Biomedical Engineering Reference
In-Depth Information
3
BIOLOGICAL SCALING AND PHYSIOLOGICAL
TIME: BIOMEDICAL APPLICATIONS
Van M. Savage and Geoffrey B. West
Bauer Center for Genomics Research, Harvard University, Cambridge,
Massachusetts; Theoretical Division, Los Alamos National Laboratory,
Los Alamos, New Mexico
In collaboration with A.P. Allen, J.H. Brown, B.J. Enquist,
J.F. Gillooly, A.B. Herman, and W.H. Woodruff
A framework for the development of quantitative theories that capture the body size and
body temperature dependence of many cellular and physiological rates and times is pre-
sented. These theories rely on basic properties of biological systems, such as the invari-
ance of terminal units, and on fundamental constraints taken from physics and chemistry,
such as energy minimization of flow through resource-distribution networks and statistics
of biochemical reaction kinetics. The primary postulate of this framework is that meta-
bolic rate—the rate at which organisms take in resources from the environment, distribute
these resources throughout their bodies, and process these resources by means of bio-
chemical reactions—is perhaps the most fundamental rate in all of biology and is a major
determinant, through both direct and indirect effects, of most cellular and physiological
rates. The pervasive effects of metabolic rate are due to the facts that cellular rates work
in concert to produce the rates manifested at the whole-organism level, and that the
power created by metabolism must be allocated to individual maintenance, ontogenetic
growth, and reproduction. Here we outline the derivations of the body size and body tem-
perature dependence of metabolic rate. Using the primacy of metabolic rate, we then de-
scribe the ongoing development of theories that connect the theory of biological scaling
to several biomedical processes, including ontogenetic growth, nucleotide substitution
rates, sleep, and cancer growth. Empirical data are presented that confirm the mass and
temperature dependence of metabolic rate as well as predictions for lifespan, ontogenetic
growth trajectories, and sleep cycle times. Insights gleaned from these theories could po-
tentially lead to important biomedical applications, such as methods for calculating
proper drug dosing or for frustrating processes related to tumor angiogenesis.
Address correspondence to: Van M. Savage, 7 Divinity Avenue, Bauer Center for Genomics Re-
search, Harvard University, Cambridge, MA 02138.
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