The historical evolution of the concept of apoptosis in rheumatic diseases

Even if the idea of apoptosis may probably be detected for the first time in a Hippocratic treatise, it was Rudolph Virchow, the founder of cellular pathology in the XIX century, who gave the first structured description of the processes underlying the term. In the course of the XX century a body of systematic observations on cell death was elaborated in an organic way. In 1908 Mechnikov won the Nobel Prize for his studies on phagocytosis, while in the '30s and '40s many studies on metamorphosis were carried out, and Fell and Canti identified cell death in chondrocytes in culture. At the end of the '40s Saunders began to observe cell death in chick limbs, and Hamburger and Levi Montalcini began their exploration of nerve growth factors. In mid '50s research on lysosomes began, and in the '60s Kerr defined shrinkage necrosis. The term apoptosis was definitely introduced by Kerr in 1972 to indicate a particular form of death in which cells commit suicide by dissolving themselves into membrane-bounded apoptotic bodies. In the '80s ced-3 was described and at the beginning of the '90s apoptosis genes were identified. In more recent times new instruments have allowed a wide range of cellular deaths to be described, including apoptosis as currently defined. Extremely interesting are its role and function in many different diseases; in particular in rheumatic ones recent evidence indicates that, far from being simple, brief and monomorphic, apoptosis is a complex, long-lasting, and pleiomorphic process.