The System as Target: Rethinking Pharmacologic Assays
A fundamental problem in the development of novel therapeutic agents and the ongoing monitoring of approved drugs is assessment of their safety and efficacy. Current methods for evaluating both efficacy and toxicity largely fail to account for the effects on integrative physiologic function. Therefore, a need exists to develop systems-based technologies that can provide a more efficient and cost-effective method for evaluating the safety and efficacy of drugs and other therapeutic interventions. This talk will discuss, in the context of complex nonlinear systems, a novel approach that provides a way to assess drugs and other therapies by measuring their effects on integrative physiologic dynamics. This approach is based on the discovery that pathologic and other maladaptive states are characterized by loss of information (for example, less complex variations between heartbeat intervals). On the other hand, information-rich states (exemplified by more complex, multiscale variability in heartbeat intervals) are consistent with healthy, adaptive function. Interventions that enhance system complexity, therefore, are likely to be associated with positive therapeutic effects; and those degrading system complexity are likely to be associated with adverse effects, which may escape detection by conventional assessments and models based on classical homeostasis.