Inductive and Deductive Approaches to Acute Cell Injury

Abstract

Many clinically relevant forms of acute injury, such as stroke, traumatic brain injury, and myocardial infarction, have resisted treatments to prevent cell death following injury. The clinical failures can be linked to the currently used inductive models based on biological specifics of the injury system. Here we contrast the application of inductive and deductive models of acute cell injury. Using brain ischemia as a case study, we discuss limitations in inductive inferences, including the inability to unambiguously assign cell death causality and the lack of a systematic quantitative framework. These limitations follow from an overemphasis on qualitative molecular pathways specific to the injured system. Our recently developed nonlinear dynamical theory of cell injury provides a generic, systematic approach to cell injury in which attractor states and system parameters are used to quantitatively characterize acute injury systems. The theoretical, empirical, and therapeutic implications of shifting to a deductive framework are discussed. We illustrate how a deductive mathematical framework offers tangible advantages over qualitative inductive models for the development of therapeutics of acutely injured biological systems.

Finding a Needle in a Haystack

“…In addition, due to its inductive nature, no hypothesis is generally required because the results drive discovery. Pre-selecting proteins of interest may result in a type I statistical error ( 12 , 13 , 14 ).…”

Nonautonomous dynamics of acute cell injury

“…The toy models have proven fruitful for giving new insights about acute cell injury, by retrodicting many known phenomena (e.g., as described in Refs. [17,20,47,52]), and by offering qualitative and semi-quantitative predictions, as we now discuss.…”

“…Most biomedical research seeks to show a causal relationship between a specific qualitative form of damage and cell death. However, we have argued this is inadequate logic given that all of the other cellular changes are not taken into account [17]. It is a problem of induction: how can a single factor be causal when, first, there are multiple injuryinduced changes, and second, our general knowledge of cellular structure and function is incomplete?…”

“…It is a problem of induction: how can a single factor be causal when, first, there are multiple injuryinduced changes, and second, our general knowledge of cellular structure and function is incomplete? Thus the failure of clinical trials stems, at least in part, from the overreliance on inductive, descriptive approaches based on qualitative molecular details and pathways at the expense of a global, quantitative understanding of the system [17]. As an alternative, we have suggested the need for a deductive, quantitative theoretical framework.…”