The story of the discovery of the function of the suprarenal capsules, followed by the isolation of the active principle of their secretion, the determination of its structure, and its subsequent synthesis, forms one of the most fascinating chapters in the history of bio-chemistry. The suprarenal capsules are two epithelial flattened bodies situated above the kidneys, each weighing about 4 grammes. Although known from early times, no suspicion was entertained of the important role which they play in the life of the individual, until experimental investigation of these glandular organs was initiated by the work of Addison published in 1855. He described a form of disease which is nearly always fatal, and is characterised by progressive anaemia, weakness of heart-beat, irritability of stomach, and general want of tone of the nervous and muscular system, together with abnormal brown patches on the skin, from which latter symptom he gave it the name bronzed skin. As the result of extensive research Addison discovered profound alterations of various kinds in the suprarenal capsules of almost everyone who had died of this disease. Following Addison's lead Brown-Sequard made a series of experiments on animals in 1856, and came to the conclusion that the suprarenal capsules were organs indispensable to life, and that their destruction was invariably followed by death. This view, however, aroused opposition, and the subject remained a matter of controversy until recently, when Brown-Sequard's results have been fully confirmed and extended. In 1891-2 Abelous and Langlois inferred that death from removal of the suprarenals is due to the accumulation in the blood of some toxic substance. It had been shown in 1890-1 by Marino-Zuco and Dutto that the suprarenal capsules normally contain a considerable amount of neurine, and that persons suffering from Addison's disease eliminate appreciable quantities of this substance. In the following year Albanese found that a dose of 1 milligram of neurine is always fatal to a decapsulated frog, while it takes four times that amount to kill one in the normal condition. From these results Marino-Zuco and Albanese concluded that Addison's disease and the effects of artificial destruction of the suprarenals are due to neurine intoxication. The work of numerous other experimentalists leaves no doubt as to the protective antitoxic action of the suprarenal capsules, though it is uncertain whether this is effected by removal of specific toxic substances, or by the secretion and output into the blood and lymph of active substances which are directly or indirectly antitoxic. It was proposed by Cybulski in 1895 that the effect of the compounds secreted by the capsules is to keep up the tone of the vasomotor, cardiac, and respiratory centres which are so acutely depressed by the destruction of these glands. He showed that intravenous injection of aqueous suprarenal extract raises arterial pressure, slows the pulse, and quickens respiration. These results were confirmed by Salvioli and Pezzolini in 1902. More recent work leads to similar conclusions, and as stated by Hoskins in 1915, The sum total of available evidence seems to indicate that the essential feature of adrenal deficiency is an interference with fundamental metabolism, possibly oxidation, in which the more active tissues of the body suffer first. The discovery of the physiological action of the substance, or substances, secreted by the suprarenal capsules led to attempts to effect their isolation. In 1896 Frankel obtained an impure substance which he termed sphygmogenine, and one year later Abel and Crawford prepared epinephrine. In 1900 v. Furth obtained a similar body under the name of suprarenin. By isolating adrenalin in the crystalline form in 1901 Takamine proved the former substances to be mixtures. Shortly afterwards Aldrich independently prepared the pure substance. Takamine proposed the formula [C. …