I.—PHYSIOLOGY. 2138 
it can be accepted as a safe guide to future progress, as it has undoubtedly 
provided the initiative and working basis for much of what has been 
accomplished hitherto. Before we deal with some of the actual results 
obtained, it may be well to consider a little more closely what Ehrlich’s 
working hypothesis involved. The problem was to discover, by chemical 
synthesis, a compound which, in virtue of its chemical structure, should 
have a maximal affinity for the protoplasm of a microscopic parasite, such 
as a trypanosome, and a minimal affinity for that of the host’s body cells. 
These affinities were pictured by Ehrlich, in the terms of his side-chain 
theory, as determined by certain side-chains of the complex protein mole- 
cule, or chemoreceptors, which endowed the protoplasm with specific 
combining properties. When it is remembered that knowledge of the 
chemistry of the protoplasm of a trypanosome is almost nil, and that what 
little we do know suggests that it is very similar to that of our own cells, 
it will be admitted that the enterprise was one calling for scientific courage 
and imagination in the highest degree. Complete failure would not have 
been surprising ; the matter for surprise, and for admiration, is that so 
_ large a measure of practical success should, at the end of two decades, 
already claim record. 
II. Trypanosomes and Spirochets. 
i. Tue Action oF Dyes AND ANALOGOUS COMPOUNDS. 
The investigations leading, in the last few years, to a clear promise, 
at last, of the successful treatment of the diseases in man and animals 
due to infections with trypanosomes, had at least two different starting- 
points, the action of dyes and the action of arsenic. Ehrlich’s early interest 
in the synthetic dyes, and his observations of the curiously selective distri- 
bution which they often exhibited among the cells and tissues of the body, 
naturally suggested the possibility of finding, in this group, a substance 
which would selectively fix itself to the parasite and poison its protoplasm, 
without injuring that of the host. The technique developed by Laveran 
and Mesnil, by which a particular strain of trypanosomes could be passed 
through a series of mice or rats, and produce an infection of standardised 
type and virulence, enabled the effect of a large selection of dyes to be 
investigated, with the view of finding one which would favourably influence 
the infection. A starting-point having been obtained, the resources of 
synthetic dye production were available to produce an indefinitely long 
series of derivatives and modifications of the active compound, each to 
be tested in its turn. In this way Ehrlich and Shiga arrived at a substance 
which gave experimental promise of curative value, a benzidine dye to 
which the name ‘ Trypan red’ was given. 
SO,H 
este eae 
| | 
NH, H.N 
SO,Na NaO,8 SO,Na 
Trypan red, 
