Jacques Dubochet

Jacques Dubochet
Dubochet in 2017
Jacques Dubochet
Born	8 6, 1942
Birthplace	Aigle, Switzerland
Nationality	Swiss
Occupation	Biophysicist
Employer	European Molecular Biology Laboratory University of Lausanne
Known for	Cryo-electron microscopy, vitrification of water for biological specimens
Education	École polytechnique fédérale de Lausanne University of Geneva University of Basel
Awards	Nobel Prize in Chemistry (2017) Royal Photographic Society Progress Medal (2018)

Jacques Dubochet (born 8 June 1942) is a Swiss biophysicist who played a central role in the development of cryo-electron microscopy (cryo-EM), a technique that allows scientists to determine the high-resolution structures of biomolecules in solution. Born in the Swiss town of Aigle, Dubochet spent decades working at the intersection of physics and biology, most notably at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and later at the University of Lausanne in Switzerland, where he holds the title of honorary professor of biophysics. His principal scientific contribution was the successful vitrification of water around biomolecules — a process that rapidly freezes water into a glass-like state without the formation of damaging ice crystals — thus preserving the native structure of biological specimens for electron microscope imaging. In 2017, Dubochet was awarded the Nobel Prize in Chemistry, shared with Joachim Frank and Richard Henderson, "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution." Known for his warmth, humor, and unconventional personality, Dubochet became something of a public figure in Switzerland following the Nobel announcement, celebrated not only for his scientific achievement but also for his candid and self-deprecating character.

Early Life

Jacques Dubochet was born on 8 June 1942 in Aigle, a small town in the canton of Vaud in western Switzerland. He grew up in the French-speaking part of Switzerland. As a child, Dubochet faced a notable personal challenge: he was diagnosed with dyslexia, which he later described with characteristic humor as one of his earliest discoveries, reportedly noting that he was the first person with dyslexia recognized as such in the canton of Vaud. In a humorous curriculum vitae that circulated widely after the Nobel Prize announcement, Dubochet listed personal milestones alongside scientific ones, including childhood memories such as overcoming his fear of the dark at the age of five. His unconventional approach to presenting his own biography would later become a hallmark of his public persona.

Little has been documented in the available sources about his family background or the details of his upbringing in Aigle. What is clear is that, despite the challenges posed by dyslexia, Dubochet pursued a rigorous scientific education and developed an early interest in the natural sciences that would eventually lead him to the forefront of structural biology.

Education

Dubochet undertook his higher education at several prestigious Swiss institutions. He studied at the École polytechnique fédérale de Lausanne (EPFL), one of Switzerland's leading technical universities, before continuing his academic training at the University of Geneva. He completed his doctoral studies under the supervision of Eduard Kellenberger, a distinguished Swiss molecular biologist, at the University of Basel. His doctoral thesis, titled "Contribution to the use of dark-field electron microscopy in biology," was completed in 1974 and addressed the application of electron microscopy techniques to biological specimens. Kellenberger's laboratory was a significant center for the study of bacteriophage structure and electron microscopy of biological systems, and working under his guidance provided Dubochet with a foundation in both the technical and theoretical aspects of imaging biomolecules at high resolution.

The combination of training in physics and engineering at EPFL with biological research at Geneva and Basel equipped Dubochet with the interdisciplinary expertise that would prove essential for his later innovations in cryo-electron microscopy.

Career

Early Research and Electron Microscopy

Following the completion of his doctorate in 1974, Dubochet continued to work on problems related to electron microscopy of biological specimens. The fundamental challenge facing the field during this period was the incompatibility between biological specimens — which exist naturally in aqueous environments — and the high-vacuum conditions required inside an electron microscope. When biological specimens were placed in a vacuum, the water surrounding and within them evaporated, causing the structures to collapse or become distorted. The standard approach at the time involved either staining specimens with heavy metals (negative staining) or dehydrating them entirely, both of which could introduce artifacts and limit the resolution of the resulting images.

During the 1970s, physicists, engineers, and biologists were collectively exploring ways to improve the resolution achievable on biological specimens with electron microscopy. This was the scientific landscape in which Dubochet began to focus on the problem of how to preserve biological samples in their native, hydrated state for imaging.

Work at the European Molecular Biology Laboratory

A pivotal stage in Dubochet's career began when he joined the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. EMBL, founded in 1974, had quickly become one of Europe's premier research institutions for molecular biology, and its collaborative, interdisciplinary environment was well suited to the kind of work Dubochet was pursuing.

At EMBL, Dubochet and his research group tackled the central problem of specimen preparation for electron microscopy: how to maintain biological molecules in a water-containing environment while imaging them under the vacuum of the electron microscope. The breakthrough came in the early 1980s when Dubochet succeeded in developing a method to vitrify water around biomolecules. Vitrification is the process of cooling water so rapidly that it solidifies into an amorphous, glass-like state rather than forming the ordered crystalline structures of ice. The formation of ice crystals during conventional freezing was a major problem because the crystals could disrupt and destroy the delicate three-dimensional structures of biological molecules. By cooling specimens extremely rapidly — plunging them into a cryogen such as liquid ethane — Dubochet was able to achieve vitrification, trapping biomolecules in a thin film of vitrified water that preserved their native conformations.

This technical achievement was not merely incremental; it represented a fundamental advance in the preparation of biological samples for electron microscopy. Before Dubochet's work, attempts to freeze biological specimens for electron microscopy had been largely unsuccessful because the ice crystals that formed during freezing damaged the specimens and scattered the electron beam, rendering the images useless. Dubochet's vitrification method solved both problems simultaneously: it preserved the specimen's structure and produced a transparent medium through which electrons could pass without significant scattering.

