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Authors: Jennifer Ackerman

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Studying the laborers is no piece of cake, either. "Getting forty-five rig workers to collect urine every four hours for fourteen days is a feat," says Arendt. "Rigs make about three million dollars a day, so interruptions of work to pee for circadian studies are not particularly welcome." Nevertheless, Arendt got her results. She compared laborers working two different shift schedules for two weeks: one a simple twelve-hour shift, with workers on either night shift or day shift; the other a "swing" rotation of seven night shifts followed by seven day shifts.

"The swing schedule was the worst," says Arendt. The urine tests from workers on this schedule revealed that their melatonin levels never synchronized with their new hours, so they had difficulty sleeping. This is true for many shift workers, who try to sleep in phases at odds with their circadian cycles, when melatonin is declining and body temperature rising. Their sleep is disjointed, and they wake up as fatigued as ever. "It's important to go to sleep at the right circadian phase," explains Arendt. "If you go to sleep during your biological day, after your temperature nadir, sleep is of poor quality." Studies suggest that shift work reduces sleep time by an average of three to four hours a night.

Arendt found signs of other serious long-term health effects. When workers on either schedule had to eat their meals late at night, their blood showed abnormally high levels of fatty acids linked with heart disease and also a reduced tolerance for glucose, a risk factor for diabetes and other metabolic disorders.

Shift work probably has the same desynchronizing effect on the circadian system as chronic jet lag: Shift workers' out-of-kilter clocks affect memory, cognition, and various body systems, causing high cholesterol, high blood pressure, mood disorders, infertility, and a higher risk of heart attack and cancer.

Research on the 78,500 women in the Nurses' Health Study revealed that nurses who had worked a graveyard shift for ten years had a 60 percent greater risk of breast cancer and a higher risk of colon cancer compared with those who did not work at night. A few years later, a Japanese study of more than 14,000 men, showed that workers who swing between day and night shifts had triple the normal rate of prostate cancer. And in experiments where researchers have tampered with the circadian rhythms of mice to mimic shift-work conditions, tumor growth accelerates.

What might account for the link between shift work and cancer?

Some scientists suspect that the answer may lie deep in our genes. The disrupted rhythms caused by shift work may dramatically change the expression of clock genes, which in turn may affect "downstream" genes that control growth. In a 2006 study, William Hrushesky and his colleague Patricia Wood showed that the body's clock genes "gate," or regulate, the enzymes that control DNA synthesis, cell division, and blood vessel formation both in normal tissue in the gut and bone marrow and, at different times, in cancerous tissue.

Artificial light has also been implicated in the circadian disruption-cancer connection. For years science has known that exposure to nighttime illumination curbs the body's normal production of melatonin. And animal studies have shown that suppressed melatonin re-lease boosts the growth of cancers. But the first strong experimental evidence of a tie between the two came in 2005.

A team of researchers drew blood from a group of twelve women three times over the course of twenty-four hours: during the day, at night, and again after exposure to bright light at night. Then the team injected the different blood samples into a human-breast tumor that had been implanted in a rat. The results showed that the tumor grew most rapidly when exposed to the blood drawn from the daytime sample and from the nighttime illumination sample. Both samples contained little melatonin. The study, say the researchers, strongly suggests that exposure to artificial light at night dampens melatonin production, which spurs tumor growth. Hence, possibly, the increased breast cancer risk in female night-shift workers.

Asking workers to labor through the night and to work different night schedules creates a major health hazard, not just for the individual worker, says Arendt, but for society at large. When workers are disoriented by circadian dysfunction and fatigued from lost sleep, accidents happen. The explosion at the Union Carbide plant in Bhopal, India, in 1984, which killed thousands of people, occurred just after midnight. The 1979 crisis at the Three Mile Island nuclear plant in Pennsylvania began at 4
A.M.,
when workers who had just moved from a day shift to a night shift failed to notice a stuck valve. And the world's worst nuclear accident, at the Chernobyl plant in Ukraine, in 1986, began at 1:23
A.M.
as a result of a series of errors made by night-shift operators.

