His observations have resonated with circadian scientists struggling to make headway at their own institutions. “John has managed to elevate the discussion or the awareness of the discussion that needed to happen,” says Elizabeth Klerman, a professor of neurology at Harvard Medical School who works in the sleep division at Massachusetts General Hospital. Frank Scheer, director of the Medical Chronobiology Program at Brigham and Women’s Hospital, has also been impressed. “We’re trying to improve the health of the most vulnerable, we have a responsibility to take care of them, and despite that, they’re in environments not conducive to sleep,” he says, of hospital patients. “I think his work is beautiful. He’s making great headway in this area.”
Although the PNAS data revealed that when hospitals deliver drugs very likely makes more operational than medical sense, it was not able to show whether that timing harms patients. If it doesn’t, why change it? Hogenesch’s team and collaborators at other hospitals are now analyzing electronic medical records to see if they can show that the times certain common drugs are given affect how well they work. This is harder than it sounds, because the data hospitals collect is primarily for billing, not research, and when patients receive services and medications is not always noted. If logging the times of procedures — of blood draws, vaccines, urine and other samples — in patients’ electronic medical records were standard practice, it could vastly improve our understanding, Zee notes. “Nowhere in your vaccination record does it say when you got it.” But doing that ought to be “so easy,” she adds. “This is all electronic.”
Any data gleaned from medical records will still be observational, but the more such data you have from a variety of sources, the more persuasive it can be. In the meantime, researchers can create larger and more representative samples by looking at multiple small studies collectively in what’s called a metanalysis. Last year, to help make the case that medication timing could have a major impact, Hogenesch and colleagues released as a preprint, ahead of peer review, a metanalysis of previous clinical trials that included the time of day that subjects received one of 48 pharmacological or surgical treatments. Unexpectedly, low-dose aspirin, which millions of people take daily to prevent cardiovascular disease and which does not come with guidance for when to take it, proved to be the most time-sensitive: Eight out of 10 studies found it to be more effective when given in the evening as opposed to in the morning.
Personalized circadian medicine may be the future. The timing of our clocks varies by individual, set by the sun, indoor lighting, genetic predisposition, our behavior, our age, one another. Scientists are still scrambling to develop a quick and easy method for telling what phase, or phases, your organs are in. But for now, absolute precision is not required to improve the coordination and strength of your biological rhythms. Circadian researchers generally suggest getting as much sunlight as you can during your day, especially upon waking, dimming the lights before sleep and making your bedroom dark. (Parking America on standard time, not daylight, would help accomplish that.) Front-load your calories earlier in the day. Most of all, try to keep your schedule comparable throughout the week, including weekends. “There’s room here to think about overall health optimization — improving mood, improving overall health,” Helen Burgess, a professor of psychiatry and co-director of the Sleep and Circadian Research Laboratory at the University of Michigan, told me. “We’re all getting older. Many of us feel like we’re languishing,” she added. “What are the tiny little things I can do to feel better?”
Circadian medicine may enhance our well-being, in other words, but most of us should not expect it to transform our lives anytime soon. There are, though, exceptions to that rule whose unusual circumstances may point towards broader applications later. As Hogenesch put it to me, “You learn from the edge cases.”
Soon after he arrived at Cincinnati, a colleague in Boston forwarded him an email from the parents of Jack Groseclose, a teenager with Smith-Kingsmore syndrome, an exceedingly rare condition caused by a mutation in a single gene that brings about pain and seizures, developmental delays, autism and a disposition to self-harm. In their letter, Mike and Kristen Groseclose explained that Jack was taking a drug to turn off the gene. It had improved many of his symptoms, but his sleep had taken on a bizarre pattern. For more than a week, he wouldn’t sleep longer than an hour or two and instead paced constantly. (A Fitbit his parents bought to track his activity showered them with congratulations.) Then, for seven to 10 days, he would sleep for 14 hours. “After 10 days of little to no sleep, his body starts to break down,” they wrote. “He becomes shaky and unsteady, breaks out with eczema.” Jack’s doctors were baffled. Hoping to generate an explanation, the Grosecloses had included in their email a bar graph of Jack’s sleep cycle and a photo of him. “He was looking poor,” Mike told me. Kristen added, “We thought a visual aid might help.”