Coagulation, flocculation, and denaturation: a century of research into protoplasmic theories of anesthesia.

Abstract

Within two decades of the discovery of anesthesia, the physicochemical concept of colloid and the biological concept of protoplasm had emerged. Fusion of these concepts into a theoretical framework, which has been largely forgotten decades ago, promised to uncover fundamental biological truths and determined research into anesthetic mechanisms for a century after "Ether Day." Observations of optical changes in unstained tissue were condensed into a theory of anesthesia by coagulation of protoplasm in the 1870s. The underlying hypotheses, conformational changes of proteins within the protoplasm cause all behavioral effects of anesthesia, continued to be pursued well into the 20th century. The goal was to explain anesthesia using physical chemistry within a fundamental cell biological framework. This large body of work, swept aside during the decades of lipid membrane hegemony, has remained in obscurity even after proteins in excitable membranes became firmly established as mediators of the immediate anesthetic effects. This article is a reminder of the prolonged interdisciplinary research effort dedicated to "protoplasmic theories" at a time when attention is increasingly directed toward examining the nature of (un)consciousness well as noncanonical consequences of anesthetic exposure that are not easily accounted for within conventional pharmacological concepts.