A group of scientists recently met at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. They were there to honor the 100-year anniversary of Sir John Kendrew, EMBL’s first director. At the last minute, they added a special celebration to the program for a 2017 Chemistry Nobel Prize to one of their own: Jacques Dubochet.

One attendee was Alasdair McDowall, director of the Beckman Resource Center at the California Institute of Technology, and a long-time Dubochet collaborator and friend. The event talks and conversations were already interesting and exciting, he says. With the added news of the Nobel Prize, “the mood was ecstatic.”

Dubochet, born and educated in Switzerland, is now a retired professor at the University of Lausanne. He did pioneering work on cryoelectron microscopy (cryoEM) in the 1970s and 1980s at EMBL. It was this research that was recognized with the Nobel Prize, shared with Richard Henderson and Joachim Frank. Dubochet’s research made it possible to use cryoEM to visualize biological samples in their natural condition—in water. 

EM of H2O

At EMBL, Dubochet’s goal was preserving the structure of biomolecules in aqueous solutions for imaging by electron microscopy. The protocols at the time involved extensive sample processing with fixatives and organic or heavy metal stains. Developing methods to view samples without fixing and staining meant that Dubochet’s group spent much of their time just imaging water. Dubochet’s EMBL colleagues didn’t always understand this work, says Professor Gareth Griffiths, Department of Molecular Biosciences, University of Oslo, who worked with Dubochet and became his friend. “I had the privilege of listening to Jacques explain the work he’s now famous for, as he was doing it,” Griffiths says. “He’d come in and say ‘Bon jour, Gareth, I have an interesting story to tell you,’ and then he’d explain what his experiments were all about.

The problem was that for electron microscopy, samples have to be in a vacuum, which dries out biological specimens. Freezing slows the desiccation but ice crystals damage cells and tissues and interfere with imaging. The breakthrough from Dubochet’s team was inventing a process for vitrifying water, so it hardens into a substance that resembles glass. In vitreous water, the H2O molecules are arranged amorphously instead of in the crystalline arrays of ice.

“Whether water was vitrified or not was not initially that interesting to us biologists,” Griffiths says, “until Jacques explained it would preserve the structure of biomolecules in the most native form possible.” He adds, “As a physicist, he had an angle on the science that we didn’t have.”Griffiths also credits McDowall for working out how to process tiny samples on small grids that must constantly be kept supercooled. 

Dubochet is also known for developments in the related technique of CEMOVIS (for cryoEM of vitreous sections). CEMOVIS images vitrified cells and tissues that have been sliced into thin samples because they are too thick to view without sectioning. The method can show the organization of cell types in tissues or the relationships among cellular structural components. “Jacques always had faith in CEMOVIS as a way to see inside cells and the nucleus,” McDowall says. In his EMBL conference remarks, Dubochet said he hopes the method will lead to “an atomic map of a cell.”

Advanced techniques with focused ion beams are now creating extremely thin, lamellae-like wafers for imaging, with less distortion than earlier CEMOVIS sectioning techniques. Applications of this method include clinical diagnoses based on structural differences between diseased and healthy tissue or changes within cells such as numbers and forms of organelles.  

Promoting science ethics

Griffiths and others have long advocated for a Nobel Prize for Dubochet. In a 2015 talk when Dubochet received EMBL’s first Lennart Philipson award for contributions to translational research in the life sciences, Griffiths is on record as saying that Dubochet’s work is “Nobel Prize worthy.” Griffiths even raised the topic of a future Nobel award when Dubochet visited him in Oslo on holiday in April. Even with these advance conversations, Griffiths says Dubochet was “saturated” by the publicity after the announcement.

Now that Dubochet is retired from the laboratory, he commits his time to causes that he has always been passionate about. He is active in local government and teaches, although not about physics, biology, or biomolecular imaging. Dubochet talks about getting scientists to be socially responsible, to go out in the world and communicate about their work and advocate for using science to improve society. “The ethics of science,” McDowall says, “has always been close to his heart.”

Dubochet has always cared about the environment, people around him, and society in general, Griffiths says. He notes that since retirement, Dubochet bought an annual Swiss train pass so he can travel to different cities and spend the day just walking around meeting and talking to people. Griffiths predicts that Dubochet will use the attention from the Nobel award to spread awareness about things he cares about, like social responsibility. In a 2003 EMBO Reports Viewpoint, Dubochet wrote that “communication with the public does not require so much a ‘public understanding of science’ but a ‘scientific understanding of the public.'” He also stated that “efforts to bridge the gap between scientists and citizens deserve the same support as fundamental research, because the harmonious development of our society is at stake.” 

Dubochet invited Griffiths and McDowall to be among his guests at Nobel Week, with its receptions, talks, and ceremonies. Dubochet’s guest list turns the week into a reunion of close friends and collaborators from the EMBL, as well as a once-in-a-lifetime formal occasion. As Griffiths says, “I haven’t used cufflinks for 40 years.”