by Donald McEachron
Life is all about timing… the unreachable becomes reachable, the unavailable become available, the unattainable… attainable. Have the patience, wait it out. It’s all about timing.
– Stacey Charter (http://www.worldofquotes.com/topic/Time/index.html)
Timing is Everything
‘Life is all about timing . . .’ This statement is so profoundly true that we sometimes forget its implications. We glance at the clock on the wall, wake up to a noisy alarm (or, often as not, sleep through it to awaken in a panic as we have missed a class or appointment), wait for the buzzer on our microwave to sound indicating our dinner or tea is done and go on through our lives seemingly organized by the temporal demands on our modern, urban 24/7 society. However, deep inside each one of us, a far more ancient timing system is at work, organizing the living processes that sustain us in fundamental rhythmic patterns. These rhythms are embedded in every process, from the most basic biochemical activities to the most intricate cognitive functions. Biological rhythms define us, change us, and sustain us in ways science is just beginning to truly comprehend. And what is emerging is a fundamental conflict between our basic biological temporal order and the demands of modern society. This conflict has profound implications for the health, well-being and productivity of every human being.
What are biological rhythms and from where do they arise? A biological rhythm can be simply defined as the periodic reoccurrence of an event within a biological system at more-or-less regular intervals1. The range of cycle frequencies is enormous, from millisecond patterns of nerve cells to multi-year predator-prey cycles as is the variety of biological systems that display rhythmicity, ranging from biochemical cycles (glycolysis) and subcellular components (mitochondria) to entire ecosystems. Indeed, in complex interconnected networks such as living systems, if one component of the network becomes rhythmic, the entire network tends towards oscillations as a result11.
However, what would make that initial component oscillate? There are a number of reasons to anticipate the evolution of rhythmicity. There is a need for timing mechanisms in any complex, goal-oriented system (such as designed into vehicles and computer systems, for example) and oscillators are an excellent method of generating such timers; many physiological systems and behaviors are inherently oscillatory – heart beat, breathing, walking – and thus it makes sense for evolution to control such oscillations with oscillators; and living systems involve a number of feedback control systems (think of a thermostat) and such systems are inherently oscillatory. However, there is one overwhelming factor that that would most likely cause the evolution of biological rhythms even if all the other factors could be disregarded – the Earth’s geophysical cycles of rotation and revolution.
The twin cycles of day and night and seasonal variation create vastly different environmental conditions on a predictable timescale to which biological organisms must adapt. Throughout evolutionary time, biological systems have evolved complex timing systems and biological clocks which allow organisms to organize their physiology and behavior to match and even anticipate environmental changes. Thus, Earth’s creatures all have their own ‘niche in time’ which saves them, not from nine, but from behavior or physiological processes undertaken at inappropriate moments.
The Paradox of Evolution
However, why should we be concerned about this issue? We are humans – we are freed from the domination of day and night. Using technology, we have eliminated the need for such ancient patterns – we create our own day and night, so does what happened millions of years ago really matter?
To answer this, one must appreciate the evolutionary process. With the fundamental goal of preserving and propagating genetic materials and relying to a large extent on the twin factors of genetic mutation and natural selection, evolution results in organisms profoundly different from what could be anticipated from the application of engineering design. Several factors are important in this regard:
1) Evolutionary processes may promote genetic propagation at the expense of individual welfare;
2) Random mutation does not always result in the best possible adaptations;
3) Organisms are always best adapted to their ancestors’ environment. It is the ancestors that successfully reproduced and propagated their genes over time, not the current representatives;
4) Emotions are as much an evolved feature as anything else and thus can be considered in light of their evolutionary cost and benefit.
The conclusion which may be derived from these factors is that any organism – including humans – will be a mixture of characteristics, some well-adapted to current conditions and others acting as legacy effects (sometimes called vestigial) which reflect the adaptations of ancestors to conditions which may no longer exist. The more rapid the pace of environmental change, the more likely organisms are to be maladapted to the new conditions. And there is nothing more rapid than the pace of cultural and technological change currently underway in human societies. These observations and arguments lead inevitably to the conclusion that human beings retain an evolutionarily determined mixture of biologically maladapted traits and behaviors ill-suited to the current urban environment.
