Light is the dominant environmental time cue for circadian clocks. In 1998, bright, narrow-spectrum blue light exposure to the back of the knees was reported to reset the human circadian pacemaker (HCP)(1). Science recognized the widely cited report as among the top discoveries that year to “transform our ideas about the natural world” and reported that several groups had repeated the finding (2). Patented treatments for circadian sleep disorders followed (3, 4). Yet the report was challenged because humoral phototransduction via the circulatory system, which was cited as a mechanism that might mediate such a circadian resetting response (5), had never before been demonstrated to reset a circadian pacemaker in any organism (6). Moreover, uncontrolled aspects of the experiments were hypothesized as being responsible for the reported results (7, 8). Indeed, in (1), subjects’ eyes were exposed to low, but biologically active (9) light intensities during the illumination of the knees, thereby potentially confounding assessment of the response to light behind the knees. Furthermore, melatonin phase estimates were not provided for control subjects (1). Using a variety of different protocols, most other groups have since been unable to affect the HCP with dermal light exposure (9). Even Campbell and Murphy reported an inability to elicit phase advance shifts when subjects were asleep (10)—contrary to their initial expectations (1, 3)—although they have reported that light to the back of the knees during sleep influenced another aspect of human brain function: REM sleep (11). Given the importance of this result to the fundamental understanding of the neurobiology of the HCP, we therefore set out to replicate the findings of (1).

Twenty-two 10-day inpatient phase-resetting trials were conducted. Constant routines (9) were used to assess circadian melatonin phase before and after exposure to one of three 3-hour-long interventions balanced by gender: 0 lux ocular and behind the knee (DK), 0 lux ocular and up to 13,000 lux behind the knee (BK), and 9,500 lux ocular and 0 lux behind the knee (BE). As in