The Great Awakening

Joel Garreau
The Washington Post
June 17, 2002

Grubb's Pharmacy is an unassuming if not seedy two-story clapboard landmark amid the grand brick townhouses of East Capitol Street. Not only is it one of the busiest pharmacies in the District. But being only four blocks from the Capitol, it is also the neighborhood provider of potions and portents to congressmen, lobbyists, super-lawyers, Supreme Court justices, ambitious aides and all those other classic Type A Washingtonians who think that whatever they're working on is The Most Important Thing in the World. And of course sometimes they may be right.

Yet Grubb's is filling only about five prescriptions a month for a drug named modafinil. "It's nothing like Viagra. That was a national explosion," says Edward F. Dillon, the pharmacist. "Or a drug like Propecia, for hair loss. Or Prozac. Let me tell you. When Time magazine put that on the cover, you could definitely see the spike."

This may be the calm before the storm, however. For modafinil may have the power to change Washington.

What it does is shut off your urge to sleep.

"It's a standing joke among sleep doctors that nobody sleeps in New York or Washington," says Helene Emsellem, director of the Center for Sleep and Wake Disorders in Chevy Chase. "Except in New York they do it for pleasure, while in Washington they do it to work."

In trials on healthy people like Army helicopter pilots, modafinil has allowed humans to stay up safely for almost two days while remaining practically as focused, alert, and capable of dealing with complex problems as the well-rested. Then, after a good eight hours' sleep, they can get up and do it again -- for another 40 hours, before finally catching up on their sleep.

Originally aimed at narcoleptics, who fall asleep frequently and uncontrollably, modafinil works without the jitter, buzz, euphoria, crash, addictive characteristics or potential for paranoid delusion of stimulants like amphetamines or cocaine or even caffeine, researchers say. As with an increasing number of the so-called superhuman, posthuman or trans-human drugs or genetic manipulations rapidly entering our lives, modafinil thus calls into question some fundamental underpinnings of hundreds of thousands of years of thought regarding what are normal human capabilities.

The implications for Washington are profound.

The Defense Advanced Research Projects Agency is searching for ways to create the "metabolically dominant soldier." Among the projects it is pursuing is the creation of a warrior who can fight 24 hours a day, seven days straight. "Eliminating the need for sleep while maintaining the high level of both cognitive and physical performance of the individual will create a fundamental change in war-fighting," says the Defense Sciences Office on its Web site. As usual, DARPA did not comment directly for this report.

William C. Dement, director of the Stanford University Sleep Center, who is known as "the father of sleep medicine" for his pioneering work in the '50s, embraces the idea of modafinil use for official Washington. "If Donald Rumsfeld had to stay awake for a long period of time, I would want him fully alert," he says.

Francis Fukuyama of Johns Hopkins University recently published "Our Posthuman Future: Consequences of the Biotechnology Revolution," a book that is scathingly critical of what he sees as runaway biotech that could rob us of our very human nature. When asked about modafinil and its effects on Washington, he responded with a 2:50 a.m. e-mail from Europe, where he was finishing a grueling three-week trip. "I haven't heard of this but I'm not surprised," he wrote.

"I better get some," he half-joked.

Modafinil and its follow-on technologies hold the potential for changing society. "This could replace caffeine," says Joyce Walsleben, director of the NYU Sleep Disorders Center.

Caffeine -- the globe's most widely used drug -- today is a bigger food additive in dollar terms than salt. The U.S. soft drink industry alone sold 10 billion 192-ounce cases of bubbly last year, most of it caffeinated.

Modafinil's sales are still small. But it did double sales to $150 million in only the last year, according to Cephalon, the pharmaceutical company that markets it under the trade name Provigil.

Its potential for changing how people work and live is intriguing. In an increasingly 24-7 world, will such medicine create even more demand for people to be available round-the-clock? Were Robert Frost's lines from 1923 prophetic?

The woods are lovely, dark and deep.

But I have promises to keep,

And miles to go before I sleep,

And miles to go before I sleep.


