Military Objective: Less Sleep, More Fight

Lexicon seeks genetic answer for allowing long hours of service without slumber

Driven by the U.S. military's quest for a super soldier who is stronger, faster and can fight for days, researchers across the nation are seeking to challenge the notion of a good night's sleep.

One of those is Lexicon Genetics. The Woodlands-based company recently received a grant from the Department of Defense, which has funded studies looking for ways to allow humans to sleep less and perform better far longer.

Lexicon's scientists have used genetic engineering techniques to create mice that are more alert and active than normal mice.

High performers
These test mice outperformed standard mice, which needed time to wake up in the morning and got tired when their energy dipped during afternoon.

"The ultimate goal of the research is to find targets for drugs that can improve sleep quality," said Brian Zambrowicz, Lexicon's executive vice president of research. "Insomnia is a huge problem, and it's crucial to find new ways to treat it."

Lexicon's scientists say they are studying whether genetically modified mice are getting a different, more restorative, kind of sleep, which boosts their energy.

These studies might lead to treatments that could, for example, prolong wakefulness or promote restorative sleep.

48 to 72 hours
The military has long been interested in performance-enhancing drugs that would enable soldiers to carry out 48 to 72 hours of continuous operations without jeopardizing their physical and mental health. By supporting long-term research projects, the Defense Advanced Research Projects Agency, or DARPA, hopes to unshackle sleep from the limits imposed by nature.

"The goal of the DARPA Preventing Sleep Deprivation Program is to research and develop technologies that will assist in maintaining the cognitive performance of war fighters despite short-term sleep deprivation," Jan Walker, a spokeswoman for the agency, which is a research arm for the U.S. Department of Defense, wrote in an e-mail.

The terms of agency's one-year grant to Lexicon have not been disclosed.
Lexicon's Zambrowicz said scientists will put genetically modified mice through a series of sleep deprivation stints to see how it affects their performance. The hope is to find chemical compounds that modify gene function without harmful side effects.

"We want to see if those two genes cause modification in the types of sleep mice are getting, which may explain why they have enhanced cognitive abilities," Zambrowicz said.

With the help of gene-knockout technology, Lexicon is researching possible treatments for diabetes, cancer, cardiovascular disease and neurological disorders.

Although the journey from a promising discovery to a marketable drug is normally a long one, there's a big potential reward if it reaches the goal of helping people sleep better.

The company could tap into the $3.5 billion market for prescription and over the counter sleep medicine, said Dr. Todd Swick, division chief of sleep medicine at the Institute of Sleep Medicine in Houston.

"The sleep medicine market is the second-largest market in the world, after the painkillers," Swick said. "People take both prescription and nonprescription pills so the market is exploding. People want a quick fix."

DARPA exists to foster research that might help the military, where the payoff is often far beyond where private investors are willing to go.

But many of the things it has promoted have become part of daily lives. It has played a key role in the creation of such things as the Internet, cell phones and the computer mouse.

"DARPA has always focused on long-term research, looking at stuff that others were not considering," said Paul Saffo, technology forecaster who has been following the agency's progress for 20 years. "The interesting thing about DARPA is that even if their projects don't have spectacular success, they discover that they have effect on something else."

Currently, the agency is supporting a number of university and industry projects across the country with the same theme — staying alert with little or no sleep for long periods.

Last year, for example, researchers at Wake Forest University in Winston-Salem, N.C., tested a stimulant drug called CX717 on rhesus monkeys. They said the monkeys showed normal alertness despite extended sleep deprivation.

Meanwhile, University of Wisconsin researchers reported on studies of genes of mutated fruit flies that slept one-third the amount of normal flies.

"As an office, we are always looking for ideas that will question existing beliefs about the physical sciences, biology, mathematics and other disciplines," Steven Wax, director of DARPA's Defense Sciences Office, said last year in a prepared statement. "We consider the assertion that something can't be done to be a challenge, not an obstacle."

Experts in sleep research say most of the sleeping pills on the market are designed to suppress the most restorative "slow-wave" sleep in favor of shallower stage II sleep.

Military researchers hope drugs that increase the slow-wave state could potentially offer the benefits of eight hours of sleep in a fraction of that time.

But some local military and medical experts say no matter how restorative the sleep is, humans will not be able to trick nature. People still need at least seven hours a day to recuperate. Failing to do so may lead to hormonal abnormalities, slow reaction times and other problems.

Affecting slow-wave sleep
Several drugs that affect slow-wave sleep are in development, according to Swick. One of them, Xyrem, produced by Jazz Pharmaceuticals, has been approved by the Food and Drug Administration for the treatment of narcolepsy.

Army Maj. Gen. Steven Best, with the 75th Division Training Support in Houston, said he believes in vigorous training rather than performance-enhancing drugs.

"We continue to increase the amount of training and the duration of training overtime to build their physical endurance," Best said. "But also we are realizing that sleep is a natural part of our body's recovery process, and there is only a certain point before they physically need to recuperate, so we take that into account."