The Royal Swedish Academy of Sciences has awarded the Nobel Prize in Chemistry 2017 to Jacques Dubochet (University of Lausanne, Switzerland), Joachim Frank (Columbia University, New York, USA) and Richard Henderson (MRC Laboratory of Molecular Biology, Cambridge, UK) for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution.
The Nobel Prize in Chemistry 2017 has been awarded to Jacques Dubochet, Joachim Frank and Richard Henderson for the development of cryo-electron microscopy (cryo-EM), which both simplifies and improves the imaging of biomolecules. This new microscope technology is said to have revolutionized biochemistry – we may soon have detailed images of life’s complex machineries in atomic resolution.
Scientific breakthroughs often build upon the successful visualization of objects invisible to the human eye. However, biochemical maps have long been filled with blank spaces because available technology had difficulty generating images of much of life’s molecular machinery. Cryo-EM changes all of this. Researchers can now freeze biomolecules mid-movement and visualize processes they have never previously seen, which is decisive for both the basic understanding of life’s chemistry and for the development of pharmaceuticals.
Electron microscopes were long believed to only be suitable for imaging dead matter, because the powerful electron beam destroys biological material. However, in 1990, Richard Henderson succeeded in using an electron microscope to generate a three-dimensional image of a protein at atomic resolution. This breakthrough proved the technology’s potential.
Joachim Frank made the technology generally applicable. Between 1975 and 1986 he had developed an image processing method in which the electron microscope’s fuzzy two dimensional images were analysed and merged to reveal a sharp three-dimensional structure.
Jacques Dubochet added water to electron microscopy. Liquid water evaporates in the electron microscope’s vacuum, which makes the biomolecules collapse. In the early 1980s, Dubochet succeeded in vitrifying water – he cooled water so rapidly that it solidified in its liquid form around a biological sample, allowing the biomolecules to retain their natural shape, even in a vacuum.
Following these discoveries, the electron microscope’s every nut and bolt have been optimized. The desired atomic resolution was reached in 2013, and researchers can now routinely produce three-dimensional structures of biomolecules.
Over the past few years, numerous astonishing structures of life’s molecular machinery have filled the scientific literature. Salmonella’s injection needle for attacking cells; proteins that confer resistance to chemotherapy and antibiotics; molecular complexes that govern circadian rhythms; light-capturing reaction complexes for photosynthesis and a pressure sensor of the type that allows us to hear. These are just a few examples of the hundreds of biomolecules that have now been imaged using cryo-EM.
When researchers began to suspect that the Zika virus was causing the epidemic of brain-damaged newborns in Brazil, they turned to cryo-EM to visualize the virus. Within a few months, three-dimensional images of the virus at atomic resolution were generated and researchers could start searching for potential targets for pharmaceuticals.
Atomic structures of complicated protein complexes achieved with cryo-EM: (a) protein complex that governs circadian rhythm; (b) sensor that reads pressure changes in the ear and allows us to hear; (c) the Zika virus.
Biochemistry is now facing an explosive development and is all set for an exciting future.
But what of ‘pure’ chemistry? Tim Hoctor, Vice President of Life Science Solutions Services, Elsevier’s R&D Solutions, has voiced concerns that this year’s award highlights some of the issues within the industry and that many chemists feel a push for applied research is stifling broader innovation.
“While the awarding of the Nobel Prize is undoubtedly the most well-known global recognition of scientific progress, the mood in the chemistry industry is more uneasy,” he says. “Recent research [a survey of 186 chemistry professionals] has found 78% of chemists feel other scientific fields have more ‘newsworthy’ breakthroughs, which contributes to potential chemists entering other fields instead, which could lead to big problems for the Chemistry Nobel Prize, and the industry as a whole.”
Tim is just one voice in an industry expressing growing concerns that, as scientific breakthroughs increasingly happen at the boundaries between disciplines, recruiting potential new chemists may become more of a challenge as they opt for roles in other sciences which are more often associated with discovery and development. As an industry, we need to ensure that we are providing our graduates not just with the right tools for the job, but also the encouragement and incentives to retain new talent. The concern is that, without changes, we could ultimately start seeing the decline of the Chemistry Nobel Prize, and a decreasing pool of chemists working to solve key challenges.
More information about this year’s Nobel Prize for Chemistry, including more detailed technical details about the development and application of cryo-EM, can be found at www.nobelprize.org/nobel_prizes/chemistry/laureates/2017.