In 1972, a paper appeared in Science which reported that the arrangement within a given day of 3-hourly doses of Cytosine arabinoside (Ara-C) had a profound effect on the survival rate of mice inoculated with L-1210 leukemia cells [1]. This study was built on extensive prior work demonstrating that all Ara-C toxicities are markedly dependent on the time, in the day/night cycle, at which the drug is administered [2],.Together, the experiments showed unequivocally that, in mice, the timing of Ara-C administration predictably modulates its therapeutic index.