The much-anticipated Nobel Prize 2017 announced on 2 October 2017, the recipient for the “2017 Nobel Prize in Physiology or Medicine”. Three US scientists – Jeffrey C. Hall and Michael Rosbash from Brandeis University in Boston, and Michael Young from Rockefeller University in New York – for their discoveries of the molecular foundations of the circadian cycle.

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

The winners were awakened with a surprised phone call in the early hours of the morning, informing them of their win. Rosbash whose initially reaction was “you are kidding me,” later joked, "the phone call at 5:10 this morning destroyed my circadian rhythms.”

The winners of the 2017 Nobel Prize accolade in physiology or medicine (left – right)—Jeffrey C. Hall, Michael Rosbash and Michael W. Young. Photo credit: The Indian Express/AP
The winners of the 2017 Nobel Prize accolade in physiology or medicine (left – right)—Jeffrey C. Hall, Michael Rosbash and Michael W. Young. Photo credit: The Indian Express/AP

Time of our lives: The discovery of our body clock

The USD1.1 million prize was awarded for the scientists’ work – which first began in the 1970s – when they questioned the possibility of identifying the genes that are responsible for controlling our body’s adaptation to the 24-hour day—through the daily regulation of metabolism, sleeping and waking, hormones and body temperature.

Beginning with fruit flies, the three discovered that mutations in an unknown gene disrupted the flies’ circadian clock and called the gene period, or “per”. Then, in the 1980s, Hall and Rosbash, found that levels of the protein, named PER, build up at night and dropped during the day.

In 1994, Young found a gene that helps control the period gene’s activity and named it “timeless gene”; and the protein it produces, TIM. He then uncovered a third gene, “doubletime” that helps adjusting the 24-hour oscillation of the “period” gene. “With exquisite precision, our inner clock adapts our physiology to the dramatically different phases of the day.

The “paradigm-shifting discoveries” were that the built-up proteins enter the cell nucleus, and in a negative feedback loop, turn off the genes that make them. Jeremy Berg, editor-in-chief of Science said one of the surprises of the work was that the circadian clock is operative in every cell, not just in brain cells, which means PER and TIM also “affect other aspects of physiology” with “implications for work schedules, sleep hygiene.”

So, what happens when sleep is disturbed?

“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,” said the Nobel committee. “There are indications that chronic misalignment is associated with increased risk for disease.”

The brain for example, is regulated by sunlight and the liver by meals. Thus, when people force themselves to stay awake, the stress hormone cortisol is released which suppresses the immune system. In the long run, this can make the body more susceptible to a range of illnesses, like cancer.

In addition, the human body never adapts to sleeping during the day and staying awake at night. Those who adopt such sleeping habit are at risk of blunted interactions, a lack of empathy, complex thinking and clear memories, depression and bipolar disorder. In such a state, people can do “overly impulsive things,” remarked Russell Foster, a professor of circadian neuroscience at Oxford University. (This explains why nurses who work the night shift are often at high risk.)

What happens when you don’t eat on time?

Fred Turek, a circadian scientist at Northwestern University says this "may be underlying the chronic diseases we face in our society today." The master clock which is set by sunlight, cues all the other clocks that it is time for rest so if a person decides to eat in the middle of the night, "the clock in the brain is sending signals saying: do not eat!" he advises.

If the person opts to eat anyway, the clock in the pancreas begins to release insulin – resulting in competing time cues and imbalance. This affects the body weight, as revealed in a finding by a team of researchers, in 2013. (The study was also published in the International Journal of Obesity.) The earlier people eat their main meal, the more successful they are in losing weight.

Drugs are also affected. "If you take a drug at one time of day, it might be much more toxic than another time of day," says Turek, adding that this could be because the liver is better at detoxifying at certain times rather than others. Scientists are using this to study how to time the administration of medicine.

And therein lies the importance of the discoveries: “Circadian biology has developed into a vast and highly dynamic research field, with implications for our health and wellbeing,” said the Nobel citation.

"The mechanism we discovered, governs at least half of gene expression," remarked Rosbash. "That, is why everything falls under the broad umbrella of circadian rhythms." "What we're doing now in medicine is what Einstein did for physics. He brought time to physics – we're bringing time to biology," expressed Turek. MIMS

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