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t is 7 p.m. on a spring Friday, and the Highland Hospital emergency room in Oakland, one of the busiest trauma centers in northern California, is expecting. When the patient—a young bicyclist hit by a car—arrives, blood is streaming down his temples. From a warren of care rooms, a team of nearly a dozen doctors and nurses materializes and buzzes around the patient. Amelia Breyre, a first-year resident who looks not much older than a college sophomore, immediately takes charge. As soon as the team finishes immobilizing the victim, Breyre must begin making split-second decisions: X-ray? Intubate? Transfusion? She quickly determines there is no internal bleeding or need for surgery and orders up neck X-rays after bandaging the patient’s head. Breyre will make a half-dozen similar critical choices tonight. Highland, a teaching hospital, is perhaps the most selective emergency-medical residency in the nation. To be here, she must be outstanding. To succeed, though, she must stay sharp. That quality of focus—amid the chaos and battered humanity that comes through Highland’s doors—is itself in need of urgent care. Andrew Herring, an emergency-room doctor who supervises Breyre and 40 other residents, is worried about the team. ER doctors are shift workers, and their hours are spread over a dizzying, ever-changing schedule of mornings, afternoons, and nights that total 20 different shifts a month. That’s meant to equally distribute the burden of nocturnal work across an entire team of physicians. But despite those good intentions, Herring says, the result is that every single one of them is exhausted and sleep deprived. That’s dangerous for doctor and patient alike. “A single night shift has cognitive effects going out for a week,” says Herring, a Harvard-trained physician. “When you are done, you are burger meat, crispy fried. People will tell you the next day that they are rested up, but they aren’t — and mistakes occur.”
This phenomenon isn’t unique to the ER. Nocturnal labor presents risks to roughly 15 million shift workers in the United States alone. Major industrial accidents, such as the meltdown at the Three Mile Island nuclear reactor in 1979, occur disproportionately in the dead hours before dawn. The graveyard shift, it turns out, is aptly named. Those who regularly endure it are also at higher risk for depression, obesity, diabetes, and cancer. In fact, the correlation is so strong that in 2010, the World Health Organization went so far as to classify late-night work as a probable carcinogen.
Biologists have come to believe that the negative effects happen because toiling through the wee hours screws with our circadian rhythms, mysterious internal timing mechanisms that can be modulated by external cues like light and temperature. In fact, every animal and plant on the planet— even certain bacteria—has evolved with these cellular oscillations. They dictate hundreds of other crucial processes, turning energy on and off in 24-hour cycles. They orchestrate our daily peak rhythms for things like cognition, fat synthesis, and even hair growth.
These internal clocks, which biologists are just starting to research and understand in detail, are constantly syncing based on the food we eat, our exercise routines, social interactions, and light patterns. And whether we know it or not, we're constantly working against them.
In 2006, University of Virginia researchers turned on the lights in the cages of lab mice six hours earlier than normal once a week for eight weeks, preventing them from resetting their clocks. In terms of light-cue changes, it was as if they’d flown from New York to Paris once a week. The result: Younger rodents got sick and displayed mentally unstable behavior; 53 percent of the older mice just dropped dead.
“I really worry we are killing ourselves,” says Herring, scanning the ER as Breyre and the others multitask, physically and mentally pushing themselves.
This past spring, Herring read about another mouse study, by researchers at the University of California at San Diego. The investigators are part of the UCSD Center for Circadian Biology, which is dedicated to the nascent and often-overlooked field of chronobiology, the science of our inner biological clocks. Its scientists study the implications of untethering humans from our natural light cycles and other external cues that regulate our bodies. The UCSD mouse study, unlike the earlier research from UVA, offered good news in its findings: a way to use twilight to adjust the mice to irregular day/night cycles.
Herring volunteered to make his team available to the researchers as study subjects. “I felt we really needed to look at this in a different way,” he says.
Susan Golden, director of the UCSD center, doesn't just talk chronobiology. She lives it. At home, she and her husband, James, a microbiology professor who also works at UCSD, cuddle up in front of the TV wearing orange sunglasses to block blue rays, which our bodies read as midday light. They've installed dimmers on their bathroom and bedroom lights so they can keep them low throughout the course of the night.
“None of us are Luddites trying to live outside technology,” Golden tells me one day in her office in the Applied Physics and Math building on campus. “But that technological lifestyle needs to be smarter,” she adds, “because we are animals that evolved on Earth.”
Like most of her 35 colleagues, Golden didn’t set out from school intent on pursuing a career in chronobiology. The field only barely existed when she did her graduate work in the 1980s. Her specialty was, and still is, studying bacteria that use light as a source of energy. But with advances in computing and analytical methods, it’s now possible to process thousands of tissue samples at once and chart changes in metabolic processes over time. Adding that fourth dimension made Golden realize how much she had been missing by looking at a single point in time for information. It made her decide that science plus time—i.e., chronobiology—was where she needed to take her career.
“What we’ve really learned in the past five years is that circadian studies cannot be treated as a boutique discipline,” she says. “It is biology. You cannot adequately study neurobiology, metabolism, microbiome without taking time into consideration. All of the processes in all of these cells and organs change over time. And if you look at a static snapshot without considering that, you don’t get the right answer. Or at least not the whole answer.”
That picture finally started to come into focus in 1972, when neuroscientists first discovered how a tiny region in the brain’s hypothalamus acted as the body’s master circadian clock. This small cluster of 20,000 neurons, named the suprachiasmatic nucleus, sends signals through the body to keep the various processes switched on or off during the right moments of our 24-hour cycles. The system uses daylight as its main cue to stay on track.
