Programmed cell death, including apoptosis, is gene-directed. "The word comes from two Greek words, apo- and ptosis-, and the p is silent," declares Jonathan C. Busser, a researcher in the department of neurology and neurosurgery at Case Western Reserve University School of Medicine. "Apo" means "separate from" and "ptosis" means "fall from"--a description of cells that naturally, and without any inflammatory fanfare, die as part of normal development, he explains. The steps of apoptosis are distinctive. The cell forms a tight sphere and its membrane undulates, resulting in bulges called blebs. The nuclear membrane breaks, and endonucleases clip chromosomes where the DNA peeks out from protective proteins. This occurs at 180-base intervals, so the DNA pieces are all the same size. Then the cell fragments, with enough membrane sequestering toxic cell contents to prevent inflammation at the site. Finally, nearby cells consume the remains. (In contrast to this process is necrosis, a nonprogrammed form of cell death that is a response to injury, in which the cell swells and bursts, causing inflammation.) The pieces of the cellular death machinery are present in the cytoplasm, proven by the fact that cells whose nuclei are removed can still undergo apoptosis. A hypothesized "death signal" activates the process. Apoptosis is so fast that researchers often can't detect it, let alone sort out the sequence of events. "Once it starts, apoptosis probably takes from a few minutes to an hour," says Douglas Green, head of the division of cellular immunology at the La Jolla Institute for Allergy and Immunology in California. On a cellular level, apoptotic cells are visualized with vital dyes and electron microscopy. On a molecular level, electrophoresis gels are used to display the telltale same-sized DNA pieces, which resemble ladders. Alternatively, the DNA pieces can be detected by labeling their 3_ ends with a biotinylated thymine analog. "Cells...
