Tired cats make lipid sleep hormone.

Asked why he robbed banks, Willie Sutton blithely responded, "because that's where the money is." Using what he describes as the "Willie Sutton logic of natural products," chemist Richard Lerner of the Scripps Research Institute in La Jolla, Calif., looked in the cerebrospinal fluid of

sleep-deprived cats for naturally produced substances capable of coaxing the brain to sleep.

The strategy paid off. Lerner and his team have identified in the tired cats' cerebrospinal fluid a simple molecule--a modified version of a fatty acid, or lipid--that induces sleep not only in cats, but in rats as well. The finding has the Scripps team speculating that they've found the first of a distinct family of brain hormones.

To hunt down a "sleep molecule," the researchers compared the cerebrospinal fluid of cats that had spent 22 hours on a slow-moving treadmill with samples from rested cats. One component appeared in somewhat higher concentrations in the sleepy cats. While it wasn't "an all-or-nothing situation," Lerner says, "it intrigued us enough to pursue it."

The researchers determined the structure of the component using a technique called mass spectrometry. As they report in the June 9 Science, the molecule they found is a simple fatty acid with a backbone of 18 carbons and a nitrogen component called an amide on one end.

To find out whether the molecule indeed plays a role in inducing sleep, the team synthesized it and injected it into rats. The rats fell asleep quickly and experienced prolonged periods of deep sleep. The compound has a similar effect on cats. The researchers even found the molecule, as well as a longer cousin, in humans.

Lerner and his colleagues don't know how the compound induces sleep, but Lerner speculates that it is actually a lipid hormone. Cells in the body readily produce fatty acids of any number of lengths, but adding an amide takes a lot of energy. "I wouldn't believe nature did it for nothing," says Lerner, pointing out that at least 50 percent of peptide hormones need an amide to function.

Lipid hormones such as prostaglandins play an important role in such functions as uterine contractions and platelet aggregation. But these, Lerner points out, are "complex, highly decorated" hormones. He suspects that the simple lipid hormones the team identified may regulate very primitive activities, including sleep and emotions.

Yusuf Hannun of Duke University Medical Center in Durham, N.C., says the lipid "is a very interesting molecule." He points out that while no one predicted the body would make such a costly compound, its discovery could "open a whole new field of study."

Lerner emphasizes that the tools of modern analytical chemistry enabled his team to find the "sleep molecule" and that the same methods may yield a "whole sea of information" about biological states such as hunger and stress.