128 A. VON MURALT VOL. 4 (1950) 



of the era. This era might be called the period of phosphorylations and it is character- 

 ized by the discovery of the PARNAS-reaction, the LoHMANN-reaction and the complete 

 series of steps in glycolysis in muscle, with the isolation of the corresponding enzymes. 



In 1939 the myosin period started with the paper of Engelhardt and Ljubimova*°, 

 which was followed by Szent-Gyorgyi and Banga's^^, Needham's^^^ Bailey's^^ and 

 Kleinzeller's^* papers. Myosin, the "muscle machine" or what A. V. Hill has always 

 called the fundamental process, became the center of attention. Myosin had been known, 

 of course, for quite a long time. In 1930 my friend John Edsall and I published experi- 

 ments, which showed that myosin must be the contractile element of muscle. The 

 important point about Engelhardt and Ljubimova's paper is, however, that they 

 found that the enzyme associated with the breakdown of ATP was associated with 

 myosin. With this it became evident at once that there is a close relation between the 

 "muscle machine" and the whole set of coupled chemical reactions. Szent-Gyorgyi 

 and his coworkers^^ have added a great deal of very interesting new information 

 about the nature of the muscle machine and thus we are just now in the midst of a 

 "myosin era". Meyerhof has attached his name to this period by the almost 

 simultaneous isolation of ATP-ase from myosin, first described by Price and Cori^^. 



What is the lesson neurophysiology can learn from this development ? 



1. A rather long period of widespread chemical research has to precede the definite 

 identification of those chemical reactions which are really essential. I am afraid that the 

 smallness of nerve and the impossibility to accumulate break-down products connected 

 with the absence of fatigue in peripheral nerve has prevented any extensive chemical 

 work. Such work preceded the lactic acid era in muscle chemistry. The ground for 

 neurophysiology therefore is not as well prepared as it was for muscle-physiology in 1907. 



2. Once the importance of lactic acid was established, an intensive attack was made 

 from all sides, yielding an astounding amount of information. Looking back it can well 

 be said, that the prejudiced concentration on lactic acid was very much worthwhile! Is 

 acetylcholine in neurophysiology a problem which will prove to be as fruitful as lactic 

 acid was in muscle physiology? I doubt it and I realize that in this respect I disagree 

 with my colleague Nachmansohn^'^ who has published an admirable amount of work 

 on the subject. 



3. In muscle the energy expenditure is the main function. In nerve, nature gives 

 us an opposite example of maximal economy in energy expenditure connected with 

 function. The energy changes are so small that it took even A. V. Hill 15 years to 

 measure them. This renders the task of corroboration between physical and chemical 

 events in nervous excitation extremely difficult and tedious. 



4. In muscle physiology it was possible to study the interesting reactions in vitro, 

 to measure the various steps of glycol^'-sis and to isolate the important enzyme-systems. 

 Sodium fluoride and isoacetic acid have been powerful tools in this work. In nerve- 

 physiology the material is complex and there is, as far as I can see, no definite clue to 

 any chemical reaction of primary importance. Gerard^^ has contributed most valuable 

 studies on nerve-chemistry by working along lines similar to those used by muscle 

 physiologists, but I think he will agree with me in saying, that our knowledge of what 

 is going on chemically in order to restore the energy expenditure of the ionic changes 

 (potassium going "out", sodium going "in" and vice versa, cf. Hodgkin^^) is very far 

 from being satisfactory. I think it is well to emphasize that brain-brei is in no way a 



References p. izg. 



