internal-clockThe Early Days of Jet Lag
In the mid 1950s, United States Secretary of State John Foster Dulles flew to Cairo, Egypt to negotiate a treaty for the construction of the Aswan Dam. Dulles and the U.S. were competing with the Soviet Union for the project, and at that early date in the Cold War, every interaction of the two Super Powers carried weight both real and symbolic. That is to say, there is no underestimating that at the time, this treaty was of grave importance; it was, in the governmental parlance of the day, an integral domino to be won or lost.

Just a short time after his arrival in Egypt, Dulles found himself involved in important meetings on the matter of the dam, during which he was haggard and unable to concentrate. Cairo is seven time zones east of Washington, D.C., a fact that proved disastrous for Dulles and his mission there. He was, he began to understand, suffering from jet lag — a relatively new phenomenon at the time — and by his own admission, did not perform well in the negotiations.

Ultimately, the American delegation lost the project to the U.S.S.R., issuing in a decade of Soviet influence in Egypt and the Middle East. Upon his return home, Dulles began urging U.S. diplomats to figure jet lag into their schedules and to allow for several days of rest before the commencement of any serious negotiations.

Since the 1950s, jet lag has come to be admitted into our popular lexicon and has been accused of causing everything from Greg Louganis to strike his head on the diving platform at Moscow’s 1979 Olympic trials to President Bush’s embarrassing televised vomiting incident in Japan in 1992. It is something we hear much about — something many of us have probably experienced. But what is it exactly?

In its essence, jet lag is a product of an age in which travel has become extremely rapid — so rapid, in fact, that we are now able to change time zones before our bodies have had a chance to adjust to the environmental cues of the new location. These cues are called zeitgebers, German for “time givers.” Zeitgebers are in large part a function of a place’s relationship to the sun. Two prominent zeitgebers, for instance, are temperature — warmer during the day, cooler at night — and the alternation between light and dark as a result of daytime and nighttime.

At noon Greenwich Standard Time in England, the most powerful zeitgeber is probably the sun’s bright light, when, at the exact same moment, on the other side of the earth, in, say, New Zealand, the most powerful zeitgeber is probably the absence of the sun: darkness. Noise, meals, and social interaction also act as weaker zeitgebers, among many other activities and occurrences — things that all happen at close to the same time each day. Our bodies, after a time, naturally synchronize with these events. Even three days into life an infant is already starting to shift her sleep habits more toward nighttime than day.

Circadian Rhythms
Zeitgebers, though, are only half the story, because they are merely cues. To whom or what are these “time givers” giving the time?

The answer, perhaps not surprisingly to anyone who wakes up every morning at exactly 6:51 am, is that we all have inside us an internal time-keeping mechanism. These internal clocks — in truth, there is not just one, but at least two — do not keep time the way the Naval Observatory’s Atomic Clock does. The most important difference is the length of a day. The average human clock runs not twenty-four hours, but twenty-five. In fact, most living things run on clocks that vary from the solar day. Animals active during the day, or diurnal species, tend to have a day longer than twenty-four hours; nocturnal species like owls and mice, conversely, tend to have a day somewhat shorter than twenty-four hours.

Internal clocks produce in living things something called circadian, or daily rhythms, from the Latin “circa,” meaning “about,” and “dies,” meaning “day.” This is as true for plants and trees as it is for chimpanzees and humans. These rhythms aid us in getting on in the world, and have, over the course of evolution, made it possible for us to be successful at things like creating offspring, giving birth, finding food, optimizing energy use and being hungry when our bodies are in need of nutrition. Essentially, circadian rhythms affect every aspect of existence.

Without the zeitgebers, however, the human biological clocks — and the circadian rhythms they create — would free-run. That is, if we didn’t have these external cues as guides, we would, in roughly a month’s time, have phase shifted our days all the way around the clock, losing an hour each night, as we stayed up later. This phenomenon was verified by a man who volunteered to live in a cave for three months in order to study body rhythms. When he entered, he took a watch with him, but with no strong zeitgebers by which to align his patterns, he eventually took to falling asleep later each night and waking later each day. Eventually he paid no heed at all to the watch; at this point, he was free-running — a phenomenon familiar to animals like beavers, whose patterns are closely linked with the solar day during summer time, but begin free-running during winter, when they’re living in the darkness of their dark and icy domiciles.

Since our clocks work on a twenty-five hour cycle, they need, in a manner of speaking, to be re-set each day to match the world around us; zeitgebers serve this purpose. It isn’t difficult to imagine the confusion we would face if everyone’s internal clock was running independently; it would make families and jobs and all sorts of social interactions at best awkward and at worst impossible.

The Search for the Clock
The idea of biological rhythms is an old one, dating at least to ancient Egypt, 2300 years ago, where a scribe by the name of Androsthenes, who, accompanying Alexander the Great to India, took note of the fact that the tamarind tree opened its leaves during the day and closed them at night. The quaint conclusion at the time was that the plant was worshipping the sun.

During the Scientific Revolution, it was widely believed that daily changes in plant life were caused by such factors as noise, sunlight and heat oscillations. But in the early eighteenth century, French astronomer Jean-Jacques d’Ortous de Mairan showed that the changes were wrought endogenously, as he closed a type of mimosa plant in a dark closet and found that it still raised and lowered its leaves each day.

