In certain areas of Paraguay there is found a small wild shrub of the composite family known locally as Kaá hé-é which, because of the remarkable sweetness of its leaves, has been the object of botanical, physiological, and chemical investigation for many years. Initially named Eupatorium Rebaudianum by Bertoni in 1899 (1), this relatively rare plant was later recognized by him as belonging to the genus Stevia and was given the name Sterna Rebaudiana Bertoni (2) which it still bears.3 Cultivation of the plant has been carried out in Paraguay both as a horticultural curiosity and on a larger scale but the latter is expensive since the seed is usually sterile and reproduction must be made by subdivision. Chemical investigation of the plant may be said to have begun in 1908 with the work of Rasenack (4) who extracted the leaves with hot alcohol and obtained a crystalline glycoside which, on acid hydrolysis, afforded a second crystalline product. However, the physical constants and analytical values reported for these substances leave their nature still in doubt. In the following year Dieterich (5) extracted the leaves and twigs with water and obtained two fractions: (a) a crystalline, alcohol-soluble part named eupatorine and (b) an amorphous, alcohol-insoluble part, designated rebaudine. Neither was adequately characterized and it was not until 1931 that real progress in this field was made. In that year Bridel and Lavieille (6) reinvestigated S. Rebaudiana and, through aqueous alcoholic extraction of the leaves, obtained a pure, crystalline glycoside which proved to be some 300 times as sweet as sucrose and thus was (and still is, to the authors' knowledge) the sweetest natural product and the only non-nitrogenous or carbohydrate-containing substance of high sweetening power yet discovered (7). The glycoside, named by these authors stevioside, was found to form a hydrate of indefinite composition, its water content varying with atmospheric moisture. While the substance was unattacked by emulsin, rhamnodiastase, air-dried brewers' yeast, and powder of Aspergillus niger, hydrolysis with 5% sulfuric acid at 100°afforded a crystalline non-sugar product, presumed to be the aglucon, and crystalline n-glucose as the only sugar component. In a succeeding paper (8) the same authors reported the successful enzymatic hydrolysis of stevioside using either the digestive juice or hepato-pancreatic juice of the vineyard snail (escargot; Helix pomatia). However, while the sugar thus liberated
