Biological Scaling and Physiological Time: Biomedical Applications

Abstract

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 presented. These theories rely on basic properties of biological systems, such as the invariance 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 metabolic 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 biochemical 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 temperature dependence of metabolic rate. Using the primacy of metabolic rate, we then describe 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 potentially lead to important biomedical applications, such as methods for calculating proper drug dosing or for frustrating processes related to tumor angiogenesis.