The study of moving-carrier-mediated transport, of which myoglobin-facilitated oxygen diffusion is the outstanding example, has roots in three separate lines of research. First, Osterhout (279), working in the early 1920’s, developed the idea that some substances, particularly protons, might be carried by lipid-soluble carriers across the oily membranes bounding cells, an idea developed by Jacobs (162, 164), h is contemporary, that is very much alive today. The relation of this phenomenon to myoglobin-facilitated oxygen transport was recognized only in retrospect. Second, Roughton(320), as long ago as 1932, suggested a possible contribution by the diffusion of hemoglobin to the transport of oxygen within the red blood corpuscle. The effect was investigated at first independently in the universities of Cambridge and of Fribourg, Switzerland. The works of these two laboratories culminated in the study of Klug, Kreuzer, and Roughton(195, 196) in which theoretical calculations were joined with experiments on the kinetics of carbon monoxide and oxygen penetration into hemoglobin solutions. In these experiments a thin layer of hemoglobin, at first deoxygenated and exposed abruptly to oxygen in the gas phase, was invaded by an advancing front of free and hemoglobin-bound oxygen. The contribution to the advance of this front made by diffusion of oxyhemoglobin was real but was overshadowed by the capacity of the deoxyhemoglobin to bind oxygen. These experiments have been reviewed by their principal architects Roughton, Klug, and Kreuzer (195, 196, 200-202, 3 19, 32 1) and are not discussed further here.

In 1959 and 1960 Wittenberg(399) and Scholander(330) independently initiated studies of the steady-state penetration of oxygen through hemoglobin solutions, with the intention of building models to mimic the function of myoglobin in muscle. Although at that time it was abundantly evident that myoglobin contributed toward oxygen entry into muscle [reviewed by Wittenberg(401)], it was by no means clear how this was brought about. The condition of steady state, obtaining in the simple model systems adopted in 1959-1960, was appropriate to reveal a very large contribution by myoglobin to the diffusive flux of oxygen. The magnitude of the effect was much greater than anticipated and it became impera-