Observation and simulation of unstained DNA images in bright field TEM

Images of unstained, unshadowed DNA prepared by the Kleinschmidt method have been obtained in bright field TEM with a usable contrast. Operating conditions include a strong defocus and a highly coherent illuminating beam. Observations suggest that a specific interaction exists between the nucleic acid and the carrier protein: cytochrome C. Computer simulations of beam-specimen interaction and of image formation were performed. The calculated dependence of contrast on defocus agrees qualitatively with the experimental results. We conclude that experiments with unstained biological specimens are feasible and are necessary (in spite of difficulties) to corroborate results obtained with stained material.