Stanford scientist who discovered cause of narcolepsy wins Breakthrough Prize

The richest award in science is going to a Stanford scientist and other top thinkers in their fields, named winners of the glitzy Breakthrough Prize on Thursday morning.

Dr. Emmanuel Mignot of the Stanford University School of Medicine will share the $3 million prize with Masashi Yanagisawa of Japan’s University of Tsukuba for discovering the cause of a sleep disorder called narcolepsy, paving the way for the development of new treatments for arousal and sleep problems.

“I think receiving this Breakthrough Prize is incredible, and I also definitely have the reward of seeing my patients completely changed by these new drugs,” said Mignot, in a prepared statement. “It’s a fantastic kind of human adventure.”

In addition, two young Stanford mathematicians, both women, were awarded the “New Horizons” prize, in which $500,000 is split among early-career researchers. Maggie Miller, a visiting fellow, won for work in the area of knot theory. Jinyoung Park won for her contributions to the field of probabilistic combinatorics, which sheds light on how structure emerges in random sets and graphs.

Mignot, Miller, Park and other researchers will join celebrities later this year in an ornately choreographed fête to celebrate $15.75 million in prizes for discoveries in math, physics and the life sciences.

As part of the ceremony schedule, they also will engage in a program of lectures and discussions to inspire the next generation of scientists.

Conceived by theoretical physicist and entrepreneur Yuri Milner of Los Altos Hills, the Breakthrough Prize Foundation aims to create a cultural shift — if scientists are toasted like celebrities, they’ll win greater public attention.

The Foundation also has pledged $3 million to support scientists forced to leave Ukraine.

The prizes, dubbed the “Oscars of Science,” are funded by Milner and his wife, Julia, and several other Silicon Valley tech titans: Anne Wojcicki, of 23andMe; Facebook CEO Mark Zuckerberg and his wife, Dr. Priscilla Chan, a pediatrician at UC San Francisco; and Sergey Brin of Google.

The winners are selected by a committee of previous Breakthrough Prize laureates in each field.

“The 2023 laureates have produced absolutely stellar science,” according to Wojcicki. “The creativity, ingenuity and sheer perseverance that went into this work is awe-inspiring.”

Winning such a prize is beneficial not just because of the cash and prestige. One study found that researchers who win prizes become more productive afterward, compared with non-prize-winning peers. There are more opportunities for public speaking. The prize may attract future students and postdocs to a winner’s research group.

Mignot, a professor of sleep medicine at Stanford, is the university’s third Breakthrough Prize winner. He joins two previous recipients: developmental biologist Roeland Nusse and psychiatrist and neuroscientist Dr. Karl Deisseroth.

Narcolepsy is a neurological problem which affects about 1 in 2,000 people and causes disordered nights of sleeping. Mignot treats several hundred narcolepsy patients each year and is involved in several clinical trials of narcolepsy drugs that show promise in reducing symptoms.

Healthy people typically take about 12 minutes to fall asleep. And their rapid eye movement (REM) stage of sleep, so-called “dream sleep,” occurs after more than an hour of non-REM sleep.

People with narcolepsy fall asleep almost immediately and quickly lapse into REM sleep. The REM stage is often accompanied by muscle movements that result in restlessness and frequent awakenings.

They suffer from sudden bouts of daytime sleepiness, which in turn can cause mental fogginess and extreme exhaustion. They may also contend with muscle weakness, known as cataplexy, that can be triggered by strong emotional excitement.

Mignot’s interest in studying narcolepsy began in 1986, when he joined the lab of the late Dr. William Dement, famed as the father of sleep medicine. He believed that narcolepsy was a tractable problem that could be understood and solved.

“I became interested in narcolepsy because I thought it was a key to understanding sleep, and because it had this human dimension of trying to help patients with this disease that nobody cared about,” according to Mignot. “When I started studying narcolepsy, people thought it was very rare. Nobody knew about it.”

Trained as a psychiatrist, he became a geneticist, embarking in 1989 on a project to find the gene that causes narcolepsy in dogs.

The gene turned out to control a receptor for a neurotransmitter called orexin, which promotes wakefulness and blocks REM sleep.  Mignot showed that narcolepsy was caused by the disruption of the orexin system in the brain – and is absent in the brains of diagnosed patients.

Independently, and simultaneously, Mignot’s fellow Breakthrough Prize recipient Masashi Yanagisawa, discovered orexin.

Further work revealed that narcolepsy is an autoimmune disorder. The neurons that produce orexin are destroyed by the body’s own immune system. Mignot is also investigating the role of autoimmunity in other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases.

The discovery of narcolepsy’s roots has led to the development of drugs that can prevent or promote sleepiness by targeting the orexin system, according to Stanford.

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Four other life scientists also won the 2022 Breakthrough Prize awards. Clifford Brangwynne of Princeton University and Anthony Hyman of the Max Planck Institute won for discovering a fundamental mechanism of cellular organization. Also, Demis Hassabis and John Jumper of DeepMind, Google’s artificial intelligence lab in London, won for developing an AI method that predicts the three-dimensional structure of proteins from their amino acid sequence.

In math, Daniel Spielman of Yale University won for contributions to the field of theoretical computer science, algebra and coding theory. In fundamental physics, an award was given to a four-member international team for foundational work in the field of quantum information.

More information on the Breakthrough Prize is available at breakthroughprize.org.