cerebral vesicle. Until recently the pituitary body has been inaccessible to surgeons and to physiological experimenters by reason of its encasement in the sella turcica of the sphenoid bone. Experimental removal of the pituitary (hypophysectomy) was essayed by Horsley (1886), Marinesco (1892), Vassale and Sacchi (1892-4), Gatta (1896), Biedl (1897), von Cyon (1898-1900) and others, with negative or contradictory findings, resulting no doubt from the difficulties encountered in approaching the gland through the skull and of insuring its entire removal under these conditions. In 1908, an important advance was made by Nicholas Paulesco of Bucharest, who devised an operation by the temporal route and showed that the pituitary body is essential to life, its removal being fatal to the animal. At the same time, he found that removal of the anterior lobe is equivalent to entire removal and that excision of the posterior lobe is negative. Paulesco's experiments were put to the test by Harvey Gushing, now professor of surgery at Harvard, and his associates at the Johns Hopkins Hospital, their experiments being performed mainly upon dogs. They found that total removal or removal of the anterior lobe alone are alike fatal, the animal dying in three days with a peculiar train of symptoms consisting of lowered temperature and blood pressure, sluggishness, unsteady gait, rapid emaciation, slowing of pulse and respiration, diarrhœa, diminished urine in adults; polyuria and glycosuria in puppies. Partial removal of the anterior lobe in normal dogs was found to produce a pronounced state of obesity, with a remarkable shrinkage of the external (male) genitalia. In other words. Gushing produced, by experiment, a genuine pathological reversion to the condition known as sexual infantilism or "dystrophia adiposo-genitalis" (Fröhlich's syndrome). In the case of the posterior lobe, which, as shown by Gushing and Goetsch, discharges its secretion into the cerebro-spinal fluid, partial removal or the production of insufficiency of the secretion by putting a clip upon the stalk of the gland, produces, at first, a temporary lowering of the animal's assimilation-limit for sugars, followed by a marked and permanent increase in its tolerance for carbohydrates, which is again promptly lowered by injection of an extract of the posterior lobe. In 1895 Oliver and Schäfer found that the mammalian pituitary possesses an active principle which, upon injection, elevates the blood pressure and increases the force of the heart beat. In 1898 Professor William H. Howell, of the Johns Hopkins University, showed that this property is possessed by the extract of the posterior lobe alone. In his Harvey Lecture of December 10, 1910, Gushing introduced the pathological idea of "dyspituitarism" or perverted function of the gland, as a generic concept, covering excess or insufficiency of its function, and for the following reasons. In accordance with the clinical and pathological findings of Parry, Graves and Basedow, exophthalmic goiter was regarded as a state of "hyerthyroidism," or excessive secretion of the gland, while the myxœdema of Gurl-
