UCLA

UNLABELLED: An engineering perspective views cells as complex circuits that process inputs – drugs, environmental cues – to create complex outcomes – disease, growth, death – and this perspective has immense potential for drug development. Logical rules can describe the features of cells and reductionist approaches have exploited these rules for drug development. In contrast, the reductionist approach serially characterizes cellular components and develops a deep understanding of each component’s specific role. This approach underutilizes the full system of biomolecules relevant to disease pathology and drug effects. An engineering perspective provides the tools to understand and leverage the full extent of biological systems; applying both reverse and forward engineering, a strength of the engineering approach has demonstrated progress in advancing understanding of disease and drug mechanisms. Drug development lacks sufficient engineering specifications, or empirical models, of drug pharmacodynamic effects and future efforts to derive empirical models of drug effects will streamline this development. At this stage of progress, the scientist engineer is uniquely poised to solve problems in therapeutics related to modulating multiple diseases with a single or multiple therapeutic agents and identifying pharmacodynamics biomarkers with knowledge of drug pathways. This article underscores the value of these principles in an age where drug development costs are soaring and finding efficacious therapies is challenging. IMPACT STATEMENT: Many untreated diseases are not monogenic and are instead caused by multiple genetic defects. Because of this complexity, computational, logical, and systems understanding will be essential to discovering novel therapies. The scientist engineer is uniquely disposed to use this type of understanding to advance therapeutic discovery. This work highlights benefits of the scientist engineer perspective and underscores the potential impact of these approaches for future therapeutic development. By framing the scientist engineer’s tool set and increasing awareness about this approach, this article stands to impact future therapeutic development efforts in an age of rising development costs and high drug attrition.