As you read these words, a tiny cluster of tyrannical brain cells perched behind your eyes are carefully monitoring your mood: your sexual appetite, hunger, thirst, alertness-your state of being. Unwavering in their vigilance, the cells quiver in the mysterious cycles of hormones and other cascading chemicals that govern your life, sending out signals that keep the other 100 trillion cells of your body in step.
These watchful cells have a jawbreaking name-the supra-chiasmatic nucleus of the hypothalamus-and have become among the most hotly pursued in science. They wield an awesome power over human existence that belies their number-they amount to no more than 10,000 neurons, barely enough to fill the head of a pin.
Yet they seem to be the way the body measures time.
The little clock in the brain is thought to be the master pacemaker that reacts to the presence or absence of light and generates circadian rhythms. All of nature dances to such internal biological clocks set to the sun or the moon. Ticking in tune with the 24-hour solar cycle. Tocking with the 29.5-day lunar month. Or slowly pulsing with the year.
The role of sunlight-or light in general-as the most powerful synchronizer of the body`s biological rhythms has been under intense study in recent years, and some startling discoveries may change the way we work and live.
Much of the excitement is due to more than a decade of pioneering research directed by a native Chicagoan, Dr. Charles Czeisler, 36, a physician-researcher at Boston`s Brigham and Women`s Hospital, and his associates at Harvard Medical School and Harvard University.
Czeisler is the son of Dr. Tibor Czeisler, who retired last year after caring for 2,000 families on the South Side for the last 50 years. Although the elder Czeisler sent his son to Harvard, the son credits the encouragement and friendship of the pioneering sleep researchers at the University of Chicago with having propelled his career into this arena.
In 1978, Czeisler presented the first evidence that the pacemaker of human beings is indeed exquisitely sensitive to light by showing that even ordinary room light is sufficient to synchronize the human circadian rhythm to a 24-hour day. The finding sent circadian research rolling like a runaway truck without brakes.
Human isolation experiments in caves or underground bunkers have proved that the master clock is internal and not merely the body`s mindless reaction to outside cues in the environment. With no way to tell actual time, the body tends to prefer a ”day” that is about 24.5 hours long. Unfettered by societal constraints, all physiological functions eventually will adopt that schedule and a person will go to sleep about an hour later each day.
Consequently, for us to keep in sync with the rest of the world, our biological clock must be reset daily. How this is accomplished has caused considerable scientific debate, but a steady stream of discoveries about this mysterious mechanism have come from Czeisler and the Brigham`s Center for Circadian and Sleep Disorders Medicine, a suite of eight soundproofed rooms specially constructed to resemble Limbo as envisioned by Czeisler. There are no clocks, no radios or TVs, nothing that might tip off the body.
”It`s not an easy thing to pin down, this fascinating pacemaker in the brain,” Czeisler notes. ”We do so by shielding patients from outside stimuli. Sometimes we keep the conditions constant, using ordinary indoor room light and looking at oscillations in the body. Often we attune patients to days of different lengths and see how long it takes them to adapt. The point is to learn about the output of the pacemaker and how it relates to sleep-wake cycles, as well as the timing of hormones and daily variations in alertness and performance.”
Circadian (from the Latin circa and diem, meaning ”about day”) rhythms influence an amazing range of human biological responses and behaviors. Sleep and wakefulness is the most obvious cycle. Yet oscillations in body temperature, metabolic rate, heartbeat, urine excretion, blood count, hormones, mental alertness and physical dexterity also follow 24-hour fluctuations. The peak onset of labor for women, for example, is between 1 and 7 a.m. Human beings tend to die around 6 in the morning. They tend to have heart attacks and strokes around 9 a.m. and are most allergic to house dust at 11.
Czeisler`s research, although fundamental, has direct clinical implications. A body out of sync with the sun may plunge into trouble ranging from the wilting discomfort of jet lag, to lethal peril-between 4 and 6 a.m., sleepy drivers are 16 times more likely have single-vehicle accidents then they are during the day, despite the absence of traffic on the highways.