Other discoveries followed. It turns out that nearly every organ has an internal ticker. Your pancreas has a mechanism that tells it when to release insulin and when to stop. Your liver knows when to stop processing glycogen and start metabolizing fat. Even your eyes have built-in timekeepers that tell them when to repair retinal cells damaged by ultraviolet rays. In other words, to understand the body and its functions, you also have to understand its timers.
All across the UCSD campus, members of the Center for Circadian Biology—which does not have its own building— are researching these timekeeping functions. Among their findings: Genes that run our circadian rhythms are linked to metabolism and its control networks. Mess with one and you mess with the other. For example, eat too late in the evening, when your metabolic defenses have powered down, and your chances of growing obese balloon. In turn, that fat can also invade your liver and thus increase your likelihood of inflammation and cancer.
Our mental health is also at risk. Researchers have found that 70 percent of people with disorders that keep them from sleeping at the usual time—possibly due to a genetic abnormality—suffer from conditions like severe depression or anxiety. In fact, nearly two-thirds of bipolar sufferers report abnormal sleep cycles.
Already, doctors treating cancer have used chronobiology’s findings to better plan their treatments. For example, undergoing chemotherapy later in the day increases patients’ chances of avoiding nausea because stomach linings better repair themselves at that time.
Much of the center’s research can seem, cumulatively, like a condemnation of our modern lifestyle. Since the dawn of electricity, we have been engaging in a massive uncontrolled experiment in disrupting ancient rhythms. And it’s not just due to shift work. There are a thousand small ways that we use artificial light to ignore the subtle cues that changes in nature give us all day. “Inside light is just terrible for you,” Golden says. “It is making us all sick.”
As man-made light keeps us awake longer or in a state of agitation throughout the night, it's also contributing to one of the biggest epidemics in America—obesity, which afflicts more than one-third (35.7 percent) of adults across the country. That role is slowly gaining attention, thanks to one of Golden's star researchers.
Satchidananda Panda works at one of the country’s pre-eminent research facilities: the Salk Institute for Biology. Although chronobiology is growing in importance, many scientists, including fellow biologists, still think it’s mostly about jet lag and sleep. No one has resisted that second-tier status more than Panda.
For more than a decade, he’s been studying the links between human metabolism and our inner clocks. He and other researchers have found that by limiting the number of hours during which obese mice can eat fatty foods, they’re able to achieve all kinds of health benefits for the plump subjects. Even when eating the same amount and type of food as control mice who could eat all day and night, the ones who Panda restricted to an eight-hour feeding schedule lost weight, shed stored body fat (particularly around the liver), and suffered less internal inflammation. In another study, a team of UCSD researchers found that when they subjected obese mice with cancer to time-restricted diets instead of allowing unrestricted gluttony, the rodents’ tumors shrank.
Despite these findings, and their potential effect on the obesity epidemic, Panda has struggled for funding and recognition. The NIH has denied all 14 of his proposals for grants to study time-restricted feeding. The grants are decided by anonymous peer review, and many of Panda’s mainstream fellows are suspect about the science of time.
“My reviewers said, ‘Humans don’t eat like mice; they eat three meals a day within 12 hours, so it has no human significance,’” Panda recalls, visibly incensed. “That really pisses me off. I’ve reviewed 150 years of human research, and most studies never asked or recorded when people eat. They asked what you had, but rarely when you ate.”
Panda’s focus on chronobiology, his belief in its role in our lives, goes back to rural India. He and his sister could tell the time of evening, for example, based on when the frogs would enter their backyard and begin croaking. To an observant child, it was apparent that the natural world has immutable rhythms. His interest has led him to explore entirely new avenues of research: In 2002, he helped discover how light sensors at the back of the eyes communicate with the brain’s master clock. In 2005, he found that the part of the retina that uses ambient-light levels to determine when the body should sleep or wake is most sensitive to blue light.
Panda decided that his only way forward was to prove his peer reviewers wrong about eating patterns. Taking a cue from Silicon Valley, he open-sourced a human experiment, using an app. He called it Mycircadianclock and recruited 156 people. He asked them to record what they ate and drank, including water and medicines, by simply snapping a photograph and uploading it via the app.
The data proved his point. We think we eat about three times a day. But we often ignore snacks. In fact, a third of Panda’s participants ate eight times a day. And they were more likely to eat around the clock. People who started their days with coffee and a bagel at 6 a.m. would post pictures of brownies, Sun Chips, pizza, and wine at 11 p.m. The later it got, the more likely they were to tuck into something fatty or alcoholic. Panda speculates that the brain “thinks it will be up all night, and so it wants us to overeat in preparation.”
Panda has since opened his app to the public, and volunteers now number in the thousands. Moreover, wherever he goes, he conducts his own informal survey of eating hours and habits. He asks every cab driver, waitress, and drugstore clerk he encounters what time they woke and when they ate their first meal. And he asks when their day will end. “You will find many of these people work two jobs,” Panda says.
After hearing of his work, the San Diego Fire-Rescue Department contacted Panda for help battling the profession’s high risk of heart attacks. Firefighters face the same kinds of challenges as Herring’s ER team. Their shifts run 24 hours on, 24 hours off, for eight-day cycles. Unpredictable alarms can play havoc with circadian rhythms. They’re also left catching up on missed meals at all hours, often with high-calorie treats from grateful neighbors. Panda wants to do a study in which he controls their eating hours to see if that alone affects their rate of cardiovascular disease.
This article was originally published in the September/October 2017 Mysteries of Time and Space issue of Popular Science.
