The dawn of muscle energetics: contraction before and after discovery of ATP.

By the beginning of the twentieth century, vitalism was generally rejected and it was accepted that biological organisms obeyed the laws of physics and chemistry. Muscle contraction was thought to be fueled by a chemical reaction. The dawn of muscle energetics began in the early twentieth century when Otto Meyerhof and A. V. Hill made bold attempts to link data from chemical and biochemical studies with those derived from thermal measurements and from the recording of mechanical work. In the search for the direct fuel for muscle contraction, lactic acid formation and phosphocreatine (phosphagen) breakdown turned out to be false trails. Nonetheless, these investigations led to the discovery of ATP and the proposal of the role of ATP as the direct fuel for muscle contraction. Furthermore, this work led to the concept of high-energy phosphate bonds. Glycolysis and phosphocreatine breakdown subsequently were identified as ATP-generating recovery reactions. It was an important and fascinating period in the evolution of muscle research that opened the door for discoveries identifying the universal role of ATP in cellular energetics. This work was done by investigators who lived through turbulent and tragic times between two world wars. The dawn of muscle energetics began in the early twentieth century when Otto Meyerhof and A. V. Hill made bold attempts to link biochemical studies with thermal measurements during muscle contraction. In the search for the direct fuel for muscle contraction, lactic acid formation and phosphocreatine breakdown turned out to be false trails. Nonetheless, these investigations led to the discovery of ATP and the proposal of ATP as the direct fuel for muscle contraction.