In the U.S., any of 21 million drivers are likely to be on the road in predawn hours because that many Americans-one man out of every four and one woman out of every six-have jobs that require them to regularly rotate shifts. These workers also face a greater risk of suffering heart attacks, ulcers, depression, anxiety and sleep disorders, according to studies. Such people may experience a jolt to their circadian system equivalent to crossing eight different time zones, Czeisler has shown. Industrial accidents are much more likely to occur during graveyard shifts when the human biological clock tells people they should be sleeping-the nuclear accidents at Three Mile Island and Chernobyl and the chemical disaster at Bhopal being only three memorable examples.
Because of such research by circadian specialists, Czeisler estimates that as many as half of the factories in the nation have changed their policies to allow shift workers to lessen the circadian shock by rotating clockwise-working daytimes, then evenings, then nights. In a classic 1982 study of potash miners at the Great Salt Lake Minerals and Chemicals Corp. in Ogden, Utah, Czeisler proved that employee morale and productivity increased by 20 percent and the number of injuries decreased after the shift rotation schedule was changed this way.
Moreover, the situation improves even more if workers remain on each shift for three or four weeks, Czeisler found, and are taught how to adapt by altering their eating and sleeping patterns.
Another promising area of research may affect the millions of Americans-as many as one person in every four living in the middle to northern latitudes-who are believed to live with balky clocks that fail to adjust to exposure to less daylight as the days grow shorter. The result is seasonal affective disorder (SAD) or winter depression, which has a broad spectrum of distressing symptoms including chronic depression and fatigue, erratic sleep patterns, food cravings-in short, the blahs.
Researchers in this area have been particularly interested in the hormone called melatonin that is secreted by the pineal gland, a small appendage in the brain (once believed to be the site of the soul) that may be vestigial in people but controls the biological clock in birds and many mammals. Northwestern University biologists Joseph Takahashi and Fred Turek are among the leading researchers who have been studying these clocks at the cellular and molecular levels and are racing to ferret out the genes that control them. Melatonin in humans is suppressed by light and otherwise seems to have a sedative effect. In particularly sensitive people, the effect could be causing trouble. In 1980, psychologist Alfred Lewy, now at the Oregon Health Sciences University in Portland, discovered that melatonin suppression hinges on exposure to very bright light-at least 10 times the intensity of normal room light. Lewy has reported encouraging success in treating more than 150 winter depressives by, in effect, tricking their bodies into believing it was summer by exposing them to light therapy.
The simplicity of such therapy-merely sitting for a few hours in front of banks of flourescent tubes that provide light at about 2,500 lux (the intensity of outdoor light shortly after sunrise) has led to speculation that the purported benefits may be more in people`s minds than in their brains. Scientists now are demanding strict controls and followup to determine if light therapy really works.
In Chicago, Dr. Charmane Eastman, director of the Biologic Rhythms Research Laboratory at Rush-Presbyterian-St. Luke`s Medical Center recently reported on an ingenious study. She compared the exposure to bright light in patients with exposure to a machine called a negative ion generator, that some people believe has beneficial effects. As a placebo control, Eastman also exposed patients to a negative-ion generator that was inoperative, to see if they thought it helped them. Intriguingly, the light therapy produced the most improvement.
Czeisler suspects that the brain`s pacemaker is not the sole source of biological rhythms. ”It sort of functions as a symphony conductor and cues the others when to come into play,” he says. ”The beauty of the system is that there are so many key players in sync with each other. And that`s the problem if this pacemaker is not working properly.”
Until fairly recently, the prevailing scientific theory was that people were not sensitive to light-resetting but were synchronized by social contact. ”It was a pretty vague concept,” Czeisler says. ”The idea was that if you interacted with another person who was synchronized to a 24-hour day, somehow your biological clock would also get reset.”
The theory was postulated in 1970 by scientists at the major research laboratory in the world working on biological rhythms, Germany`s Max Planck Institute in Munich. If the theory was true, it made humans very different from the rest of the animal kingdom, where light is the major synchronizing agent in every single organism that has been studied. Czeisler was so curious about the research that he eagerly joined a group of international scientists who were invited to tour the laboratory. What he found there made him smile.