 

 

If I really wanted company this time of night, I know where I'd go. The lamps are burning brightly at the teaching hospital down the street, where physicians in training are working up to thirty hours straight and as many as eighty hours per week.

Here's another example of modern life pushing the circadian envelope. The tradition of long work hours for medical interns in this country is the legacy of William Steward Halsted, a brilliant surgeon who worked around the turn of the twentieth century at Johns Hopkins Hospital in Baltimore. In medical circles, it's well known that Halsted promoted the idea that young physicians should live at the hospital and work around the clock, the better to be exposed to as many patients as possible. What most people don't know is that Halsted was addicted to cocaine. Today his system of "heroic" schedules remains the hallmark of medical education, despite mounting evidence of its risks.

Right about now, with no sleep in the last twenty-four hours, how well would you do making a critical decision about diagnosis, dosage, possible danger to a patient? How would you feel about being treated by a young doctor in a similar position?

Despite all the research showing that sleep deprivation impairs cognitive performance, until recently there have been few studies measuring its effects on medical errors. In 2004 a team of scientists at the Harvard Work Hours, Health, and Safety Study reported that medical interns working thirty-hour shifts suffered twice as many failures of attention while working at night as interns whose work was limited to sixteen consecutive hours. Moreover, the thirty-hour group made significantly more serious medical errors and five times as many major diagnostic errors. "When people have been awake for 17 to 19 hours, their performance is equivalent to someone with a blood alcohol level of .05 percent," explains team member Charles Czeisler. When they're awake for twenty-four hours, it's .10 percent. "The risk of making a mistake after working for 24 hours is so great," he says, "that sleep experts and legislators in Massachusetts have suggested it may be ethically imperative for hospitals to notify patients if the doctor treating them has been awake for 22 of the past 24 hours."

The safety risks of interns' long work hours are not confined to hospital patients; the interns themselves are endangered. A 2006 study by the Harvard group found that interns working these marathon shifts had a 61 percent increased risk of stabbing themselves with a needle or scalpel while working, thereby exposing themselves to the risk of contracting hepatitis, HIV, and other blood-borne illnesses. A lapse in concentration and fatigue were the most commonly reported factors contributing to the accidents.

Overworked interns may also be a hazard to themselves and to others when they're on the road home from their shifts. Studies of people who sleep only five or six hours a night on a regular basis (the average for most interns) have found that their median reaction time triples. "That means that when interns are driving home from an extended shift, if a kid dodges in front of their car," says Czeisler, "it will take them three times longer to move the steering wheel or put their foot on the brake." In 2005, Czeisler's group reported that interns working an extended shift of more than twenty-four hours had double the risk of having a car crash while driving home, and five times the risk of a near miss.

"In the face of this evidence, it might be reasonable to ask what the medical profession is doing to address the problem," suggests Chris Landrigan, a member of the Harvard team. In 2003, the profession implemented national work-hour limits for physicians in training. "But the rules still allow interns and residents to work as many as thirty hours straight—far beyond the limit considered acceptable in other safety-sensitive industries," Landrigan says. Pilots, truckers, and nuclear plant workers, for example, are all limited to eight to twelve consecutive hours of work. Moreover, a study conducted by Landrigan in 2006 reported that 84 percent of interns don't comply with the limits. "Limiting residents' work hours undoubtedly represents a cultural and financial challenge within medicine," says Landrigan, "but it's one that has been successfully tackled in other countries: in the United Kingdom and New Zealand, for instance, where the consecutive work hours of physicians in training are limited to 13 and 16, respectively."

Now imagine that the young American doctor treating you had a drug that could defeat drowsiness, a pick-me-up pill popped in the morning that promised two full days of perpetual wakefulness. There are, in fact, such "lifestyle" drugs, designed to murder drowsiness and improve cognitive performance, among them, modafinil and CX717, described as "unique wake-promoting agents" with "unknown specific mechanisms of action." CX717 is under study as a wakefulness promoter for soldiers in combat. Called eugeroics (from the Greek, meaning "good arousal"), these drugs seem to have few of the drawbacks of other stimulants: the jitters, the risk of addiction, the post-pill crash. Despite their benefits, however, they're not always entirely effective. According to a 2005 study by Czeisler's team, for instance, some people who take modafinil to get through a night of work may still have excessive sleepiness and impaired performance.