The following analogy may help to clarify why this evolutionary perspective matters. If one considers the operating parameters of a typical internal combustion engine, it is clear that such engines function most effectively at fairly high temperatures. However, heating these engines is not typically part of the design process since the heat generated during normal operations is more than sufficient to warm the device. Indeed, such operations generate too much heat, requiring a cooling system be designed to allow the engine to run for sustained periods. The physics of the process means that the designer can safely ignore specifically heating the device but must instead focus on cooling it to compensate for normal operations.
With biological systems, more than mere physics is involved – evolution comes into play as well. Consider the benefits of moderate exercise for human beings. The benefits are so great that one wonders why humans are so emotionally reluctant to engage in it. Surely evolution should have outfitted humans being with a desire for such activity given its evident advantages. Passing for the moment on the reality that it is advantages at a genetic, and not individual, level that determine the course of evolution, how can this paradox be explained? If you consider that our hominid ancestors lived in an exercise-intensive environment with fairly scare resources, this inconsistency is no longer so difficult to comprehend. Evolution did not need to equip humans with a desire to exercise – exercise was imposed upon them by the demands of their environment and lifestyle. However, in the face of scarce resources, rest and resource hording through inactivity makes great evolutionary sense. Thus, the more adapted hominid was the one who rested whenever possible and did not exercise without cause. He or she would then have more energy remaining for the critical activities of survival and reproduction. The process of evolution could safely ignore creating a desire for exercise but instead focused on generating a longing for inactivity and resource hording.
What was good for human ancestors, however, is not so beneficial in modern times. With neither the environment nor lifestyle imposing exercise, our ancestral adaptation in terms of inactivity and resource hording has contributed to an epidemic of obesity. Hopefully, this analogy makes it clear why evolving organisms, such as human beings, may not desire – or design – what is actually needed.
OK, so theoretically, humans have legacy effects and maybe you (and I) visit the donut shop a bit too often but what does this have to do with biological rhythms? Well, as it turns out, evolution has equipped all eukaryotes (organisms with a cell nucleus) with biological clocks able to match the near 24-hour light/dark (day/night) cycle. These clocks are called circadian clocks and the rhythms they produce are called circadian rhythms. The environmental effects of the Earth’s rotation were so profound and consistent over such a long period that everything about you changes on a daily basis – body temperature, neurotransmitter levels, heart rate, reaction time, hormone levels, grip strength, liver enzyme activity – you name it, it varies over 24 hours. In a truly fundamental way, you are not the same person at 2 am as you are at 2 pm. Somewhat unsettling, but true.
I can actually give you evidence for this without resorting to a laboratory setting or expensive experimental setup. Try to recall the last time you kept a really regular schedule. Perhaps on Co-OP or a situation where you had to be somewhere at the same time every day. At first, you probably relied on your alarm clock to awaken you every morning. But gradually, something really surprising occurred – you began to wake up right before the alarm sounded. As you kept up your schedule, this began to happen more and more until it seemed as if the alarm clock had become superfluous. That is, until you had to change your schedule, when everything went haywire and your alarm clock was again a temporal lifeline.
What was happening? Well, your circadian clocks are not perfect – they do not run at a frequency of exactly 24 hours but a bit longer than that in humans. In fact, no organism’s clocks are perfect. Thus, in order to position an organism into its temporal niche, the clocks must be periodically reset to match the environmental cycle, usually the day and night cycle. This is what is happening with your regular schedule and the alarm clock. The consistency of your schedule acted to synchronize your circadian system to the schedule. Once synchronized, the circadian system could signal you physiologically that it was time to wake up and the alarm clock was not longer needed. Once you changed your schedule, the synchronization was broken and had to be reestablished. A similar sort of desynchronization occurs when traveling across multiple time zones and is popularly referred to as ‘jet lag’.
