Nobel laureates cracked the mysteries of sleep-wake cycles

Nobel laureate Jeffrey C. Hall spoke Monday with a visitor to his Cambridge, Maine, home.
Nobel laureate Jeffrey C. Hall spoke Monday with a visitor to his Cambridge, Maine, home.Robert F. Bukaty/Associated Press

If you keep a plant in a dark room, its leaves will open when the sun rises outside. A person living in a cave will awaken in the morning, the body somehow recognizing an unseen sunrise.

This is the power of the internal “clock,” or circadian rhythm, which enables all multicellular organisms to keep time with the earth’s rotation.

Scientists have puzzled over this phenomenon for centuries, and this year the Nobel Prize in Physiology or Medicine honors three researchers who — by working with fruit flies — discovered the key mechanisms that make it possible.

The recipients are Jeffrey C. Hall and Michael Rosbash of Brandeis University and Michael W. Young at Rockefeller University in New York.


“Our well-being is affected when there is a temporary mismatch between our external environment and this internal biological clock, for example when we travel across several time zones and experience ‘jet lag,’ ” the Nobel Assembly wrote in its announcement. ‘‘There are also indications that chronic misalignment between our lifestyle and the rhythm dictated by our inner time keeper is associated with increased risk for various diseases. . . .

“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 well-being.”

Dr. Charles A. Czeisler, chief of the Division of Sleep and Circadian Disorders at Brigham and Women’s Hospital, said the award “honors an extraordinarily important discovery.”

Hall, Rosbash, and Young “discovered in a fruit fly a basic fundamental property in life,” Czeisler said. Even the most ancient organisms needed to anticipate daylight so they could obtain energy from the sun, and prepare for nightfall to preserve energy in the dark.

Scientists are starting to understand that, with today’s 24-hour access to light, upending those primordial rhythms can lead to illnesses such as heart disease, diabetes, and cancer, he said.


For example, human metabolism was designed for eating in the daytime and fasting at night. Night eating puts food into the body at a time when the metabolism is less sensitive to the hormones that regulate glucose, raising the risk of diabetes and obesity.

In 1984, Hall, Rosbash, and Young isolated the gene — known as “period” — that controls circadian rhythms.

Hall and Rosbash further discovered that cells use the period gene to make a protein called PER, which builds up at night. That accumulation triggers the PER protein to block the period gene, preventing its own synthesis and degrading over the course of the day.

This cycle, made possible by other genes and proteins that Young discovered, regulates the biological rhythms of day and night.

In the ensuing years, the researchers went on to explore other aspects of this process, including the mechanism by which light can alter the clock. This is why people feel sick from jet lag but gradually recover as they are exposed to sunlight on a new schedule.

C. Robertson McClung, a biology professor at Dartmouth College who studies circadian rhythms, said that just about everyone working in chronobiology thought that a Nobel in the field was long overdue.

“The real question was not if, but when and who,” McClung said. “The studies that these three did were clearly pioneering . . . They are richly deserving.”

McClung noted that the design of the biological clock “is the same in a fungus, in a plant, in a mouse, in a fruit fly, and in a human,” and studies of organisms as simple as pink bread mold can help explain human biology.


Leslie Griffith, Brandeis professor of biology and neuroscience, called the research “a great illustration of the value of basic science. The idea that studying the activity rhythms of an insect would have an impact on human health was not something that many people would have thought about 25, 30 years ago. But it has.”

Felice J. Freyer can be reached at felice.freyer@globe.com. Follow her on Twitter @felicejfreyer.