How safe is it for physicians or other safety-sensitive workers to operate under the assumption that they're alert because they took a pill that's supposed to make them so? More and more, doctors are prescribing the drug for shift workers, pilots, truck drivers, and fellow doctors to sustain alertness. And just over the pharmacological horizon is another wave of drugs, these offering a condensed dose of sleep purportedly more restorative than the natural kind, reducing need for the real time-out.

No one knows the long-term effects of sabotaging natural sleep and tampering with the body's timepieces. Just how far will we go to oblige a twenty-four-hour society?

 

 

Have you dozed? It's sometime between 3 and 4
A.M.,
the peak hour for night-work errors, for auto and truck crashes, for congestive heart failure and gastric ulcer crisis, for sudden infant death syndrome and bone breakdown, for migraine headaches and asthma attacks. In a few hours will come the peak hour for dying of any cause—perhaps because of the rise in blood pressure and boost in Cortisol occurring now, in anticipation of waking time. It seems odd that we should more often finish life not toward the close of day but at its start, as if to deny that death is an ending. But that's the way of the body, all paradox, surprise, contradiction.

This, the hour of the wolf, is also when body temperature falls to its nadir, and spirits too, when fears loom large, and regrets, and misgivings. "In the real dark night of the soul it is always three o'clock in the morning," wrote F. Scott Fitzgerald. Now, when sleep should be sweet and deep, the wakeful mind worries things kept at bay by daylight and distraction: remorse over a misspoken word or a love not bestowed, mounting debt, the frenetic pace of life, the creeping decrepitude of aging.

Look up the word "time" in
Webster's Third New International Dictionary
and you'll find that it takes up more space than "life" or "love," more than "God" or "truth." And that's not counting the myriad compounds and time-bound expressions, time-out, timeworn, time flying or racing, time lost, seconds split, time relative but always relentless. "The gods confound the man who first found out how to distinguish hours," wrote the Roman playwright Plautus. "Who in this place set up a sundial, to cut and hack my days so wretchedly into small pieces!"

Since Plautus, we have become even more hopelessly time-minded, mincing our days into smaller and smaller portions. In the past half century, we have increased by orders of magnitude the precision with which we measure time. Quartz clocks are accurate to one second a month; the finest cesium atomic clocks, to one second in thirty million years. In 2005, scientists devised an "optical lattice" clock that is a thousand times more accurate than even the cesium clock; it uses the element strontium, which "ticks" at 429,228,004,229,952 times each second.

As if all of this precise measurement would make time flow as we wish—swifter during acute pain, for instance, or slower as we age.

Vladimir Nabokov once said that the first creatures on earth to become aware of time were also the first creatures to smile. I don't know. When digital clocks first came into fashion, I mourned the loss of the circular clock face, with its hands mimicking the cyclical sweep of shadow over a sundial. Perhaps this was simple nostalgia for youth, when I could run the perimeter of the playground or smear circles of finger paint, red, blue, and yellow, round and round into slick loops of brown, and believe at the end that I was precisely the same age I had been at the start.

Up to a certain age, time feels, well, cyclical. Dawn to dawn, one day rounding into the next, every end a beginning, and so on until you're forty or fifty, when the problem in life, as Virginia Woolf wrote, is "how to grasp it tighter and tighter to you, so quick it seems to slip, and so infinitely desirable is it." Suddenly the twenty-eight thousand days in a long human life seem cruelly brief and inadequate. Suddenly you're well on your way to old, to tooth rot, sagging chin and gimpy knee, senility.

These days, time seems a fleet arrow indeed, which makes all the more comforting a surprising secret gleaned about the clocks that run our bodies: In a way, they defy linear time.

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