Salad days in the rhythms trade.

ONE of the nicest things anyone ever said about our workwas ina(necessarily) anonymousgrant review from the early 1990s in which the author commented that our lab had contributed greatly to moving the study of circadian rhythms ‘‘out of the era of spoon-bending.’’ Some years later Bob Metzenberg, who always cherished a well-turned phrase, fessed up to having written this, and it is easy to see his quick wit and word play. I mention it here because it nicely encapsulates the 25 years that I want to cover, a period that extends from the era when belief in intracellular circadian rhythms stretched the credibility of all but devotees to the years when the problem was cracked and rhythms truly entered mainstream science (Science News and Editorial Staffs 1997, 1998). During this time, analysis of rhythms moved from the use of genetics—which opened up the black box and exposed the feedback loops—to molecular biology, where the field is now. Although it is tempting to write about all the vistas that opened up during this time based on work in Neurospora, from clock mechanism to clock output, I have restricted this Perspectives to studies on the circadian mechanism and will leave output to other, highly capable hands (Loros 2008). It is an account of what drew me to rhythms work and to the Neurospora circadian system and of what led our lab to identify the factors and interactions that contributed to the denouement of the question of the molecular bases of circadian rhythms: the assembly, a little over a decade ago, of a complete interconnected regulatory cycle.