What Makes Us Tick

From elk to eels to electricians, all living things have internal devices that keep track of time. How do they work?

12-01-1999 // Sharon Levy

Your computer may go haywire on January 1, but in the natural world the passage to 2000 will proceed without a hitch. That´s because animals, plants and even microbes have built-in timepieces that help them know when to rest, when to wake up, when to mate or when to migrate. These living clocks will keep on ticking, Y2K bug or no.
Lately, scientists studying everything from fruit flies to human volunteers have begun to unlock the secrets of biological clocks. And as other people fret over the advent of a new millennium, these clock biologists say things have never been better. "Right now we´re at the peak," says Steve Kay of The Scripps Research Institute in La Jolla, California. "We´re discovering how the biological clock is built, and there´s a tremendous amount of interest."

What Makes Us Tick magazine layout - deer and clock in the sunset

The study of biological rhythms is very old: As early as the fourth century B.C., Androsthenes, scribe to Alexander the Great, noted that the leaves of certain trees opened during the day and closed at night. In 1729, French scientist Jean Jacques D´Ortous de Mairan found that even if heliotrope plants are kept in total darkness, they´ll continue to open and close their leaves on schedule--the first proof that living things can keep time without being cued by the sun. Researchers have since learned that animals kept in the dark will also track time, showing patterns of rest and activity close to those they would normally keep in the wild.

Everyday rhythms in behavior--such as sleeping, waking or searching for food--are the most obvious signs that a creature is subject to the ticking of its internal timer. But scientists also study subtler clues. In many mammals, body temperature drops at night and peaks during the day, revealing the cycle of the clock.

These cycles (called circadian, from the Latin phrase for "about a day") will keep running if animals are kept in the dark. But in normal life, biological timers are attuned to the sun. The clock resets when it is exposed to light around dusk and dawn, whether it ticks inside a bacterium or a human being. This ability of the clock to synchronize with the environment is crucial. As the length of the day changes with the seasons, it allows animals to adjust their clocks appropriately. This is why night creatures such as bats and flying squirrels can emerge from hiding at dusk, regardless of the time of year.

How do these innate timepieces work? Over the past three decades, researchers have begun to find some answers, using new genetic techniques to explore the mechanism of the biological clock. The first breakthrough came in the early 1970s, when researchers Ronald Konopka and Seymour Benzer, working at the California Institute of Technology, created fruit flies with broken clocks. They exposed adult male flies to a chemical known to cause mutations. These flies fathered thousands of offspring, a few of which had abnormal clocks--their sense of timing was too fast or too slow, or was completely lost. Later, Konopka and other scientists traced these broken clocks to mutations in specific genes. These genes tell the flies´ cells how to construct the proteins that keep biological clocks ticking.

An old-fashioned watch has a spring that, when wound up tight, drives the gears that tick away, keeping time. Every day the watch must be rewound, so that the cycle can start again. In the biological clocks that tick inside our cells, there are genes instead of a spring. These genes instruct the cell to produce clock proteins, which are the gears of the clock. When the number of clock proteins in the cell reaches a certain level, the clock genes shut down and stop making new proteins. In a few hours, the clock proteins break apart and disappear, signalling the genes to go back into action--like rewinding a watch spring. In our cells, as in the watch, this cycle takes about 24 hours.

Researchers have learned about the basic design of biological timers by studying creatures with mutant clocks. But they still don´t know just how clock cells signal the rest of the body that it´s time to wake up or hit the sack.

A small section of the mammalian brain that is packed with timekeeper cells has long been considered the "master clock" that directs many bodily functions. The fruit fly also has a clock in its brain that was thought to control its sense of time. So biologists were startled by Steve Kay´s recent discovery that flies--and other animals--have clocks scattered all over their bodies.

Kay´s path to this finding began when he found a way to make the clock cells in a plant light up like a bunch of tiny bedside alarm clocks. He borrowed the glow-in-the-dark protein from fireflies and grafted it onto the plant´s clock proteins. It worked so well that Kay and his colleagues decided to try the same trick in fruit flies. They used night-vision cameras attached to microscopes to detect the glow of the flies´ clock cells. To Kay´s amazement, they found that fruit flies are cluttered with clocks--in their antennae, wings, legs and internal organs such as the testes. In later experiments, Kay and his students found that these clocks keep ticking even if they are disconnected from the fly´s brain.

