I.—PHYSIOLOGY. 217 
_ there are some curious records of treatment in man, in which the symptoms 
of sleeping-sickness have disappeared, but the trypanosomes are still 
found in the cerebro-spinal fluid, suggesting that, though the parasites 
have not been killed, they have lost their virulence and their power of 
invading the brain substance. 
The features of the action of this remedy, however, which have most 
interest for the physiologist and the biochemist are those related to the 
long persistence of its effect. ‘205’ has a large molecule, but itis extremely 
soluble in water, and diffusible through collodion membranes. How, in 
such circumstances, can we explain the persistence of its sterilising and 
prophylactic action for months after an injection? At first sight one is 
tempted to regard it as incredible that a substance with these properties 
should persist in the body for such a period, and to suggest that the action 
must be due to its stimulation of the body to form its own protective sub- 
_ stances. This possibility, however, seems to be excluded by the fact that 
_ the serum of the protected animal does not lose its curative properties if 
heated. On the other hand, there have recently appeared, some of them 
only in preliminary abstract, a series of highly suggestive observations, 
indicating that ‘205’ has properties of entering into a combination of 
some kind with the serum proteins. After standing for an hour or two 
in serum, ‘ 205’ no longer passes into an ultra-filtrate through collodion, 
and if the proteins are coagulated by heat is not to be found in the filtrate. 
The proteins of the blood, moreover, are stated to lose many of their charac- 
teristic properties by entering into this combination, the blood losing its 
normal power of clotting, and the serum proteins not being precipitated 
by mercury salts or tannin. 
It would be both useless and presumptuous for a mere onlooker to 
speculate in detail on the significance, for the curative action of * 205,’ of 
properties which are only now beginning to be investigated. One conclusion, 
however, I think we are entitled to draw. It is sufficiently evident that 
here is no question of a substance curing simply on account of its 
affinity for parasites and lack of affinity for the host’s tissues. What direct 
action on the parasite ‘205’ itself may possess has still to be demon- 
strated ; we may feel reasonably certain, on the other hand, that its 
affinities for the constituents of the host’s blood and tissues play an 
important part in its remarkable and peculiar curative properties. 
ll. DERIVATIVES OF ARSENIC. 
In the case of the other series of investigations which I mentioned, that 
dealing with the organic derivatives of arsenic, we find again many 
difficulties, in the way of the simple theory, of a cure due to distribution by 
chemical affinities. None of the compounds of this series, which have 
reached practical trial and success in the treatment of spirochetal or 
trypanosomal infections, atoxyl, salvarsan, or tryparsamide, has a 
directly lethal action on the parasites in dilutions at all comparable to 
those which can be safely and effectively produced in the body of the host. 
The paradox of this direct inertness of atoxyl, the starting-point of the 
‘Series, seemed to be explained when Ehrlich showed that its reduction to 
the corresponding arsenoxide produced a substance with an intense 