For those science and engineering types among you, the process of synchronization between an environmental cycle and a biological clock is called entrainment and is not different in principle than what might be observed between electronic or mechanical oscillators. An environmental cycle capable of synchronizing a biological clock is called a Zeitgeber (German for ‘Time-Giver’).
In the world of your hominid ancestors, the consistent pattern of sunrise and sunset provided a powerful and stable Zeitgeber. Similar to the vast majority of organisms, hominids could rely on this pattern and evolution outfitted them with light sensors in the retina and a master circadian clock in the brain (an area called the suprachiasmatic nuclei (SCN) in the hypothalamus) to control the body’s various cycles. Even the cultural development of fire did not significantly alter this pattern. As it turns out, the light sensors for circadian rhythms are different from those we use to locate objects and the absorption spectrum (light sensitivity) is shifted towards blue-green wavelengths10. Until recent history, hominids, and then humans, were at peace with their temporal environment, or, as a colleague once put it, there is no such thing as wagon-lag.
Music or Noise – It’s All in the Timing
If you have ever arrived early for a symphony, you have probably had the experience of hearing the orchestra tune up. Individuals on various instruments play innumerable tunes and melodies with little regard for each other or for the ears of the audience. The noise that is produced can be disconcerting to say the least. Suddenly, the conductor appears and there is a blessed silence. The arms are raised and in a matter of exquisite timing and coordination, music is produced taking you on a voyage of artistic discovery. Music or noise, it is all a matter of timing.
In your body, the SCN serves as conductor. This area of the brain helps to coordinate various rhythmic phenomena to ensure that biochemical, physiological and behavior processes occur in the right temporal relationship, both to each other and to the external environment. When everything is functioning, it is a miracle of efficiency and coordination. When it does not, the noise generated in biological systems can make a tuning orchestra sound like Beethoven’s Moonlight Sonata in comparison.
What causes noise in your biological timing system? Many things can do this, but a critical factor is the Zeitgeber. Remember, your circadian system did not evolve with artificial lighting – the system evolved to expect a gradual increase in lighting (sunrise) and powerful, sustained lighting (daylight) and a gradual decrease in lighting (sunset) followed by a profound darkness (night). If any of you have been in a forest at night away from any human habitation, you know what is meant by profound darkness. These effects involve both intensity and wavelength variations in perceived lighting. Focusing on illuminance alone, a moonless overcast night may provide only about 10-4 lux, while full daylight provides 10,000-25,000 lux and direct sunlight 32,000–130,000 lux (A lux is a measure of illuminance) (http://stjarnhimlen.se/comp/radfaq.html – 10). The actual levels depend on both your location on the Earth and weather, but clearly the circadian system evolved to expect a dynamic range of lighting over some 6-9 orders of magnitude. If this is what the system has evolved to expect and would generate the most biologically appropriate results, what does urban society actually deliver and what are the consequences?
Modern humans are by and large isolated from the natural lighting environment. For example, a study in the early 1990’s indicated that dayshift workers experienced only about 52 minutes per day of light over 1500 lux while nightshift workers only experienced 13 minutes on average8. In fact, minimum lighting levels for most office environments range between 300 and 500 lux (http://www.gsa.gov/portal /content/ 101308) and measured values in several Drexel classrooms have ranged in the 500-700 lux range, even during daylight with large windows present. Nor is dark really dark – streetlights, interior lighting, even night-lights – decrease the level of darkness present at night. Even a small night-light can produce a lux or two of illumination. Consider the position of the modern human in going from a legacy expectation for the range of the lighting Zeitgber to be between 10-4 to 105 lux in the natural environment to an actual range of 1 to 500 lux in our modern urban settings. This is a difference of almost 20,000%! Nor is this the only problem. Not only is the range of the lighting Zeitgeber far below the system evolved to expect, artificial, on-demand lighting provides light without regard to time-of-day. Thus, not only is the synchronizing signal weak, it is so irregular that it may provide contradictory signals to the biological clocks, causing disruption and desynchronization. Adaptable as humans are, it is unreasonable to expect that an environmental change of this magnitude will be without consequence.
