Frank Low and the first images of the ultrastructure of the pulmonary blood-gas barrier.

Frank N. Low (1911-1998) has the distinction of publishing the first electron micrographs showing the ultrastructure of the pulmonary capillary and particularly the blood-gas barrier. This work in 1952 and 1953 was enabled by the progress in fixation and staining of tissue made by George Palade and was part of the very rapid advance in electron microscopy during the previous 25 years. Low's micrographs clearly showed the three layers of the blood-gas barrier: capillary endothelium, extracellular matrix, and alveolar epithelium. The images immediately resolved the debate about the composition of the blood-gas barrier that had been raging for 100 years. The first published micrographs were rather poor, but the quality rapidly improved and a major event was the first electron micrograph of the human blood-gas barrier published in 1953. These images had an enormous influence on the development of pulmonary physiology and biology. For example, for the first time it became clear that the barrier separating the blood from the alveolar gas was vanishingly thin. The discovery of the extracellular matrix layer ultimately clarified how this barrier, despite its extraordinary thinness, was sufficiently strong to avoid mechanical failure. Despite the major advances made by Low, his name is almost unknown in pulmonary physiology and biology, and perhaps this tribute will help to give him his due.