The method developed by Dubochet complemented and built upon the work of his future Nobel co-laureates. Richard Henderson had demonstrated in the 1970s that it was possible to obtain a three-dimensional image of a protein at atomic resolution using an electron microscope, while Joachim Frank had developed image-processing methods that could transform the fuzzy, two-dimensional images produced by electron microscopy into sharp, three-dimensional structures. Dubochet's vitrification technique provided the crucial missing piece: a reliable method for preparing specimens in a near-native state. Together, these three advances formed the foundation of modern cryo-electron microscopy.

University of Lausanne

After his highly productive period at EMBL, Dubochet returned to Switzerland, where he joined the faculty of the University of Lausanne. He held a position in biophysics and continued his research on cryo-electron microscopy and related techniques. At Lausanne, Dubochet contributed to the further development and refinement of cryo-EM methods while also training a new generation of researchers in the field.

Upon his retirement from active research, Dubochet was appointed an honorary professor of biophysics in the Department of Ecology and Evolution at the University of Lausanne, a title he continues to hold.

Impact of Cryo-Electron Microscopy

The technique of cryo-electron microscopy, which Dubochet helped to develop, has had a transformative impact on structural biology and biochemistry. By allowing researchers to visualize biomolecules — including proteins, nucleic acids, and large molecular complexes — in their native, hydrated state and at near-atomic resolution, cryo-EM has opened new avenues for understanding biological processes at the molecular level. The Royal Swedish Academy of Sciences noted at the time of the Nobel Prize announcement that cryo-EM "both simplifies and improves the imaging of biomolecules" and that the technique had "moved biochemistry into a new era."

As NPR reported at the time of the award, the development of cryo-EM enabled "views of human cells working at the atomic level," providing scientists with unprecedented access to the molecular machinery of life. The technique has since become one of the dominant methods in structural biology, used by laboratories around the world for applications ranging from drug discovery to understanding viral structures.

Personal Life

Jacques Dubochet is known for a personal style that stands in contrast to the typical reserve associated with Nobel laureates. His humorous curriculum vitae, which surfaced widely in the media following the Nobel Prize announcement in October 2017, included whimsical entries alongside genuine academic milestones. Among the entries was a note that at the age of five he had discovered that he was "no longer afraid of the dark," and he also referenced his dyslexia diagnosis, noting it as a formative experience. Swiss media, including the Radio Télévision Suisse (RTS), highlighted the playful nature of his CV, which was seen as reflective of his approachable and unconventional personality. The Swiss newspaper Le Temps described Dubochet as an atypical scientist — un savant atypique — who combined scientific rigor with a distinctly human and sometimes irreverent public persona.

Dubochet has been noted for his engagement with public and social issues in Switzerland, including environmental questions, though detailed documentation of these activities is limited in the available sources. He resides in the canton of Vaud, Switzerland.

Recognition

Nobel Prize in Chemistry (2017)

On 4 October 2017, the Royal Swedish Academy of Sciences announced that Jacques Dubochet, together with Joachim Frank and Richard Henderson, had been awarded the Nobel Prize in Chemistry "for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution." The prize recognized the collective contributions of the three laureates to transforming cryo-EM from a niche technique into a powerful and widely used tool for structural biology.

At the Nobel Banquet on 10 December 2017, Dubochet delivered a characteristically warm and witty speech, addressing the Swedish royal family, fellow laureates, and guests. His speech was noted for its combination of humor and thoughtfulness, consistent with his public reputation.

Royal Photographic Society Progress Medal (2018)

In 2018, Dubochet received the Progress Medal from the Royal Photographic Society, shared with his Nobel co-laureates Joachim Frank and Richard Henderson. The medal was awarded for "an important advance in the scientific or technological development of photography or imaging in the widest sense," reflecting the profound impact of cryo-electron microscopy on the field of scientific imaging.

Other Honors

Dubochet has been recognized by his home institution, the University of Lausanne, where he was conferred the title of honorary professor of biophysics. EMBL has also recognized Dubochet as a distinguished alumnus of the laboratory.

Legacy

Jacques Dubochet's legacy is rooted in the practical and conceptual transformation of structural biology through his contribution to cryo-electron microscopy. The vitrification method he developed in the early 1980s at EMBL resolved a problem that had stymied the field for decades — how to preserve the native structures of biological molecules during electron microscopic imaging — and opened the door to a revolution in how scientists visualize the molecular components of living systems.

The impact of cryo-EM extends well beyond basic research. The technique has become central to modern drug discovery and has been used to determine the structures of numerous medically important proteins and molecular complexes, including, in subsequent decades, the spike proteins of coronaviruses and many other targets of pharmaceutical interest. The Nobel Committee's recognition of cryo-EM in 2017 reflected the maturity and widespread adoption of the technique across the biological sciences.

As described in the Proceedings of the National Academy of Sciences, the three 2017 Nobel laureates in Chemistry each contributed a distinct and essential element to the development of cryo-EM. Dubochet's contribution — the vitrification of biological specimens — was the key sample preparation advance without which the imaging and computational innovations of Henderson and Frank could not have achieved their full potential. The synthesis of these three advances into a single, integrated methodology has had a lasting and ongoing impact on the life sciences.

Dubochet's influence extends also to the culture of science. His openness about his dyslexia, his humor, and his engagement with the public have made him a distinctive figure in the scientific community, challenging stereotypes about who can succeed in research and how scientists present themselves to the world.