There are Always Consequences
The best method for determining the long-term consequences of circadian disruption is to study it in extreme forms. For humans, this means analyzing the consequences of shift work and repetitive travel over multiple time zones. I recently reviewed these data11as have others3-7,9. The majority (but not all) studies indicate that multiple time zone travel and shift work are associated with a variety of behavioral and physiological issues. The physiological issues include sleep disruption, reproductive problems, gastrointestinal complaints, metabolic abnormalities, enhanced danger of cardiovascular problems and an increased risk for certain types of cancers. Behavioral issues include decrements in cognitive performance, depressed mood, psychiatric complaints and increased reports of neuropsychological problems.
This may make sense, given the role of environmental Zeitgbers in synchronizing circadian rhythms and the circadian systems’ role in orchestrating biological cycles, but what does shift work have to do with the average student, faculty or staff at Drexel University? Sure, there may be shift workers on campus and they should be concerned about the long-term impact of such activities on their health, but that does not really impact the average student, does it? Do not be so sure. I recently collected data on student schedules and sleep and the results were disturbing to say the least.
Presented at the International Behavioral Neuroscience Society meeting in 2012, the data revealed that college students are both chronically sleep deprived and following schedules reminiscent of shift work2. As described above, such schedules can generate both health problems and cognitive impairment. Although the data are still be analyzed, the issue may be a serious one. Indeed, I strongly suspect an undiagnosed epidemic is developing where students engage in schedules leading to both circadian disruption and sleep deprivation and counter the effects temporarily using stimulants and energy drinks. This can, of course, lead to a counter-productive feedback system where energy drinks lead to desynchronization and sleep disruption which require more stimulants to counter the effects, leading to further disruption and desynchronization and so on. The long-term consequences of such activities are not known at present.
What Can Be Done?
What can you, as an individual, do about your temporal health? For those of you who are truly interested in developing a more effective approach, there are a number of books available. Practical guidebooks include The Body Clock, by Michael Smolensky and Lynne Lamberg (2000) or The Body Clock Advantage by Matthew Edlund (2003). The books provide a comprehensive overview of how you can arrange your schedule to promote temporal health as well as how to use the variations in physiology and cognitive functions throughout the day to your advantage.
Of course, there are practical limitations to how well you can adjust your lifestyle to fit the biological imperative of rhythmic coherence. If modern society is in fundamental conflict with biological temporal order, then college life is perhaps one of its most severe battles. The often-changing schedule of classes and uneven timetables of requirements with significant overloading at certain times (such as finals week) almost makes a mockery of the concept of temporal stability. However, there are some steps you can take to minimize the impact. Time management is a critical skill to develop, not just for the sake of learning and productivity but for your personal health as well. Try as much as possible to plan a regular schedule of sleep times (sleep is a critical component for both mental and physiological health) across the term, even on the weekends. Exposure to sunlight is an important element, so get outside especially in the morning near your wake-up time (with the proper skin protection against UV radiation, of course). When you go to sleep, darken the room as much as possible. Even small amounts of light can suppress melatonin, a neurohormone released during darkness which helps synchronize circadian rhythms in your body and promotes sleep as well. If you have to be up past your regular sleep time, the more red-shifted the lighting to which you are exposed, the less impact it will have on your circadian rhythms and less disruptive it will be to them. And finally, as difficult as this may be, try and limit your dependence on energy drinks and other stimulants. If you find that you must have these drinks to function, this is excellent evidence that your temporal health is impaired. See what you can do to cut back on your use of these stimulants.
These are minor adjustments and probably will not be enough to bring you totally back into synchronization. You will most likely continue to have irregular schedules and the partial sleep deprivation that goes with them. It is important to note that there will be consequences. Irregular schedules and partial sleep deprivation may lead to weight gain, as the body is unable to keep its metabolic processes properly aligned. You immune system may also be slightly impaired, making you more susceptible to illness – be more vigilant in this regard. Such schedules may also make learning and retention of materials more difficult – be prepared for this and try not to use ‘all-nighters’ to cram for finals. You may pass the examination but lose much of the material you struggled so hard to learn. Your reaction time can be significantly reduced by sleep deprivation, which has been compared with ethanol intoxication (drunkenness) in its effects, so driving or operating devices while so impaired is to be avoided. Finally, such schedules combined with partial sleep deprivation can affect your emotional stability and balance, making even small problems seem insurmountable. In the already high stress environment that is college life, such impacts can be significant, compromising your judgment. Be aware of this and be willing to step back, relax a minute and consider whether or not the issue you are facing in worth the anxiety you are associating with it. It will be time well spent.