Will people feel that they need to routinely control their sleep in order to be competitive? Will unenhanced people suffer fewer promotions and raises than their modified colleagues? Will this start an arms race over human consciousness?

To get some hint of what such a Washington life might be like, the bulk of the writing of this article, a task not unlike others with many moving parts -- software development or the juggling of a diplomatic flap -- was accomplished in one 40-hour period enabled by the prescribed use of modafinil.

10 a.m. Thursday. Third hour awake. Back from working out at the gym. Gazing at the white 200 mg. tab of modafinil. Hey, how scary can this be. It's not like this is life's first all-nighter. This one is even legal. Ironic. Four decades after the '60s, some of the most startling drugs are those available by prescription. But safety first. Take the advice of the sleep docs. Cut the tab in half. If, as sometimes happens, there is going to be a headache or nausea, start with a low dose.

Humans have been manipulating their sleep chemistry for a long time. Caffeine is as old as coffee in Arabia, tea in China and chocolate in the New World.

For at least as long, sleep has been seen as a universal solvent.

"Now blessing light on him that first invented this same sleep!" says Sancho Panza in "Don Quixote." "It covers a man all over, thoughts and all, like a cloak; 'tis meat for the hungry, drink for the thirsty, heat for the cold, and cold for the hot. 'Tis the current coin that purchases all the pleasures of the world cheap; and the balance that sets the king and the shepherd, the fool and the wise man even."

The effects of medicated sleeplessness on a vast healthy population is still unknown. "Before you start taking it for the rest of your life, find out what it does to your heart valves or some damn thing," Dement says. "A lot of people know the story of fen-phen or thalidomide. If you take it all the time, and try to stay awake all the time, there's a big chance that there may be some hitherto unknown toxic effect."

Nonetheless, modafinil (pronounced mo-DAF-i-nil) is distinguished by its apparently precise neurological focus. Nobody knows exactly how modafinil works, but researchers marvel at the way it seems to target very specific regions of the brain believed to regulate normal wakefulness. It's that narrow effect that is lacking in other stimulants, resulting in their notorious side effects.

In fact, on the wall of his office at a company named Hyperion, off Boston's Interstate 495 near Worcester, Mass., sleep researcher Dale M. Edgar has a sign. "It's about the sleepiness, stupid," it reads.

As with the rest of the cascade of new drugs that promise to augment human performance, here are three groups of people who will ultimately be attracted to new wakefulness drugs, researchers say. In this order, they are:

" The sick.

" The otherwise healthy with a critical need.

" The rest of us.

It's the future of the third group -- the millions who, in the immortal words of Kiss, "wanna rock and roll all nite and party every day" -- that deeply concerns the sleep business.

The Food and Drug Administration so far has approved modafinil marketing only to narcoleptics, as the FDA reminded Cephalon in January, when it charged that the company's promotional materials were overreaching. Cephalon will soon submit an application to the FDA to expand its marketing to people with other sleep disorders, including the ones associated with sleep apnea and Parkinson's disease.

There are only 125,000 to 250,000 narcoleptics in the United States. Cephalon brags that hundreds of thousands of patients have taken Provigil, with over a million prescriptions written as of 2001, and sales soaring. Nonetheless, Cephalon spokesman Sheryl Williams says that "we are not aware of any significant prescribing of the drug for nonmedical conditions."

What exactly is a "nonmedical condition"?

This enters the murky world of the second group -- healthy people engaged in "mission-critical tasks for which sleepiness is not an option," as Edgar puts it.

"Like flying a big C-17 transport plane from Charleston Air Force Base to Afghanistan virtually nonstop," says Edgar. "That happened. There are lots of examples in the Air Force. It's what they call susops -- sustained operations. You really, really need something on those long flights, and not just for the pilots. The payload specialists in back have no place to sleep, and they have to be on the ready to deploy the load. It's hard, but it's also critical to the success of the mission, and reducing accidents."

The crucial issue is not staying awake. It's doing so without making lethal mistakes. The fatal decision to launch the Challenger space shuttle was made by people handling very complex data after days of irregular work hours and insufficient sleep, as all sleep researchers remind themselves.

