Nobel prize in chemistry awarded for method to visualise biomolecules

Jacques Dubochet, Joachim Frank and Richard Henderson receive £825,000 prize for developing method for generating 3D images of life-building structures

The Nobel prize in chemistry has been awarded to three scientists for developing a technique to produce images of the molecules of life frozen in time.

Jacques Dubochet, Joachim Frank and Richard Henderson will receive equal shares of the 9m Swedish kronor (£825,000) prize, which was announced by the Royal Swedish Academy of Sciences in Stockholm on Wednesday.

The technique, called cryo-electron microscopy, allowed biomolecules to be visualised in their natural configuration for the first time, triggering a “revolution in biochemistry”, according to the Nobel committee. The latest versions of the technology mean scientists can record biochemical processes as they unfold in film-like sequences.

Earlier imaging techniques, such as X-ray crystallography, required samples to be studied in a rigid state, revealing little about the dynamics of proteins and enzymes – many of which could not be successfully crystallised in any case. Another microscopic technique, the electron microscope, was only suitable for imaging dead matter, because its powerful beam destroyed delicate biological structures.

Henderson, a Scottish scientist and professor at the MRC Laboratory of Molecular Biology, was the first to successfully modify the electron microscope to image a protein involved in photosynthesis, by using a weaker beam and taking pictures from many angles.

Joachim Frank, a German-born professor at Columbia University in New York, developed mathematical algorithms that allowed the method to be applied to a wider array of molecules. Dubochet, who is Swiss and an honorary professor at the University of Lausanne, pioneered a flash freezing method that turned the water inside cells into a glassy solid, rather than ice crystals which would damage the cellular structure. His vitrification technique allowed biological samples to be frozen while retaining their natural shape.

Speaking to journalists after the announcement, Frank said the practical uses for the technique were “immense” and meant medicine no longer focuses on organs but “looks at the processes in the cell”.

Cryo-electron microscopy has allowed scientists to explore the architecture of everything from the proteins that cause antibiotic resistance to the surface of the Zika virus. Last year the 3D structure of the enzyme producing the amyloid of Alzheimer’s disease was published using this technology. By capturing snapshots of the same system at different time-points, scientists can even stitch together jittery film sequences of biological processes as they unfold.

This has paved the way for both new basic insights into life’s chemistry and for the development of pharmaceuticals.

The development of cryo-electron microscopy:
The development of cryo-electron microscopy: The final technical hurdle was overcome in 2013, when a new type of electron detector came into use. Photograph:

Venkatraman Ramakrishnan, president of the Royal Society, said the win underscored the value of patiently supporting basic science for decades, which in this case led to immense payoffs. “It has already been used by drug companies to do structures of important drug targets, and it is used to understand fundamental biology that can change medicine in the future – so it just goes to show you how all these things are linked,” he said.

Dr Carsten Sachse, of the European Molecular Biology Laboratory in Heidelberg who worked with Henderson in Cambridge, describes his former colleague as a “visionary”. “When I worked with him that was a time when it was not clear how far the technology really would go but he had it all worked out in his head and he just had to make this happen,” he said.

The nine science Nobel prize winners this year include include seven Americans (Frank and Rainer Weiss, who won the physics prize yesterday, are both German-born US citizens). The academy’s secretary-general, Göran Hansson, commented on this success after the announcement: “The United States has after the Second World War allowed scientists to perform fundamental research, to focus on important questions in science, not forcing them to do immediate applications, not controlling them in a political way,”

Prof Magdalena Zernicka-Goetz, professor of mammalian development and stem cell biology at the University of Cambridge, said: “A visual image is the essential component to understanding, often the first one to open our eyes, and so our minds, to a scientific breakthrough,” she said.

Dame Athene Donald, a professor of experimental physics at the University of Cambridge whose work has focussed on understanding biological structures, said the technique had made an enormous difference to her field, adding that she had been struck by a talk by Henderson that she attended during her PhD. “It was stunning work,” she said. “It’s a long time ago but it’s brilliant to see the developments finally be rewarded by this year’s award.”

Barry Fuller, professor in surgical sciences at University College London Medical School, said Dubochet is widely known as a “star” in his field. “The technology is aimed … on imaging biomolecules in the life process ‘frozen’ in time – so they are called to immediate halt,” he said.

In the future, Fuller added, understanding the configurations and stability of biomolecules at ultra-low temperatures could also accelerate efforts in cryobiology, where scientists are focused on how to vitrify human tissue and organs to allow them to be preserved for long durations.

Last year’s prize went to three European chemists for developing “nano-machines”, an advance that paved the way for the world’s first smart materials.

On Monday, three American scientists shared the 2017 Nobel prize in physiology or medicine for their painstaking work on circadian rhythms and the Nobel prize in chemistry went to another American trio for the first observation of gravitational waves.


Hannah Devlin and Nicola Davis

The GuardianTramp

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