that this transformation, by which insoluble and non-diffusible proteid matter was converted into a soluble and diffusible product, was a form of hydration, comparable to the change of insoluble starch into soluble sugar, and he named the hypothetical product albuminose. Mialhe’s study of the matter in 1846 was followed by Lehmann’s15 investigation of the subject, and the coining of the word peptones as an appropriate name for the soluble products of gastric digestion. The peptones isolated by Lehmann were described as amorphous, tasteless substances, soluble in water in all proportions and insoluble in alcohol. They were likewise precipitated by tannic acid, mercuric chloride, and lead acetate, and were considered as weak acid bodies, having the power of combining with bases to form salts of a more or less indefinite character. Twelve years later, in 1858, Mulder16 gave a more complete description of peptones, but his study of the subject failed to advance materially our knowledge of the broader questions regarding the nature of the process, or processes, by which the so-called peptones were formed. A year later, in 1859, Meissner17 brought forward the first of his contributions, and during the following three or four years several communications were made representing the work of himself and pupils upon the question of gastric digestion, or more especially upon the character of the products resulting from the digestive action of pepsin-hydrochloric acid.

The general tenor of Meissner’s results is shown in the description of a row of products as characteristic of the proteolytic action of pepsin-acid on proteid matter. In other words, there was a clear recognition of the fact that proteid digestion in the stomach, through the agency of the ferment pepsin, is something more than a simple conversion of the proteid into one or two soluble products. The several bodies then isolated were named parapeptone, metapeptone, dyspeptone, α, β, and γ peptone; names now seldom used, but significant as showing that at this early date there was a full appreciation of the fact that digestive proteolysis as accomplished by the ferment pepsin is an intricate process, accompanied by the formation of a series of products which vary more or less with the conditions under which the digestion is conducted.

This was the commencement of our more modern ideas regarding digestive proteolysis, but only the commencement, for it ushered in an era of unparalleled activity, in which Brücke, Schützenberger, and Kühne each contributed a large share toward the successful interpretation of the results obtained. Further, knowledge regarding the proteid-digesting power of the pancreatic juice was rapidly accumulating, thus broadening our ideas regarding digestive proteolysis in general. Corvisart18 had called attention to the proteolytic power of the pancreatic juice in 1857, and although his observations were more or less generally discredited for a time, they were eventually confirmed by Meissner,19 Schiff, Danilewsky,20 and Kühne,21 the latter particularly contributing greatly to the development of our knowledge concerning this phase of digestive proteolysis. The proteolytic power was proved to be due to a specific ferment or enzyme, now universally called trypsin, which digests proteid foods to the best advantage in the presence of sodium carbonate. Digestive proteolysis in the human body was thus shown to be due mainly to the presence of two distinct enzymes, the one active in an acid fluid, the gastric juice, the other in an alkaline-reacting fluid, the pancreatic juice, but both endowed with the power of digesting all varieties of proteid foods, with the formation of a large number of more or less closely related products.

So much for the early history of our subject, and now, without attempting any exhaustive sketch of its gradual development during the last decade and a half, allow me to present to you digestive proteolysis as it stands to-day, developed somewhat, I trust, by the results I have been able to contribute to it during the last twelve years.

THE GENERAL NATURE OF PROTEOLYTIC ENZYMES.

These peculiar bodies owe their origin to the constructive power of the gland-cells from which the respective secretions are derived. During fasting, the epithelial cells of the gastric glands and of the pancreas manufacture from the cell-protoplasm a specific zymogen or ferment-antecedent, which is stored up in the cell in the form of granules. These granules of either pepsinogen or trypsinogen, as the case may be, are during secretion apparently drawn upon for the production of the ferment, and it is an easy matter to verify Langley’s22 observation that the amount of pepsin, for example, obtainable from a definite weight of the gland-bearing mucous membrane is proportionate to the number of granules contained in the gland-cells. During ordinary secretion, however, these granules of zymogen do not entirely disappear from the cell. When secretion commences and the granules are drawn upon for the production of ferment, fresh granules are formed, and inasmuch as these latter are produced through the katabolism of the cell-protoplasm it follows that anabolic processes must be simultaneously going on in the cell, by which new cell-protoplasm is constructed. Hence, as Heidenhain, Langley, and others have pointed out, during digestion there are at least three distinct processes going on side by side in the gland-cell, viz., the conversion of the zymogen stored up in the cell into the active ferment, or other secretory products, the growth of new cell-protoplasm, and the attendant formation of fresh zymogen to replace, or partially replace, that used up in the production of the ferment. Consequently, we are to understand that in the living mucous membrane of the stomach there is little or no preformed pepsin present. Similarly, the cells of the pancreatic gland are practically free from the ferment trypsin. In both cases the cell-protoplasm stores up zymogen and not the active ferment, but at the moment of secretion the zymogen is transformed into ferment and possibly other organic