New drugs promise to keep us sharp even when we need shuteye—but at a cost.
A different version of this article was published in Reader’s Digest.
IN AN ANTISEPTIC ANIMAL LABORATORY in Worcester, Mass., 160 rodents in oversized cages are hooked up, via thirty miles of wire, to a bank of computers that continuously record their vital signs: what their brainwaves look like, whether they’re awake or asleep, how much they’re eating, drinking, and moving about. The information beams across a flat double-screen on the desk of Dale Edgar, the 48-year-old chief scientist at the biotech firm Hypnion. “This is our little portal that takes us into another dimension—the rat world,” he says with a grin.
Each creature is taking a medication designed to alter its sleep patterns, and the computers chart how its physiology is affected by the drug. Edgar, a neurobiologist who left California’s Stanford Sleep Research Center to start Hypnion in 2000, hopes to use this information to unlock the mysteries of sleep and wakefulness. There’s a lot scientists don’t understand: What is the exact brain chemistry that causes healthy humans to grow tired and fall asleep at roughly the same time each night? Why do we wake up refreshed eight hours later? And what happens inside the brain when someone continuously nods off, or is forced to stay up night after night, working the assembly line or driving a truck?
Edgar is on a mission to discover the perfect remedy for our collective sleep deficit: a drug more powerful than coffee but without the side effects, that can keep us awake for extended periods without an exhausted crash at the end. There is already one new stay-awake drug on the market, called modafinil, but its effects are relatively tame and it has been shown to be mind- and mood-altering. Edgar, by contrast, hopes that by targeting the precise locations in the brain that trigger sleep and wakefulness, his company can produce a medicine that is not only safer but also more potent.
If Hypnion succeeds, the results could be staggering. A safe, strong wakefulness pill could keep pilots, flight attendants, and soldiers alert during round-the-world plane trips. It could allow rescue workers to pull all-nighters at disaster sites. It could help factory workers drive home from the midnight shift without drooping at the wheel. “I’m trying to save lives,” Edgar says. “I’m trying to reduce the number of people maimed in auto accidents. I’m trying to reduce the number of errors that affect the productivity of people in the real world.”
But the prospect of such a product is stirring up a bioethical battle. For every soldier or rescue worker, there are probably hundreds of college students and young professionals who would love to get their hands on a quick fix for sleeplessness. Physicians and ethicists worry that medicines like these offer too much temptation to an already sleep-deprived nation. “Two-thirds of Americans don’t get enough sleep,” says Audrey Chapman, an ethicist at the American Association for the Advancement of Science. “If people are under a great deal of pressure to get ahead, and there’s the possibility of working three, four, five, six days around the clock, they’re going to try to get the drug, even illegally.” Chapman worries that workers will feel compelled to use wakefulness drugs to keep up with their next-cubicle neighbors. “Once this starts,” she asks, “are we going to start a pharmacological arms race?”
NO ONE FULLY UNDERSTANDS THE IMPORTANCE of slumber, but there’s increasing evidence that doing without can have dramatic consequences. “Most people think a sleeping person is not biologically active,” says Michael Smolensky, a professor of environmental physiology at the University of Texas School of Public Health. “In fact, at night, our biology is organized to repair tissues that have been assaulted—by pollution, by stress, by the workplace. If we take this away, we could be playing with danger.”
The evidence of this danger has been mounting. At the University of Chicago, researchers have discovered that when someone tries to survive on four hours a night, certain biochemical systems go awry, triggering symptoms of type-2 diabetes, memory loss, and premature aging. A recent Harvard study even showed that female nurses who work on rotating night shifts for 30 years or more, never falling into regular sleep rhythms, have a 36 percent higher rate of breast cancer than those who never worked rotating shifts.
Still, Americans are getting less sleep than ever before. According to the National Sleep Foundation, adults under 55 average just 6.7 hours per weeknight. We now spend one-fifth less time in bed than we did a century ago.
Until recently, there were only two types of medicines to keep the sleep-deprived awake: methylphenidate (Ritalin) and amphetamines. Both are sledgehammer drugs: They indiscriminately stimulate the central nervous system, leading to anxiety, appetite loss, heart palpitations, even psychosis. At the same time, they’re both highly addictive, making doctors naturally wary of prescribing them.
