Source: Guardian
Date: 29 July 2004,

Wired awake

miltary modafinil?

Soldiers in the field go for days without rest. Now, a Guardian investigation discovers that the MoD has been buying a new stimulant in bulk. Ian Sample reports on the dangers of sleep deprivation

On April 17 2002, an incident just outside Kandahar in Afghanistan thrust one of the military's least favourite subjects into the media spotlight. Two US F-16 pilots, Major Harry Schmidt and Major William Umbach mistakenly bombed a Canadian infantry unit, killing four and injuring eight. But while the "friendly fire" incident was terrible in itself, worse was to come for the military. In the ensuing legal case, it was claimed that the pilots had been pressured into taking amphetamines - speed - to sharpen their senses.

The authorised use of drugs by military forces is rarely acknowledged by officials, but despite accidents like the one in Afghanistan, interest in using drugs to improve performance remains high. Yet as money is directed into the hunt for newer and better pills to squeeze more out of exhausted troops, some military researchers believe it's time to quit the drugs and try something radically different.

It's not only the American military that is putting its faith in pharmaceuticals. A Guardian investigation has learned that over the past six years, the Ministry of Defence has bought significant quantities of a controversial new drug, Provigil, which is designed to help people with specific medical conditions shrug off the effects of tiredness. Preliminary studies in America show that pilots popping the pills remained alert even after 40 hours without sleep. Other tests have looked at how troops function after staying awake for 85 hours on the drug.

According to figures released by the Defence Medical Supplies Agency, which provides medical items "to sustain UK military capability", the MoD has bought more than 24,000 tablets of Provigil since 1998, at prices at least 10% lower than those charged to the NHS. Released under the open government code, the figures show that orders for the pills peaked in 2001, the year allied forces entered Afghanistan, with the next largest order being delivered in 2002, the year before troops invaded Iraq. Provigil is licensed in Britain for alleviating daytime tiredness in people suffering from the rare sleep disorder narcolepsy and a condition called obstructive sleep apnoea. Its introduction into the UK triggered concern from some groups who believe it will rapidly be abused, becoming a lifestyle drug for a 24/7 society.

Dealing with sleep deprivation is a perennial problem for the military. Troops are typically fighting in strange time zones, in unfamiliar climates and sleeping in less than five-star hotel accommodation, if they have a roof over their heads at all. Add to that the fact that even the best planned campaigns can be knocked off course by surprises, and the demand on troops' time is unpredictable. Opportunities to sleep may come suddenly and unexpectedly, or in the worst cases, not for a number of days.

The effect of sleep loss is dramatic. "What you see is people's reactions becoming impaired, their ability to make decisions is affected, and before long they are absolutely no use to you," says Charles Heyman, an ex-army major and senior consultant with Jane's defence consultancy. Tests by Greg Belenky at the Walter Reed Army Institute of Research in Silver Spring, Maryland, show that performance, in terms of physical and thinking ability, drops on average 25% for every 24 hours without sleep. "Once you've been up for three days, you're pretty much useless for anything," he says. While drugs to combat sleepiness have their risks, so too does deploying troops who aren't sufficiently rested.

The problems are considered most acute among special forces who may have to be alert and active in enemy territory for 48 hours, and pilots on long duration sorties. During the conflict in Kosovo, B2 stealth bombers flew from bases on the US mainland, and so concerned were military commanders that the pilots might nod off en route that they installed garden sun loungers from Wal-Mart (a bargain at $8.88) behind the pilots' seats in case the opportunity for a rest arose.

With sleep at such a premium, much of the military functions with the help of simple stimulants such as caffeine, and sleeping pills, referred to as hypnotics by military medics. Because brewing up is not always an option, new US army "first strike" rations contain caffeine-laced chewing gum, each stick providing the equivalent of a strong cup of coffee. "We needed something simple, something that everyone's familiar with, that you don't need a medic to dole out," says Belenky.

Stronger stimulants, namely amphetamine, have been authorised in some countries, and mostly for pilots. The reasons are simple. Because there are so few pilots relative to other military personnel, each can receive specific medical prescriptions for set quantities of drugs. There's an added incentive, of course, to keep pilots sharp: few ground troops are in sole control of multimillion pound machines courtesy of the taxpayer.

But amphetamine has drawbacks that are all too well-known. The danger is that pilots might be flying before they get anywhere near their jets. "If you take a high dose, you can end up making more errors than you would have without it," says Sam Deadwyler, who is studying stimulants called Ampakines for the military at Wake Forest University in North Carolina. As well as possibly distorting people's perceptions, Deadwyler says that in extreme cases, addiction and withdrawal from speed can also become an issue.

The concerns over amphetamines have helped to spur research into improved stimulants. The Ampakines that Deadwyler studies work in a different way from speed, targeting more specific parts of the brain, rather than "going in and magnifying everything". The hope is that by working in a more subtle manner, they may help to treat the symptoms of tiredness without producing a high.

Provigil, sold by the Pennsylvania-based company Cephalon, caught the eye of the military after studies claimed that modest doses could help narcoleptics. Military trials were soon set up to see just how far the benefits of Provigil could be pushed. Researchers in France were quickly impressed: the French Foreign Legion took the drug as early as the Gulf war in 1991.

