Method for Capturing the Smallest Details of Life Nabs Chemistry Nobel

With cryo-electron microscopy, tiny living molecules can be seen in their natural states

Nobel Chem
A graphic showing the high image resolutions achieved with cryo-electron microscopy Martin Hogborn / Royal Swedish Academy of Sciences

Scrutinizing the world at a molecular level is difficult. But trying to focus on molecules in motion is an even more daunting task. This year's Nobel Prize in Chemistry honors the work of three scientists who developed a technique to flash freeze the miniscule building blocks of life and study them up close.

In chemistry, structure often relates strongly to the function of a molecule and so by intimately examining the structures that make up all walks of life—from viruses to plants to humans—researchers may be able to work toward better treatments and cures for disease.

"A picture is a key to understanding," according to the Royal Swedish Academy of Sciences press release announcing the award.

Since the 1930s, electron microscopes—in which beams of electrons are used to image the minute details of objects—have allowed scientists to glimpse the very smallest parts of our world. But this technology is not ideal when it comes to studying the structures of living organisms, reports Laurel Hamers for Science News.

For the electron microscope to properly function, the sample must be in a vacuum, which dries out living tissues and can distort some of the structures scientists hope to study. The sample is also bombarded with harmful radiation. ​Other techniques, such as X-ray crystallography, can't image life in its natural state because it requires the molecules of interest to remain rigidly crystallized.

For Scottish molecular biologist Richard Henderson, these restrictions were simply unworkable to look at the molecules that make up living cells. Starting the 1970s, he developed a technique using an electron microscope to image a protein down to the atomic level, reports Erik Stokstad of Science. The microscope was set at low-power, which created a blurry image that could later to edited into a higher-resolution one using the repetitive patterns of the molecule as a guide.

But what if samples weren't repetitive? That's where German biophysicist Joachim Frank came in. He developed a processing technique to create a sharp 3-dimensional images of non-repeating molecules. He took the low-power images at many different angles, and then used a computer to group similar objects and sharpen them creating a 3D model of the living molecule, reports Kenneth Chang of the New York Times.

In the early 1980s, Swiss biophysicist Jacques Dubochet figured out a way to use moist samples under the vacuum of the electron microscope. He found that he could quickly freeze water around the organic molecules, which preserved their shape and structures under the distorting pull of the vacuum.

Together, these techniques have "opened up essentially a kind of new, previously unapproachable area of structural biology," Henderson said of cryo-electron microscopy in an interview with Adam Smith of Nobel Media.

Since their discoveries, scientists have worked to continuously refine the resolution of this technique, allowing even more detailed images of the smallest organic molecules, reports Ben Guarino of the Washington Post. The technique has found broad use in molecular biology, and even in medicine. For example, in the wake of the devastating Zika virus epidemic, researchers were able to quickly to determine the structure of the virus with cryo-electron microscopy, which can help work into producing vaccines.

“This discovery is like the Google Earth for molecules,” says Allison Campbell, president of the American Chemical Society, reports Sharon Begley of STAT. Using this cryo-electron microscopy, researchers can now zoom in to examine the tinest details of life on Earth.

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