The regulation of sleep has been a source of curiosity and study for centuries. Many early scientists believed that gases rising from the stomach during digestion brought on the transition to sleep. Others thought that the lack of activity and reduction in external stimuli during the night was enough to induce sleep.

Clues to the actual mechanisms responsible for controlling sleep and wakefulness came as a result of an outbreak of a viral brain infection during World War I. A neurologist named Constantin von Economo observed patients stricken with encephalitis lethargica that exhibited either profound sleepiness or insomnia. He found that the nature of each patient’s sleep problem depended on the precise area of the brain that had been damaged by the disease.