Biological ultrastructure research; the first 50 years\

The second half of the 20th century has witnessed the birth and growth of biological ultrastructure research-a branch of cell biology in which electron microscopy plays an important role. After a humble start in around 1950, when only a limited arsenal of instrumentation was available, a wealth of auxiliary methodologies were developed and gradually put in use. Here we review these techniques: ultramicrotomy of 'optimally' fixed and prepared samples, histochemical methods such as immuno-electron microscopy and electron microscope autoradiography, negative staining techniques, freeze-fracturing and other techniques. Closer to the millenium shift, various cryotechniques have gradually developed. Together with computer-based reconstruction methods they are likely to play increasingly more important roles in the future. (C) 2003 Published by Elsevier Ltd.