From envelopes to atoms: The remarkable progress of biological electron microscopy

The electron microscope has, in principle, provided a powerful method for investigating biological structures for quite sometime, but only recently is its full potential being realized. Technical advances in the microscopes themselves, in methods of specimen preparation, and in computer processing of the recorded micrographs have all been necessary to underpin progress. It is now possible with suitable unstained specimens of two-dimensional crystals, helical or tubular structures, and icosahedral viruses to achieve resolutions of 4Å or better. For nonsymmetrical particles, sub-nanometer resolution is often possible. Tomography is enabling detailed pictures of subcellular organization to be produced. Thus, electron microscopy is now starting to rival X-ray crystallography in the resolution achievable but with the advantage of being applicable to a far wider range of biological specimens. With further improvements already under way, electron microscopy is set to be a centrally important technique for understanding biological structure and function at all levels-from atomic to cellular.