His observations have resonated with circadian surveillance scientists who are struggling to make progress in their institutions. “John was able to raise a discussion or awareness that a discussion had to take place,” says Elizabeth Klerman, professor of neurology at Harvard Medical School, who works in the sleep department at Massachusetts General Hospital. Frank Scheer, director of the medical chronobiology program at Brigham and Women’s Hospital, was also impressed. “We are trying to improve the health of the most vulnerable, we have an obligation to take care of them, and despite this, they are in conditions that are not conducive to sleep,” he says of the hospital patients. “I think his work is wonderful. He is making great strides in this area.”
While the PNAS data showed that when hospitals deliver medicines it likely makes more practical than medical sense, they failed to show whether the time is hurting patients. If not, why change? Hogenesch’s team and staff at other hospitals are currently analyzing electronic medical records to see if they can show that the timing of certain common medications affects their effectiveness. This is more complicated than it sounds because the data collected by hospitals is primarily for billing, not research, and it’s not always noted when patients receive services and medications. If recording the timing of procedures—blood, vaccine, urine, and other sample collections—in patient electronic health records were standard practice, that could greatly improve our understanding, Zee notes. “Nowhere on your vaccination card does it say when you got it.” But doing it should be “so easy,” she adds. “It’s all electronic.”
Any data obtained from medical records will still be observational, but the more such data you have from various sources, the more convincing it can be. At the same time, researchers can create larger and more representative samples by looking at several smaller studies together in a so-called meta-analysis. Last year, to show that the timing of medication can make a big difference, Hogenesch and colleagues released a preprint before peer review: a meta-analysis of previous clinical trials that included the time of day when subjects received one of 48 pharmacological or surgical interventions. Surprisingly, low-dose aspirin, which millions of people take daily to prevent heart disease and which doesn’t tell you when to take it, was the most time-sensitive, with eight out of 10 studies showing it to be more effective. when taken in the evening, not in the morning.
Personalized Circadian Medicine may be the future. The timing of our watches depends on the person, on the setting of the sun, the lighting in the room, genetic predisposition, our behavior, our age and each other. Scientists are still trying to develop a quick and easy method to determine what phase or phases your organs are in. But it doesn’t take absolute precision to improve the coordination and strength of your biological rhythms yet. Circadian rhythm researchers generally suggest getting as much sunlight as possible during the day, especially after waking up, dimming the lights before bed, and darkening the bedroom. (Parking America during standard time rather than daytime will help achieve this.) Load your calories early in the day. First of all, try to keep your schedule comparable throughout the week, including weekends. “There’s room here to think about general health optimization — better mood, better overall health,” Helen Burgess, professor of psychiatry and co-director of the Sleep and Circadian Laboratory at the University of Michigan, told me. “We are all getting older. Many of us feel we are languishing,” she added. “What tiny little things can I do to make myself feel better?”
In other words, circadian medicine can make us feel better, but most of us shouldn’t expect it to change our lives anytime soon. However, there are exceptions to this rule, the unusual circumstances of which may subsequently indicate wider application. As Hogenesch told me, “You learn from edge cases.”
Shortly after he arrived in Cincinnati, a colleague from Boston forwarded an email to him from the parents of Jack Grosseclose, a teenager with Smith-Kingsmore syndrome, an extremely rare disease caused by a single gene mutation that causes pain and seizures, a developmental disorder. delays, autism and a tendency to self-harm. In their letter, Mike and Kristen Grosseclose explained that Jack was taking the drug to turn off the gene. This improved many of his symptoms, but his sleep became strange. For more than a week he hadn’t slept for more than an hour or two, and instead he was constantly pacing back and forth. (Fitbit, bought by his parents to track his activity, showered them with congratulations.) Then for seven to ten days he slept for 14 hours. “After 10 days of almost no sleep, his body is starting to break down,” they wrote. “He becomes shaky and unsteady, covered with eczema.” Jack’s doctors were confused. Hoping for an explanation, the Grosseclows included a histogram of Jack’s sleep cycle and a photograph of him in their email. “He didn’t look good,” Mike told me. Kristen added, “We thought a visual aid might help.”