Stopping Sleepiness: The Search for Biomarkers That Flag Fatigue Before We Know We’re Impaired

A small group of scientists around the world are working on a new frontier in sleep research: Finding a biomarker or a way to test people for exhaustion. Andrea Petersen has details on Lunch Break.

The hunt is on for a so-called biomarker, a characteristic or substance—or, more likely, several substances—in the body that will indicate if someone is sleepy and, if so, how sleepy. These researchers want to measure acute sleepiness in order to identify the risk of “performance failure” before it happens. That could apply to a morning commuter about to nod off on the freeway, a surgeon preparing for a complicated procedure or a pilot settling into the cockpit before a trans-Atlantic flight.

Research is also looking at chronic sleepiness, which people can feel after just days of less-than-adequate sleep. A growing number of studies have found that not sleeping enough night after night raises the risk of health problems, including obesity, diabetes and heart disease. A biomarker could change the way people view the role sleep plays in their overall health, says Paul J. Shaw, an associate professor of neurobiology at the Washington University School of Medicine in St. Louis. “If people knew they were sleepy, they might say ‘I’m going to turn off Leno and go to bed.’ ”

This area of sleep research is in the early stages, and actual biological tests are likely years away. It holds the promise of helping the average person make what could be crucial health decisions. How bad is it to pull an all-nighter before a big presentation? Is consistently getting less than seven hours of sleep a nuisance—or a serious health risk? If people had a firm measure of how much sleep they need, they could take steps to ward off drowsiness.

Researchers already have identified some potential biomarkers related to sleepiness. Scientists at the University of Pennsylvania studying pairs of identical and fraternal twins have found six proteins in the blood that change relative to sleepiness. Dr. Shaw has found that the enzyme amylase, which is present in human saliva, rises in sleep-deprived flies.

People who are sleepy have slower reaction times, decreased attention and problems learning and processing information. What makes sleepiness especially dangerous is that most people are generally not aware of how sleepy—and how impaired—they actually are. A driver, for example, may not know he is too drowsy to drive until he actually veers off the road. “The brain is not quite fully awake and alert and not fully asleep,” says David F. Dinges, a professor in the department of psychiatry at the University of Pennsylvania and the director of a sleep lab that is researching the effects of sleep deprivation on healthy people.

A pivotal 1997 study published in the journal Nature showed that being awake for 24 hours resulted in the equivalent level of cognitive impairment as having a blood-alcohol concentration of 0.1%. In the U.S., it is illegal for adults to drive with a concentration of .08% or above.

Most adults need between seven and nine hours of sleep a night. But about a quarter of those age 19 to 64 say they get less than seven hours on weeknights, according to the National Sleep Foundation’s 2011 Sleep in America poll.

In recent years, scientists have proven something that may seem obvious to anyone who has encountered those lucky enough to feel fine after an all-night work session or red-eye flight: People vary dramatically in how well they handle a lack of sleep. The reason is likely partly genetic. Dr. Dinges’s lab at the University of Pennsylvania has identified three genes that may be associated with vulnerability to sleep loss. The ability to pinpoint who handles sleep loss poorly brings up ethical issues. For example, for positions that involve a lot of travel or long hours, would companies want to screen candidates for their natural ability to weather sleep loss?

In another Penn lab, Nirinjini Naidoo has been analyzing plasma samples from a subset of 56 pairs of identical twins and 42 sets of fraternal twins who were kept awake for 36 hours. Her lab has divided participants into two groups: Those who seem resistant to the cognitive effects of sleep loss and those who fall apart. She has identified 110 proteins that change markedly in the resistant group and 53 proteins in the sleepier group. “We’re looking for things that make you feel worse and those that may be protective,” says Dr. Naidoo, associate professor, Division of Sleep Medicine.

Dr. Shaw in St. Louis has found that amylase, an enzyme that breaks down starches, rises in flies that are sleep deprived. Like humans, sleepy flies don’t learn well and will sleep more than usual when they have the chance.

In Dr. Shaw’s experiment, flies were observed in a T-shaped maze: To the left, there was a light-filled vial (flies like light) that also contained quinine (flies don’t like its bitter taste). To the right, there was a dark vial. In the experiment, sleepy flies never learned to override their attraction to light to avoid the quinine—and head right instead of left.

The problem with amylase as a biomarker is that multiple factors affect its levels. “If you eat a sandwich, it goes up,” Dr. Shaw says. “We’re going to need a panel of markers, each of which is going to be imprecise on its own.”

Meanwhile, researchers are working on other ways to identify sleepiness before people are so impaired that they get into trouble. In some small studies, Edward Haeggstrom, a professor of applied physics at the University of Helsinki in Finland, has found that balance changes can predict how long people have been awake. “The longer you’ve been awake, the more you sway. They are bigger sways with less control,” Dr. Haeggstrom says. He says he became interested in the link between sleepiness and balance during his military service in Finland during the early 1990s: He noticed sleepy soldiers swayed when standing in formation.

There’s more evidence for the link between sleepiness and the speed of eye blinks. As people get sleepier, they have an increasing number of slow eyelid closures. Many studies have concluded that these slow eyelid closures can accurately predict when someone is becoming impaired by sleepiness.

Some entrepreneurs are using this science in actual products. Optalert Ltd. of Melbourne, Australia, has developed eyeglasses equipped with an infrared sensor that continually measures the position and velocity of the wearer’s eyelids. It uses that information to give its customers, which include mining and trucking companies, a score for each driver in real-time.

Anything over a five out of a 10 means “people are not fit to be driving,” says Murray Johns, Optalert’s founding director and chief scientist. The company plans to introduce a model for individual drivers within the next two years.

Some car companies, including Mercedes and Toyota’s Lexus, are adding features they say can help sleepy drivers. Mercedes’ “Attention Assist” technology senses steering wheel movements and the position of the driver via a sensor in the steering column.

If a driver’s head lingers too long on the head rest or there are erratic steering movements, for example, an alarm will go off and the message “Time for a break?” will appear on the dashboard with a picture of a coffee cup.

By Andrea Petersen, from: http://online.wsj.com/article_email/SB10001424052970204369404577206952841644944-lMyQjAxMTAyMDAwNzEwNDcyWj.html?mod=wsj_share_email_bot

Write to Andrea Petersen atandrea.petersen@wsj.com