In 1961, an inventive Englishman, named Peter Mitchell, proposed a radically novel hypothesis to explain how energy is conserved during respiration and photosynthesis, and applied to the generation of ATP and other kinds of functional work. The chemiosmotic hypothesis sparked an intense controversy that lasted for 15 years. Today, Mitchell's conception of proton currents and their role in phosphorylation and active transport is generally accepted, and has ramified into many corners of cellular physiology. His most profound contribution may have been (...) to introduce spatial direction into biochemistry, and thereby transform our perception of the relationship between molecules and cells. BioEssays 23:848–855, 2001. © 2001 John Wiley & Sons, Inc. (shrink)