PRESIDENTIAL ADDRESS. 683 



familiar fact that the concentration of water plays a large part in the position 

 of equilibrium attained in reversible reactions of hydrolysis and synthesis. A 

 synthetic process is brought about by diminution of the effective concentration 

 of water. There are, doubtless, means of doing this in the elaborate mechanisms 

 of cell life, and, in all probability, it is by adsorption on surfaces, which are 

 able to change their ' alfinity ' for water. 



I pass on to consider briefly some other cases in which the phenomena at 

 phase boundaries require attention. 



Let us turn our gaze from the interior of the cell to the outer surface, at 

 which it is in contact with the surrounding medium. From the nature of 

 adsorption there can be no doubt that, if the cell or the surrounding liquid 

 contains substances which decrease surface energy of any form, these constituents 

 will be concentrated at the interface. There are many such substances to be 

 foimd in cells, some of lipoid nature, some proteins, and so on. Further, the 

 experiments of Ramsden have shown that a large number of substances are 

 deposited in surface films in a more or less rigid or solidified form. We are 

 thus led to inquire whether these phenomena do not account for the existence 

 of the cell membrane, about which so much discussion has taken place. We find 

 experimentally that there are facts which show that this membrane, under 

 ordinary resting conditions, is impermeable to most crystalloids, including 

 inorganic salts, acid.s, and bases. There is no other explanation of the fact that 

 the salts present in cells are not only in different concentration inside from that 

 outside, but that there may be absence of certain salts from one which are 

 present in the other, as, for example, sodium in the plasma of the rabbit not in 

 the corpuscles. Moreover, the experiments of Hoeber have shown that electro- 

 lytes are free in the cells, so that they are not pi'evented from diffusion by being 

 fixed in any way. The mere assumption of a membrane impermeable to col- 

 loids only will not account for the facts, since, as I have shown in another 

 place, this would only explani differences of concentration, but not of com- 

 position. The surface concentration of cell constituents readily accounts for the 

 changes of perme.ability occurring in functional activity, since it depends on 

 the nature of the cell protoplasm and chemical changes of many and various 

 kinds occur in this system. If such be the nature of the cell membrane, it is 

 evident that we are not justified in expecting to find it composed of lipoid oi 

 of protein alone. It must have a very complex composition, varying with the 

 physiological state of the cell. Indeed, complex artificial membranes have been 

 prepared having properties very similar to that of the cell. 



This view that the membrane is formed by surface condensation of coii; 

 stituents of the cell l^ea•dily accounts for the changes of penneability occun-ing 

 in functional ;i«tivity, since its composition depends on that of the .cell proto- 

 plasm, and chemical changes of various kinds take place in this system, as it 

 ie scarcely necessary to remind you. In fact, the cell membrane is not to be 

 regarded as an independent entity, but as a working partner, as it were, in 

 the business of the life of the cell. In the state of excitation, for example, 

 there is satisfactory evidence that the cell membrane loses its character of 

 semi-permeability to electrolytes, &c. This statement has been shown to apply 

 to muscle, nerve, gland cells, and the excitable tissues of plants, as well as to 

 unicellular organisms. We shall see presently how this fact gives a simple 

 explanation of the electrical changes associated with the state of activity. 



If, then, the cell membrane is a part of the cell system as a whole, it is not 

 surprising to find that substances can affect profoundly, although reversibly, 

 the activities of the cell, even when they are unable to pass beyond the outer 

 surface. The state of dynamic equilibrium between the cell membrane and 

 the rest of the cell system ie naturally affected by such means, since the 

 changes in the one component involve compensating ones in the other. Inter- 

 esting examples of such actions are numerous. I may mention the effect of 

 calcium ions on the heart muscle, the effect of sodium hydroxide on oxidation 

 in the eggs of the sea-urchin, and that of acids on the contraction of the jelly- 

 fish. Somewhat puzzling are those cases in which drugs, such as pilocarpine 

 and muscarine, act only during their passage through the membrane and lose 

 their effect when their concentration has become equal inside and outside the cell. 



The work of Dale on ana.phylaxi3 leadg him to the conclufiion that the 



