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Do you ever wonder what wakes you up in the morning or how birds know when to migrate? As dissimilar as these two phenomenas might seem, they both exemplify biological clocks at work. Somehow, an animal's molecular biology keeps track of time and triggers signals accordingly, like: "Wake up!" Today, investigators around the world examine these clocks at levels ranging from behavior to biochemistry. A tour of sites on the Web reveals that some scientists focus on understanding the mechanisms behind these clocks and others concentrate on manipulating them. You can get a general introduction to this field from the biotiming tutorial at the NSF Center for Biological Timing.
When a biological clock follows a 24-hour rhythm,
scientists call it circadian, from the Latin words for "about" and "day."
Although the most familiar rhythm of this sort is our sleep-wake cycle, a
number of other aspects of human physiology demonstrate similar cyclical
variations. For example, hormonal physiology changes with time of day, as
do core body temperature, blood pressure, and immune-system function.
Remarkably, these oscillations occur even in the absence of the alternating
light and dark periods that we call day and night. That characteristic
classifies a circadian clock as free-running. In other words, a person
will settle into a roughly 24-hour cycle of sleep and activity, even in
continuous darkness.
In some cases, a person's clock can function imperfectly because of a physiological disorder or a work schedule that is incompatible with daylight cues. This can have serious consequences when we perform tasks that require skill or judgment, such as operating equipment, at times when our bodies expect to be asleep. In some cases, this can lead to disaster. The NSF Center for Biological Timing's site includes a page called Industrial Applications, which shows that the vast majority of serious accidents occur in the early morning hours. For example, the Chernobyl contamination clocked in at 1:23 A.M. and the trouble at Three Mile Island started at 4:00 A.M. Fatigue is also the most frequently implicated cause for fatal tractor-trailer accidents, which occur most often between 4:00 and 7:30 A.M. Nevertheless, shift work - working evenings or nights, or rotating or extending shifts - remains a necessity of the transportation and medical industries, to name only two. A number of industries strive to lessen the impact of shift work on the biological clock by using special lighting or limiting the number of continuous working hours allowed.
Sleeping problems and other physiological disruptions in
circadian rhythms can be triggered by a variety of things. Aging, for
instance, often leads to fragmented sleep patterns, which indicate a clock
dysfunction. The increasingly sedentary and indoor lifestyle of older
people exacerbates clock degeneration by removing typical stimuli,
including light, exercise, hormonal regulation, and regular meals. Some of
the same strategies that can help shift workers trick their normal clock
machinery can also alleviate the effects of these circadian disorders. For
instance, some sleeping disorders improve with daily light therapy, which
you can learn more about from the Society for Light Treatment and
Biological Rhythms. This nonprofit organization of researchers in
biological timing disorders also offers an excellent compilation of related
Web sites.
Recently, the manipulation of circadian rhythms has received considerable press from discussions of the hormone melatonin, which normally is released by the brain at night. Worldwide Labs' Melatonin Central posts vast amounts of information on melatonin, but keep in mind that this company also sells it. Although how melatonin actually works remains obscure, many producers sing its praises as a wonder drug - supposedly able to relieve jet lag, boost the immune system, relieve hangovers, and more. A variety of studies suggest that low, acute doses of this hormone really can help with jet lag and sleep disorders. However, the effects of chronic usage and the ways it might influence the efficacy of other drugs remain unknown. Before using melatonin for any purpose, you might want to contact the National Institute on Aging's Information Center, which offers a review (available by regular mail) of the latest findings.
For those looking for a more general understanding of
biological clocks, several molecular techniques have helped investigators
understand what makes us tick. A summary of recent advances is provided by the
Molecular Biology of
Circadian Rhythms Mini Review, from Cambridge Scientific Abstracts. The review
explains, for example, that organisms as diverse as mice, fruit flies, and
the fungus Neurospora have provided most of the molecular clues
available to date to about mechanisms behind biological rhythms. To dig
out these details, investigators often uncover genes that encode proteins
whose levels vary in a 24-hour cycle. These proteins are thought to
influence the expression, activity, and stability of additional proteins,
which combine to influence physiology in a circadian manner.
