In my attempts to make sense of some of the recent commentaries about single-particle cryo-EM, I found much earlier evidence of excitement about the technique. Arthur Robinson, in a 1976
Research News article published in Science entitled “Electron Microscopy: Imaging Molecules in Three Dimensions,” starts by explaining the principles of 3D reconstruction using Jim Lake’s now-familiar cartoon with ducks and their transforms. The article then goes on with an appreciation of the ground-breaking work by Richard Henderson and Nigel Unwin on the structure of bacteriorhodopsin obtained from glucose-embedded two-dimensional crystals in the purple membrane of the bacterium Halobacterium halobium. The article concludes with the following words: “Joachim Frank of the State of New York Department of Health, Albany, has been exploring theoretical methods for averaging data from arrays of identical objects that are not periodic. If such methods were to be perfected, then, in the words of one scientist, the sky would be the limit.”
Well, we have reached the sky now, but the history of the single-particle techniques that brought us here goes back quite a few years.