THE THEORY OF ANESTHESIA. 347 



thesia: "The irritable substance in protoplasm is a molecular 

 oxygen-protoplasmic union or a peroxide union, unstable and 

 similar to oxy-haemoglobin. By stimulation this unstable mol- 

 ecular union passes by molecular rearrangement into a stable 

 form, oxidation taking place and carbon dioxide being directly 

 or indirectly produced. The anaesthetic produces anaesthesia by 

 occupying the oxygen-receptors of the cell, thus forming a non- 

 irritable, dissociable, anaesthetic-protoplasm compound. The va- 

 rious facts of anaesthesia are explicable on this theory." 



Now it is a striking fact that the concentrations of the lipoid- 

 solvent anaesthetic required to inhibit oxidations under the 

 influence of enzymes, inorganic catalysts, or dead cells are far 

 higher than those required for true anaesthesia, and are closely 

 similar in their order of magnitude to the cytolytic concentra- 

 tions. As already mentioned, Vernon found that the concentra- 

 tions at which the activity of the kidney-oxidase began to be 

 decidedly lowered corresponded closely with those found by 

 Fuhner and Neubauer for haemolysis; i. e., in Vernon's words, 

 "those which dissolve the lipoid membrane of the corpuscles." 

 The concentrations required for anaesthesia in tadpoles are from 

 eight to ten times lower. It thus seems doubtful that the 

 anaesthetic effects can be referred to a direct inhibitory action on 

 oxidases. The prompt and complete reversibility of anaesthesia 

 is also a fact unfavorable to this view. According to Vernon's 

 results, tissue-oxidases are rapidly destroyed by those concentra- 

 tions of lipoid-solvent anaesthetics which reduce their activity 

 to half its original value. We find, in fact, that in those cases 

 where anaesthesia is associated with decrease of intracellular 

 oxidations, the inhibitory effect is obtained in relatively low 

 concentrations; while in order to induce an equal decrease of 

 oxidations in tissue-extracts, or in disintegrated tissues or cells, 

 the required concentrations must be much higher. In other 

 words, destroying the structure of the tissue destroys its sensitive- 

 ness to the inhibiting action of low concentrations of the anaes- 

 thetic. This fact seems to indicate that the anaesthetic acts on 

 living cells primarily by altering certain organized or structural 

 elements, upon the condition of which the normal rate of oxidation 

 and of other metabolic processes depends. Experiments on 



