DAVID NACHMANSOHN AND IRWIN B. WILSON 



after Claude Bernard's first observations, to achieve this prog- 

 ress and to explain satisfactorily the exclusive action of curare 

 upon the neuromuscular junction and its failure to affect con- 

 duction. But the mysteries and complexities of the living cell 

 will not be revealed even with such methods. Is it really so 

 surprising that by such crude techniques as, e.g., injecting ace- 

 tylcholine into the cell interior, we just interfere with the physi- 

 ological progress but cannot reproduce it exactly? that we 

 cannot reproduce in a precise way the effect of acetylcholine 

 released in a few millionths of a second at very special points 

 either simultaneously or in a special sequence and acting upon 

 the receptor at a distance of a few Angstroms, probably in a 

 highly peculiar and refined structural organization? The 

 warning of Hippocrates : 



■^Seirelpaa-cpaXepr], r)8eKpl(nsxoi\eTrri 



(the experiment is deceptive, the judgment difficult) is certainly 

 true for the study of intact living cells. 



Recognition of the complexity of a function such as conduc- 

 tion, or in fact of any biological function, is the prerequisite for 

 any real progress in analyzing its mechanism. Conclusions 

 based upon biochemical studies permit certain tests on the 

 living cell. It was indeed justified to postulate, for instance, 

 that if the view of the primary role of acetylcholine in conduction 

 was to be accepted, it was necessary to demonstrate the impos- 

 sibility of dissociating conduction and acetylcholinesterase 

 activity. Claims that such a dissociation is possible presented 

 therefore a real challenge. In those cases the experiments were 

 based upon inadequate techniques and the diflSculties over- 

 looked have since been amply explained. With a great variety 

 of techniques and many different types of nerves, conclusive 

 evidence has been provided that a dissociation is impossible and 

 that conduction fails if the enzyme concentration falls below 20 

 per cent of the initial (e.g., 46). The successful demonstration 

 of the necessity of acetylcholinesterase activity for conduction 

 was due to the availability of highly specific inhibitors and the 



648 



