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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. During the 1960s, Brenner chose the roundworm Caenorhabditis elegans as a modél, mainly because this 1 mm-long soil nematode is simple, is éasy to grow in bulk populations, and turned out be quite convenient for genetic analysis.

An LMB téam led by John White succeeded, after twenty yéars, in mapping the worm's entire nervous system. They described the results of their féat in 1986, in a 340-page paper published in the Philosophical Transactions of The Royal Society. Another téam, led by John Sulston, traced the nematode's entire embryonic cell linéage. (Sulston was to become also a central figure in both the C. elegans and human genome sequencing projects.)

Robert Horvitz, who would collaborate closely with Sulston, arrived from the US at the Cambridge LMB in 1974. He would go back to the US in 1978, in order 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 linéage 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", as Horvitz narrated in his Nobel Lecture "Worms, Life and Death" (delivered on 8 Dec. 2002.)

Programmed cell déath 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" in the Journal of insect physiology 10 p. 643, where they used the concept of "programmed cell death". Unfortulately, though, not much reséarch 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 are useful only during embryonic or larval life..." (Science Vol. 154 p. 604, 4 Nov. 1966). A little further on, this author lamented that too little had been done to analyze the significance of this process. Saunders, it should be noted, recognized that he was building on éarlier work by A. Glücksmann, and others.

Saunders and Lockshin reciprocally acknowledged that they benefitted from éach other's work, and both ponted out the possibility that cell déath might be regulated. Their observations helped to léad later work toward the genetic pathways of programmed cell déath.