Greg Hannon's group at Cold Spring Harbor Laboratory was one of many labs scrambling to identify Slicer, the enzyme doing the cutting in RNA-mediated interference. Using biochemical mutagenesis, in vivo knockouts, and enzymatic assays, they had all but pegged Argonaute2. But, says Hannon, "We were stuck ? We could go right up to the edge of saying it was Argonaute without actually saying it."
Just before he accepted defeat, however, a CSHL colleague, Leemor Joshua-Tor, invited him into a darkened room and gave him a pair of 3D glasses. She'd solved the crystal structure of Argonaute, and it revealed a structural homology to RNAse H providing guidance for targeted mutagenesis. "There's just no substitute for when you see it sitting there in 3D," Hannon says. The labs published their milestone findings together in 2004.