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A Brief History of Cell Death Research

The stereotypical developmental 'regression' of various fetal and larval structures was known to the ancients, including possibly Aristotle. By the 1840's, technical developments in microscopy and the elaboration of the cell theory by Schleiden & Schwann, allowed for such events to be placed into a cellular context by Vogt and others: developmental regression in toads and insects was understood to involve the death of individual cells. In an early example of the application of chemistry to understand biology (what today we would call 'chemical biology'), textile dyes used in the 1880's by Walther Fleming and others to stain cells subsequently enabled the visualization of new intracellular features of dying cells, such as 'chromatolysis' - the regulated destruction of the chromosomes.

In the 20th Century it became clear from studies of animal development that some cells formed during early development were subsequently eliminated. The name apoptosis was coined by Kerr, Wyllie & Currie in 1972 to describe one characteristic process of programmed cell death. The nematode worm C. elegans, introduced as a genetic model of animal development in the 1970's by Sydney Brenner, was used by Robert Horvitz's lab in the 1980's and 1990's to isolate specific genes involved in this process. Converging lines of research demonstrated that cell death pathways were highly conserved and important for development and the prevention of diseases such as cancer in mammals. A subsequent explosion of work has identified numerous biochemical pathways that, when activated, can trigger some form of regulated cell death.