"I'm jet-lagged right now," confesses Masashi Yanagisawa a day after his return to Dallas from Tokyo. One might think that an expert on the sleep/wake cycle would know how to prevent this problem. But "it's 15 hours earlier in Tokyo than in Dallas, the opposite of day and night here, so your circadian clock will be out of sync for a while," he says. "That's unavoidable."

Yanagisawa, an HHMI investigator at the University of Texas Southwestern Medical Center at Dallas, recently made five round-trips to Tokyo within six months to set up a satellite lab there.

He suggests that travelers try to prevent extreme fatigue by "sleeping as much as possible during the flight. Then you won't have a sleep debt on top of your circadian debt." His own policy is to try to fall asleep naturally after the meal. "That would be the best solution, since normal sleep includes several periods of REM (rapid eye movement) sleep," he explains. If he cannot fall asleep within an hour or two, however, he takes an ultra-short-acting sleeping pill called Sonata, a prescription drug approved by the Food and Drug Administration in 1999. Although the drug does inhibit REM sleep, "you lose only one or two REMs and can pick them up later."

It's better not to lose any REMs at all, however. So Yanagisawa hopes a new kind of sleeping pill that shuts down orexin, the "wake-up" neuropeptide he discovered, will be available in the near future. He imagines the pill would induce REM and non-REM sleep alike.

Upon arrival in Tokyo, Yanagisawa uses one of two opposite strategies to deal with the circadian problem, depending on his intended length of stay. The human body takes about two weeks to adjust to a new time zone, he explains. So if the visit to Tokyo will only be a couple of days, "I try to keep my rhythm intact. For example, I don't expose my eyes to bright light in the morning." It's actually easier to fly back almost immediately, before you've had a chance to adjust to the new time zone, he believes. When staying longer, Yanagisawa does his best to adapt to the new day/night cycle as soon as possible.

"The worst is to stay just one or two weeks," he says, "because then coming back is more difficult—just as you're starting to adapt to the new time zone, you're hit again with a time shift during your reentry."

—Maya Pines

Photo: Nancy Newberry

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Reprinted from the HHMI Bulletin,
March 2003, pages 8-13.
©2003 Howard Hughes Medical Institute