143 
1919 - 20 .] The Harmala Alkaloids in Malaria. 
ceased to execute even undulatory movements. This effect could not have 
been due to incomplete mixing of the harmaline solution with the blood. 
In the experiment quoted some of the trypanosomes had ceased to move 
in half an hour, whereas a few of them were actively, and to all appearance 
normally, motile five hours later ; the organisms in the control tube being 
meanwhile uniformly active. It is difficult to avoid the conclusion that 
some of the trypanosomes are markedly less susceptible to harmaline than 
others. The phenomenon may be similar to that observed in partial 
haemolysis, where blood corpuscles, exposed to the same concentration of 
a haemolytic agent, may be haemolysed to the extent, for example, of ninety 
per cent., the remaining corpuscles not being haemolysed. This type of 
effect cannot well be due, in the experiment quoted, to some of the organisms 
taking up the poison before the others and leaving too little in the solution 
to kill their fellows, because in that case the effect would not, as it does, 
happen with much stronger solutions containing proportionately four times 
the amount of harmaline to the same number of trypanosomes. 
Possibly these facts may have some bearing upon the problem of the 
treatment of protozoal diseases. For, if this difference in susceptibility 
between the fully developed organisms which is shown to occur in vitro 
occurs also in vivo — as there is every reason to believe it must, — then it is 
clearly possible for a dose of a therapeutic agent to kill off the great 
majority of those organisms and yet leave a few unharmed ; and this sur- 
vival of a few may occur after a much larger dose of the therapeutic agent 
than is necessary to kill the majority of the organisms. If this be true, 
relapses of malaria or trypanosomiasis occurring after treatment, especially 
relapses after a short interval, may be due merely to the survival of a few 
more resistant adult organisms, and not necessarily in every case to the 
persistence of spore forms. 
Experiments in vivo. 
Two types of experiment were employed. In the first, the surra blood 
was exposed in vitro to a solution of harmaline before injection into the 
animal ; in the second, the surra blood and the harmaline were both injected 
subcutaneously into opposite flanks of the animal. Both sets of experi- 
ment were suitably controlled. 
( b ) 27th February 1911. A rat that had been injected with surra four 
days previously was killed, and its blood made up to 8 c.c. with citrated 
saline. Into a small tube A was put 1 c.c. of this blood mixture + 05 c.c. 
citrated saline; into a tube B, 1 c.c. of the same blood mixture -f-0’5 c.c. of a 
solution of the harmaline 1 in 1000 dissolved in the citrated saline solution. 
