3 scientists win Nobel Prize in medicine for biological clock research

The 2017 Nobel Prize in Physiology or Medicine was awarded on Monday morning to Jeffrey Hall, Michael Rosbash, and Michael Young for their discoveries of the molecular underpinnings of the circadian rhythms that help organisms adapt to our 24-hour days.

The scientists “were able to peek inside our biological clock and elucidate its inner workings,” said Thomas Perlmann, Secretary of the Nobel Committee for Physiology or Medicine, who announced the prize in Stockholm. “Their discoveries explain how plants, animals, and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions.”

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Hall, of Brandeis University; Rosbash, also of Brandeis; and Young, of Rockefeller University, will share a prize of 9 million Swedish krona, or about $940,000.

When Perlmann called Rosbash, the newly minted laureate was initially silent, and then said, “You are kidding me.”

As far back as the 1970s, scientists asked whether it would be possible to identify genes that control the daily rhythm of metabolism, sleeping and waking, and other basic processes in fruit flies. They found that mutations in an unknown gene disrupted flies’ circadian clock and named the gene “period,” or per.

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In the 1980s Hall and Rosbash, working at Brandeis, and, separately, Young at Rockefeller isolated the circadian rhythm genes. Hall and Rosbash then discovered that levels of the protein the gene makes, dubbed PER, build up during the night and drop during the day, oscillating over a 24-hour cycle. The gene Young found in 1994, called timeless, makes a protein named TIM that was also required for a normal circadian rhythm.

(L-R) Jeffrey C. Hall, Michael Rosbash and Michael W. Young Winners of the 2017 Nobel Prize in Physiology or Medicine. Credit: JONAS EKSTROMER/EPA-EFE/REX/Shutterstock

The “paradigm-shifting discoveries,” as the Nobel citation called them, were that the proteins enter the cell nucleus, where its genes reside, and turn off the DNA that had been busy making them. In other words, the build-up of the protein causes the production of the protein to shut down, in one of nature’s more elegant negative feedback loops.

People’s circadian rhythms are controlled much as flies’ are, with gene expression cycling through a 24-hour (or so) period. “Since the seminal discoveries by the three laureates, circadian biology has developed into a vast and highly dynamic research field, with implications for our health and wellbeing,” the Nobel citation said.

Jeremy Berg, editor-in-chief of Science and former director of the National Institute of General Medical Sciences, called the laureates’ work “very elegant and fundamental.” Before their discoveries, he said, “the nature of the circadian clock was a great mystery. Through genetics and the emerging tools of molecular biology, a very elegant molecular pathway was sorted out involving a feedback loop where a protein controls its own expression.”

One of the surprises of this work, Berg said, is that the circadian clock operates in essentially all cells that contain a nucleus, not only specialized cells in the brain, allowing PER and TIM to “affect other aspects of physiology” with “implications for work schedules, sleep hygiene,” and more, ushering in the field of chronobiology.

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