On October 4th, 2017, the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry to Joachim Frank, Richard Henderson, and Jacques Dubochet for “developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution.” These researchers spent decades at their respective labs at Columbia University, MRC Laboratory of Molecular Biology in the UK, and the University of Lausanne in Switzerland, developing high-resolution, 3-dimensional images of living things at the atomic scale.
So why does this matter? For scientists, pictures are key to understanding processes that occur in nature, such as the mechanisms of sight, or the pathology of diseases.
Unfortunately, this understanding has been largely limited. This is mostly because the available technology has had difficulty generating detailed images of life’s molecular machinery - scientists have been unable to effectively create pictures using the available technology. One of the most advanced imaging tools available is the electron microscope, which uses beams of accelerated electrons that project on a screen to produce highly detailed images of impeccably small substances. However, electron microscopes could initially only be used for imaging dead substances, because the biomolecular structures collapsed in the electron microscope. As a result, researchers had to make trade-offs when they wanted to create images. Visualization required dyes, stains, or labels that would often extensively damage the sample while providing only low-resolution 2-dimensional photos.
This began to change in the 1970’s, when Joachim Frank developed an image processing method to combine these fuzzy 2-dimensional images into a clearer, 3-dimensional structure. This increased the resolution of the blurry images that researchers originally had.
Jacques Dubochet took this a step further in the 1980s. He knew that biomolecules in an electron microscope collapsed because the liquid water in the microscope’s vacuum evaporated. Perhaps, he realized, that by rapidly cooling a specimen by embedding it in a thin layer of ice before putting it in the microscope, he would be able to prevent the structure of the protein from getting destroyed by the electron beam. This discovery provided the final piece of the puzzle - by cryogenically freezing the biomolecule, he was able to keep the biological structures in their original shape while they were being scanned.
In the 1990s, Richard Henderson used these findings to create a 3-dimensional structure of a protein down to the individual atoms using an electron microscope. Researchers now had the tools to routinely produce 3-dimensional structures of biomolecules without destroying them.
These pictures tell us a lot about the world. For example, scientists used cryo-electron microscopy to identify potential targets for a vaccine to the Zika Virus. However, much of this technique still needs to be perfected. Scientists anticipate much better visualizations of biological structures in the coming years, due to improvements in the technology of cryogenics, as well as within the electron microscope itself. Needless to say, the future of Biochemistry just got more exciting.