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Capecchi used his grant money exactly how the NIH had told him not to—a potentially career-ending move if the experiments failed. Fortunately, by the time he needed to renew the grant in 1984, he had succeeded in making gene targeting work in mammalian cells. The same year, Capecchi heard a talk, by a graduate student of British researcher Martin Evans, explaining how their lab had cultured embryonic stem cells from mouse embryos. Capecchi's goal had always been to build a mouse with his targeted mutations, so he called Evans to ask if he and his wife, Laurie Fraser, could visit Evans' laboratory to learn how to work with these cells.
Meanwhile, Oliver Smithies had been working on the very problems Capecchi was pursuing, albeit with a different approach. While Capecchi wanted to induce mutations in mice, Smithies hoped to repair bad DNA with a view to gene therapy. Evans made his cells available to Smithies as well.
The situation was a recipe for a classic scientific rivalry. Yet what resulted was magnanimity, based on mutual respect and support. In an interview with the Nobel Foundation shortly after learning he'd won the prize, Smithies said, “I so much admire the work of Mario Capecchi and Martin Evans. So that's a big delight to me, to share it with them.”
“There are many stories about two Nobel prize winners who won't talk to each other,” says Capecchi. “That would be awful. In this case, all three of us actually are good friends. We were following our own pathways, but at the same time we tried to help each other.”
That's not to say Capecchi was broadcasting his progress. In 1987, he published a paper on introducing targeted mutations; Smithies followed almost immediately with a study showing how he had repaired a faulty gene. In both cases, the research was based on mouse embryonic stem cells. Two years later, Capecchi published a description of his first knockout mouse.
As the camerawoman continues filming, Capecchi returns the OCD mouse to its cage and walks the Italian TV crew through the rest of his lab. A short man with waves of well-groomed, if still somewhat unruly, gray hair, he is dressed for the interview in a crisp tan shirt and dark silver paisley tie, his black clogs the only hint of his standard campus wardrobe. There are rows of benches and cold rooms where the 39 people who make up Capecchi's lab—researchers, technicians, and support personnel—continue working. Three weeks after the Nobel announcement, they seem numbed to the presence of reporters.
Back at his office, he settles into a gray desk chair, picks up his laptop, and brings up an impressionistic oil painting of two kids at an outdoor picnic table. “That's my mother and her brother,” he explains, as the camerawoman zooms in. The artist, Capecchi's grandmother, raised her American children abroad. The next photo, a black and white, is of his uncle as an adult. Edward Ramberg was a physicist whose work helped lead to the invention of the electron microscope and television. “He wasn't very proud of the latter,” Capecchi says. “TV wasn't allowed in his house.” The focus then turns to a framed etching of his mother, also made by his grandmother, on the wall across from Capecchi's desk.