Wednesday, January 12, 2005

ClockTutorial #1 - What Is Chronobiology?

There are traditionally three approaches to research and teaching of physiology: biochemical, energetic, and homeostatic. The three are by no means exclusive and all good physiologists will include all three in their work and teaching, but each with a different emphasis.

Biochemical approach is typical of human/medical physiology. Physiological mechanisms are described at lower and lower levels, until the molecules involved are all described. This is most definitely a useful approach and has great practical application as well, yet it has its drawbacks. First, it ignores evolution (it can even be done by a Creationist) which may lead one to miss the big picture, thus guidance in which direction will research be most productive. Second, it provides a great description, but not an explanation of the mechanisms. It answers the question How something works, but does not attempt at all to answer Why.

Energetic approach is based on the notion of symmorphosis, i.e., that physiological adaptations are optimal in an engineering sense, particularly in their utilization of energy. All physiological processes are seen through the lense of energetics: how is energy acquired, stored, used, recycled and dissipated by the organism. Some heavy-duty economics formulas and models have been modified for use in physiology over the past century or so. It is assumed that every mutation that leads to better energetic efficiency of the organism will be preserved by natural selection. This may or may not be correct, but as a working hypothesis, it is mightily powerful. This approach is mostly seen in comparative/ecological/evolutionary physiology courses and textbooks and it is more geared towards answering the Why than the How questions.

Homeostatic approach has lately gone out of favor, for a number of reasons, mainly due to its inefficiency as a generator of real scientific progress. Physiological processes are seen as mechanisms for the maintanance of all aspects of the internal milieu of the body (first discussed in this way by Claude Bernard in the late 19th century). Environmental events tend to move various biological constants away from their optimal values, and various physiological mechanisms "kick in" to counter these perturbations and return all values back to normal.

One of the problems with this approach is linguistic: the very term homeostasis is misleading. "Homeo" means 'similar, same' and "stasis" means 'stability'. Thus, the word homeostasis (coined by Walter Cannon in the early 20th century) suggests strong and absolute constancy. Imagine that you were told to draw a graphical representation of the concept of homeostasis in 10 seconds. Without sufficient time to think, you would probably draw something like this:




The main characteristic of this graph is that the set-point is constant over time. But that is not how it works in the real world. Set point changes in a predictable and well-controlled manner. For instance, the set-point for testosterone levels in the blood in human males over the course of a lifetime may look like this:




That would be an example of developmental control of a set-point. At each point in time, that set-point is defended by homeostatic mechanisms, but the set-point value is itself controlled by other physiological processes. Another example of controlled change of a set-point may look like this:



This would be an example of an oscillatory control of a set-point. In the early 1980s, Nicholas Mrosovsky coined a new term to replace 'homeostasis' and specifically to denote controlled changes in set-points of all biochemical, physiological and behavioral values - rheostasis. Rheostasis, and particularly oscillatory examples of it, is the object of study of the biological discipline called Chronobiology. One of the strengths of chronobiology as a field is its equal emphasis on all three approaches of study: biochemical/molecular, energetic/evolutionary, and homeostatic/rheostatic (http://sciencepolitics.blogspot.com/2004/12/wwdd-what-would-darwin-do-or_02.html). Such a strategy is likely to be the reason why the field is exploding at incredible speed of exciting discovery.

Another example of an exploding field is evo-devo (evolutionary developmental biology), and I believe this huge success is also the result of a balance between the three approaches. Just look at this gorgeous BioAssays review, for example, as explained by PZMyers: http://pharyngula.org/index/weblog/comments/evolution_of_hormone_signaling/. It is deeply molecular, it is as comparative/ecological/evolutionary/energetic as can be, and the object of study is developmental rheostasis and evolutionary changes of its physiological control .

If all you do is genetics (especially in just one model organism), you describe but cannot explain. If you do comparative studies without genetics you are at a too high level of organization to make effective comparisons. And you ignore temporal changes at your own peril - an organism is not just its adult mature form (the standard specimen stuffed in the museum downtown), but a whole life cycle, a dynamic entity that changes all the time.

Often, a physiological mechanism is studied as an adaptation to the external environment. We teach how curious creatures manage to survive in depths of the oceans, on high mountains, in deserts, around the Poles, in salty water, or fresh water. Each of these environments presents specific challenges to its inhabitants who evolve often amazing specializations for survival in such conditions. What we tend to forget is that each organism has to be adapted to a whole range of environments. The egg, the larva, the pupa, and the adult live in different environments, have different needs, and have evolved different physiological (and biochemical and behavioral) mechanisms to satisfy those needs. But that is the one and the same organism, just going through different life-stages. It has to have all of those adaptations stored somewhere inside, some expressed at one stage, others at another stage of life, and has to evolve switches that turn these mechanisms on and off at appropriate times. This is studied by Evo-Devo.

But even within a single life stage, an organism needs to be adapted to more than one environment. A rabbit in a meadow experiences a very different environment during the day, during a dark night, and during a moonlit night. The same meadow is very different in winter from what it was last spring, summer or fall. A migratory bird's or whale's breeding grounds and overwintering grounds are likely to be very different from each other. A crab encounters a different beach during high and low tides. An organism has to have evolved biochemical, physiological and behavioral adaptations to all those disparate environments, as well as switches that turn these adaptations on and off at appropriate times, often very quickly. Because the switches have to act so fast, many of them have evolved to act independently of the environmental triggers. The environmental cycles, like day and night, tides, moon phases and seasons, are very predictable, thus a switch can get started in advance of the environmental change, thus rendering the organism "ready" for the new environment just in time for its appearance. Even if the organism is removed from the cyclical environment, the switches keep going on and off, and the physiological state of the organism keeps oscillating on its own, becoming a timer: a biological clock. The mechanisms of such oscillations, as well as various uses that organisms put their clocks to are studied by Chronobiology.

In the weeks and months to come, I will be writing about Chronobiology in many different ways: fun facts and quotes, anecdotes and gossip, tutorials and editorials, commenting on news and media reports, describing classical experiments, dipping into the history of the field, as well as analysis of brand new research papers. Oh, am I going to have fun doing this!


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