While Britain's largest research and development company, Qinetiq, for merly owned by the MoD, refuses to discuss work it may have done with Provigil, and has yet to publish any studies on the drug, US military researchers are more open.

In Maryland, Belenky's team has studied the effects of caffeine, speed and Provigil (also known as modafinil) on troops kept awake for up to 85 hours. "In short, they all do the same thing. You give them to someone who's tired and they feel better, but we find modafinil works longer than amphetamine and both work longer than caffeine," he says.

While the effect of caffeine lasted for around four to six hours and amphetamine for eight to 10 hours, Provigil lasted typically for 10 to 12 hours. Where the jury remains out, according to Belenky at least, is whether Provigil is better at helping people regain their ability to perform complex tasks on little sleep.

Some researchers believe that the long-lasting effects of Provigil make it ideal for use in some operations: the French military recommends it for 24-hour missions. But others see a downside in a drug that works for so long. "In any combat operation, there may be an unexpected lull and so a chance to sleep, so a short-acting drug can have benefits. You've a better chance of being able to sleep if the opportunity arises," says Belenky.

As with any drug, Provigil has side effects. According to the Home Office, the list is substantial, including nervousness, insomnia, excitation, irritability, tremors, dizziness and headaches. It may also cause "gastrointestinal disturbances", including nausea and abdominal pain, dry mouth, loss of appetite and cardiovascular effects such as high blood pressure, palpitations and tachycardia - a fast heart beat.

While stimulants, or "go pills" have an almost inevitable place among some quarters of the military, some researchers are pulling back from the urge to develop new drugs in the hope of finding alternative ways of dealing with tired troops. "All three of the drugs we've tested are temporary fixes at best," says Belenky. "The thing that really restores full-on performance is a nap for starters and then decent amounts of sleep."

Jane's consultant Charles Heyman says there are other issues with fostering a pill-popping culture. "Without pills, we know very well how long people can last and how quickly they deteriorate, and you can anticipate problems," he says. "When you start filling in with pills, all your planning assumptions go out of the window. And when the effects of the pills wear off, you've no idea what kind of a zombie you're going to be left with."

The uncertainties that surround stimulants have prompted tentative forays into radical research which could yield drugs that don't combat the effects of sleep, but remove, at least in part, the need to sleep at all.

As a starting point, Ruth Benca at the University of Wisconsin in Madison, is trying to understand how certain animals manage to function perfectly for long periods on a fraction of the sleep they are used to. Her work, which is funded by the US Department of Defence, focuses on white-crowned sparrows that migrate some 4,300km between California and Alaska twice a year, a feat that can take months. During that period, the birds survive on just one third of the sleep they are used to, while coping with the physical effort of flying and navigating by night, and foraging by day. While special forces operatives may beg to differ, Benca says there are significant parallels between troops on covert missions and migrating birds.

"Special forces that have to go into enemy territory and accomplish a mission before returning have to do a lot of the same things migrating birds do," says Benca. "Birds have to go into unfamiliar territory day after day, they have to find food, avoid predators, and at night they have to navigate and cover ground. There are extreme physical and cognitive demands on them, because they have to solve all these problems as they go."

So far, Benca's group has yet to find any signs that the birds' performance suffers when they skip on sleep, and intriguingly, they do not appear to need to make up for the lost hours. "They can go at least a week without taking a night off," she says. "They just seem to be able to cope." Ultimately, Benca hopes to identify the biological secrets that allow the birds to work so hard on so little sleep. "If we can find the molecular basis for it, we could try and reproduce the behaviour in humans. In other words, we could develop not simply stimulants that keep you awake, but drugs that go a long way to removing the need for sleep," she says.

If there was a way to do it, many military officials would like to see drug use phased out altogether. "The MoD for one is absolutely paranoid about getting sued, pushing pills into people and giving them injections and then getting sued further down the line," says Heyman. "What if you have a drug and then it reacts with something else you've been given? A soldier going into an operational theatre might have had half a dozen injections of different sorts." In keeping with Heyman's suggestions, the MoD has asked Qinetiq researchers to look into new ways of managing sleep. The plan is to develop procedures so troops get the most sleep they can on a given operation.

At Belenky's lab, efforts are under way to turn sleep into a commodity of war, much like bullets and fuel. In the next few months, troops will go on exercises wearing wristwatches that carefully monitor how much sleep they get. The information from each troop will be beamed back to a central command post and fed into a computer model that will work out when each unit is ready to fight, and when it must rest.

The watches will also give advice on what stimulants, if any, should be taken, depending on the mission ahead. "The idea is to turn sleep into an item of logistic supply," says Belenky. "We want to treat it like fuel - how much do people have, how long will it last them, and when do we need to fill them up again," he says.

How the drugs work

  • In its pure form, caffeine, or trimethylxanthine, is a bitter-tasting, white crystalline powder. In the brain, it works by binding to adenosine receptors, preventing adenosine from doing its job, which is to make us feel sleepy.

  • Amphetamine, or methylphenethylamine, is something of a pharmaceutical sledgehammer, working throughout the brain to boost levels of a range of neurotransmitters. Its broad effect of turning up everything, helped to earn it the name speed.

  • Provigil, or 2-[(diphenylmethyl)sulfinyl] acetamide, is also a crystalline powder. The precise mechanism by which it works is unknown, leaving medical authorities to describe it vaguely as a central nervous system stimulant.




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