As a boy, Clarence Cook Little kept mice as pets, but his hobby became serious inquiry when he began studying Mendelian inheritance of mouse coat color under William Castle at Harvard University. Wilhelm Johannsen, the Danish botanist who coined the term "gene," showed the value of inbreeding to fix characteristics, and Little applied that idea to mice. In 1909, he produced the first inbred mouse strain, DBA, from repeatedly mating brother-sister pairs. Against a "fixed" genetic background, Little sought to sort a trait far more complex than coat color: cancer susceptibility. DBA, however, showed certain frailties from inbreeding that compromised its usefulness when more resilient strains came along.
Sometime around 1914, Little obtained a female mouse, code numbered 57, and a male, numbered 52, which he inbred through at least twenty generations (3-4 generations a year). He named the resulting strain C57BL/6 (a J was added later to indicate the Jackson Laboratory, which Little founded in 1929).