DAVID NACHMANSOHN AND IRWIN B. WILSON 



even more complex than it was suspected. But here too we are 

 in the initial state, and as far as the active membrane of con- 

 ducting cells is concerned there exists not even yet a beginning, 

 especially as to the detailed properties of this structure. 



The generation of bioelectric potentials is one of the most 

 delicate and fastest biological functions known. Obviously, 

 pharmacological methods, i.e., injection into blood vessels of 

 whole animals or the application of chemicals or drugs from the 

 outside, are wholly inadequate as methods of analysis of this 

 mechanism. Such observations may raise interesting problems 

 and occasionally permit conclusions as to certain aspects to an 

 extremely limited extent. A. J. Clark (4) wrote in 1933: 

 "The physical chemist can reasonably hope to simplify his con- 

 ditions and to reduce the number of variables, until he obtains 

 a system that provides formal proof of the laws which he enun- 

 ciates, but the pharmacologist is interested in the action of 

 drugs on the living cell and any attempt to simplify this material 

 results in death. Hence he cannot hope to obtain formal proof 

 for his theories and must be content with intelligent guesses. 

 Even in the most favorable cases where quantitative relations 

 have been established for the action of drugs on cells there 

 probably remain dozens of unknown variables, and there is 

 usually a considerable range of possible alternative explana- 

 tions." 



Certain factors, as for instance the existence of permeability 

 barriers surrounding nerve fibers and impervious to certain 

 chemical structures, have been overlooked for a long time and 

 this situation led to the conclusion that acetylcholine has a 

 physiological function only at synaptic junctions. The experi- 

 mental demonstration of such barriers in a variety of ways has 

 shown that the failure to produce effects with acetylcholine, 

 prostigmine, curare, and related compounds upon the propa- 

 gation of the spike potential does in no way contradict the as- 

 sumption of the essentiality of the acetylcholine system for 

 conduction, but is simply due to the fact that the system is pro- 

 tected by permeability barriers. 



646 



