Apoptosis: a general comment.

isauniversal biologicalphenomenon indeveloping vertebrate and invertebrateanimals. Gl#{252}cksmann(1)firstclassified developmental celldeathonthebasisofitsusefulness forthedeveloping organ-ism.Saunders (2)proposed thatthepattern ofcelldeathisprogrammed asanormal morphogenetic eventinthede-velopment ofmulticellular organisms. Theuseofthetermprogrammed hasoftenbeeninterpreted asmeaning thatdeathwasaconsequence ofayetundefined intrinsic cellularprocess. Thus thegeneral concept emerged thatcelldeathmaybetheoutcome ofcomplex coordinated eventsinthede-veloping organism andmayrequire anempirical definition.Kerrhaddrawn attention totheimportance ofgrowingevidence thatcelldeath occurred bydistinct anddifferentmechanisms (3).Shortly thereafter, effortstodevelopacom-prehensive scientific hypothesis of cell death weresignificantly advanced in1972byKerr,Wyllie, andCurrie(4).Basedonmorphological characteristics ofcelldisintegra-tionin avariety oftissues, theydeveloped theconcept ofapoptosis todescribe naturally occurring celldeaththatplaysacomplementary butopposite roletomitosis inregulationofanimal cellpopulations. Theyalsoproposed thatlivingcellshaveametabolic cascade, which when activated canleadtotheirremoval. Theseauthors werethefirsttorecom-mendthatcelldeaththatresultsfromsevereenvironmentalperturbations