Your fingers exist because the cells between them chose to die
In a developing embryo, hands start out as paddles. The digits separate only because the cells in between switch on a built-in self-destruct routine. Such programmed cell death shapes plants and animals alike, and when it fails, as with an overactive gene called BCL2, cells that should die can survive and turn cancerous.
Programmed cell death, sometimes called cellular suicide, is death triggered from within the cell, usually to the organism's benefit. Its main forms are apoptosis and autophagy. Necrosis, death from outside causes such as injury or infection, was long thought to be purely accidental, but in the 2000s researchers recognised a programmed version called necroptosis, possibly a backup for when apoptosis is blocked by viruses or mutations. Richard Lockshin and Carroll Williams used the phrase programmed cell death in 1964 while studying insect development, about eight years before the word apoptosis was coined.
Apoptosis has a recognisable look: the cell shrinks, its surface bubbles, the chromatin condenses and the nucleus and DNA break into fragments. During development, cells appear to be actively instructed to die; in adult tissues, the loss of survival signals can tip them over. Division and self-destruction seem linked, with the balance set by growth and survival factors. Autophagic death, by contrast, involves large vacuoles consuming organelles in sequence before the nucleus is destroyed.
Two routes lead to apoptosis, both relying on enzymes called caspases. The extrinsic route begins at the surface, when signalling molecules such as FAS ligand or TNF-alpha lock onto their receptors, or when a cytotoxic T cell attacks. The intrinsic route responds to internal damage, such as from DNA injury or ultraviolet light, and runs through the mitochondria. Proteins named BAX and BAK punch pores in the outer mitochondrial membrane, cytochrome c escapes, and a complex called the apoptosome activates the executioner caspases. Pruning damaged cells this way helps prevent the overgrowth behind diseases like cancer.
BCL2 provided the first mechanistic clue. Unlike most cancer genes, it does not speed up division; it stops cells from killing themselves. A swap of material between chromosomes 14 and 18 can make it overactive, a change often found in follicular lymphoma. The field's importance was marked by the 2002 Nobel Prize in Physiology or Medicine for Sydney Brenner, H. Robert Horvitz and John Sulston.
Source: Programmed cell death