Interest in the rhythms of living things began to catch on. In 1754, the Swedish naturalist Carolus Linnaeus famously designed a garden of plants — including such specimens as morning glories, four ‘o clocks and evening primroses — by which the time of day could be told, apparently causing some concern among clock makers of the day.

But it wasn’t until well into the twentieth century that the basis of all these apparent rhythms began to be uncovered. A student of the behaviorist James Watson, Curt Richter, was the first to identify the location of a biological clock. Richter, after many decades of inquiry — driven by a belief that the rats he studied were propelled by something internal to carry on such activities as eating, sleeping and running at particular intervals each day — discovered that at least one biological pacemaker existed somewhere within the hypothalamus, the region of the brain long known to be responsible for things like sleep and wakefulness. He found that when he damaged the hypothalamus of his rats, they carried on all of their normal activities — eating, sleeping, running and drinking — just as they always had, only their patterns for doing so were now extremely haphazard.

The hypothalamus is a small region of the brain just below the thalamus and it is an integral communication link between the brain and the endocrine system, as it controls the pituitary gland just below it. But to say that the hypothalamus is responsible for our internal clock is like saying that the Empire State Building is on the East Coast; it is grossly imprecise. After Richter made his discovery in the 1960s, the hunt was then on to find the exact part of the hypothalamus responsible for what was suspected to be The Clock.

The SCN and Beyond
In 1972, two research teams — one at the University of California at Berkeley and the other at the University of Chicago — finally ran down the culprit through some ingenuous maneuvering. Both teams recognized the importance of light in setting circadian pacemakers, and following this idea, they traced the neural pathways from the part of the eye that detects light, the retina, to the hypothalamus. Thus, a retinohypothalamic tract was identified, one which leads to a part of the hypothalamus called the suprachiasmatic nucleus, or the SCN. The SCN, a boomerang-shaped group of nerve cells, is named for its position atop the optic chiasm, which is a major junction for nerves to the eyes. The destruction of the SCN, the two teams discovered, eradicated many of the circadian rhythms of the body. Here, they discovered, was the long-sought-after biological clock. Or one of them.

It is important to note that some rhythms indeed persist in the absence of the SCN, indicating that another “clock” exists. It is suspected that this second clock is very closely linked with the SCN and also in the hypothalamus — probably in the ventromedial nucleus or the lateral hypothalamus area.

More recent studies have demonstrated some astounding things about our internal clocks. A destroyed SCN, for instance, can be replaced by the SCN from another organism and circadian functions will be restored. Also, a disembodied SCN will carry on keeping time in vitro (Moore-Ede, p. 192). An article published in the December 24, 1999 issue of Science indicates that researchers have had some success in locating the messenger clock cells — a peptide called PDF is the likely candidate — responsible for carrying the time message to the parts of the brain that drive various behaviors.

Implications of the Clock
It is difficult to even conceptualize our world without these pacemakers — our very thoughts are in part dependent on such rhythms. But we can — and already have begun to — imagine how our lives might be affected or improved by a better understanding of them.

Some ideas on the matter that have been circulating for some time include improvements to work schedules — particularly for those employed in shift-work. And as the world economy spirals toward globalization, more and more of us will be spending our nights working and our days sleeping. One recommendation for shift-work that has been heeded to some degree is that when a worker changes shifts, the time-movement is toward later in the day, or forward, rather than backward. This is because it is easier for our rhythms to eventually catch-up with the change in this direction, just as it easier on our bodies to fly from New York to Los Angeles than the other way around. Our twenty-five hour clock gives us an advantage when going from east to west, and a disadvantage going from west to east. Once in our new location — just as during the first days at our new time slot at work — our bodies must adapt to the zeitgebers of that time zone or that time of day.

Because circadian clocks have so recently come into the sphere of medical science, our understanding of them in this context is still rudimentary. The current thrust of circadian medical research is going into areas like drug therapies, which appear to be affected a great deal by the time of day a medication is given — and in surprising ways. An antihistamine, for instance, taken at 7:00 a.m. “lasts fifteen to seventeen hours, twice as long as it does if taken at 7:00 p.m.” (Lamberg, p. 111) Nutrition is another area of medical research gaining attention. A now-classic University of Minnesota study, for example, has shown that subjects eating only a 2,000 calorie meal at the same time every day for a week lose weight when eating it at breakfast, and gain weight when eating it at dinner — a fact certainly related to body rhythms.

In the latter half of the twentieth century, two new research possibilities have opened up for the study of circadian rhythms — the use of the south pole and outer space, both of which, in their unique environments, have contributed greatly to researchers gaining a new perspective on the subject. Like so many other facets of brain-related research, the study of circadian rhythms is relatively new, and because of its far-reaching implications, there seems little doubt that we’ll soon be hearing of new breakthroughs in the field which will undoubtedly come to bear on how we live our lives.

References:
Lamberg, Lynne, Bodyrhythms: Chronobiology and Peak Performance. William Morrow and Company, Inc., New York: 1994.

Moore-Ed, Martin C.; Sulzman, Frank M.; Fuller, Charles A., The Clocks That Time Us: Physiology of the Circadian Timing System. Harvard University Press, Cambridge, Massachusetts, 1982.