Wizards of Visualisation
(October 5th, 2017) Jacques Dubochet, Joachim Frank and Richard Henderson win this year's Nobel Prize in Chemistry for developing cryo-Electron Microscopy.
Microscopy again. Only three years after the 2014 Nobel Prize in Chemistry went to Stefan Hell, Eric Betzig and William E. Moerner for their super-resolution microscope technologies, the Nobel Prize committee has once more decided to honour three wizards of visualisation. Swiss Jacques Dubochet from the University of Lausanne, German-born Joachim Frank from Columbia University in New York and Scot Richard Henderson from the MRC Laboratory of Molecular Biology in Cambridge received the prize, worth nine million Swedish krona (ca. €1,000,000), for “developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution”.
Electron Microscopy has long been the only method that scientists could use to visualise miniscule structures, such as organelles or viruses. But this high resolution comes at a price: Sample preparation is laborious and the intense electron bombardment easily destroys the precious sample. Thus, for almost as long as Electron Microscopy has existed - Ernst Ruska received the Nobel Prize in Physics in 1986 for developing the technique in the 1930s - scientists have been thinking about how to improve it.
The three Nobel laureates all did their share to take Electron Microscopy to the next level and obtain ever sharper images of biomolecules. Richard Henderson has experimented with the technique since the 1970's, trying to understand the structure of membrane protein bacteriorhodopsin. Developing different preparation strategies to lower electron intensity, he finally succeeded in 1990 in visualising the protein at the atomic scale. Jacques Dubochet, back then at the European Molecular Biology Laboratory in Heidelberg, had his own ideas for sample preparation. He froze samples so quickly that no ice crystals, which would destroy small structures, could form. Applying his method, Dubochet turned water into a glass-like solid, which doesn't refract the electron beam. Joachim Frank, last but not least, made cryo-EM possible by developing a suitable software and mathematical tools for image analysis. From fuzzy two-dimensional images, the computer creates sharp three-dimensional structures.
Of course, development of the method did not stop in the 1990s. Recently, new and better electron detectors have been developed which increase the signal-to-noise ratio and spatial resolution further. No suprise then that this technology has become ever more popular in life science labs around the world. According to PubMed, numbers of publications have almost doubled within the last three years.
“In a way, cryo-EM is just another method of finding out what the atomic structure - high-resolution structure - of your molecules are. But the difference is there are quite a lot of structures in biology that were resistant, were recalcitrant to the other methods, like x-ray crystallography or nuclear magnetic resonance spectroscopy. So it has opened up essentially a kind of new, previously unapproachable area of structural biology”, says Richard Henderson in his first interview as newly-minted Nobel Prize winner.