VOL. 4 (1950) MUSCLE CHEMISTRY AND NEUROPHYSIOLOGY I27 



thus giving the first well founded evidence for chemical events, and suggesting that 

 glucose and lactic acid increase at the expense of glycogen. It seems almost unbehevable 

 that M. v. Frey wrote even in 1909 about chemical changes in muscular activity . . . 

 "which acid is responsible cannot be stated to-day, since lactic acid seems not to account 

 for it" (referring to the acidification of active muscle!) 



The importance of phosphates seems to have been recognized for the first time 

 by Salkowski^", who described the liberation of inorganic phosphate from an organic 

 compound during activiry, a finding which was rejected by v. Furth, another of those 

 most unfortunate cases (which occur so often!) where the authority of one man has 

 delayed development. 



It was MacLeod^i who took up the point and found that inorganic phosphate in- 

 creased and organic phosphate decreased, and Monari^^ f^^st seems to have observed 

 that the creatine-content of muscle increases with activity (phosphagen not being deter- 

 mined in his experiments). These — in our present point of view — most important 

 findings could not be corroborated at that time to give a clear conception and were 

 almost hurried by a great deal of other chemical evidence which we consider to-day as 

 entirely uninteresting and which filled the periodicals of the time. 



The lactic acid era started in 1907 with the classical paper of Fletcher and 

 HoPKiNS^^, in which they definitely established that fact that lactic acid is formed 

 during activity and that it is absent (or practically absent) in resting muscles. This 

 opened up a vast field and led to Meyerhof's great work, which is summarized in a 

 hypothesis, which was called the lactic acid theory of Hill and Meyerhof. The mile- 

 stones of this development were the discoveries of the Pasteur-Meyerhof reaction, 

 of the independence of initial heat of oxygen, the very accurate measurements of muscle 

 heat by A. V. Hill and his colleagues, and their relation to chemical and calorimetric 

 values obtained by Meyerhof, the extensive study of lactic acid metaboHsm in muscle 

 in all conditions of work, rigour and death, and finally the brilliant adaptation of this 

 theory to muscular work in man by A. V. Hill^^ and his conception of oxygen-debt. 

 It was a one-sided picture — as we all know to-day — and yet it is one of the golden pages 

 of scientific discovery, because every new finding fitted into the theory and led to a very 

 clear conception of what is taking place in a working muscle. It was very fortunate, 

 that Meyerhof published in 1930 his famous book on chemical events during muscle 

 contraction, in which he gave an admirable account of the lactic-acid hypothesis^^. 



The year 1930 brought, what A. V. Hill called the revolution in muscle physiology. 

 Lundsgaard's^^ paper on mono-iodoacetic acid poisoned muscles and the absence of 

 lactic acid formation in these muscles was — as it seemed at first — a heavy blow to the 

 lactic acid hypothesis. It is very interesting to read to-day the conclusions Bethe^' 

 drew at that time and it is equally astonishing to see, how quickly Meyerhof reacted 

 and how he and Lundsgaard kept the lead. The conception of energetic coupling 

 between different reactions was worked out and proved to be a new and extremely 

 useful aspect in the classification and understanding of the chemical events including 

 adenylpyrophosphate, creatinphosphate and fructosediphosphate breakdown. Ritchie^* 

 introduced the idea that all chemical events might be recovery processes and therefore 

 furnish the energy for the next contraction. This led to the conception that energetically 

 coupled reactions furnish in steps the necessary free energy to restore the energyloss 

 which occurs in an explosive way during contraction. This conception has been recently 

 summarized by Meyerhof^^ in an article which contains all the classical points of view 

 References p. izg. 



