Constitutive Control: How Experimental Control Strategies Co-Evolved with Biological Knowledge in 19th-Century Physiology

Abstract How do different experimental control strategies shape the production of biological knowledge? This paper examines Emil du Bois-Reymond’s electrophysiological investigations and Claude Bernard’s toxicological research in 19th-century physiology. Rather than viewing these as opposing methodologies, I analyze their approaches to nerve-muscle communication as complementary responses to shared epistemic challenges. Using Schickore’s framework for experimental control (2025), I show through a detailed historical analysis that experimental control functioned constitutively rather than merely technically in both research programs. Both scientists engaged in extensive second-order experimentation, systematically exploring their experimental setups to determine what factors needed controlling. Du Bois-Reymond’s non-polarizable electrodes made possible new ways of understanding biological electricity as quantifiable phenomena, while Bernard’s ligature preparation constituted a method for understanding physiological functions as systematically separable within integrated organisms. Control practices and theoretical commitments co-evolved such that what counted as legitimate operationalization of theoretical principles was shaped by experimental practice. This analysis shows how experimental methodology and biological knowledge co-develop, suggesting implications for understanding methodological tensions in contemporary biological research.