Giovanni Dietler, EPFL
This year Nobel Prize in Chemistry is awarded to J. Dubochet (University of Lausanne), J. Frank (Columbia University) and R. Henderson (MRC Laboratory of Molecular Biology, Cambridge, UK), who have contributed to the development of electron microscopy up to the point that protein three-dimensional structure can be determined with a spatial resolution of few Ångström using electron microscopy.
This year Nobel Prize is actually awarded for a typical interdisciplinary work. The choice of the Chemistry label is actually just an expedient to award the Nobel Prize to an advancement in a field that does not belong to the classical divisions in science. The interdisciplinarity of this research comes from the fact that at least three elements were needed for the breakthrough: a) freeze the sample without damaging it and without creating water crystals that will interfere with the electron beam; b) have a mathematical procedure to reconstruct from the many 2 dimensional projections of a three dimensional object its 3 dimensional structure; and c) show that it can have a real impact on structural biology (branch of biology whose main task is to determine the 3 dimensional structure of biological samples).
It has to be said that biology has based its endeavor to understand living matter on the now famous dogma which states that “a strict relation between structure and function of a protein” exists. No wonder that biologists were avidly looking for 3 dimensional structures of proteins. The first high resolution structures of biological samples were myoglobin (Nobel Prize in Chemistry, 1962) and DNA (indirectly Nobel Prize in Physiology, 1962) obtained by X-ray diffraction method. X-rays remained the method of choice until NMR arrived (Nobel Prize in Chemistry, 2002). This trend lasted until few years ago when high computing capabilities arrived with modern Transmission Electron Microscopes equipped with direct electron detection cameras: with these improvements combined with cryo-microscopy, the game of structure determination radically changed. The main consequence is an almost exponential growth of the number of protein structures determined by this method and a strong competition between x-ray/NMR methods and cryo-electron microscopy method. It has to be said that x-ray and NMR methods will remain important tools when atomic precision is needed for a given structure.
The Nobel Prize to Jacques Dubochet  recognizes his contribution to the part related with the sample preparation. In fact, it is advisable that biomolecules should be observed and imaged in their natural environment, namely water. But water is not compatible with the vacuum condition required by electron microscopes and therefore the need of freezing the sample arose. This new requirement however came with additional experimental constraints: the frozen water should not be in crystalline state and the thickness should be small enough to permit to the electron beam to traverse it. The water crystals would partially damage the biological specimen while at the same time they would diffract the electron beam. The solution was found in the quick cooling of the sample in liquid ethane which permitted to freeze the water in an amorphous state (liquid like frozen state of water or vitrified state). The other major ingredient was the thickness of the sample on the electron microscope grid which should be thin enough to let the electron beam traverse it: the solution was found in spanning a thin water film on a specially treated electron microscopy grid. Detailed experimental conditions to operate the electron microscope play an important role and a slight defocusing of the electron beam improved the contrast for biological sample at the price of reducing the resolution.
More recently, the recording of the image received a strong impetuous with the Direct Detection Detector (direct electron imaging) and with electron counting techniques: this had the effect of strongly reducing noise and improving resolution. Improvements also in the alignment of the images of the single proteins in order to be averaged contributed to the emergence of cryo-electron microscopy combined with the increased computer power.
What should we expect for the future developments? Where is biophysics now heading? The physics community is already preparing the next revolutions along two paths: one is the single protein structure determination  and the other is the ultrafast X-ray diffraction method for investigating dynamics of biological molecule with atomic resolution using the x-ray free electron laser  and Switzerland is at the forefront of these revolutions.
 J. Dubochet, Biophysical J., 110 (2016) 756-757.
 J.-N. Longchamp et al., PNAS, 114 (2017) 1474-1479.
[Released: November 2017]