A chronobiotic is an agent that can cause phase adjustment of the circadian rhythm (biological body clock). That is, it is a substance capable of therapeutically entraining or re-entraining long-term desynchronized or short-term dissociated circadian rhythms in mammals, or prophylactically preventing their disruption following an environmental insult such as is caused by rapid travel across several time zones. The most widely recognized chronobiotic is the hormone melatonin, secreted at night in both diurnal and nocturnal species. History The concept of chronobiotics arose from the characterization of the pineal gland. In 1917, Carey Pratt McCord and Floyd Pierpont Allen at Johns Hopkins University demonstrated that tadpoles hatched in water that contained crushed pineal gland were much lighter in color than tadpoles hatched in normal water. No one could explain this phenomenon, and pineal gland research halted until the 1950s. Mark Altschule and Julian Kitay, both physicians at Harvard, summarized the body of pineal gland literature in the 1950s. Their main conclusion was that pineal gland hormones affected the size of rats' gonads, although the hormones had not yet been identified. Melatonin was originally discovered by Aaron Lerner, a Yale dermatologist, and colleagues, who had hoped it could be used to treat vitiligo. Although melatonin did not prove to be relevant to dermatology treatments, it was quickly confirmed to be secreted by the pineal gland to affect the brain. Further research found that circadian melatonin rhythms persisted under constant darkness, which suggested that light alone is not responsible for the cycle of melatonin secretion. Rather, endogenous melatonin serves to internalize light cues, making melatonin responsible for modulating neuroendocrine functions. The suprachiasmatic nucleus, or SCN, is a small region within the anterior hypothalamus of the brain that is responsible for orienting the organism's internal measurement of time to external time cues like daylight. The SCN was first identified to be the "circadian pacemaker" responsible for generating circadian rhythms in 1972. Both Robert Moore at the University of Chicago and Irving Zucker at the University of California, Berkeley linked the SCN to circadian rhythmicity at the same time by lesioning regions of the brain and observing their effects on circadian rhythms. When the SCN region was lesioned in rodents, the rodents did not exhibit circadian rhythms, which established the SCN as the circadian pacemaker. Robert Moore and David Klein first studied the SCN in the context of melatonin secretion by the pineal gland in