthrax bacilli, subsequently injected. 

 Similarly Hata showed that an amount of methylene 

 blue, five hundred times that required to kill Borrelia 

 reciirrentis (the causal organism of relapsing fever) in 

 vitro had no influence on the course of the infection in 

 mice. The converse may also be true ; prontosil is 

 without effect on Streptococcus pyogenes when tested on 

 cultures of the organism but is a most useful drug in the 

 treatment of streptococcal infections. 



In all cases its toxicity to the host is the limiting factor 

 which determines w^hether or not a given substance can 

 be used as a therapeutic agent. Almost always a sub- 

 stance which is harmful to micro-organisms is also 

 harmful to the cells of the host so that the choice of a 

 suitable drug depends on the difference in intensity 

 between the two actions. The ordinary disinfectants 



