Cryo-electron tomography: the realization of a vision

The vision of using electron tomography (ET) for studying the 3D organization of biological materials – from molecules to cells – emerged in the late 1960s. However it was only in the 1990s that this vision began to materialize. Cryogenic sample preparation techniques replaced the artifact-prone techniques of the past, and automated acquisition schemes made possible the recording of tomographic data sets at subcritical electron dose. The development of advanced image processing methods allowed to extract a maximum of information from noisy tomograms. Today, at resolutions of 2-4 nm, cryo-ET provides unprecedented insights into the molecular organization of cellular landscapes and helps to bridge the gap between molecular and cellular structural studies performed in situ. Here we review milestones in the development of ET which made this