From left: Jacques Dubochet, Joachim Frank and Richard Henderson. (University Lausanne /Columbia/Cambridge University/EPA-EFE/REX/Shutterstock)
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 K. 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 ultrahigh 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 flash-freezes 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.
Stockholm University biochemist Peter Brzezinski said on Wednesday that the future of cryo-electron imaging will not be simply taking still images but those of moving molecules, creating movies that illuminate a world in motion on the atomic scale.
“If three people should have been picked to represent the many, many people field, these are the right three,” Dave Agard, a biochemist at the University of California, San Francisco, told The Washington Post.
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 four 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.
Cryo-EM makes it possible to portray biomolecules after freezing them very fast (vitrification method) so its natural shape is preserved. pic.twitter.com/SXgeAVUk24
— The Nobel Prize (@NobelPrize) October 4, 2017
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.
Rossmann, a member of the team that recently imaged the Zika virus surface, said that the microscopy field is entering a period of “resolution-revolution.” That is, scientists are scanning molecules in finer and finer detail. In January, Rossmann and his colleagues announced they'd located the envelope proteins that enable Zika to meld with the host cells it infects.
The Purdue physicist said he had “high respect” for the work of these scientists, but this Nobel Prize failed to capture the breadth of those responsible for the technique. “I don't want to take away from what they've done — they are wonderful people,” Rossmann said. “But they're not the only people involved.” Nor, he said, are they playing key roles in the current resolution revolution.
The final technical hurdle was overcome in 2013, when a new type of electron detector came into use. pic.twitter.com/Ue9c0R6v7y
— The Nobel Prize (@NobelPrize) October 4, 2017
This revolution means new drugs, Agard said. He pointed to the recent work of David Julius and Yifan Cheng, two researchers at UC San Francisco. They recently mapped tiny heat receptors — the bits of your cells that alert you to the wasabi burning your tongue — in atomic detail. Similar membrane receptors sense pain and cold. Their research inspired industry scientists, Agard said, to use cryo-electron microscopy on the hunt for new pharmaceutical targets.
“There will be a whole class of protein molecules and receptors that will be critically important for fighting disease,” Agard said.
This years winners of science Nobel Prizes (in physiology or medicine, physics, and now chemistry) include seven Americans. Asked after the announcement why the U.S. has produced so much Nobel-winning work over the years, Hansson pointed out that since World War II, the U.S. has invested heavily in science and has “allowed scientists to perform fundamental research to focus on important questions of science, without forcing them to have immediate applications and not controlling them in a political way.”
The Royal Swedish Academy of Sciences has awarded 109 prizes in chemistry. Jacobus Henricus van 't Hoff, a pioneer in physical chemistry, won the inaugural award in 1901. Last year, the Nobel committee recognized three chemists who created truly micro machines: engines just a few molecules in size. The researchers defeated molecular equilibrium to design shapes that, like microscopic wheels, move on command.
For this year's award, some Nobel prognosticators gave the nod to John B. Goodenough, 94, inventor of the lithium-ion battery. Gene-editing system CRISPR-Cas9, too, has been an oft-cited contender during the Nobel award season.
Microbes evolved CRISPR to defend against viruses. Scientists have wielded CRISPR as a tool to shape organisms' genes, demonstrating what a few researchers say is its Nobel-worthy potential. In one recent study, biologists grew butterflies with strange new wing colors. Others created the first mutant ants. Geneticists implanted a black-and-white movie in E. coli bacteria, using CRISPR to store pixels as DNA snippets.
But contention over who should get primary credit for the work — a patent dispute that pits MIT and Harvard's Broad Institute against the University of California at Berkeley — may be keeping CRISPR from being awarded a Nobel, bound as the committee is by its rule that only three winners can share the prize.
The Nobel Prize in literature will be announced on Thursday, followed by the peace prize on Friday. An award in economics, not one of the original prizes but now conducted in memory of Alfred Nobel, will be announced Monday.
This article has been updated.
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