Soft X-ray Microscopy in Biology and Medicine: Status and Prospects

There are two central motivations for developing new scientific methods. One is, of couse, to accomplish what established methods cannot. A second is for comparison: To verify the conclusions of established methods. That is, are results obtained by one method congruent with those obtained by another independent means of measurement? In regard to microscopic imaging in biology, this means that we seek to ground our view of microscopic structure on more than a single methodological standard, with whatever particular uncertainties that standard presents. These are the motivations that underlie the current impetus for the development of x-ray microimaging methods. Our knowledge of the internal structures of biological cells has been shaped in great part by 40 years of study applying and developing the methods of electron microscopy. This has led to the evolution of a model of the cell that contains defined structures with established details and known spatial relationships. Belief in the fidelity of this model to the natural cell rests in great part on the understanding that the preparative procedures commonly used in electron microscopy, procedures that greatly modify the natural object, do not alter or distort intracellular structure as to form, location or high resolution detail. Even though the cell as seen in the electron microscope most certainly resembles the natural object, important questions of the faithfulness of the image often remain.