TOP ROW, L TO R: THE ELEMENTS OF GENETICS, MACMILLAN (1950); COURTESY OF TOM ELLENBERGER, WASHINGTON UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS, AND DAVE GOHARA, SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE. MIDDLE ROW, L TO R: CHEMICAL HERITAGE FOUNDATION, PHOTOGRAPH BY DOUGLAS A. LOCKARD; BMC CANCER, 2012, 12:21, 2012. BOTTOM ROW, L TO R: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES, NATIONAL INSTITUTES OF HEALTH; © THE NOBEL FOUNDATION. PHOTO: ULLA MONTAN
In the mid-1980s, Oliver Smithies, then at the University of Wisconsin–Madison, and Mario Capecchi of the University of Utah independently used homologous recombination—a molecular process to repair broken DNA—to change specific regions of the genome in cultured mouse cells (Nature, 317:230-34, 1985; Cell, 44:419-28, 1986). The technique involved sandwiching an altered copy of a gene between two regions of code identical to those flanking the endogenous gene, which would be swapped out for its engineered counterpart.
But Capecchi and Smithies couldn’t introduce genetic changes into living animals until Martin Evans, now of Cardiff University in the U.K., established a method for culturing mouse embryonic stem cells (ESC). Only ESC or cancer cells could be kept in culture long enough to produce enough genetic material to ...
