Albert Claude and the Beginnings of Biological Electron Microscopy

The grcat potential value of electron microscopy for biological research was often strcsscd and quickly understood in the middle 1930s, at the time when thc first laboratory models of transmission electron microscopes were being built by Ruska, yon Borrics (1, 2), and Marton (3, 4). The reasons were clear: the new instruments were expected to have a resolving power 40-50 times higher than the best light microscopes then available. It was also understood from the bcginning that a new technology was needed for preparing biological specimens for electron microscopy, definitely more refined and in some respects quite different from the traditional histological technology then in use for light microscopy. The limited pcnctrafion power of electrons, and the ease with which thcy arc scattered by any atom required that specimens of unusual thinness-for the thinking and experience of thosc times-bc examined in a relatively high vacuum (~ 10-4 torr). The microtomcs then in use for light microscopy could not cut tissue sections thinner than I t~, while the desirable specimen thickness for electron microscopy was estimated at ~-~0.1 ~ or less. In addition, since the specimens were examined in vacuo, they had to withstand the removal of their volatile components, primarily the removal of water, without collapse or deterioration of their structure. Two choices were available for bringing specimens within the acceptable range of thickness for electron microscopy: comminution or microtomy. In the first alternative, large structurcs were fragmented or dispersed by a variety of mechanical means, and