220 SECTIONAL ADDRESSES. 
be caused to disappear by any dose of atoxyl which the mouse would 
tolerate. The strain, having once acquired this resistance, would retain it, 
on passage through an indefinitely long series of mice, without further 
treatment. Mesnil and Brimont, however, made the remarkable observa- 
tion that, if the strain of trypanosomes was transferred to a rat, it imme- 
diately became in that animal susceptible again to treatment with atoxy]l, 
remained so as long as it was kept in rats, to reacquire its old resistance 
to atoxyl as soon as it was re-transferred to mice. Such a fact seems to 
be not at all explicable on the theory that the directly active agent, to 
which the trypanosome becomes resistant, is a mere reduction product 
of atoxyl; it is much more easily reconciled with a mechanism such as 
that described by Levaditi, in whichaconstituent of the host’stissues enters 
into the formation of the trypanocidal substance. We can imagine 
the trypanosome becoming immune to Levaditi’s mouse-trypanotoxyl, 
and remaining susceptible to the corresponding rat-product. 
The whole question of this acquired resistance of the parasites to the 
action of curative drugs bristles with points of difficulty and interest. 
Ehrlich attributed the sensitiveness of the parasite, for a particular curative 
agent, to the possession by its protoplasmic molecule of a special form of 
side chain, or ‘ chemoreceptor,’ which determined its affinity for that agent. 
When the trypanosome became resistant, it was simple to suppose that it 
did so by losing the appropriate chemoreceptors; an atoxyl-resistant 
trypanosome, for example, had lost its atoxyl receptors. Apart from the 
objections already mentioned, this conception met a new difficulty, when 
in Ehrlich’s laboratory it was found that the resistance was by no means 
as rigidly specific as it had first appeared to be. Not only imperfect 
treatment with atoxyl, but treatment with a particular group of dyes, having 
no kind of chemical relation to it, was found to produce a race of trypano- 
somes resistant to atoxyl and to other arsenical derivatives. To suggest 
that the chemoreceptors for arsenic and for these dyes are identical is 
merely to restate the fact of this reciprocal action in terms having no defi- 
nite meaning. Obviously no more precise conception as to its significance 
can be formed until we know something more of the conditions on which 
resistance and susceptibility depend. A recent suggestion by Voegtlin 
has interest in making, at least, an attempt at interpretation in more 
definite biochemical terms. Voegtlin and his co-workers point out that 
arsenious oxide and its derivatives readily combine with substances con- 
taining a sulphydrile grouping, and find that the toxic action of the organic 
arsenoxides, on trypanosome and mammal alike, is depressed by the 
simultaneous injection of excess of various sulphydrile compounds. 
HS-R ea 
R-As=O +s = RAs. 4H,0. 
S-R 
III. Suggested Reaction of an Arsenoxide with a Sulphydrile 
Compound. 
The work of Hopkins, showing the importance of one such sulphydrile 
compound, reduced glutathione, in the hydrolytic oxidation-reduction 
processes of the cell, suggests to Voegtlin that a combination with such 
groups, and consequent suppression of this vital function, may explain 
