1 58 THOMPSON YATES AND JOHNSTON LABORATORIES REPORT 
combining physically or chemically (in unstable combination) with the anaesthetic, 
that the concentration of the anaesthetic in that substance of the cell must vary 
inversely as the solubility of the anaesthetic in water, because the anaesthetic distributes 
itself always according to its relative solubilities in the two media between which it is 
distributed. 
This, we maintain, is all that is shown by the experiments of Meyer and 
Overton, who have not experimented with the lipoids, but with olive oil, to which 
no one attributes the production of anaesthesia, and we regard it as dangerous to 
transfer the results of experiments made with olive oil and water to lecithin or other 
lipoids, and water 1 . 
Again, determinations have not been made, except in a few cases, of the coefficient 
of distribution of the anaesthetic between even olive oil and water, but instead, only 
rough determinations of the maximum solubilities in these two media. Also, one 
meets in, by tar, the greater number of Overton's experiments with the statement 
that the anaesthetic, under experiment, is soluble in all proportions in one or other of 
the two solvents, usually the olive oil. In fact, throughout whole tables of comparison 
of different anaesthetics belonging to the same organic group, it is observable that the 
whole of the substances tested are soluble in olive oil in all proportions, and hence, 
there is no means of knowing what influence relative solubilities in olive oil possess 
since such relative solubilities do not exist. Under such circumstances it is impossible 
to tell how the coefficient of distribution is varying, for, of course, the fact that an 
anaesthetic is soluble in all proportions in olive oil, and has only a low solubility in 
water, does not indicate that the coefficient of distribution between olive oil and water 
is infinity. For example, quoting the figures given by Overton 2, for two cases, ether 
is soluble in all proportions in olive oil, and dissolves to the extent of 6*6 per cent, 
in water, yet its coefficient of distribution between oil and water is only 4/5 ; chloro- 
form is soluble in all proportions in olive oil, and in water to 0-72 per cent., yet its 
coefficient is only 30 — 33. 
The observation that the anaesthetizing power of indifferent organic substances 
such as chloroform and ether vary inversely as their solubility in water had already 
been made by Richet, and is referred to by Overton 3 as Ricbefs rule ; but Richet 
thought the explanation a different one, and ascribed the action to the fact that such 
substances being but feebly soluble in water, did not normally enter into the cell or 
act upon it, and hence exerted a toxic action when they did enter. This explanation, 
1. The explanation given for the use of olive oil, instead of the lipoids, or lecithin, is, that the latter are so difficult to 
isolate in sufficient quantity for the experimental determination of the coefficients of distribution ; but an ethereal extract of 
brain can easily be obtained in large quantities, and lecithin can now be isolated in large quantity, and with, comparatively, 
little expense from either brain or egg yoik (see paper succeeding this in the present volume, p. 201). A real difficulty in 
determining these coefficients in the case of lecithin or the lipoids, lies in the physical properties of these bodies, which are not 
fluids, but plastic solids, and hence it is not possible to bring a mixture of these and water into equilibrium with such solvents 
as chloroform, etc., and then to determine the fractions of the chloroform, etc., in the lecithin, or lipoids, and in the water 
respectively. The difficulty is still further increased by the swelling up and suspension of the lipoids, or lecithin, in the water. 
2. Overton, Studien uber die Narkose, SS. 96 and 100. 
3. Ibid., S. 45 
