Shift work is killing you

Mod­ern life­styles are at war with the way our bod­ies evolved to func­tion, and the bat­tle is wip­ing us out. Chono­bi­ol­ogy could help us get back on track.

Popular Science - - CONTENTS - BY LES­LIE KAUFMAN ILLUSTRATIONS BY VIK­TOR KOEN

“Trauma level 2,” a fe­male voice warns over the loud­speaker. “Ar­riv­ing in 10 min­utes.”

It 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

THE GRAVE­YARD SHIFT, IT TURNS OUT, IS APTLY NAMED.”

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

‘IN­SIDE LIGHT IS JUST TER­RI­BLE FOR YOU. IT IS MAK­ING US ALL SICK.’”

im­mutable rhythms. His in­ter­est has led him to ex­plore en- tirely 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.

Panda hopes his app’s data can per­suade the NIH to fund hu­man tri­als on re­stricted feed­ing. Suc­cess is the nec­es­sary im­pri­matur to move pub­lic pol­icy— Panda’s ul­ti­mate goal. And an ur­gent one. Rates of diabetes and high blood pres­sure are ris­ing among Amer­i­cans, with 85 per­cent of adults 65 years or older suf­fer­ing two chronic dis­eases. That’s about 70 mil­lion peo­ple whose con­di­tions cost $2,500 a year each to man­age. Not treat, man­age. “If we could de­lay one chronic dis­ease by one year in only 1 mil­lion peo­ple,” Panda says, “that is $2.5 bil­lion dol­lars in healthcare sav­ings, and you’re help­ing peo­ple live health­ier lives.”

Many of those ben­e­fits, he be­lieves, are per­fectly at­tain­able—if we sim­ply start pay­ing at­ten­tion to time.

BACK AT THE HIGH­LAND ER in Oak­land, Her­ring let UCSD re­searchers out­fit 20 of his res­i­dents with Ac­ti­watches—wrist­bands that mea­sure sleep, ac­tiv­ity, and light lev­els—for a month, while they also con­ducted cog­ni­tive test­ing. Michael Gor­man, the sci­en­tist who led UCSD’s mouse study, is eval­u­at­ing the re­sult­ing data. Ide­ally, his find­ings will help chrono­bi­ol­o­gists ex­plain how physi­cians suc­cess­fully or un­suc­cess­fully cope with shift work, and in­form sched­ule-change rec­om­men­da­tions and fu­ture stud­ies. At the mo­ment, though, Her­ring’s crew is swiftly headed to­ward that night’s cir­ca­dian nadir.

For all of us, this takes place roughly be­tween 2 a.m. and 5 a.m., when our bod­ies seek to fully shut

down. Any­one who has stayed up late at night, work­ing or study­ing, knows how it feels to try to push through this point in­stead of doz­ing: “It is like hit­ting a wall,” Her­ring says. “You be­come cold, you be­come ex­hausted, your think­ing slows down, and you be­come gassy.”

Her­ring re­calls a spooky hap­pen­ing dur­ing this stretch, which is also when an ER is down to a min­i­mal crew. A mid­dleaged pa­tient came in at 3 a.m. with chest pains that could have sig­naled ei­ther heart­burn or a heart at­tack. The EKG was nor­mal. Un­sure, Her­ring faced the pa­tient alone and de­cided how to pro­ceed. In­stinct told him to do a bed­side echocar­dio­gram, which showed that a mas­sive heart at­tack was, in fact, in progress, re­quir­ing an emer­gency catheter­i­za­tion. Ev­ery­thing turned out fine for the pa­tient. But in ret­ro­spect, Her­ring thinks it was a close call. In the day­time, he sus­pects, that kind of de­ci­sion would have been much more clear-cut.

Since Oak­land is a pub­lic hos­pi­tal with grow­ing de­mands and lim­ited re­sources, it might not have the abil­ity to ad­dress Her­ring’s con­cerns about shift work. So he and fel­low doc­tors have come up with a Band-Aid based on the best sci­ence they can find. They’re adopt­ing a so­lu­tion used by Cana­dian ER doc Pat Croskerry. A pro­fes­sor in emer­gency medicine at Dal­housie Univer­sity in Hal­i­fax, Croskerry is an ex­pert in cog­ni­tion and di­ag­nos­tic er­rors. He is also a trained ex­per­i­men­tal psy­chol­o­gist. He ad­vo­cates us­ing a so-called casino shift: In­stead of hav­ing one doc­tor work through the en­tire night, you have two doc­tors split the evening, with each of them sleep­ing for a bit dur­ing the witch­ing hour. Even a lit­tle shut-eye at this time seems to im­prove doc­tors’ fo­cus and re­duce po­ten­tial er­rors.

But bet­ter ways of dol­ing out late-night work won’t make the un­der­ly­ing prob­lem go away. Keep­ing such hours will still push doc­tors to their lim­its. “You need to bake in the cost of night work,” Her­ring says. “The phys­i­o­log­i­cal cost on your body. The psy­cho­log­i­cal cost. We some­how have to get the greater so­ci­ety to un­der­stand the ter­ri­ble toll this is tak­ing.”

Heart Dis­ease Fire­fight­ers and ER doc­tors face sim­i­lar sleep chal­lenges. Work­ing overnight shifts—and eat­ing at odd in­ter­vals— seems to put them at a higher risk for heart at­tacks and other car­dio­vas­cu­lar prob­lems.

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