Presentation Speech by Professor Carlos Ibáñez, Member of the Nobel Assembly at Karolinska Institutet, Member of the Nobel Committee for Physiology or Medicine, 10 December 2017Your Majesties, Your Royal Highnesses, Esteemed Nobel Laureates, Ladies and Gentlemen,
Phileas Fogg, the main character in Jules Verne’s acclaimed novel Around the World in Eighty Days, could not have suffered from jet-lag during his trip, despite crossing multiple time zones. His body had plenty of time – more than 3 days per time zone – to get adjusted to the time differences encountered along his journey. Today, in the era of jet travel, we can cross several time zones in only a few hours; but our bodies suffer, as they struggle to adapt to the new time at our destination. Many of our foreign guests this evening are surely experiencing this now. Why can’t our physiology adapt more rapidly? What keeps it behind?
Our physiology is regulated by an internal clock that generates daily rhythms known as “circadian”, from the Latin circadiem, meaning “around one day”. Circadian rhythms are ancient and exist in all forms of life. Life on Earth is adapted to the rotation of our planet, and the internal clock anticipates day/night cycles, helping organisms optimize their physiology and behavior. Although the existence of a biological clock has been known for nearly a century, only recently have we begun to understand what it is made of and how it keeps ticking.
Our story begins in 1729, when French astronomer Jean-Jacques de Mairan took a mimosa plant, which leaves are open during the day but close at night, and placed it in constant darkness. He observed that the leaves still opened and closed rhythmically at the appropriate time, suggesting an endogenous origin of the daily rhythm. Physiology is controlled by genes, and the biological clock is no exception. In 1971, Seymour Benzer and Ron Konopka isolated mutant flies that had alterations in their normal 24h cycle of activity. Fifteen years later, Jeffrey Hall and Michael Rosbash, working together at Brandeis University in Massachusetts, and Michael Young, at Rockefeller University in New York, isolated the mutated gene, called period.
As instrumental as this was, however, the isolation of the period gene did not tell very much about the mechanism of the biological clock. It was a remarkable series of discoveries made during the 1990s by this year’s Nobel Laureates that finally elucidated how our biological clock ticks. The basic principle, first proposed by Jeffrey Hall and Michael Rosbash, is deceptively simple. The period gene produces a protein that accumulates in the cell and, after reaching a certain level, blocks the gene and hence its own production. As protein levels subside, the gene becomes active again and the cycle resumes. As many things in biology, however, the devil is in the details; as it was still unclear how the period protein can be stabilized long enough and then enter the cell nucleus to inhibit its own production. Michael Young discovered two additional genes, he named them timeless and doubletime, that partner with period and together contribute to the generation of robust oscillations of approximately 24hs.
The discomfort of jetlag is evidence of the strength of our biological clock, as it takes time for the machinery to readjust to a sudden change in environmental conditions. Although sunlight is scarce this time of year in Stockholm, the good news is that food is also a strong resetting stimulus, so the banquet that follows after this ceremony will surely help towards adjusting our internal clocks.
The 2017 Nobel Laureates have uncovered a mechanism controlling a truly fundamental process in physiology, how our cells and bodies keep time. Such time-keeping is essential for our adaptation, and has important implications for human health; not just jetlag, but also the incidence of chronic syndromes, such as cancer, metabolic and sleep disorders, and several neurological conditions.
Professors Hall, Rosbash and Young:
Your brilliant studies have solved one of the great puzzles in physiology. Your discoveries have unraveled the cogs and wheels of the biological clock, an essential mechanism for the survival of life on our planet.
On behalf of the Nobel Assembly at the Karolinska Institute, I wish to convey to you our warmest congratulations. May I now ask that you step forward to receive the Nobel Prize from the hands of His Majesty the King.