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TABLE 9–1 Some Important Discoveries in the History of Light Microscopy 1611 1655 1674 1833 1838 1857 1876 1879 1881 1882 1886 1898 1924 1930 1941 1952 1968 1981 1984 1988 1994 Kepler suggests a way of making a compound microscope. Hooke uses a compound microscope to describe small pores in sections of cork he calls “cells”. Leeuwenhoek reports his discovery of protozoa. He sees bacteria for the first time nine years later. Brown publishes his microscopic observations of orchids, clearly describing the cell nucleus. Schleiden and Schwann propose the cell theory, stating that the nucleated cell is the unit of structure and function in plants and animals. Kolliker describes mitrochondria in muscle cells. Abbé analyzes the effects of diffraction on image formation in the microscope and shows how to optimize microscope design. Flemming describes with great clarity chromosome behavior during mitosis in animals. Retzius describes many animal tissues with a detail that has not been surpassed by any other light microscopist. During the next two decades, he, Cajal, and other histologists develop staining methods and lay the foundations of microscopic anatomy. Koch uses aniline dyes to stain microorganisms and identifies the bacteria that cause tuberculosis and cholera. In the following two decades, other bacteriologists, such as Klebs and Pasteur, identify the causative agents of many other diseases by examining stained preparations under the microscope. Zeiss makes a series of lenses, to the design of Abbé, that enable microscopists to resolve structures at the theoretical limits of visible light. Golgi first sees and describes the Golgi apparatus by staining cells with silver nitrate. Lacassagne and collaborators develop the first autoradiographic method to localize radiographic polonium in biological specimens. Lebedeff designs and builds the first inference microscope. In 1932, Zernicke invents the phase-contrast microscope. These two developments allow unstained living cells to be seen in detail for the first time. Coons uses antibiotics coupled to fluorescent dyes to detect cellular antigens. Nomarski devises and patents the system of differential interference contrast for the light microscope that still bears his name. Petran and collaborators make the first confocal microscope. Allen and Inoué perfect video-enhanced light microscopy. Agard and Sedat use computer deconvolution to reconstruct Drosophilia polytene nuclei. Commercial confocal microscopes come into widespread use. Chalfie and collaborators introduce green fluorescent protein (GFP) as a marker in microscopy.