1. The 2017 Nobel Prize: Explaining How Living Things Keep a Daily Rhythm
In 2017, the Nobel Prize in Physiology or Medicine was awarded to three scientists: Jeffrey Hall, Michael Rosbash, and Michael Young. They received the prize for their "discovery of molecular mechanisms controlling circadian rhythms" [1]. Circadian rhythm is the rhythm of the body that repeats in a cycle of about 24 hours. The Nobel Committee explained that plants, animals, and humans all adjust their biological rhythms to match the Earth's rotation [2].
When we think of a clock, we often imagine gears and springs. Is there something like that inside the body? The clue was found in flies.
2. 1971: Mutant Fruit Flies With No Rhythm, a 19-Hour Cycle, and a 28-Hour Cycle
In 1971, Ronald Konopka and Seymour Benzer found three mutant strains of fruit flies. One strain had no rhythm at all. Another had a cycle that was shorter, about 19 hours. The third had a cycle that was longer, about 28 hours [3]. Since a normal fly has a cycle of about 24 hours, these were like flies with clocks running too fast or too slow.
All three mutations were located in the same place on the X chromosome. This gene was named period [3]. A change in just one gene could stop the clock, make it run fast, or make it run slow. The flies showed that the parts of the clock are written in the genes.
However, at that time, the idea of "homeostasis"—keeping the body's state constant—was the main focus. Research on circadian rhythms was not widely looked at for a long time [4].
3. 1984: How Two Research Teams Isolated the period Gene
Thirteen years after 1971, in 1984, researchers succeeded in isolating the period gene. Hall and Rosbash did this at Brandeis University in Boston, USA. Young did it at Rockefeller University in New York. This was not a joint study; they succeeded in separate laboratories [5].
Once the gene was obtained, scientists could study what it made and when it worked. From this point, research into the inside of the clock advanced.
4. The Feedback Loop: How the PER Protein Switches Off Its Own Gene
The protein made by the period gene is called PER. PER builds up inside cells during the night and breaks down during the day. Its amount increases and decreases in a cycle of about 24 hours [2].
The key point is what happens next. When PER increases, it stops the activity of the gene that makes it [6]. In 1990, Hardin, Hall, and Rosbash showed that the amount of RNA copied from the gene rises and falls periodically, and that PER regulates this. When the product increases, the source stops. When it stops, the amount decreases. When it decreases, the source starts again. This "loop" creates the periodic rise and fall.
A common comparison is a toilet tank. When water fills the tank, a float rises and stops the water. When you flush, the water comes back in. But in reality, PER is not water, and there is no float part. The protein helps regulate the activity of its own gene.
However, for this loop to turn in "exactly 24 hours," a delay in time is needed. Who creates this delay?
5. The timeless and doubletime Genes: Parts That Create the Delay in the Clock
In 1994, Young found a second clock gene, timeless. The protein made by this gene, called TIM, was necessary for a normal rhythm [2].
Young also found a gene called doubletime. The protein DBT slows down the accumulation of PER. This delay is described as one clue to understanding how the cycle gets close to about 24 hours [7].
If you slightly narrow the opening where water enters a tank, it takes longer to fill up. The work of DBT is similar to this. But in reality, it is not narrowing an opening; it is changing the speed at which PER accumulates.
So far, this story has been about the inside of a fly's body. Does it apply to humans?
6. Body Clocks in Humans: How Flies' Clock Mechanism Relates to Our Bodies
It is explained that the mechanism found in flies has parts that are common with the human body [7]. The body clock is involved in sleep, appetite, hormones, blood pressure, and body temperature. A central clock in the hypothalamus of the brain is said to coordinate these functions [7].
If the clock and your daily rhythm are out of sync, it is said to be related to susceptibility to various diseases. However, this is a statement about "association." It does not mean that being out of sync is the direct cause of the disease [7].
The relationship with light and human clock genes are separate topics. These are things you might want to explore next.
7. A Home Activity: Noting Your Sleepiness and Waking Times to See Your Daily Rhythm
For 3 days, try making notes of the time you felt sleepy at night and the time you woke up in the morning. If you line them up, you might see your own daily rhythm. There is no need to compare yourself to others to decide if it is good or bad.
Look for books about "body clocks" in the library. Compare the toilet tank analogy in this article with the explanations in the books. Where are they the same, and where are they different?