DRUG-FAST STRAINS 151 



action of emetine are discussed below (p. 255). Morgenroth (1918) 

 believes that quinine combines with the red blood-corpuscles, and thus 

 prevents the entry into them of the merozoites of the malarial parasites. 

 Quite recently Yorke and Macfie (1924a) have suggested that in malaria 

 quinine acts by causing a destruction of a certain number of parasites, 

 the broken-down parasites then acting as a vaccine in stimulating the 

 host to produce antibodies, which finally rid the host of all remaining 

 parasites. So far the presence of the antibodies has not been demonstrated. 

 Another illustration of what may be the indirect action of a drug is seen 

 in " Bayer 205." This medicament is remarkably trypanocidal when in- 

 jected into animals infected with certain trypanosomes. Animals which 

 have recovered as a result of treatment or uninfected animals which have 

 received a dose of the drug remain immune from infection for compara- 

 tively long periods. It is possible that this resistance is due to the pro- 

 duction by the host of antibodies as a result of the action of the drug 

 upon its cells. On the other hand, it has to be remembered that when 

 a drug is administered to an animal it does not follow that the drug 

 remains unaltered. The fluids of the body act upon it chemically, and 

 may in this way produce other substances which are definitely toxic to 

 the parasites. It is known that arsenic compounds in which the arsenic 

 is in the trivalent form are toxic to trypanosomes in vitro, and are also 

 therapeutically active, whereas when the arsenic is in the pentavalent 

 form there is no action in vitro, though there is a therapeutic action which, 

 however, requires some time to develop. This difference has been 

 explained by the fact that in the body of an animal the pentavalent 

 arsenic radical is transformed into a trivalent one. 



Another feature of the action of drugs on Protozoa is the development 

 of drug-fast strains. In the case of mice, for instance, infected with 

 pathogenic trypanosomes, the repeated treatment of the infection with 

 such a drug as atoxyl in doses which are insufficient to prevent a sub- 

 sequent relapse will finally result in a strain of trypanosome which is 

 quite unaffected by the drug administered to the animals. This strain 

 maintains its resistance when passed through a series of new mice, but 

 as Mesnil and Brimont (1908 b) discovered, it is susceptible to the drug 

 when inoculated into rats, and is still resistant when again passed into 

 mice. Such a fact appears to be explicable only on the assumption that 

 the trypanosomes have not become resistant to atoxyl itself, but to a 

 substance resulting from the action of the drug on the tissues of the 

 mouse, but not of the rat. Furthermore, it has been demonstrated that 

 trypanosomes can be rendered arsenic resistant by the inoculation of 

 infected mice with substances which contain no arsenic. Many writers 

 refer to quinine-fast strains of malarial parasites and emetine-fast strains 



