History and Highlights in Apoptosis Research - Early Research, and The "worm People" at Cambridge

Early Research, and The "worm People" At Cambridge

Sydney Brenner's studies on animal development began in the late-1950s in what was to become the Laboratory of Molecular Biology (LMB) in Cambridge, UK. It was at this lab that during the 1970s and 1980s, a team led by John Sulston succeeded in tracing the nematode Caenorhabditis elegans entire embryonic cell lineage. In other words, Sulston and his team had traced where each and every cell in the roundworm's embryo came from during the division process, and where it ended up.

H. Robert Horvitz arrived from the US at the LMB in 1974, where he collaborated with Sulston. Both would share the 2002 Nobel Prize in Physiology or Medicine with Brenner, and Horvitz would go back to the US in 1978 to establish his own lab at the Massachusetts Institute of Technology.

Brenner's original interests were centered in genetics and in the development of the nervous system, but cell lineage and differentiation inevitably led to the study of cell fate:

One aspect of the cell lineage particularly caught my attention: in addition to the 959 cells generated during worm development and found in the adult, another 131 cells are generated but are not present in the adult. These cells are absent because they undergo programmed cell death - Horvitz: "Worms, Life and Death," 2002.

Programmed cell death had been known long before "the worm people" began to publish their celebrated findings. In 1964 Richard A. Lockshin and Carroll Williams published their contribution on "Endocrine potentiation of the breakdown of the intersegmental muscles of silkmoths", where they used the concept of programmed cell death during a time when little research was being carried out on this topic. John W. Saunders, Jr., stated the following in his 1966 contribution titled "Death in Embryonic Systems":

Abundant death, often cataclysmic in its onslaught, is part of early development in many animals; it is the usual method of eliminating organs and tissues that is useful only during embryonic or larval life

Saunders and Lockshin reciprocally acknowledged that they benefited from each other's work, and both pointed out the possibility that cell death might be regulated. Their observations helped to lead later work toward the genetic pathways of programmed cell death.