DAVID NACHMANSOHN 



of 10^^ to 10'^ molecules. On the assumption that one molecule of 

 acetylcholine may cover 20 to 50 sq. A., 10 to 100 millions of square 

 microns of nerve suiface may be covered by the amount which may be 

 metabolized in one gram of brain in one millisecond. Even if half 

 of the enzyme were localized outside the cell, the figures are still im- 

 pressive and suggestive of a relationship between function and quantity 

 found. 



It is of paramount importance for the investigation of a problem 

 to know the inherent possibilities of methods, as well as their limita- 

 tions. Medicine depends on the use of drugs. Since it cannot wait 

 until the mechanism of their action has been explained, drug effects 

 must be tested on intact cells and intact animals. Such in vivo tests 

 are necessary because, owing to the great number of unknown factors 

 in in vivo studies, the effect of a drug is unpredictable merely on the 

 basis of its affinity for enzymes in vitro and of its possible relation to 

 cell mechanisms. But if we realize this, then, for the same reason, it 

 appears inadvisable to draw any conclusions about the physiological 

 mechanism from drug effects. In any case, it seems difficult to use 

 effects observed with drugs as an argument against conclusions based 

 on biochemical data. 



It is equally important to know the limitations of enzyme 

 chemistry. As mentioned above, only if a number of facts or a series 

 of reactions and some relationship with events in the intact cell have 

 been established can conclusions as to the mechanism become possible. 

 In muscle, several physically recorded changes observed during con- 

 traction could be correlated with chemical reactions. In regard to 

 the mechanism of nerve activity, the observations on the electric fish 

 have permitted the correlation of biochemical data with occurrences 

 observed on the intact animal, and recent experiments on the giant 

 axon of squid have provided direct evidence for the dependence of the 

 nerve action potential on the normal function of choline esterase. 

 Many more are possible even with presently available methods, and it is 

 reasonable to hope that the continuous improvement of the available 

 methods and the development of new chemical and physical methods 

 will open more opportunities for approaching the great number of 

 unsolved problems. There is not yet evidence for the assumption that 

 all chemical reactions supplying energy have already been determined, 

 since the exact amount of heat produced has not yet been correlated 



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