THIS year’s Nobel prize for chemistry has been awarded to Jacques Dubochet of Lausanne University, in Switzerland, Joachim Frank of Columbia University, in New York, and Richard Henderson of the Laboratory for Molecular Biology, in Cambridge, Britain. Each has contributed to the development of cryoelectron microscopy, a technique that permits the shapes of biological molecules, such as proteins, to be seen without many of the difficulties involved in preparing them for older techniques, such as X-ray crystallography or conventional electron microscopy.
Dr Dubochet invented a way of freezing samples that has proved crucial to the technique. A sample—say, a protein of interest—is suspended in water and then dripped onto a thin metal mesh. This mesh is then plunged into liquid ethane, at a temperature of around -180°C. The speed of plunging is crucial. Do it too slowly and the water in the sample will turn into ice crystals that destroy the protein molecules. If done fast enough, though, the water turns not to ice, but into a glassy state that preserves the proteins for study.
Dr Henderson turned to this technique when a protein he was trying to prepare for x-ray studies would not crystallise, and could not, therefore, be examined. In 1990, after more than 15 years of effort, he became the first to use it to produce a picture of a protein, bacteriorhodopsin, that was as detailed as those X-ray crystallography can provide.
Dr Frank’s contribution was mathematical. He developed a method for deducing the three-dimensional structures of proteins from the flat snapshots that a cryoelectron microscope produces. The upshot, after years of refinement, is a new and better way of examining biological molecules. Since it is often the shapes of those molecules that determine their function, finding out exactly what those shapes are is crucial for researchers. For instance, it allows drugs to be designed to interact with molecules rather than simply guessing what chemicals might act as such drugs and screening them by the million.