Sleep is orchestrated by two systems. The first is the so-called biological clock, which runs the body on a roughly twenty-four-hour cycle of sleeping and wakefulness. We all have slightly different circadian rhythms, which explains why some people (larks) get up early and others (night owls) stay up late. The second system is the homeostatic drive for sleep: the longer you are awake, the tireder you get. One’s circadian rhythm and one’s drive for sleep usually work in tandem, but they can fall out of step, Amita Sehgal, a chronobiologist and an investigator at the University of Pennsylvania’s Howard Hughes Medical Institute, told me. When you’re badly sleep-deprived, you want to go to bed no matter what time it is. (Our reactions to sleep deprivation seem to have a genetic basis, too: after thirty-eight hours awake, identical twins, who are born with identical DNA, performed more similarly on tests of reflexes and alertness than nonidentical twins did.)
People with extreme sleep patterns first became a focus of genetic research in the nineties, after a neurologist at the University of Utah, Chris Jones, met a woman who regularly went to sleep in the early evening and woke up in the middle of the night. Her granddaughter had the same sleep patterns, and Jones had a hunch that their habits might be explained by DNA. He got in touch with Louis Ptácek, a neurogeneticist at U.C.S.F., who helped him identify a DNA mutation that seemed to play a role. Fu joined Ptácek’s research team in 1997. “I was very good at finding mutations,” she told me.
In response to the team’s findings—some of the first on how DNA influences sleep—thousands of people reached out. Many had irregular bedtimes and wake times but slept a consistent number of hours per night. An exceedingly small number, Fu said, went to bed very late and woke up very early. Curiously, they didn’t have the complaints that people with insomnia or other sleep disorders often do. In 2009, after studying a mother and a daughter who were both short sleepers, Fu published a paper about a variation in a gene called DEC2, which influences the production of orexin, a hormone associated with wakefulness. (Orexin deficiency is one of the main causes of narcolepsy.) When Fu bred mice with the same mutation, they slept less than other mice.
Since 2009, Fu and her colleagues have published research on six mutations across five genes linked to reduced sleep needs. (A few more genes are being researched, Fu told me.) Osmond and her sisters have variations on a gene that affects receptors for glutamate, an excitatory neurotransmitter with many functions throughout the brain. A different mutation was found in a father and a son in 2019; when Fu’s team introduced it into mice, the animals didn’t show memory deficits that usually appear in sleep-deprived mice.
Sehgal, who has studied sleep in fruit flies, and who was not involved in Fu’s research, was intrigued by the fact that these genes do not seem to be connected by a particular sleep process or brain pathway. “It’s not one specific thing that stands out,” she said. Mehdi Tafti, a neurophysiologist and a geneticist, said that the unsolved mystery of short sleepers reveals our ignorance about how sleep works. When he looked for DEC2 mutations in hundreds of patients with irregular sleep patterns, he couldn’t find any. Fu believes that short sleepers have developed different ways of sleeping efficiently. Sehgal offered a different explanation: maybe their bodies don’t accumulate as much damage while awake.
In theory, the genetic mutations associated with short sleep—and the pathways they seem to affect—could point to targets for drugs that would safely reduce our sleep needs. The discovery that orexin is linked to narcolepsy has sparked new pharmaceutical research, and last year an experimental orexin-blocking medication showed promise for insomnia in a clinical trial. Experimental drugs increasing orexin may also help people with narcolepsy stay awake longer. But it will be more challenging to develop a drug that transforms us into Osmonds. Fu said that, by finding short sleepers and then backtracking to single mutations, she may be missing out on other, more subtle genetic factors. When scientists scoured samples from nearly two hundred thousand people, in the U.K. Biobank, those mutations alone weren’t associated with extreme sleep patterns. And sleep is so important that Fu would want drug developers to proceed with caution. “The worst thing is, you come up with a drug and have horrible side effects,” she said. “You sleep less, but then, five years later, you get Alzheimer’s.”