962 



SCIENCE 



[N. S. Vol. XXXVII. No. 965 



hibited by substances of the most diverse 

 chemical character. Acids in low concen- 

 tration depress the irritability of many 

 tissues ; in some cases alkali has this effect ; 

 gases like carbon dioxide and nitrous oxide 

 have marked anesthetic action ; solutions of 

 magnesium, calcium and strontimn salts 

 cause local anesthesia in frog's muscle and 

 nerve; pure solutions of sugar and other 

 indifferent non-electrolytes have similar 

 effects ; in these tissues irritability depends 

 on the presence of certain electrolytes, espe- 

 cially sodium salts, in the media and re- 

 turns on replacing the tissues in solutions 

 containing these salts. But the most sig- 

 nificant relationships are seen in the case 

 of the large class of substances, differing 

 widely in chemical constitution and prop- 

 erties, which possess in common the phys- 

 ical property of dissolving fats or of dis- 

 solving in fats. These substances include 

 the majority of the anesthetics in common 

 use, as ether, chloroform, ethyl chloride, 

 urethane, etc. The connection between fat- 

 dissolving power and anesthetic property 

 was in fact early recognized — first by 

 Bibra and Harless in 1847 ; and this rela- 

 tionship is of great physiological signifi- 

 cance, since it indicates that the anesthetic 

 is selective in its action on the cell constitu- 

 ents, and produces its effects by changing 

 the state of fatty or fat-like substances in 

 protoplasm. It indicates further that the 

 state of these substances determines the de- 

 gree of irritability of the cell. All cells, so 

 far as known, contain such substances; 

 they are the so-called "lipoids" which in- 

 clude lecithin and cholesterin, and various 

 other ether-soluble compounds of usually 

 complex constitution. Historically these 

 substances were first grouped into a class 

 simply on account of their fat-like solubili- 

 ties, so that they form, chemically speaking, 

 a somewhat heterogeneous group, some 

 members of which, as cholesterin, are not 



fats in any sense. Others, as lecithin, are 

 more closely related to the fats proper. 

 They appear to be invariable constituents 

 of protoplasm — a fact which in itself is not 

 surprising in view of the amino-acid consti- 

 tution of proteins: since proteins are 

 largely derivatives or condensation-com- 

 plexes of amino-fatty acids, fat-like sub- 

 stances might be expected to appear in cells 

 during metabolism. It is clear, however, 

 that these substances are not mere by-prod- 

 ucts of protein metabolism, or reserve ma- 

 terial like fats, but play a fundamental role 

 in cell-processes; the profound physiolog- 

 ical effects produced by all lipoid-solvent 

 substances are a sufficient proof of this, al- 

 though regarding the precise nature of this 

 role we know little as yet. In some intimate 

 way the lipoids appear to be essential to 

 the irritability of the cell, and altering 

 their state causes corresponding changes of 

 irritability. 



About fifteen years ago Overton and 

 Hans Meyer investigated the relation be- 

 tween the lipoid-solvent power of a large 

 number of organic anesthetics and the in- 

 tensity of their narcotic action, and reached 

 independently the conclusion that the 

 chief factor determining this action was 

 the value of the partition-ratio of the an- 

 esthetic between water and a typical lipoid 

 like lecithin. That is, for any series of 

 lipoid-soluble compounds the narcotic ac- 

 tion increases as the lipoid-solubility in- 

 creases and the water-solubility decreases. 

 These two solubilities usually show an in- 

 verse relation to each other. Now, the view 

 that this form of anesthetic action depends 

 essentially upon a modification of the cell- 

 lipoids — which was put forward simultane- 

 ously and independently by Overton and 

 Meyer — is undoubtedly well founded, and 

 is accepted by most physiologists, even 

 although in the absence of any definite and 

 final knowledge of the physiological role 



