214 - SECTIONAL ADDRESSES. 
Two years later, Mesnil and Nicolle, proceeding further along the same path, 
described an even more favourably active blue toluidine dye, ‘Trypan blue.’ 
NH20H 
Ce cing en 
NaO,S kag “er Aiba CH3 
OH NH, 
$US funda Ay Sade, 
CH, NaO,S SO,Na 
Trypan blue. 
This is the only one of the dyes which has hitherto had a genuine practical 
success in the treatment of a protozoal infection, not indeed by a 
trypanosome, but by an intracorpuscular parasite of the genus Piroplasma, 
which infects dogs and cattle. This successful application of Trypan blue 
to an animal disease has a special interest for us to-day, in that it resulted 
from the joint labours of last year’s President of this Section, Professor 
Nuttall, with a Canadian collaborator, Dr. Hadwen. 
We may turn aside at this point to inquire how far the results even of 
these earlier investigations corresponded with the theory which gave them 
their impetus. Did these dyes really act by selectively staining and killing 
the parasites, and leaving the host’s cells untouched ? The evidence was 
certainly not in favour of such a view. Ehrlich and Shiga themselves 
observed that Trypan red, even in relatively high concentrations, was 
practically innocuous to the trypanosomes outside the body. The trypano- 
somes, like other cells, were not stained by the dye until they died, and 
there was no clear evidence that they died sooner in the Trypan-red solution 
than in ordinary saline. Again, Trypan red cured an infection by the 
trypanosome of ‘ Mal de Caderas’ (7. equinum) in the mouse, but not the 
same infection transferred to the guinea-pig, rat, or dog ; nor did it cure 
an infection with the trypanosome of Nagana (TZ. brucei) in mice. Now, 
to explain such a difference by stating that the affinity of Trypan red for 
T. equinum was much higher than its affinity for the tissues of the 
mouse, but not than its affinity for those of the rat, would be merely 
to restate, in terms of the theory, the observed fact that the mouse was 
cured while the rat was not; and the lack of direct affinity for the dye 
shown by trypanosomes outside the body made such an interpretation 
in any case unsatisfactory. One point, however, appeared very significant, 
and it is met repeatedly in studying the action of effectively chemothera- 
peutic substances, namely, that the trypanosomes treated with the dye 
m vitro, though neither obviously stained nor visibly harmed, had lost 
their power of infection, and died out promptly if introduced into the body 
of a mouse. Under such conditions only minimal traces of the dye are 
introduced into the animal, and we are left with a series of alternative 
possibilities. It is possible that sufficient dye has been taken up by the 
trypanosomes to kill them eventually, the period of survival in vitro being 
inadequate to display its action; or that Trypan red is converted by the 
