Like every other animal, the nematode worm C. elegans begins life as a single fertilized cell. This divides into two, and then four, and then eight. By the time the worm is an adult, that original cell has become either 959 or 1031, depending on its sex. The number of cells never changes—it’s the same from one individual to another. And we know where every single one of them came from because a man named John Sulston spent 18 long months in the early 1980s, hand-drawing worms in a darkened room.
Sulston worked alone, in silence, hunched over a microscope for eight hours a day. By studying and drawing worms of various ages, he figured out the ancestor and descendants of each of their cells. It was a monumental piece of science. Sulston mapped the complete history of an individual, the comprehensive family tree of a single body. “We had the entire story of the worm’s cells from fertilized egg to adult,” he later said, upon accepting the Nobel Prize for his work.
Studying C. elegans was a smart call. The worm is small, so it only has a thousand or so cells. It’s transparent, so every cell could be easily observed. And it develops the same way every time, so each cell has an invariant fate. By contrast, mapping cell lineages in a bigger, opaque, and more variable animal—say, a fly or mouse—is much harder. Jay Shendure started thinking about ways of doing this in 2000, when he was a graduate student. “I worked for six months, and after my first lab meeting, a postdoc grabbed me. He said this would take a few decades to do,” Shendure recalls. “I switched projects but I always had this in the back of my head.”