Fort Rucker, Ala., is 58,000 hot and steamy acres of Southern pine and the occasional wild magnolia. All the Army's helicopter pilots are trained there. John Caldwell has a low, impressively equipped, sprawling brick sleep laboratory with the Air Crew Health and Performance Division of the U.S. Army Aeromedical Research Laboratory. His modafinil study is the one that kept awake the helicopter pilots -- "normals without any pathological conditions," as he so clinically puts it.

The pilots flew a simulator in which they had to respond quickly to commands -- to fly for two minutes straight and level at 3,000 feet maintaining 120 knots at a heading of 180, for example, then perform a turn of 360 degrees over exactly two minutes, maintaining speed and altitude. Then the pilots had to perform four different tasks simultaneously -- watching warning lights come on and dials deviate from normal, while monitoring the fuel levels and clearing blockages, while holding a target constant, while responding on the radio to someone commanding, "NGT 504, NGT 504, set communications radio to 121.5"

Caldwell expresses a sentiment volunteered by almost every sleep researcher. "One thing I want to make clear -- when we look at compounds like modafinil or amphetamines or caffeine, those are emergency kinds of measures, not a replacement for sleep. It's not nice to fool with Mother Nature."

Says Stanford's Dement: "The real problem is the accumulated sleep debt, not daily need. It's established fact that lost sleep accumulates. You quickly become too tired to be functional." Even with a substance like modafinil that can keep you wakeful, if you don't ultimately catch up on the sleep you missed, bad things will happen, sleep researchers have always believed.

"Your grandmother was right. If you don't get enough sleep, you're going to get sick," says Chevy Chase researcher Emsellem.

When you're facing a critical situation, however, it's better to have help being alert, Caldwell firmly believes. "Combat operations are very unpredictable." Even with a 14-hour-a-day rest schedule, "if the enemy attacks during the 14 hours off, we're going to have to respond."

"There are a lot of other medically justified scenarios," says Edgar. "Think of emergency medical services. What happens when a building collapses? As we unfortunately learned recently, teams work around the clock. Can you justify it to save lives? Absolutely. Particularly if it's a hazardous situation. Somebody needs to do the job, and if there is something that is safe, effective, and non-habit-forming, I think the answer is yes."

Sleep research is a very young science, and the number of things it doesn't know about substances like modafinil is daunting.

"How long can somebody stay awake and not suffer? Hard to say. The jury is still out," says Edgar, who is on leave from Stanford. He is now ensconced in a serene research facility sporting green glass that matches the stripes of the mallard ducks on the pond. Inside are a sophisticated array of computers and hundreds of mice and rats. In his small office, wraparound screens stream brain wave activity being transmitted live from around the world over the Internet. Edgar has taken up a new role as senior vice president for preclinical research at Hypnion, which he describes as the world's first biotech company specifically dedicated to solving problems of sleep-wake disorders.

"Do you function as if you were rested? The answer is you're probably better off than if you haven't taken it, but you're not at 100 percent. Where are you? Fifty percent on cognitive performance? Is that good enough?"

But then Edgar drops the bomb.

"The next generation of wake-performing therapeutics will be more effective. You'll be able to stay awake for X amount of time and not add sleep debt. Ideally, it means being able to be up all day, all night, and all the next day and not have incremental increase in sleepiness or in sleep debt. It would be medication that gives you an interest-free loan.

"It could change the world. A complete paradigm shift. I'm not trying to plug my company. But we are in the forefront. We could see this being a reality, starting to become available, in about five years."

Friday, 2 a.m., Hour 19. The effortless mental focus brought on by modafinil is remarkable. No attention deficit here. The feeling is that you have been given a gift of time, and it is too precious to waste.

The focus is almost more interesting than the sleep-avoidance. In fact, it makes you wonder what it will be like to grow up in a world in which this stuff is common. Suppose you are just getting started in a career and you're a basket of insecurities. Suppose you could regularly produce at levels unheard of even by today's workaholic standards simply by popping a pill. Could you resist it? Worse yet, suppose you were competing for raises and promotions against someone who was happy to grab whatever enhancements were available. Will it become routine to hear "There'll be plenty of time to sleep when you're 40"?