Why would a creature have clocks all over its body? Probably to help coordinate various bodily functions with the daily cycle of light and dark. Moths, for example, have a strong circadian rhythm in sperm production, which peaks in the middle of the night when moths are most active.

Researchers have also found clocks cycling in the hearts, lungs, livers and testes of mammals. But if the master clock in the brain is damaged, these peripheral rhythms stop. "These tissues have their own clocks," says Kay, "but in mammals, they listen to the tapping of the master clock, like an orchestra conductor in the brain."

How important is the master clock to a creature in the wild? Patricia Decoursey, an ecologist at the University of South Carolina, is one of the few researchers who has been studying this question. Decoursey is looking at the survival of eastern chipmunks in the wild after the master clock in their brains has been surgically altered. Her early findings suggest that chipmunks with broken clocks are more likely to be targeted by predators than their normal counterparts, but so far the results are not conclusive.

Circadian clocks also give vital cues for seasonal changes, telling many birds and mammals when to prepare for mating in the spring or migration in the fall. It can take weeks for a white-crowned sparrow to put on the layer of fat it needs to survive migration, for example. Arctic mammals such as the Siberian hamster need time to change to their white winter coats. These and other creatures use their circadian clocks to measure changes in day length and give them advance warning of the changing seasons.

Some animals time seasons without measuring changes in day length, however. Golden-mantled squirrels, for instance, hibernate underground for six months of each year. In their dark burrows, they can´t use changes in day length as a cue, yet they emerge on time every spring, ready to do all their mating in two short weeks. This requires precise timing, since the squirrels´ reproductive organs shrink and go dormant during hibernation. Males need several weeks to gear up their gonads for mating season--a process that takes place while they´re still in the dark.

No one knows just how the squirrels track these annual rhythms. But biologist Norman Ruby, working with hibernating squirrels in a laboratory at Stanford University, has shown that they need a healthy master clock to time their winter retreat. Squirrels whose master clocks have been altered will still go into hibernation in the winter, but most never come out of it in the spring. "They just keep hibernating," says Ruby. "That is a completely unprecedented result, one we could never have predicted."

A clash between modern technology and the ancient rhythm of our own internal clocks may explain why many humans feel like hibernating on Monday mornings. A 1999 study directed by Charles Czeisler of Boston´s Brigham and Women´s Hospital, shows that human biological clocks are extremely reliable, but often at odds with lives lived in the glow of electric lights.

Clock researchers had long believed that human circadian rhythms are more variable than those of most other creatures, which cycle at close to 24 hours even when the animal is kept in the dark with no external time cues. Previous studies suggested that people´s clock cycles could vary from 13 to 65 hours, and that they become less precise as people age. In Czeisler´s study, 24 volunteers lived for a month in a room without time cues. The researchers imposed an artificially extended 28-hour day.

Czeisler tracked his volunteers´ circadian rhythms by measuring changes in the levels of the hormone melatonin--produced only at night--and in body temperature, which peaks during the day. He found that despite the artificially lengthened day, people´s clocks continued to cycle every 24 hours. Age doesn´t seem to affect our timing, either. Volunteers in their sixties kept a 24-hour cycle just as well as those in their twenties.

Czeisler concludes that typical Monday morning sluggishness is a result of our exposure to bright artificial light hours after the sun has gone down. Staying up late by the light of electric lamps resets our clocks, so that our bodies still want to sleep when the alarm says it´s time to wake up.

The recent research by Czeisler and others suggests that biological clocks, although they can be reset, are surprisingly accurate. So if every digital clock should suddenly grind to a halt in the new year, we´ll still be surrounded by perfect rhythms: Plants will open their leaves by day, ground squirrels will know just when to emerge in the spring and moths will be right on time for love.

California journalist Sharon Levy wrote about Earth´s magnetic fields and migration in the October/November 1999 issue.

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