352 RALPH S. LILLIE. 



centrations are required to produce such effects than to anaes- 

 thetize the intact living cells. Such facts indicate that when 

 anaesthetics influence oxidative and other metabolic processes 

 within the cell, they do so not directly, but through their influence 

 upon some specially sensitive intermediary, which is a part of the 

 organized structure of the cell and itself controls the rate of the 

 intracellular chemical processes. It is this intermediary which 

 is directly influenced by the anaesthetic. Its part may be com- 

 pared to that of a sensitive starter or relay in a complex mechan- 

 ical or electrical system. 



Various general considerations support this view. When an 

 irritable element, e. g., a muscle-cell, is stimulated by a mechanical 

 impact, it is difficult to suppose that the primary effect of this 

 impact is to hasten oxidative processes; it is true that an increase 

 in oxidations does follow, but this effect represents a later stage 

 in the complex sequence of interdependent processes constituting 

 the response to stimulation (and of which the contraction is the 

 most evident). If the muscle is previously treated for a short 

 time with an anaesthetic, or if the magnesium or calcium-content 

 of the medium is sufficiently increased, contraction no longer 

 results. The entire sequence of processes normally following 

 stimulation is prevented. It seems more probable that the 

 primary event in the physiological sequence is the one directly 

 interfered with; if this is prevented so also are the others. It 

 further seems clear that in an irritable cell this primary or deter- 

 minative change must be a surface-change; obviously that part 

 of the irritable element which is directly in contact with the 

 medium is the one first affected by the stimulus; and there is 

 ample evidence that the direct action of many stimuli is confined 

 to this surface-layer. Indirectly the activity of the whole cell 

 is of course affected ; but this must be by means of some influence 

 transmitted from the surface throughout the cell-interior. The 

 nature of this influence forms in fact the chief problem of the 

 physiology of stimulation. 



The fact that a surface-effect is sufficient to set in motion the 

 whole complex apparatus of response in the cell-interior is a 

 cardinal one in any theory of anaesthesia. Unmistakable evi- 

 dence that this is the case is seen in the delicacy of the response 



