The self-same beat of time's wide wings.

S progress is punctuated with revolutions of insight andyor technology that at least temporarily cast aside valid frames of thought. Like the Titanic losers to the Olympian gods in Keats’ unfinished epic Hyperion (1) from whence the title of this commentary comes, ‘‘vanquished’’ ideas or approaches frequently offer important alternatives to prevailing model systems. The successes of molecular genetics in biological circadian clocks are an excellent example of this dynamic, and the paper by Brandstätter et al. (2) in this issue of PNAS is a testament that systems analyses of clock function still have much to offer the circadian clocks field. It demonstrates that the clock within the avian pineal gland ‘‘remembers’’ the time of year, as well as the time of day, important characteristics for the adaptive function of clocks, which cannot be explained by current, more popular preparations. Further, the paper shows that the ability of the pineal gland to faithfully reflect photoperiod depends at least in part on its integration with other components of a larger, more precise circadian system (3, 4). The avian pineal gland once held very high office in the Pantheon of circadian model systems. Thirty years ago, Gaston and Menaker (5) showed that pinealectomy of house sparrows, Passer domesticus, abolishes circadian locomotor rhythms in constant darkness (DD), demonstrating the pineal was critical for rhythmic behavior. They also showed that the gland is only part of a circadian system; pinealectomized sparrows entrain to light dark (LD) cycles and, on transfer from LD to DD, only gradually become arrhythmic. The role(s) played by the pineal gland in rhythms and the mechanism of its rhythmic regulation of behavior became more apparent when Zimmerman and Menaker (6) demonstrated that pineal transplantation into the anterior chamber of the eye to pinealectomized, arrhythmic sparrows conferred rhythmic locomotion to the recipient birds. These data indicated the pineal confers its message via humoral signals, because rhythmicity returned to the recipients within a day of their transplant. Importantly, the study showed that the pineal gland carried within it a physiological correlate of time of day. Recipient birds expressed an earlier time of activity if they received pineal glands from donors entrained to an early LD cycle, whereas recipients who received pineal glands from donors entrained to a later LD cycle expressed later activity cycles. After the discovery and characterization of the pineal hormone melatonin and its biosynthetic pathway (cf. ref. 7), several groups showed the pineal’s humoral signal to be melatonin. Further, the avian pineal gland was found to express circadian rhythms of melatonin biosynthesis, content and release in vitro (8–11), that could be entrained to LD in vitro (8–11). Thus, the avian pineal is important for overt rhythmicity, has physiologically relevant input (light), an endogenous circadian oscillator and an easily measured rhythmic output, melatonin (Fig. 1A).