Circadian rhythms of activity and physiology are evident across the animal kingdom as well as in plants and some bacteria. The scientific study of biological clocks goes back almost 300 years to a French astronomer called Jean-Jacques d’Ortous De Mairan, who discovered that the diurnal closing of Mimosa leaves persisted under conditions of constant darkness. Whether this was due to mysterious “magnetic rays”, or to the presence of an equally mysterious internal clock in the plant was controversial, but it later became clear that light-independent twenty-four hour clocks could also be found in animals. The mechanisms underlying such clocks were a long-standing puzzle until the Shaw Prize Laureates of 2013, Jeffrey C Hall, Michael Rosbash and Michael W Young discovered two key components of the endogenous clock mechanism of the fruit fly, Drosophila melanogaster. Over the course of the last twenty-five years, thanks to the work of these pioneers, details of the clock mechanism in animals have steadily emerged. It is a much more complicated molecular machine than any theorist had imagined.
The crucial first step for the molecular understanding of biological clocks came in 1971, when Ronald Konopka and Seymour Benzer identified three mutant strains of fruit flies that showed heritably altered circadian rhythms. Mapping the mutations revealed a single gene, Period, or Per, that could be mutated to give either shorter or longer cycles of activity, or no rhythmic activity cycles at all. Clearly, Per was intimately connected with the clock. But how the clock worked could only be a matter for speculation until the Per gene was cloned, a challenging feat that was achieved in 1984 by Michael Young at Rockefeller University and, independently, by a collaboration between Jeffrey Hall and Michael Rosbash at Brandeis University. But the deduced protein sequence of Per did not at first reveal its nature or function.