By the 1980s, Sydney Brenner’s “worm project” was in full swing. Brenner and his crack team of researchers at the Laboratory of Molecular Biology (LMB) in Cambridge, UK, had already constructed a detailed genetic map of the nematode Caenorhabditis elegans and described the worm’s embryonic and nervous system development in exquisite four-dimensional detail. What was missing, however, was an efficient way to isolate the genes for molecular analysis.
To address this problem, Alan Coulson and John Sulston developed a high-resolution “fingerprinting” technique to line up DNA fragments cloned using hybrid plasmid vectors called cosmids; by 1984 they had successfully assembled a physical map that spanned about 60% of the worm genome. Bob Waterston of Washington University in St. Louis, who spent a sabbatical at the LMB in 1985, then devised a different approach to complete the map. Together with Coulson and Sulston, he created yeast artificial chromosome (YAC) clones for ...