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In 2017, the Nobel Prize in Chemistry was awarded to three key pioneers in the birth and development of cryoelectron microscopy (cryo-EM):  Dubochet, Joachim Frank, and  Henderson. As a starting graduate student in England, moving from physics to biology and the study of macromolecular structure, I had the fortune of attending one of the early conferences in the, at the time, embryonic field of cryo-EM. It was 1990, and  Dubochet (Fig. 1), whom I met at the conference, and coworkers (1) had provided the scientific community a few years before with a simple, highly practical way to “vitrify” solutions of biological samples that they used, for example, to visualize intact viral particles (2). Dubochet’s charming recounting of the early days in his own words can be found in a recent perspective (3). By then, there was already access to commercially available cryoholders to use standard transmission electron microscopes for the study of frozen-hydrated samples. Thus, major practical bottlenecks had already been overcome, but the cryo-EM community could still be counted on one’s fingers. That year of 1990 saw the publication of the long-time-coming atomic model of bacteriorhodopsin using electron crystallography (not quite vitrified, discussed below) by Henderson et al. (4) (Fig. 2). This publication was the needed demonstration that electrons could provide this kind of detailed structural description of radiation-sensitive biological samples. That paper became a true inspiration for me and for a whole generation of cryo-EM practitioners.Fig. 1. Jacques Dubochet. Image courtesy of Felix Imhof (photographer), © Universite de Lausanne (UNIL).Fig. 2. Richard Henderson. Image courtesy of Medical Research Council (MRC) Laboratory of Molecular Biology.While there was a very long history of the electron microscope’s use to visualize both cellular ultrastructure and molecular architecture, few were aware, at the time, of the capabilities of the technique to … [↵][1]1Email: enogales{at}lbl.gov. [1]: #xref-corresp-1-1

Profile of Joachim Frank, Richard Henderson, and Jacques Dubochet, 2017 Nobel Laureates in Chemistry