by which the necessary supply of transformable energy and of building material is secured. Both kinds of reactions are equally responses to stimulation; and both are alike physiologically indispensable. In fact, the characteristic self-conserving or regulatory power of organisms, without which they could not continue to exist, depends essentially upon their ability to respond in this way, i. e., upon their irritability.
It is thus apparently not difficult to understand the general biological significance of irritability. What is still largely obscure, however, is the physico-chemical nature of the mechanism which renders possible the response of an organism to stimulation. Physiological experimentation has enabled us to simplify the problem to some degree. We find that not only the intact living organism, but many of its isolated tissues and even cells, react in characteristic ways to stimulation. This is especially true of the tissues that subserve the motor activities of the animal, the muscles, nerves and sense organs. Thus the problem of the nature of the stimulation-process becomes one of the general problems of cell-physiology, and may be stated as follows: What are the essential physicochemical peculiarities that render the irritable elements of these living tissues so sensitive to stimulation? and what is the physico-chemical nature of the process of stimulation itself? These are the questions which I shall attempt briefly to discuss in this paper. Any answers which can be given at present are incomplete and in part provisional. But recently some definite progress—as it seems to me—has been made toward their solution, and I shall try in what follows to give some account of this recent work and of the more important general conceptions to which it has led.
We have first to define more clearly what we mean by "stimulus" and what by "response." We find on reflection that it is a difficult matter to formulate definitions that are at once exact enough and comprehensive enough to characterize adequately all of the highly varied phenomena included under these terms. We may perhaps best define a stimulus as some change of condition that arouses a previously quiescent tissue or organism to activity, or appreciably modifies the activity of one already active; and the response as the resulting activity or change of activity. In many cases the response may be negative in kind; i. e.; the previous activity may be decreased or completely arrested; inhibition is in fact a very frequent mode of response and one perhaps fully equal in importance to the more positive or active modes as a means of biological adjustment. But what is perhaps the most characteristic peculiarity of the relation between stimulus and response is the fact that there is, broadly speaking, no definable relation of an energetic kind between the two. One of the most striking and distinctive features of stimulation is that an external event or change of condition which causes directly a very slight alteration in the irritable system or organism may yet arouse in
