Jeffrey C. Hall, Michael Rosbash and Michael W. Young were awarded the Nobel Prize in Physiology or Medicine on Monday for discoveries about the molecular mechanisms controlling the body’s circadian rhythm.
The three scientists used fruit flies to isolate a gene that controls the rhythm of a living organism’s daily life. Dr. Hall, Dr. Rosbash and Dr. Young were “able to peek inside our biological clock,” helping “explain how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions,” the Nobel Prize committee said.
By examining the internal workings of fruit flies, the investigators helped determine that the gene they were analyzing encoded a protein that accumulated in cells at night, and then degraded during the day.
Why Is the Work Important?
Over decades of research, these scientists identified the mechanisms governing the clockwork inside the cell, shedding light on the biology of humans and other multicellular organisms whose biological clocks function on the same principles.
“With exquisite precision, our inner clock adapts our physiology to the dramatically different phases of the day,” committee members noted. “The clock regulates critical functions such as behavior, hormone levels, sleep, body temperature and metabolism.”
The researchers studied fruit flies in which a gene called period seemed to control circadian rhythm; when it was mutated, the insects lost that rhythm.
But what was period, and how did it work? The questions were relevant not just to flies: All organisms, including humans, operate on 24-hour rhythms that control not only sleep and wakefulness but also physiology generally, including blood pressure and heart rate, alertness, body temperature and reaction time.
In 1984, the scientists isolated the period gene and discovered that cells use it to make a protein that builds up at night, during sleep. In daytime, the protein degrades in accordance with the insects’ sleep-wake cycle.
The researchers believed that this protein, which they called PER, somehow blocked the period gene during the day. As PER was broken down in daytime, the gene regained its function and worked again the next night, directing the synthesis of PER.
The entire system turned out to involve several other proteins needed to control the accumulation of PER. These include one that attaches to PER, helping to block the period gene, and another that slows the buildup of the protein.
Continuing to investigate this biological system over the years, the scientists went on to discover still other components, notably one that allows light to influence the 24-hour rhythm.
Their work was pivotal, the Nobel committee said, because the misalignment between a person’s lifestyle and the rhythm dictated by an inner timekeeper — jet lag after a trans-Atlantic flight, for example — could affect well-being and over time could contribute to the risks for various diseases.
Who Are the Winners?
Jeffrey C. Hall received his doctorate in 1971 from the University of Washington. He joined the faculty at Brandeis University in 1974 and is now a professor emeritus of biology.
Michael Rosbash received his doctorate in 1970 from the Massachusetts Institute of Technology. Since 1974, he has been on the faculty at Brandeis University, where he is a professor of biology and holds an endowed chair in neuroscience.
Michael W. Young received his doctorate from the University of Texas at Austin in 1975. He is a professor of genetics at Rockefeller University in New York.
Statements From the Winners
Dr. Rosbash said he got the call at 5:10 in the morning from a representative of the Nobel committee: “I was dead asleep. My first thought was that someone in the family had died.”
He was astonished, noting that the fruit fly work had been “a little more trendy” a few years ago, before other developments like cancer immunotherapy and gene-editing hit the news. “It’s a great day for the fruit fly,” he said.
Dr. Young, too, was stunned by the announcement.
“I really had some trouble getting my shoes on this morning,” he said. “I’d go and pick up my shoes and then I’d realize I need socks, and then I’d realize I need to put my pants on first.”
As the researchers began their work, he added, “We were hopeful that what we saw in the fly would pertain more widely. I don’t think we ever thought a beautiful mechanism would emerge.”
“The field had long been speculating on this Nobel Prize. This is great recognition for the field of circadian rhythms that are intimately linked to our health and disease, including diabetes, obesity, cancer and cardiovascular disease.”
— Dr. Frank A.J.L. Scheer, associate professor of medicine at Harvard Medical School and director of the Medical Chronobiology Program at Brigham and Women’s Hospital
“It is fabulous to see the foundational discoveries of this trio recognized in this richly deserved and long overdue Nobel Prize.”
— James E. Rothman, professor of cell biology at Yale University, who won the 2013 Nobel Prize in Physiology or Medicine for his work on how molecular messages are transmitted inside and outside of human cells
“Michael is a truly great scientist who has done much very fine work. His discovery of the 24-hour cycling of a clock protein provided the basis for all following work in the critical field of chronobiology and was definitely work that deserved a Nobel Prize.”
— David Baltimore, professor of biology at Caltech and winner of the Nobel Prize for Physiology or Medicine in 1975
Who Was Overlooked for the Prize This Year?
As always, there were other groundbreaking discoveries in contention. They included work by Dr. James P. Allison of the MD Anderson Cancer Center, Gordon J. Freeman of the Dana-Farber Cancer Institute, and Dr. Arlene Sharpe of Harvard Medical School; they have learned how to harness the body’s immune system to fight cancer.
Another contender was Crispr, a gene-editing system that is rapidly transforming medical research. It was discovered by four scientists: Jennifer A. Doudna at the University of California, Berkeley, Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Berlin, Feng Zhang of the Broad Institute and George Church of Harvard.
(They have been involved in a high-profile dispute over patent rights; in any event, the Nobel can be shared by a maximum of three scientists.)
Also overlooked this year were investigators who discovered genes that predispose to cancer and who found drugs that home in on cancer-causing mutations, as well as scientists who discovered how proteins can muffle DNA and others whose work was crucial to brain imaging.
Who Won the 2016 Physiology or Medicine Nobel?
Yoshinori Ohsumi, a Japanese cell biologist, was recognized for his discoveries on how cells recycle their content, a process known as autophagy, a Greek term for “self-eating.” Disorders in autophagy is thought to play an important role in a variety of diseases and in aging.
When Will the Other Nobels Be Announced?
Five more awards will be announced in the coming days:
■ The Nobel Prize in Physics will be announced on Tuesday in Sweden. Read about last year’s winners, David J. Thouless, F. Duncan M. Haldane and J. Michael Kosterlitz.
■ The Nobel Prize in Chemistry will be announced on Wednesday in Sweden. Read about last year’s winners, Jean-Pierre Sauvage, J. Fraser Stoddart and Bernard L. Feringa.
■ The Nobel Prize in Literature will be announced on Thursday in Sweden. Read about last year’s winner, Bob Dylan.
■ The Nobel Peace Prize will be announced on Friday in Norway. Read about last year’s winner, President Juan Manuel Santos of Colombia.
■ The Nobel Memorial Prize in Economic Science will be announced Oct. 9 in Sweden. Read about last year’s winners, Oliver Hart and Bengt Holmstrom