By Ewen Callaway
For 18 months in the early 1980s, John Sulston spent his days watching worms grow. Working in twin 4-hour shifts each day, Sulston would train a light microscope on a single Caenorhabditis elegans embryo and sketch what he saw at 5-minute intervals, as a fertilized egg morphed into two cells, then four, eight and so on. He worked alone and in silence in a tiny room at the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK, solving a Rubik’s cube between turns at the microscope. “I did find myself little distractions,” the retired Nobel prize-winning biologist once recalled.
His hundreds of drawings revealed the rigid choreography of early worm development, encompassing the births of precisely 671 cells, and the deaths of 111 (or 113, depending on the worm’s sex). Every cell could be traced to its immediate forebear and then to the one before that in a series of invariant steps. From these maps and others, Sulston and his collaborators were able to draw up the first, and so far the only, complete ‘cell-lineage tree’ of a multicellular organism1.
Although the desire to record an organism’s development in such exquisite detail preceded Sulston by at least a century, the ability to do so in more-complex animals has been limited. No one could ever track the fates of billions of cells in a mouse or a human with just a microscope and a Rubik’s cube to pass the time. But there are other ways. Revolutions in biologists’ ability to edit genomes and sequence them at the level of a single cell have sparked a renaissance in cell-lineage tracing.
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