 Mitchell’s hypothesis was met with considerable skepticism, in spite of the fact that Mitchell and a co-worker were quickly able to produce experimental evidence in its favor. Specifically, he was able to demonstrate that isolated respiring mitochondria indeed expel protons (thus leading to a detectable acidification of the surrounding solution), as his hypothesis predicted. However, this evidence was dismissed by most of the biochemists at that time as inconclusive. For it was difficult to rule out at that time that the proton expulsion by respiring mitochondria was a mere side-effect of respiration, while the energy coupling was still mediated by a chemical intermediate.