19TH-CENTURY RESEARCH ON NATURALLY-OCCURRING CELL-DEATH AND RELATED PHENOMENA

Research on naturally occurring cell death is older than current opini on gives credit. More than 100 nineteenth century publications deal wi th it, and we review most of these. Soon after the establishment of th e cell theory by Schleiden and Schwann, Carl Vogt (1842) reported cell death in the notochord and adjacent cartilage of metamorphic toads. S ubsequent landmark discoveries included the massive cell death that oc curs in pupating diptera (Weismann 1864), chondrocyte death during end ochondral ossification (Stieda 1872), phagocytosis associated with cel l death in the muscles of metamorphic toads (Metschnikoff 1883), chrom atolytic (apoptotic) cell death in ovarian follicles (Flemming 1885), the reinterpretation of ''Sarkoplasten'' as ''Sarkolyten'' in metamorp hic amphibia (Mayer 1886), the programmed loss of an entire population of neurons in fish embryos (Beard 1889), the death of scattered myocy tes and myofibres in mammalian muscle (Felix 1889), and the death of m any motor and sensory neurons in chick embryos (Collin 1906). Other li nes of nineteenth century research established concepts important for understanding cell death, notably trophic interactions between neurons and their targets, and intercellular competition.