You can't get high on modafinil. There's no euphoria to it. When they first take it, a lot of test subjects figure they must have gotten the placebo.

On this do sleep researchers base their hope that wakefulness agents won't be the next glam drug phenom, hyped on magazine covers and distributed with abandon to people for whom they were never intended, under circumstances that have never been studied.

But they know the facts. Two-thirds of all Americans don't get enough sleep, according to the National Sleep Foundation. Sleep deprivation may be a factor in the national epidemic of obesity. America is full of people burning the candle at both ends, wanting to know only where they can get more wax.

"Most of them are impaired. A lot of jobs you can do almost in your sleep -- lifting boxes onto shelves in a department store," says Dement. "But I'm frequently an expert witness in cases that involve falling asleep at the wheel. A recent case involved a man who was working two jobs, and on the night job he was frequently observed to fall asleep. His supervisor escorted him out the door. He drove into an oncoming lane and killed three people."

The graveyard shift is hardly just for factory workers anymore. The world is open 24-7 -- restaurants, health clubs, Wal-Marts, Home Depots, help desks, stock and commodities traders, catalogue sales and overnight shippers, to mention a few. Why do people getting off the red-eye from Los Angeles or to London seem so ruefully proud even when they look like dog meat? The classic hero figure of capitalism is the CEO who says he never needs more than a few hours of sleep -- he's proud of being on the go all the time.

Washington has its own special breeds of sleep-defiers. Think of the rat calculus of campaign strategists running the maze of late October before Election Day. Hunched and harried, they work the phones to the Coast until 2 or 3 in the morning, while writing the candidate's talking points for the next day, and then hitting the Eastern time zone phones at dawn. The badge of special honor is simultaneously to be advising campaigns from Washington in the time zones of Britain and Israel.

Friday, 4 a.m., Hour 21. When this stuff takes over, it takes over. Gently, not violently. No apparent loss of acuity. But you have definitely kicked into a gear you didn't know you had.

Playing computer games like FreeCell as an informal way of testing cognitive ability. Do you dare send e-mails? Will you regret them when you return to normal?

Speaking of rhythms, remember to eat. Got to keep up strength. Discomfort still far less than it would have been had coffee been used to accomplish this task. Getting awful sick of herb tea, though.


So what about the dreaded third group -- the rest of us, those who are in a fundamentally different situation from the first two groups? We have a choice whether to live a saner life or try to solve our problems with a pill.

"The young professional who wants to work and play and do everything, and doesn't want to spend time sleeping?" asks University of Pennsylvania sleep researcher David Dinges. "That's another matter."

Yes, sleep researchers grudgingly admit, there are going to be some way-off-label users. The college students crashing on term papers. Truck drivers. Barge operators. Airline pilots. The physician in long hours of training. The new parent. Ever watch the White House-based television show "The West Wing?" They never seem to go home. That is not fantasy.

"Sleepiness is everywhere," says Neil Feldman, medical director of the St. Petersburg, Fla., Sleep Disorder Center, who is conducting a shift work study for Cephalon. "We're a 24-hour society. We no longer live by the night/day cycle. We live by whatever our occupation demands. Physicians on call at night. Nuclear power plant operators. Police, firemen. Plus the world is becoming a smaller place. Trans-meridian travel, commonly known as jet lag. There are economic demands -- more than one job -- plus raising children.

"How many have fallen asleep at the wheel of a car? Something like 25 percent at least momentarily once during the year. Sleep deprivation is everywhere. Our society looks at people who sleep as less strong people. People who nap are slugs."

Suppose a lawyer came to you and said, "I have a client on death row and the governor has just given me three days to draft his appeal before he is executed."

"I'd probably prescribe the drug," Feldman said. "But three pills. Not a hundred. I can rationalize that."

