Dr Jeffrey C Hall, Dr Michael Rosbash and Dr Michael W Young have been awarded the Nobel Prize in physiology or medicine for discoveries about the molecular mechanisms controlling the body’s circadian rhythm, reports The New York Times.
The three scientists used fruit flies to isolate a gene that controls the rhythm of a living organism’s daily life. Hall, Rosbash and Young were “able to peek inside our biological clock,” helping “explain how plants, animals and humans adapt their biological rhythm so that it is synchronised 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.
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.
The report says 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.
The report says 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 is quoted in the report as saying, 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.
Like last year’s solo laureate – Yoshinori Ohsumi, a Japanese biologist who studies autophagy, the process by which cells dispose of their garbage – 2017’s winning trio came as something of a surprise, writes Jerome Groopman in the New Yorker. The three Americans’ names did not appear on any of the major Nobel prediction lists, and when Rosbash was awakened by the phone call from Sweden, early in the morning, he reportedly said, “You’ve got to be kidding.”
Groopman writes that prior to the announcement, the smart money had been on either immunotherapy, which uses the body’s defenses to fight cancer, or CRISPR, the revolutionary gene-editing technique. (Both remain strong candidates for a future Nobel.) Compared with advances like these, the circadian rhythm is decidedly less in vogue right now – so fundamental, perhaps, that many handicappers forgot about it.
Groopman writes that the deliberations of the prize committee are cloaked in secrecy, "but years ago I crossed paths with one of its members, who happened to come from the same region in Eastern Europe as my grandmother. After he had shared reminiscences of that vanished life, he described in general terms how the committee selects the winners. Nominations flow in from across the world, and there is considerable debate about who ought to get credit for which discovery. But there is also discussion, he said, about what message is sent by choosing to honor one scientist or discovery over another."
Groopman says that his read of the announcement, and last year’s, is that both are about the divide between basic research – the pursuit of scientific knowledge for its own sake – and applied research, which focusses on work with obvious, immediate effects. (The latter is typified by the prize given, in 2008, to Françoise Barré-Sinoussi and Luc Montagnier, for the discovery of HIV)
This year’s prize, in other words, is a kind of rebuke, Groopman says. Basic science is under siege, particularly in the US. Congressional Luddites love to highlight federally funded projects that, according to their own stunted definitions, pursue meaningless questions that don’t readily translate into talking points for a public that is intent on curing cancer or preventing Alzheimer’s disease.
He writes that it is possible that, in today’s political environment, Hall, Rosbash, and Young would never have received money for their research. After all, do we really need to know what makes a fruit fly tick? But, as the Nobel committee has made clear, the science that informs and occasionally upends our understanding of human health and disease often comes from unexpected places.
Groopman writes: “Ohsumi used yeast cells to explore autophagy, but a similar garbage-disposal system exists in you and me. Similarly, studies of the circadian rhythm in flies have shed light on the genes and proteins that synchronize our own bodies with the day; they may lead to treatments for a wide range of maladies, from jet lag to obesity to heart disease.
“The joy of science is to learn for learning’s sake; whatever wondrous insights emerge may then be used to address the problems that we confront in our daily lives. The message embedded in today’s Nobel Prize announcement couldn’t come at a better moment – or a more fraught one.”
[link url="https://www.nytimes.com/2017/10/02/health/nobel-prize-medicine.html?action=Click&contentCollection=BreakingNews&contentID=65899589&pgtype=article"]The New York Times report[/link]
[link url="https://www.newyorker.com/tech/elements/the-real-message-of-the-2017-nobel-prize-in-physiology-medicine"]New Yorker report[/link]