Abstract
The concept of cell death dates back to 1858, when cell death at the gross level was discussed in Virchow’s Cellular Pathology as degeneration, mortification, and necrosis equivalent to the term “gangrene”1. Carl Weigart in 1877 described coagulation necrosis in which he observed that necrotic cells lose their nuclei 2. When stains became available in 1885, Walther Flemming described spontaneous cell death as a physiological event3. This was perhaps the first morphological description of apoptosis. He observed that the epithelial lining of regressive ovarian follicles was full of cells whose nuclei were breaking up. The broken nuclei ultimately disappeared. He described half-moons of pyknotic chromatin and loose chromatin in the follicular cavity. He termed the entire process “chromatolysis”. Soon after the description of Walther Flemming, Franz Nissen, a German medical student, described chromatolysis in the lactating mammary gland4. Chromatin margination was described in 18905. In 1892, Strobe gave a detailed account of chromatolysis and nuclear pathology in breast cancer cells, which would be a modern description of apoptosis6. Ludwig Grapher in 1914 published a paper in German under the title “Eine neue Anschauung uber physiologische Zellausschaltung”, whose English translation is, “A new point of view regarding the elimination of cells”7. His hypothesis was that there must be an amitotic mechanism to counterbalance mitosis. Based upon his studies, he concluded that physiological elimination of cells occurs by chromatolysis during the shrinkage of organs; a sister cell engulfs a neighboring cell that breaks down. Glucksmann understood the significance of chromatolysis in morphogenetic mechanism. In a landmark paper, he described physiological cell death in the embryo8. In 1960 Majno et al, using a model of ischemic cell death, established a role of protein denaturation in cell death9. The concept of cell suicide was proposed by De Duve, who postulated that the cells might be killed from within by an explosion of their lysosomes acting as “suicide bag s”10.
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Gupta, S. (1996). Apoptosis/Programmed Cell Death. In: Gupta, S., Cohen, J.J. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VI. Advances in Experimental Medicine and Biology, vol 406. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0274-0_1
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