THE hypothesis underlying this series of experiments was first formulated by one of us in November, 1920, t while reading an article dealing with the relation of tlte isles of Langerhans to diabetes. 1 From the passage in this article, which gives a résumé of degenerative changes in the acini of the pancreas following lijcntion of the ducts, the idea presented itself that since the acinous. but not the islet tissue, degenerates after this operation, advantage might be taken of this fact to prepare an active extract of islet tissue. The subsidiary hypothesis was that trypsinogen or its derivatives was antagonistic to the internal secretion of the gland. The failures of other investigators in this much-worked field were thus accounted for.

The feasibility of the hypothesis having been recognized by Professor JJE Macleod, work was begun, under his direction, in May, 1921, in the Physiological Laboratory of the University of Toronto.