The essay below is among the more influential of the many that Nature Biotechnology has published over the past quarter of a century. We thank the editors for permission to reprint it. (Otis)
Commentary
Nature
Biotechnology 21, 477 - 479 (2003)
The
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 laws (refs. 1,2) , 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 of course, 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 of understanding
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 of living 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 for
agency must be recognized as an epistemological error of great moment3.
Nevertheless, molecular biology has now followed the genotype-to-phenotype
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.
For those scientists accustomed to explanations of disease and health in terms of genes and proteins, this approach might appear nearly incomprehensible. And yet, not only does this view reveal a sophisticated science of dynamical systems, it also suggests several practical approaches to disease prevention and health promotion in populations, and to disease therapy for individuals. This is because almost all of 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 systems theory applied at many levels of biological organization—from molecular biology to populations.
[The complete essay is available as a PDF file here.]
Richard
Strohman is emeritus professor of the University of California at Berkeley,
Department of Molecular and Cell Biology. He is a former research director of the American Muscular Dystrophy Association. (Hank)
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