We may conclude that the feeding of dried thyroid gland to tadpoles causes an early differentiation in proportion to the quantity fed or the percentage of iodine content of the gland used. With the larger doses and the higher iodine percentages, metabolism is stimulated to such an extent that the animals emaciate rapidly and die early, before there is time for much differentiation. With smaller amounts and lower iodine percentages the size of the animals is roughly inversely proportional to the amount or percentage, so that a close association of differentiation with pigmy size is not characteristic of thyroid feeding as such, as Gudenatsch seems to conclude. One may see early and marked differentiation along with large size. It all seems a question of dosage. The larger sizes are associated with slower differentiation, the smaller sizes with more rapid differentiation, and the smallest sizes may show no differentiation at all, due to the extremely rapid and marked emaciation, and early death. Non-thyroid iodine does not have this effect. The thyroid effect is inhibited by exposure to cold and by cracker feeding. Exposure to cold probably acts by lowering metabolism; cracker feeding, by substituting food other than the animal's own tissues to meet the increased demands caused by the stimulating effect of the thyroid feeding.

Gudenatsch in his earlier paper speaks of the thyroid as stimulating metabolism, which leads to early differentiation and suppresses growth. Later he seems to lean to the view that the thyroid possesses some specific influence on differentiation. It may all be a matter of words, but our present conception is that we are simply dealing with the well known action of thyroid on metabolism. As the iodine content increases, the thyroid increasingly stimulates the metabolism of the tadpole, which undergoes changes in size, increased growth or rapid emaciation, according to the strength of the action. The tadpole being a larval form, the tissues first to be stimulated to increased metabolism, and later the first to be consumed, are naturally those tissues whose normal function is approaching a normal end, and which, in the normal course of events, are about to undergo metamorphosis. Hastening of differentiation seems then to ensue not as a specific stimulation of differentiation, but only to be the normal result of the stimulation of general metabolism. The seeming specificity of the result lies not in a new action of thyroid, but in its application to a living organism at a specific time in its development.

Most important, of course, is the confirmation of what we may be justified in regarding as an established fact; namely, that the activity and potency of the physiologically active substance of the thyroid is measurable in terms of its percentage iodine content.

Finally, it may be pointed out that the reaction of tadpoles to thyroid feeding is so sensitive that the procedure might well serve as a biological test for the activity of thyroid tissue, superior even to chemical methods.

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