Cell death: history and future.

Cell death was observed and understood since the 19th century, but there was no experimental examination until the mid-20th century. Beginning in the 1960s, several laboratories demonstrated that cell death was biologically controlled (programmed) and that the morphology was common and not readily explained (apoptosis). By 1990, the genetic basis of programmed cell death had been established, and the first components of the cell death machinery (caspase 3, bcl-2, and Fas) had been identified, sequenced, and recognized as highly conserved in evolution. The rapid development of the field has given us substantial understanding of how cell death is achieved. However, this knowledge has made it possible for us to understand that there are multiple pathways to death and that the commitment to die is not the same as execution. A cell that has passed the commitment stage but is blocked from undergoing apoptosis will die by another route. We still must learn much more about how a cell commits to death and what makes it choose a path to die.