 Besides the challenge of creating preparations sufficiently thin to be penetrated by the electron beam, researchers confronted a number of other challenges in preparing biological material for electron microscopy. For example, specimens must be placed in vacuum, and this requires first removing all water, the primary constituent of cells, without inducing to many distortions. Several historians and philosophers (Rheinberger 1995, Rasmussen 1997, and Bechtel 2006) have examined how biologists confronted these challenges and evaluated the reliability of the resulting micrographs. How they addressed one challenge—that of creating sufficient contrast in the images—greatly affected the images that were produced. This was already a challenge with light microscopy: cell material is mostly translucent so that the light transmitted is mostly of the same wavelength, making it hard to differentiate the various structures in the image. To address the challenge, light microscopists in the mid-nineteenth century began experimenting with dyes used for fabrics. As noted in  Section 2,  Flemming named the nuclear structures he observed chromatin since they bound the aniline dye he was using. The problem for electron microscopy was similar—cell components differ little in their ability to block electron transmission. Electron microscopists found that several of the fixatives used in light microscopy, especially those involving heavy metals, enhanced the ability to block electrons, and accordingly the contrast in the resulting images. Given that there was little knowledge about what given chemicals would bind to within the cell, the investigation of these stains was mostly pursued by researchers trying out different compounds and procedures for applying them (exemplified in Palade’s 1952, study of osmium tetroxide) to see what images they could generate. Indeed, different stains (osmium tetroxide, glutaraldehyde, etc.) did yield different images.