There is So Much More
In a sense I feel like a person who was asked to describe the essence of the universe to someone while he or she stood on one foot. It is not possible to describe such a critical component of life and living systems as rhythms in a short article. Indeed, when I was contracted to write a brief text on the subject, I discovered to my chagrin (and the publishers’) that the short 120-160 page book had expanded to over 250 pages and was only half completed. Thus, Chronobioengineering, Volume 1 instead of just chronobioengineering. I do teach a two-quarter sequence here at Drexel University, BMES 411/531 and BMES 412/532, Chronobioengineering 1 and 2, and would welcome new students. There are also a number of excellent web sites where one can be introduced to the concepts and potential applications of chronobiology (the study of biological rhythms). I have listed a few below:
National Institute of General Medical Sciences – http://www.nigms.nih.gov/Education/Factsheet_CircadianRhythms.htm
Halberg Chronobiology Center – http://www.msi.umn.edu/~halberg/
Medical Chronobiology Program at Harvard University – https://sleep.med.harvard.edu/research/labs/54/medical+chronobiology+program
Society for Research on Biological Rhythms – http://www.srbr.org/Pages/default.aspx
Society for Light Treatment and Biological Rhythms – http://www.sltbr.org
I hope that I have inspired you to find out more about biological rhythms, because timing really is everything!
What is time? The shadow on the dial, the striking of the clock, the running of the sand–day and night, summer and winter, months, years, centuries–these are but arbitrary and outward signs, the measure of time, not time itself. Time is the life of the soul.
-Henry Wadsworth Longfellow
- Aschoff, J. (1981). A survey of biological rhythms. In Aschoff, J. (ed.) Handbook of Behavioral Neurobiology 4: Biological Rhythms. Plenum Press: New York, pp. 3-10.
- Baynard, M and McEachron, D.L. (2012). Sleeping in Class: Are Students Schedules Physiologically Inhibiting Learning? Presented at the 21st Annual Meeting of the International Behavioral Neuroscience Society, June 5-10, 2012, Kailua-Kona, Hawaii.
- Costa, G. (1996). The impact of shift and night work on health. Applied Ergonomics 27(1): 9-16.
- Davis, S. and Mirick, D.K. (2006). Circadian disruption, shift work and the risk of cancer: a summary of the evidence and studies in Seattle. Cancer Causes and Control 17: 539-545.
- Davis, S., Mirick, D.K. and Stevens, R.G. (2001) Night shift work, light at night and risk of breast cancer. Journal of the National Cancer Institute 93(20): 1557-1562.
- Harrington, J. (1994). Shift work and health – A critical review of the literature on working hours. Annals of the Academy of Medicine, Singapore 23(5): 699-705.
- Haus, E. and Smolensky, M. (2006). Biological clocks and shift work: Circadian dysregulation and potential long-term effects. Cancer Causes Control 17: 489-500.
- Koller, M., Kundi, M., Stidl, H.-G., Zidek, T., and Haider, M. (1993). Personal light dosimetry in permanent night and day workers. Chronobiology International 10: 143 – 155.
- Knuttson, A. (2003). Health disorders of shift workers. Occupational Medicine 53: 103-108.
- Lockley, S.W., Brainard, G.C. and Czeisler, C.A. (2003). High sensitivity of the human melatonin rhythm to resetting by short wavelength light. Journal of Clinical Endocrinology and Metabolism 88(9): 4502-4505.
- McEachron, D. L. (2012). Chronobioengineering, Volume 1. Morgan & Claypool Publishers: San Rafael, CA.