"People ask me about it almost daily," says Dement. "Everybody would like to be able to have more time to do whatever they want to do. I could stand in front of a roomful of Stanford undergrads right now and say, 'If you feel tired, raise your hand,' and every hand would go up."

Such a fundamental change in human nature is hardly without risks. "Emphasize the idea that we may be playing with fire here," says Emsellem. "Who knows why we get cancer? Chronic sleep deprivation may be a risk factor for long-term disease. I would love to get by on five hours of sleep because I don't like to lie in bed, leashed by a sleep requirement. I would love to be unleashed. But at the same time, prove that it is safe. I don't need another round of winter flu, thank you very much. Getting sick, being constitutionally exhausted."

"When you have debate on this topic," says Edgar, "on one side, people say: 'Just sleep more. Do what you have to do and the economy be damned. Get the sleep that you need and that's that.' On the other side, people are saying: 'But wait a minute. This is a 24-hour world. Those services have to be performed at the highest level they can. People make mistakes.' "

How do you compete?

Edgar sighs.

"This gets into this fair and legitimate debate. Type A people in Washington go until they drop. You don't know the ultimate consequences. The extra load on the kidneys, liver, pancreas, endocrine functions. This could be really important."

"The final twist is that caffeine is a food additive," says Edgar. Replacing caffeine with modafinil -- "that would be the revolutionary next step. Just as one replaces sugar with NutraSweet. Everybody drinks soda pop with caffeine from the age of 5 up. Yeah. You're changing the world. Yeah. I'm telling you as a sleep scientist the kinds of things we see on the horizon. It's exciting. Changing lives. Saving lives. That's for certain.

"Is it appropriate for college students pulling an all-nighter? No. Sleep physiologists will all tell you the same thing. There is no true substitute for sleep itself. We say that with conviction," Edgar says.

Suppose that will no longer be the case?

"The more far-out question is: What if we eventually had something that was absolutely safe that could substitute for sleep?" asks Dinges. "Is that the direction we want to go? Many would say yes. I don't know what the implications are for our species. Probably not bad. This is pure speculation. Should humans try to live without sleep? I don't know. We're already trying to do that."

Friday afternoon, 4 p.m., Hour 33. Tired from all this writing. But not sleepy. Interesting to imagine a future in which those are two distinctly separate things. The problem isn't wakefulness. The problem is cranking through three or four days' worth of work in one burst.

Started to yawn at 8 a.m., at the bottom of circadian rhythms. Lay down for a two-hour nap. As researchers say, this stuff doesn't prevent you from sleeping, it just controls the desire to. Arose alert. Went back to productive work. Naps are good, as the sleep researchers ceaselessly point out.

Glad this experiment occurred in a home office, and not downtown. Wouldn't relish driving at this point. Don't feel impaired, but wouldn't want to test the proposition. Have no interest in taking any more pills to further the experiment. Looking forward to returning to the planet of the mortals with a glass of wine and a good supper.

Wonder what this will read like after a good night's sleep? The concern is this: One is always taught never to hand in a complicated project at the end of the day. Read it over one last time with fresh eyes in the morning. But fresh eyes are optional, when you don't have to sleep. Fatigue still hasn't set in. It wouldn't be hard to hand this in and begin preparations for the next project with a whole afternoon in front of you. What happens when fresh eyes are a choice, not an inevitable part of the rhythms of life?


We will be asking ourselves these questions about human nature with increased frequency as biotechnology advances and drugs originally designed for the sick begin to augment the healthy. We have already seen this happen with Viagra. It now sponsors network evening news shows, a development that would have boggled scenario planners just five years ago. More drugs are in the works that attack shyness, forgetfulness and the mental decline of aging. Others add muscle mass and boost the ability to learn, at least in mice.

Saturday morning, 10 a.m., Hour 51, after eight hours of sleep. Would need to have an awfully compelling reason to want to do this again. But can imagine how others might differ. Sure was a lot of living packed into the last two days. Got so much done that there is a whole unencumbered weekend in sight. What a concept.


© 2002 The Washington Post Company


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