That’s why sleep scientists were so excited when the U.S. Food and Drug Administration (FDA) announced its approval of the drug modafinil in 1999. Sold by the pharmaceutical firm Cephalon under the brand name Provigil, it induces wakefulness without blasting the whole nervous system with stimulation. “Provigil works in a much more localized part of the brain, the hypothalamus, which controls the sleep-wake cycle,” says Cephalon vice president Paul Blake. Though monkey studies show the drug comes with some potential for addiction, experts still consider it much safer than its predecessors. “It’s not a very abusable drug,” says Jim Walsh, president of the National Sleep Foundation. “People who take it don’t get a rush or get high.”
Sales of Provigil have skyrocketed since its introduction. In 2000, physicians wrote 350,000 prescriptions for the medication; by 2002 that number had risen to 1.1 million. Though the FDA initially approved Provigil only for people with narcolepsy, a disease of excessive daytime fatigue, physicians immediately began prescribing it for other purposes, particularly the sleepiness associated with depression and multiple sclerosis. Military researchers have used the drug, too, keeping pilots awake for 40 straight hours during simulated helicopter flights. Now off-shore Internet pharmacies have begun marketing modafinil, making it easy for healthy people to obtain it illegally. “I work 10 to 14 hours a day, so I would have no personal life if I didn’t sacrifice some sleep,” one California user told his online support group. “At the right dosage, this wonder drug is really great.”
DALE EDGAR THINKS HE CAN DO EVEN BETTER. “The first drug in its class is not always the best,” he says. “Modafinil is better than nothing, but there are a lot of people with excessive sleepiness for whom modafinil does not promote sufficient wakefulness.”
At Stanford University, Edgar had his “15 minutes of fame” when he discovered the clock structure in the brain that keeps us awake. Known as the suprachiasmatic nucleus, the structure rings like an alarm throughout the day, growing most quiet as the darkest hours of night descend. At the same time, another system called “sleep homoeostasis” —still poorly understood—keeps track of how long we’ve been up and makes us grow sleepy when we’ve been out of bed for too long. It is the balance of these two systems, Edgar realized, that regulates our daily sleep-wake rhythms.
At Hypnion, Edgar hopes to push his research even further: to find the exact location within the brain’s complex chemistry where these two mechanisms intersect, and then to find a medicine that stimulates that chemistry without affecting the rest of the nervous system. Hypnion expects to begin clinical trials on such a drug within the year.
Such a breakthrough would be welcome news for patients with narcolepsy, as well as those who suffer daytime fatigue from ailments like multiple sclerosis, sleep apnea and Alzheimer’s disease. It would also be useful for soldiers, rescue workers and firefighters. But where does one draw the line? Graveyard-shift factory workers whose body rhythms have been badly disrupted? Corporate lawyers who need to fly halfway around the world before handling tedious, adversarial negotiations? Students cramming for exams? Doctors already struggle with these scenarios when it comes to prescribing modafinil. “I’ve seen some truck drivers, and for reasons of lifestyle or economics or stubbornness, they refuse to get enough sleep,” says Harvard neurologist Thomas Scammel. “They say, ‘I want this drug, and if I don’t get it, I might get into an accident.'” Scammel won’t prescribe modafinil under those circumstances—though he understands why others would.
Indeed, a trucker taking modafinil might be safer on the highway, and that lawyer might be more alert for the negotiations. But, if sleep is required to maintain basic biochemical functions, how will they fare over the long term? “If a drug drives certain systems faster than they’re used to going, then those systems can wear out,” says Michael Wincor, associate professor of clinical pharmacy, psychiatry and the behavioral sciences at the University of Southern California.
Some critics believe we need to take a huge step back—and find non-pharmaceutical solutions to our collective sleep loss. “We really should be trying to work with people’s biology, not using drugs to patch up unhealthy societal patterns,” says Scammel. Take late-night factory work, one of the most common sources of poor sleep. “The best way to deal with shift work is for employers and employees to understand the limits of human biology and come up with sensible schedules,” he says. “For some companies, it might mean having more employees.”
Edgar, though, believes it’s a pipe dream to talk about restructuring society around our sleep needs. Instead, he believes, the solution to our national sleep deprivation will come in orange plastic vials. “Are we going to shift away from a 24-hour society? Not a chance,” he says. “The train has left the station, and it’s not coming back. The economy of the country and the world is not going to move backward. We now have to find ways to improve the quality-of-life of the 24-hour society we have created.”
Postscript: Three years after this article was published, Hypnion was acquired by Eli Lilly.
