The electron microscope has been around for a while—there were prototypes as early as 1931—but it had serious limitations for biologists. Samples must be contained in a vacuum, which dries out biological molecules and warps molecular structures. Then the samples are pelted by a beam of radiation that can fry sensitive biomolecules. Beginning in the 1950s, x-ray crystallography allowed biologists to create static images of the structure of proteins. But it requires obtaining copious amounts of purified protein and then coaxing all the identical copies to pack into a regular crystalline orientation—impossible for many large proteins and multi-protein complexes. In the 1980s, nuclear magnetic resonance began providing protein structures, but mostly for small proteins in solution
http://www.sciencemag.org/news/2017/10/cold-clear-view-life-wins-chemistry-nobel
