In 1981, Martin Evans and Matthew Kaufman, working at the University of Cambridge, UK, and Gail Martin, working at the University of California, San Francisco, independently and simultaneously discovered methods to isolate mouse embryonic stem (ES) cells and grow them in culture. The hard part, they assumed, was over. "Everyone thought that within five minutes we'd have embryonic stem cells from everything," including the mouse's cousin, the rat, says Mia Buehr, a postdoc at the University of Edinburgh. But that achievement would take another 27 years.
By the early 1990s, researchers were routinely altering the DNA in mouse ES cells to create genetically engineered mice with missing, added, or modified genes. But the same techniques did not work in rats.
Buehr joined Austin Smith's Edinburgh lab in 1994 tasked with smoking out stem cells from the impervious rat, whose larger size and behavioral sophistication make them more effective animal models ...