Abstraction and Idealization in Biomedicine: The Nonautonomous Theory of Acute Cell Injury

Abstract

Neuroprotection seeks to halt cell death after brain ischemia and has been shown to be possible in laboratory studies. However, neuroprotection has not been successfully translated into clinical practice, despite voluminous research and controlled clinical trials. We suggested these failures may be due, at least in part, to the lack of a general theory of cell injury to guide research into specific injuries. The nonlinear dynamical theory of acute cell injury was introduced to ameliorate this situation. Here we present a revised nonautonomous nonlinear theory of acute cell injury and show how to interpret its solutions in terms of acute biomedical injuries. The theory solutions demonstrate the complexity of possible outcomes following an idealized acute injury and indicate that a “one size fits all” therapy is unlikely to be successful. This conclusion is offset by the fact that the theory can (1) determine if a cell has the possibility to survive given a specific acute injury, and (2) calculate the degree of therapy needed to cause survival. To appreciate these conclusions, it is necessary to idealize and abstract complex physical systems to identify the fundamental mechanism governing the injury dynamics. The path of abstraction and idealization in biomedical research opens the possibility for medical treatments that may achieve engineering levels of precision.

Nonautonomous dynamics of acute cell injury

“…1), but generally present across the entire I-range up to I max , after which the outcome is 100% death. As we discussed previously [52], this provides a more realistic model of acute cell injury.…”

“…( 6) so that they functionally resemble the bifurcation diagram solutions of Eq. ( 3) [52]. At each I, time courses are calculated across ranges of initial conditions (0 < D 0 < D 0,max and 0 < S 0 < S 0,max ) [Fig.…”

“…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.…”