In the event of a disease caused by an unknown pathogen, it is hard to know which reagent to pick. Other tests involving molecular and serological methods require that a specific probe be available for virus identification. One of the main advantages of using EM for viral diagnosis is that it does not require organism-specific reagents for recognizing the pathogenic agent. Even today, taxonomy books include electron micrographs of viruses in their descriptions ( 22). That virus was later determined to be the cause of transient aplastic crisis in patients with sickle cell disease and of “fifth disease,” a childhood exanthem. Cossart et al., in noticing an anomalous reaction while testing normal blood for hepatitis B virus, excised a precipitation band from a gel and, using EM, demonstrated that it contained a very small virus (parvovirus B19) ( 16). Early virus classification depended heavily on morphology as shown by EM ( 2, 4, 60), and many of the intestinal viruses were discovered by EM examination of feces after negative staining ( 32, 46, 54, 96). The first image of poliovirus was taken in 1952 ( 74), and virus-host relationships began to be studied in the mid-1950s ( 24, 25). In 1948, differences between the virus that causes smallpox and the virus that causes chicken pox were demonstrated by EM ( 62, 92). Other historical electron microscopic observations have led to the discovery of new viruses. Eight years later, Ruska and colleagues Kausche and Pfankuch were the first to visualize viruses (tobacco mosaic virus) with the EM ( 47), and in 1986, Ruska shared the Nobel Prize with Binnig and Rohr, developers of the scanning tunneling electron microscope. Ernst Ruska, with his mentor Max Knoll, built the first electron microscope in 1931 as the project for his Ph.D. Organisms smaller than bacteria have been known to exist since the late 19th century ( 11), but the first EM visualization of a virus came only after the electron microscope was developed. Electron microscopy (EM) has long been used in the discovery and description of viruses.
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