T.—PHYSIOLOGY. 215 
influence of the body fluids and tissues into something which is effectively 
lethal for the parasite ; or, again, that the effect of the drug is not directly 
to kill the trypanosomes, but, leaving their individual vitality and motility 
unimpaired, so to modify them that they have lost the power of rapidly 
reproducing themselves and invading the fluids and tissues of the mouse’s 
body—in other words, have lost that complex of adjustments to the various 
factors of the host’s natural resistance which we crudely summarise as 
‘virulence.’ Such possibilities involve either storage or modification of 
the dye by the host’s tissues, or their essential co-operation in its curative 
effect. 
One other active dye must be mentioned as providing the link with a 
recent, most important advance. Mesnil and Nicolle in 1906 made some 
promising experiments with a dye, Afridol violet, which differed from any 
previously tested, in that its central nucleus was diamino-diphenyl-urea. 
NH, OH 
Py N= —NH—CO—NH— 
NaO,8 ANG A S0,Na 
OH NH, 
TRE ig te La 
NaO,8 ae y S0,Na 
Afridol violet. 
From this time onwards there was no further public indication of progress 
along these lines until 1920, when Hiindel and Joetten published the results 
obtained with a remarkable substance which, as the result of some fifteen 
years of continuous work by their scientific staff, had been introduced by 
the great dye and chemical firm of Bayer. This substance, which is nota 
dye, but the colourless, water-soluble salt of a complex sulphonic acid, has 
hitherto been known as Bayer ‘ 205,’ and, for reasons which need not con- 
cern us, the firm decided not to publish its formula. To students of their 
patent specifications, however, it seemed pretty certain that it would 
prove to be one of a long series of compounds, formed of chains of amino- 
benzoyl radicles, united by amide linkages, with a central urea linkage, 
like the dye last mentioned, and terminal naphthylamine sulphonic acid 
groupings. A number of these substances, having no diazo-linkages, 
were not dyes, but there was no indication as to which constitution, out 
of an immense number possible, would prove to be that of the remarkable 
substance numbered ‘ 205.’ There is a reasonable probability that its iden- 
tity has now been settled by the recent work of Fourneau and his co-workers 
in the Pasteur Institute, who made and investigated an extensive series of 
compounds of this general type, and found one, which they numbered 
*309,’ which conspicuously excelled all others, even those closely related 
to it, in the favourable ratio which it displayed, between'a just toxic dose 
and that which caused a trypanosome infection in mice to disappear. 
Asin the case of ‘ 205,’ the ratio, the ‘ chemotherapeutic index ’ of Ehrlich, 
was found by Fourneau, in some experiments with his compounds, to 
