As several enzymes act readily in neutral or slightly alkaline fluids, it is evident that if they existed free in every part of the animal body, they would soon lead to its speedy destruction. Accordingly, we find that they do not normally exist free, except at the times and places they are required.

This fact was first discovered by Kuhne in relation both to the stomach and pancreas, and was announced by him in the course of lectures which he delivered at Amsterdam in 1868-69, which I attended. In my note-books of those lectures I find that he stated that there seems to exist 'a pepsin-giving substance,' because if a 'slice of stomach is thrown directly into dilute HC1 of 4 parts to 1,000 of water at 40° C. no digestion takes place,' l a fact which shows that pepsin is not always present in it. In regard to the pancreas, he not only recognised the existence of a ferment-yielding body, but described a mode of obtaining ferment from it in the following words : - 'Glands which have no action on fibrine can be made active by digesting in very dilute acid and then neutralising or alkalising, there seeming to exist a ferment-forming substance in the pancreas.'

Kuhne's discovery of the existence of ferment-yielding bodies does not seem to have become widely known, and it was again made independently by Liversedge 2 in regard to the amylolytic ferment of the pancreas, and by Heidenhain in regard to trypsin. These observers found that when glands which did not contain ferment were exposed to the air ferments were formed.

Heidenhain3 also investigated more fully these ferment-forming substances, and gave to them the name of zymogens.

The methods by which we obtain ferments from zymogens are, therefore, exposure to air and treatment with acids.