214 Mutation in Micro- Orr/anisms 



the toxin, it is found, after reinocalation into a mouse, to have acquired 

 a marked resistance to it. A subtilis-toxin-refiisto-nt strain of T. bnwei 

 has been thus produced which remains as such during subsequent animal 

 passages — that is, the acquired resistance of the Trypanosomes is trans- 

 mitted hereditarily. 



Most important and extensive work in this direction has been 

 recently published by Gonder (1911), whose results may now be con- 

 sidered in some detail. The work, was carried out in Ehrlich's 

 laboratory, where it was begun by Werbitzki. 



In his experiments, Gonder used two strains of T. lewisi. These 

 were, first, a strain from wild rats, grown in tame laboratory animals 

 and susceptible to arsenic. An injection of 01 gm. of arsenophenyl- 

 glycin per kilogram body-weight of rat sufficed to kill all the Trypano- 

 somes in its blood. Tliis strain, after numerous passages through 

 normal rats, always remained susceptible to arsenic. The second 

 strain was one which had been made arsenic-resistant'. It was made 

 by accustoming the Trypanosomes to minute but gradually increasing 

 doses of arseuophenylglycin. Finally — after two years — a strain of T. 

 lewisi was obtained which was resistant to the drug to such an extent 

 that it was unafifected by injections of 0"2 gm. per kilo. Passage of 

 this strain through untreated rats showed that the arsenic -resistance 

 had become fixed, and was transmitted hereditarily. At the twentieth 

 passage, the resistance was unchanged". As regards structure, and 

 behaviour in other ways, the Trypanosomes were found to be indis- 

 tinguishable from the normal race. 



Gonder found that both the non-resistant and the resistant race 

 could be transmitted from rat to rat by the rat louse, Haematopinus 

 spinulosus — which is supposed by some workers to be the usual inter- 

 mediate host of T. lewisi in nature. The incubation period in the louse 

 was found to be 15 — 17 days in the case of the normal race (3 rats); 

 25 — 30 days (6 rats) in the case of the arsenic-resistant race. The two 

 races of Trypanosomes were then tested as regards their resistance to 

 arsenic. And the results showed that all the Trypanosomes — whether 

 they had previously been resistant or not — were non-resistant to arsenic 

 after development in the body of the louse. 



' Arsenic-resistant strains of Trypanosomes can be rapidly prodaced by treatment with 

 a number of different organic arsenic compounds, and also by the action of dyes of an 

 ortlioquinoid type (Ehrlich, 1911). 



- Similar arsenic-resistant races of other Trypanosomes had, of course, been previously 

 produced by Ehrlich and others. 



