I am greatly honoured by the invitation to give this Lecture, within a mile of the site of Thudichum's private laboratory and about 100 years after his last report to the Privy Council on his research on the brain (Thudichum, 1874). His investigations extended much beyond cerebral systems, which occupied some 16 years of an extremely busy scientific life. For Thudichum was a pupil of Liebig, was also a clinician, had held academic posts, and had carried out effective work on chemical constituents of urine and bile before working on the brain (see Drabkin, 1958; McIlwain, 1958a, b). After the 16 neurochemical years, he turned abruptly to other subjects. Thudichum's work on the brain sought the solution of major medical problems of his times: the deliria and coma of infectious diseases, especially of the fevers, and especially of cholera. He quite specifically sought to understand and control such deliria by chemical investigation of the brain. He was given good and for his time quite exceptional support from public funds to do this, and had assistants working with him. Thudichum found that not sufficient was known about cerebral chemistry, and set about making good the lack of knowledge. This became an end in itself, so that he concluded his preface to the book (Thudichum, 1884) in which he gives the major report on his work on the brain, with an often-quoted statement about needing to 'know the normal chemistry (of the brain) to its uttermost detail' before devising means of therapy. We may, now, smile at the 'uttermost', but we can welcome Thudichum's overwhelmingly correct view that material investigation of the brain necessarily involves chemical isolation, characterizationand measurement of its constituents. Such was the great thing Thudichum knew, and practised. I use this phrase in the following context : 'The fox knew many things, but the hedgehog knew one great thing' and rolled up accordingly, spikes exposed and impervious. For Thudichum was a prickly character and much, including probably these eponymous lectures, has followed from that characteristic. Isolates I: Chemical Constituents Thudichum's work on the brain is indeed all about isolating materials and their chemical characterization, which is why I have chosen to talk about cerebral isolates, beginning with Thudichum's type and proceeding to two others (Table 1). It is to be emphasized that Thudichum obtained his isolates in a particular way: particular both in its chemical detail, which was necessarily of his time, and also in its methodological approach, whichwas not. Heextracted, fractionatedandcrystallized to obtain substances of constant composition and properties, within the limits then available. He organized his results to give a highly schematic manner of presentation, as indicated by Table 2. Curiously, as may be noted from Table 2, Thudichum called his isolates 'principles'.