”The evidence that the light-dark cycle was not a synchronizer came from studies in which the overhead fluorescent lights were switched on and off during a 24-hour period and didn`t make any difference,” he says. ”But when I saw the lab, I immediately noticed that even in the so-called `dark` phases, the subjects still had access to bedside lamps, desk lamps, and kitchen and bathroom lights.
”`What`s it like when it`s dark in here?` I asked the experimenters.
”`What do you mean?` they replied. `It is dark.”`
Although the overhead lights didn`t seem to affect the patients`
synchrony with the 24-hour cycle, the German scientists had ”discovered”
that if they inserted periodic alarm signals and other noises into that regimen, the patients did get in sync. The scientists interpreted this finding as meaning that when the patients heard the alarms, they felt they were in social contact with the experimenters. ”My interpretation,” Czeisler drily notes, ”is that the noises merely woke them up, like an alarm clock.”
A few years later, another influential study found that airline travelers fought off jet lag much more quickly if the went outdoors instead of staying in their hotels after arriving at their destination. ”The accepted interpretation was that this occurred because people were getting more social contact that way,” Czeisler explains. ”But I would say it was because they were getting more light. It all depends on your perspective, I suppose. Sometimes in science, we really have to question our assumptions.”
By 1986, with 16 years of research under his belt, Czeisler began to believe he perhaps could become a circadian watchmaker. Maybe he could take people whose internal clocks were sent to the wrong time of day and reset them.
A central focus of his research is aimed at trying to understand the basis of disrupted sleep in the elderly. Czeisler has a theory: ”The reason that many older people wake up in the middle of the night and can`t go back to sleep is because their internal clock is running a little bit faster than it is in young people. So older people reach the same point of their day earlier. ”This can be very frustrating for them. If you`re an older person, there`s nothing to do if you wake up every morning at 3 a.m. There`s nobody to talk to. And the flip side is that in the evening when your family and friends are with you, you find yourself nodding off. Your biological clock is telling you it`s time to sleep.”
In a celebrated 1986 experiment, a 68-year-old woman came to Czeisler complaining of just that. By then Czeisler and Harvard mathematician Richard Kronauer had compiled what they call a ”human response curve,” a chart showing how much a person`s biological clock should be reset, depending on when the proper exposure to light is given.
”I asked my patient what time she wanted to get up in the morning,”
Czeisler says. ”She looked at me strangely. I don`t think she believed any of this stuff.”
He exposed the woman to three hours of bright light between 8 p.m. and midnight. The light was about 48 times the intensity of normal room light-”it was comparable to the level you`d see in Chicago just after dawn on a clear day.”
He did this for three days, trying to trick her body at midnight into believing it was really only dusk. Animal studies had indicated that the most Czeisler could hope to adjust the woman`s clock was an hour or two each day. However, in just two days, he`d reset it by six hours.
”It was wonderful,” he says. ”She had to be awakened each morning by an alarm clock at 7:30, and she was able to stay up later in the evenings. When she left here, she told me, `I can`t believe what you people can do these days.`
”The point is, the treatment had a big impact on her life, and we think that other people with the same problem may also be helped.”
Czeisler was so encouraged by the experiment, that he reported on it, although protocols involving just one patient usually don`t get reported. But Czeisler believed he was onto something fundamental. ”Once you`ve seen a frog jump,” he said at the time, ”you know you`re not dealing with a turtle.”
Using the woman`s case a guide, Czeisler put a series of other patients through three days of treatments. They received five hours of bright light each day, with Czeisler timing the exposure to various points during their circadian cycles. The results were amazing: the treatments reset internal clocks by as much as 12 hours-a finding so dramatic that it was without precedent in human research. Nobody could have predicted the human biological clock was so flexible, so capable of being changed under the proper conditions.
Such research, Czeisler stresses, is still in its adolescence. But hope for a wide range of sleep and psychiatric disorders-not to mention the blahs- may be in the offing. ”Those of us in the field really believe we`re onto something,” Czeisler says. ”This work utterly fascinates me.”
