In 1983, John Sulston and Alan Coulson began to construct a complete physical map of the genome of the nematode worm Caenorhabditis elegans, and started what became known as the C. elegans Genome Project. At the time, several people wondered why John, who had just described all of the cell divisions in C. elegans (the cell lineage), was interested in this project rather than in a more 'biological' problem. He replied by joking that he had a "weakness for grandiose, meaningless projects". In 1989, as the physical map approached completion, the Genome Project, now including Bob Waterston and his group, embarked on the even more ambitious goal of obtaining the complete genomic sequence
In a dimly lit laboratory room in Gottingen, West Germany, Einhard Schierenberg bent his long, angular frame over his microscope, watching and counting, recording what he saw on charts and videotapes, hour upon hour, day after day, intermittently for six years. Five hundred miles away in a tiny, starkly equipped cubbyhole in Cambridge, England, John Sulston was doing the same thing, hunched over his microscope, earphones on his head to block any sound that might divert him from the image in his eyepiece. Sometimes he would sit watching all day long, diligently marking in a notebook with his colored pens. Schierenberg and Sulston were learning, cell by cell, how to build a worm.
Twenty years ago Sydney Brenner described an electrode-less plan for attacking the problems of neural development and physiology in the small nematode Caenorhabditis elegans. He proposed to set the groundwork by reconstructing the entire nervous system of the worm by serial section electron microscopy. Given the resulting wiring diagram, he thought it might be possible to make guesses as to how the nervous system worked. A second aspect of his plan was genetics: single-gene mutants exhibiting aberrant behaviour, such as uncoordinated movement, were to be analysed to address the question of how genes specify development and function of the nervous system. In two papers beginning on page 334 of this issue, McIntire et al. demonstrate that work on Brenner's plan, with a few tricks added over the years, is progressing very nicely.