The enormous radiation doses required for the observation of biological specimens in the electron microscope suggest that the observation of unstained unshadowed macromolecules should be called microtephroscopy, the study of ashes with the microscope. In this light, our observation of fine-structure well below 10 Å in the dark-field electron micrographs of myokinase and protamine becomes an exciting starting point from which to attempt the reconstruction of the biological structure of macromolecules at such a resolution. Moreover, the repeated observation of virtually identical images, as well as correlation with structure determined by X-ray crystallography argues that much of the detail observed is still biologically meaningful structure.

Light optical techniques, including high and low spatial frequency filtering and superposition of images, have been applied to dark field electron micrographs of uranium, platinum, iodine, and palladium atoms in small model molecules, and osmium atoms bound to DNA. Contrast in the images is increased and the signal to noise ratio enhanced. The improvement for a series of images of one small molecule is so great that substructures of the molecule are revealed, substructures consisting of groups of atoms as light as arsenic and carbon that are completely masked by noise in the untreated images. These results corroborate that images of single atoms are seen in the original micrographs.