Heredity in Protozoa 509 



the blood is repopulated by a relapse strain. This relapse strain is re- 

 sistant to the trypanocidal antibody which is still present in the host and 

 is still active against the original strain {passage strain). Two explana- 

 tions have been suggested: (1) the activity of the antibody brings about 

 selection of a resistant strain (the relapse strain) from an originally mixed 

 population; (2) as the result of an antigenic change, the trypanocidal 

 antibody is no longer specific for flagellates which give rise to the relapse 

 strain. The second interpretation receives support from the fact that an 

 infection started with a pure line of T. brucei showed the usual develop- 

 ment of a relapse strain (67). The treatment of different strains of Para- 

 mecium aurelia with homologous antisera also has induced antigenic 

 changes which are inherited (89). 



Similar phenomena have been observed in chemotherapy of trypano- 

 somiasis. Most of the flagellates are killed, but a few may survive to pro- 

 duce a resistant strain — often termed an "arsenic-fast" or "antimony-fast" 

 strain, depending upon the type of drug, although such a designation 

 may not be entirely accurate. In tests of several substituted phenylarsen- 

 oxides, for instance, trypanosomes have seemed to develop resistance to 

 substituent basic or acidic groups on the phenylarsenoxide molecule 

 rather than to the arsenoxide group as such (72). This drug resistance 

 may persist for long periods. Strains of T. rhodesiense have remained 

 resistant to atoxyl, tryparsamide, and acriflavine for 7.5 years through 900 

 mouse transfers (52), and to atoxyl for 12.5 years through 1,500 mouse 

 transfers (17). A strain of T. brucei was still tryparsamide-resistant after 

 59 transfers through guinea pigs and four through Glossina 7norsitans 

 (52). A tryparsamide-resistant strain of T. rhodesiense has been produced 

 also by repeated treatment of the flagellates in vitro. The trypanosomes 

 were exposed to the drug, washed, and then inoculated into a mouse. 

 The strain was recovered from the mouse and the procedure was repeated 

 a number of times, with the result that the flagellates became at least 

 500 times as resistant as the original stock (103). Among the malarial 

 parasites, Plasynodium gallinaceum has inherited paludrine-resistance in 

 five cyclical transfers through mosquitoes without intervening drug treat- 

 ment (4). The mechanism involved in development of resistance to drugs 

 is unknown. One suggestion is that resistant trypanosomes have lost their 

 normal ability to absorb active drugs (23). In addition, differences in 

 stainability of normal and resistant strains have been demonstrated, and 

 the development of resistance may accompany shifts in isoelectric points 

 of various trypanosomal proteins (72). 



Although genetic significance has not been considered m many studies 

 of acclimatization in free-living Protozoa, inherited modifications have 

 been reported in a few instances. Neuschloss (53, 54) acclimatized Para- 

 mecium caudatum to quinine, arsenic and antimony compounds, and 



