Bench to Bedside
Why chaos matters
By Athos J. Rassias, M.D
When I was a medical student, I was browsing through the Dartmouth Bookstore one day and chanced on a title that hit me at a visceral levelFrom Clocks to Chaos: The Rhythms of Lifeso I bought and read it. Two McGill physiologists, Leon Glass and Michael Mackey, described nonlinear dynamics and its then nascent application to biological systems. They caught my imagination with their fresh description of how the mathematics and physics of nonlinear dynamics, also known as chaos, apply to biological systems.
The Oxford English Dictionary defines "chaos" as 1) the formless void of primordial matter, the great deep or abyss out of which the cosmos or order of the universe was evolved, and 2) a state resembling that of primitive chaos, utter confusion, and disorder (the latter being the more common use). One might think, then, that a chaotic system is a random one. But it's not.
Mathematical modeling implies that a system needs to be
complex in order to adapt to external perturbations.
Underlying patterns: A chaotic system is, however, so complex that it appears random. Theoretically, if we could understand the initial condition of a chaotic system and the underlying patterns and laws that guide it, we could predict its behavior.
The French mathematician Henri Poincare noted early in the 20th century that "a very small cause which escapes our notice determines a considerable effect that we cannot fail to see and then we say that the effect is due to chance." This principle was further articulated by meteorologist Edward Lorenz and popularized in 1987 by James Gleick in Chaos: Making of a New Science, a national bestseller. The analogy Lorenz developed was that the tiny perturbation of a butterfly flapping its wings in South America could lead to a dramatic change in the North American weather pattern. The minute alterations in the underlying conditions (or initial conditions) caused by a butterfly's wings can have a large effect on weather conditions because the physical rules determining weather events are highly complex.
Concept of chaos: This concept of chaos, when applied to biological systems, can be unsettling to physicians. We learned in medical school that if we make every physiological parameter normal, then a sick patient should improve. But, according to chaos theory, all the systems of the human body are involved in complex, seemingly random, ongoing interactions. Mathematical modeling implies that a system needs to be complex in order to maintain equilibrium. Otherwise it is less able to adapt to external perturbations.
Claude Bernard, a 19th-century French physician whose words still resonate in hospital wards, wrote: "La fixite du milieu interieur est la condition de la vie libre, independante" ("The constancy of the internal environment is a precondition of the free and independent life"). That one could maintain health in the face of constant and severe perturbations must imply that the body works hard to preserve homeostasis. One hundred years later, American physiologist Walter Canon expressed the same concept: "Our bodies . . . are composed of highly unstable material. They are subjected frequently to disturbing conditions. The maintenance of a constant state within them is evidence that agencies are acting or are ready to act to maintain this constancy."
From slow beginnings in the 1980s, applications of nonlinear dynamics to the biological sciences have grown exponentially. Chaotic systems have been observed in every area of medicine, including variability in the heart rate, brain wave frequencies, hormone levels, and gait control. Furthermore, a reduction in the complexity (a measure of how chaotic a system is) of biological rhythms is associated with disease. For example, heart attack patients who experience a reduction in the complexity of their heartbeat time intervals are more apt to develop lethal arrhythmias.
Mark Yeager, my research mentor at DMS, and I were intrigued by a Washington University study showing that the complexity, or variability, of the heart rate is reduced in response to inflammation. We often care for patients who suffer from sepsis, a severe and sometimes fatal inflammation usually caused by infection or tissue trauma. As the immune, hormonal, and autonomic nervous systems respond to in- flammation in the body, they all show reductions in complexity. The hormone cortisol, the cellular immune system, and heart rate variability are dramatically affected by inflammation; as complexity decreases, the body breaks down.
Sepsis: According to a prominent researcher, Steven Pincus, a reduction in a system's complexity implies that it has lost appropriate interactions with other systems. So in the body, a loss of complexity in any one system can compromise the entire body's ability to fight infection and thus lead to a high mortality rate for severe sepsis.
Can chaos be restored to an altered system? Would this be a good thing? Several researchers have applied techniques, initially developed in the nonbiological sciences, to control chaos in biological systems. For example, an appropriately timed electrical impulse can return a preparation of cardiac pacemaker cells from a pathological rhythm to a normal rhythm.
Could we save the lives of those who might die of sepsis by restoring chaos? We would first have to analyze the degree of complexity and then perturb the system to restore it to its "normal" state. We'd be providing patients with a way to adapt to the stress of inflammation.
In the meantime, we all need to remember that the hallmark of health is chaosappropriate chaos, that is.
"Bench to Bedside" explores the research underlying advances in clinical medicine. Rassias, a DMS '89, is an associate professor of anesthesiology and critical care medicine.
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