Thermodynamics—old laws in medicine and complex disease
Richard Strohman © 2003 Nature Publishing Group http://www.nature.com/naturebiotechnology
he search for new laws in biology is associated with the beginnings of molecular biology and with Max Delbruck who brought the idea from physics that living systems, although ultimately reducible to universal physical laws,displayed qualities not shared by nonliving matter, and might harbor new laws unique to life itself. The rich history of twentieth century molecular biology has included a failure to find such laws1,2, and that failure is seen as the major force driving biological research to find so-called genetic laws from which would come understanding of life and of our many diseases, inherited or otherwise. And ofcourse, this failure has prompted the question: “If not in the genome”—and organisms are clearly programmed in some sense of that word—“then where is the program and what is its nature?” Fifty years after the emergence of molecular biology, at the Ciba Conference on The Limits of Reductionism in Biology in 1997 (ref. 2), the philosopher Thomas Nagel reflected on this stubborn absence ofunderstanding in biology. He concluded: “…our finite mental and computational capacities mean that we either cannot grasp the ultimate physical explanation…or we can’t fruitfully link the old universal physical laws to higher order phenomena.” Therefore, he said, repeating Delbruck, perhaps biologists needed to discover new laws for life. The nature of the linkage between physical laws and phenotypes ofliving matter has now begun to take on new dimensions, although one such key juncture has been known for some time: the laws of thermodynamics and kinetics are linked to the phenotypes of organisms through the agency of dynamical systems. Sadly, this essential point has been all but ignored in the rush to find agent-based genomic-proteomic explanations. Looking back, that substitution of agents foragency must be
recognized as an epistemological error of great moment3. Nevertheless, molecular biology has now followed the genotype-tophenotype trajectory to an end point identified as open, self-organizing, molecular systems within which controls and constraints are distributed among many interacting subsystems, each with robust behavior. The universal metabolic system represented by the‘Chart of Metabolism’ known to all biochemists is a prime example of such a system.
the disease states in question manifest as bioenergetic deficiencies—whether induced by gene or protein variation, by environmental insult, by excess calorie consumption, by insufficient physical activity. These issues were discussed late last year at a conference in Bethesda, MD*, and ranged over dynamical systemstheory applied at many levels of biological organization—from molecular biology to populations.
Thermodynamics and linkage of phenotype to genotype
What is becoming clearer is that it is just this dynamic metabolic territory where the universal laws of thermodynamics and kinetics join with an organism’s phenotype.
What is becoming clearer is that it is just this dynamic metabolic territorywhere the universal laws of thermodynamics and kinetics join with an organism’s phenotype. The levels of organization where this linkage is usefully employed are: first, cell and organ-system physiology; and second, the level of the human organism as a whole, and the population. In the latter case, the linkage is again laws of dynamic physiological systems on the one hand and, on the other, theage-experience-diet-exercise-related trajectories of aging and senescence. Thus, the language of bioenergetics is able to describe the potential and kinetic energy level of a cell, tissue, organ, entire organism and, in a sense, the population as a whole. For those scientists accustomed to explanations of disease and health in terms of genes and proteins, this approach might appear nearly...