The Nobel Prize in chemistry this year goes to the three pioneers of cryo-electron microscopy, a technique that takes accurate and detailed pictures of living things at atomic scales.
Developed over decades by laureates Jacques Dubochet at the University of Lausanne in Switzerland, Joachim Frank at Columbia University, and Richard Henderson at the MRC Laboratory of Molecular Biology in the United Kingdom, cryo-electron microscopy is a rare feat of science and engineering that makes things both simpler and better. Using it, scientists have made high-resolution, 3D images to target cancer drugs and demystify the Zika virus.
It’s become such a valuable tool that last year, the National Institutes of Health named cryo-electron microscopy its “method of the year.” The acting director of the National Cancer Institute noted he was particularly excited about its potential for advancing structural biology and cancer drug development.
Previously, researchers had to make drastic trade-offs when they wanted to look inside the smallest units of life. Visualizations of cell function required cumbersome dyes, stains, or labels that would alter their behavior and only provide a coarse picture in only two dimensions.
This left conspicuous blind spots in scientists’ understanding of molecular biology. Most had a sense of what components were important, but were hazy about how they looked and what functions they performed. This was especially true for the structures associated with DNA, the blueprint for all living things.
But in the years between 1975 and 1986, Frank figured out how to stitch two-dimensional micrographs together to yield a sharp 3D picture. In 1990, Henderson was able to use this technique to visualize a protein in 3D down to its atoms with an electron microscope.
Dubochet provided the final piece of the puzzle in the early 1980s. He found that by rapidly cooling a specimen before putting it in an electron microscope, water would form a solid shell without freezing, keeping biological structures in their original shape while they are scanned.
What all these steps eventually yielded was the ability to take biologically-accurate snapshots of the tiniest machinery of life mid-movement. That in turn provides scientists with a more detailed look at diseases and the chance to develop better drugs.
In the Zika virus, for example, scientists found unique parts of the pathogen’s structure using cryo-electron microscopy, identifying a potential target for a vaccine.
Cryo-electron microscopy has rapidly improved since its inception as engineers have developed better hardware, with visualizations going from shapeless blobs to detailed structures, as seen here:
And the technique is still getting better. Scientists say it’s still short of the upper physical limit of its resolution and they anticipate better visualizations of biological structures in the coming years. The three laureates will equally split the $1.1 million in prize money.
This is the third prize announced from the Nobel committee this week, with the Nobel in medicine or physiology going to scientists working on circadian rhythms and the Nobel in physics awarded to research on gravitational waves.