In the early 1980s, Oliver Smithies, at the University of North Carolina, initially pursues a therapeutic goal: correcting via homologous recombination the mutations that cause hereditary blood diseases, introducing into cells correct copies of globin genes to specifically replace defective versions. In 1985, Smithies and his collaborators succeed in demonstrating something of greater conceptual reach than their original therapeutic goal: that an artificially introduced DNA segment can be specifically directed to the human globin chromosomal locus and recombine with it, regardless of whether that gene was active or silenced in the cell. This observation suggested that, in principle, any gene in the genome — not just actively transcribed ones — could be accessible to targeted modification via this technique, a result obtained through an experimental route completely different from and independent of the one Mario Capecchi was pursuing in parallel. Combining both approaches with the mouse embryonic stem cells contributed by Martin Evans made it possible to generate the first "knockout" mice with specific genes heritably inactivated, becoming the most widely used tool in mammalian biology for more than two decades. Smithies and Capecchi shared the Wolf Prize in Medicine in 2002; the 2007 Nobel recognized both together with Evans.