Molecule imaging wins trio Nobel in chemistry
Special microscopy could transform ‘structural biology.’
Biophysicists Jacques Dubochet, Joachim Frank and Richard Henderson have won the Nobel Prize in chemistry for inventing new and better ways to see molecules.
The Nobel committee praised the trio in its announcement Wednesday “for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution.” Cryo-electron microscopy is “a cool method for imaging the materials of life,” said Nobel committee member Göran Hansson from Stockholm. The development allows scientists to visualize proteins and other biological molecules at the atomic level.
Dubochet, 75, a Swiss citizen, is a professor at the University of Lausanne in Switzerland. Frank, 77, born in Germany and now a U.S. citizen, is a Columbia University professor in New York. Henderson, 72, of Scotland, works at Cambridge University in Britain.
To see the structure of molecules at ultra-high resolution, scientists must hold molecules in place in their natural configuration. Other microscopic techniques, such as X-ray crystallography, are far more rigid than cryo-electron microscopy.
The technique flashfreezes a sample to create a layer of ice like a pane of glass over a layer of liquid where the molecules can retain their natural shape.
“If three people should have been picked to represent the many, many people field, these are the right three,” said Dave Agard, a biochemist at the University of California, San Francisco.
Keeping biological molecules still poses a conundrum to scientists: Remove the water and the particles might collapse. Freeze the water and ice crystals will distort microscopic images.
But in the late 1970s and early 1980s, Dubochet figured out how to cool water so quickly that crystals would not form. “Discovery of water vitrification and development of cryo-electron microscopy,” notes his curriculum vitae, describing how he spent the year 1978. (Another important entry in his CV, which for most scientists is a very serious list of academic achievements, is a highlight from when he was 4 years old: “1946. No longer scared of the dark, because the sun comes back; it was Copernicus who explained this.”)
When he first submitted the discovery of water vitrification for publication, it was rejected — the publishers did not believe water could be manipulated this way.
Yet developing cryo-electron microscopy required no miracles, “not even fundamental discoveries; the progress came from a large numbers of incremental improvements affecting all the various steps of the specimen preparation protocol,” he wrote in 2011. During 25 years of labor, the biophysicist wrote, “a good dozen dedicated colleagues, mostly doctoral students” worked to refine the microscopic technique.
Frank created three-dimensional pictures from electron microscopes’ two-dimensional images. For him, he said, the “coolest molecule has always been the ribosome.” The ribosome, a cluster of RNA and protein, is tiny and hard to image. Its width is less than the wavelength of visible light. Cryo-electron microscopy allowed Frank and his colleagues to view the camera-shy particle.
“Cryo-electron microscopy is about to completely transform structural biology,” said Frank, calling remotely to the Nobel conference on Wednesday.
In the 1990s, Henderson showed that cryo-electron microscopy could be as detailed as X-ray crystallography when he made an atomic model of a membrane protein found in microorganisms.
The technique “made it possible to look at large biological and molecular assemblies at atomic resolution. That’s chemistry,” said Michael Rossmann, a physicist and microbiologist at Purdue University in Indiana. “Chemistry is a question of how atoms bond and work together.”
Scientists used cryo-electron imaging to quickly determine the shape of the Zika virus once it was identified as the cause of severe birth defects. Knowing the shape of a virus can speed up research into vaccines.
The Nobel Prize in literature will be announced today.