<p>GABA_A and protein hypotheses aside, the lipid theory remains the most influential account of anaesthetic effects in modern pharmacology. An apparent aspect of the lipoidal model’s continued dominance is its long historical pedigree, frequently aligned with a process of steady refinement from Bibra and Harless to Hermann, Pohl, and finally Meyer/Overton. This paper problematizes this continuum by placing the genesis of a short-lived experimental entity—protagon—at the centre of the transition from the fat-solvation theory to the modern lipoidal theory of anaesthesia, which broadly identifies fat as a central mediating substance. A ‘historical ontology’ of protagon and an outline of the 19th century history of brain composition in relation to the early history of anaesthetic pharmacology, it treats the initial appearance of fat-oriented theories of anaesthesia as emergent of the focus on cerebral fat endemic to early 19th century organic principle analysis. </p>