To keep up with advances in this field, you might turn to three peer-reviewed journals that are specifically devoted to studies of circadian rhythms and sleep: the Journal of Biological Rhythms (JBR), which published a special issue on melatonin; Sleep; and Biological Rhythm Research. The latter two journals post their abstracts online. Another resource is Sleep Research Online, a peer-reviewed electronic journal that aims for rapid publication of cutting-edge basic and clinical sleep research.
Rather than checking the contents of each of these journals individually, you can let others do the work for you. The Center for Biological Timing's site compiles monthly lists, going as far aback as 1994, of Publications in Biotiming Research that cover all the research papers relevant to the field. For sleep-related references you can visit BiblioSleep, which currently goes back to 1992.
Judging from the wealth of resources on the Web, people
spend many waking hours reading about sleep. SleepNet (reviewed in the current issue
of HMS Beagle) claims to have "everything you wanted to know about
sleep disorders but were too tired to ask." The University of California at Los Angeles hosts
the Sleep Home Pages, which
include current papers, support organizations, and even book
recommendations, as well as the BiblioSleep archive. The San Diego Sleep and
Rhythms Society also provides a broad variety of information, including
a special section devoted to rhythm and sleep
analysis software.
The San Diego group also offers a unique site: the San Diego Hamsters, an online running-wheel experiment that shows visitors the activity of a particular hamster in its cage. You can see what the hamster is doing at the time of your visit, as well as the history of its activity over the past several days. This is part of an experiment in which researchers are testing the effects of various medicines on the hamsters' activity patterns. If you would like to do your own experiments on circadian rhythms, visit Classroom Activities at the Center for Biological Timing. This page describes several group and individual activities, designed for middle-school and high-school students, that are inexpensive and do not require a tremendous amount of preparation.
Although I have concentrated here on circadian rhythms,
many biological phenomena follow other cycles. For a brief review, take a
look at the Other
Rhythms page at the Center for Biological Timing. Long rhythms, called
ultradian rhythms, operate on monthly, yearly, and even longer time scales,
and affect activities such as mating, migration, and hibernation. Many
animals also exhibit tidal rhythms that help them cope with the twice-daily
changes in their environment. Moreover, biological rhythms are not
restricted to animals: many plants respond to light and dark by opening and
closing their leaves and flowers in circadian and ultradian patterns. In fact, the famous taxonomist Carolus
Linnaeus could tell the time of day by observing which plants' flowers were
open in his garden.
It is not surprising that, over the 4 billion years of Earth's existence, its creatures have evolved their own patterns that reflect its period of axial rotation. However, this does pose a problem for extended colonization of other planets; our 24-hour cycle is so hardwired that we would probably experience perpetual jet lag on a planet with a different light-dark cycle. Fortunately, this is probably the least of the obstacles to interplanetary imperialism, and given the present vigorous level of activity in biological rhythms research, by the time that is possible, we will probably know enough about the mechanisms to adapt. In the meantime, surf the Web to find out what keeps your clock ticking.
Kate Winkler is a graduate student in the Pharmacology Department and the Cell and Molecular Biology Program at Duke University where she studies the cell-division cycle.
Caleb Brown is an illustrator and biologist living in Montana. By day he drives a delivery van, and by night he draws pictures with his computer.
Endlinks
Circadian Rhythms - a page maintained by the Mayo Clinic that details how human physiology reflects circadian rhythms, as well as linking to a page with Tricks to Try When You're Out of Sync.
Clocks and Rhythms - an article by Luiz Menna-Barreto that highlights the circadian patterns in core body temperature.Photobiology Online - links to news, events, journals, and a variety of other sites. Maintained by the European and American Societies for Photobiology.
ShiftWork Systems, Inc. - a discussion of circadian rhythms as they relate to shift workers and the efficacy of the specialized lighting systems that the company markets.
Society for Research on Biological Rhythms - chronicles the society's recent meetings and includes some useful links.
Mood Disorders Clinic - discusses symptoms and treatments for seasonal affective disorder. Maintained by the University of British Columbia and Vancouver Hospital & Health Sciences Center.
Rock-a-Bye Web Site - SleepNet reviewed in HMS Beagle.
Web sites mentioned in this column:
Take a Walk on
Biology's Mechanical Side Locating Mind with
Magnetism
Cell Death's Links to the Web of
Life
Forensic Biology
Molecular
Modeling: Internet Resources for Biologists
Science News on
the Net: Fast Food, Bistro, or Order In