VOL. 4 (1950) A CHALLENGE TO BIOCHEMISTS 7 



off one phosphate is about 0.05 cal/g, corresponding to about 20 twitches. Is it not 

 possible that as stimulation proceeds a balance is reached at some intermediate level 

 between breakdown and restoration ? That is the case with phosphagen and lactic acid ; 

 in a muscle steadily stimulated (in the presence of oxygen) a certain amount of phos- 

 phagen is broken down, a certain amount of lactic is formed, and a steady level is reached 

 between breakdown and recovery. At a still earlier stage one might expect steady 

 stimulation to provide at least a temporary balance between ATP breakdown and 

 restoration. 



In frogs' muscles at 20° C, if ATP were the only source of energy a maximal tetanus 

 would lead to its complete breakdown in about 0.5 sec. The suggested balance, if it 

 occurred, would presumably be reached within that time, and when the stimulus ended 

 restoration of the ATP might be completed within another 0.5 sec. The times involved 

 are far too short for chemical manipulation: but biochemists need not be disheartened, 

 frogs' and rabbits' muscles are singularly ill-suited to the enquiry, they are much too 

 quick, why not use muscles which contract more slowly? The muscles of the Mediter- 

 ranean land tortoise, Testudo graeca, commonly imported before the War into England 

 and sold on barrows for i/- in London streets, take about fifteen times as long to con- 

 tract as those of a frog and their speed can be further reduced about nine times by 

 lowering the temperature from 20° C to 0° C, or about five times by lowering it to 5° C. 

 This means that the time available for chemical manipulation can be reckoned in large 

 fractions of a minute instead of fractions of a second. Provided, therefore, that the 

 chemical technique is capable of determining a substantial part of the total ATP with 

 reasonable accuracy, the time involved can be made so long that sufficient resolution 

 ought easily to be obtained. 



The experiment ought certainly to be made and nobody could make it better than 

 Otto Meyerhof — for he knows how to handle living muscles. The result may not be 

 unequivocal — but it very well may. If no change in ATP is found, but only a change 

 in phosphagen, the status quo remains and we can all believe what we like, provided 

 it is consistent with the physical facts described below. But suppose it is found that 

 ATP is broken down at a rate decreasing from the start, reaching a steady concentration 

 after half a minute's stimulation (corresponding to half a second in a frog's muscle at 

 20° C) and is restored to its original level after (say) a further half minute of rest and 

 recovery. Then at least we can be assured that ATP is really concerned either with the 

 contractile process itself, or with the very early stages of recovery. There are other 

 possibilities and, without trying, it is useless to speculate tco much. A German clinician is 

 said to have remarked : "Der Versuch muss gemacht werden und sollte er hundert Bauem 

 kosten". A decision on this important matter is certainly worth a hundred tortoises. 



But whatever may be the outcome of this challenge to biochemists, I would invite 

 them also, in their speculations about muscle, to take note of the following facts, all 

 referring to contraction and relaxation, as distinguished from recovery. 



1. There is no sign of an endothermic process at any stage of contraction or relaxa- 

 tion. If endothermic processes occur they are balanced, or overbalanced, by exothermic 

 ones. 



2. No heat at all is produced during relaxation, apart from that derived from the 

 degradation of work previously performed during contraction (in raising a load, or in 

 stretching elastic material in series with the muscle). When a muscle relaxes without 

 load or tension, no heat is produced after the contractile phase is over. 



References p. 11. 



