6o8 SCIENCE PROGRESS 



dose is needed to accomplish the result with pituitary than 

 with thyroid — as would indeed be expected from a knowledge 

 of the effects of presumed hyper-function of the two glands 

 upon the basal metabolism in clinical cases. 



Other endocrine glands and tissues of various sorts have 

 so far been found to be without effect. The retarding effect 

 of thymus diet upon metamorphosis is not always elicited, 

 and is probably, as Uhlenhuth has shown, due solely to a 

 deficiency of some substance in the organ. The prostate has 

 been stated to be active, but attempts at repetition have met 

 with failure, or have at best produced slight changes in one 

 or two organs only (15). Many other substances have been 

 tried— muscle, corpus luteum, pineal, liver, gonad, and so on 

 and so forth, some as food and some as injection, but so far 

 without effect. 



The net result of this quaHtative study has been to show 

 that metamorphosis is normally brought about by the secretion 

 of two of the endocrine glands, the thyroid and the pituitary, 

 and of these the thyroid is quantitatively by far the more 

 important. 



With these prolegomena, we can embark upon our main 

 quest. Metamorphosis is caused by thyroid and pituitary. 

 But what causes these to act at one particular moment rather 

 than at another ? Why is it that the common frog normally 

 takes nearly the whole summer to metamorphose, while the 

 American toad is ready in half the time, and the bull-frog 

 spends three seasons in the larval condition ? Why does the 

 Axolotl normally never metamorphose, in spite of being the 

 possessor of a thyroid which, when grafted into a frog-tadpole, 

 will cause precocious metamorphosis ? Why will no amount 

 of combined thyroid and pituitary treatment cause the perenni- 

 branchiate Necturus to transform, while even this species is 

 shown by grafting experiments (29) to possess a physiologically 

 active thyroid ? 



Let us for the moment simplify the problem by considering 

 only the thyroid. The question is then seen to resolve itself 

 into one of time-relations — the time required for the thyroid 

 to develop to a certain stage relative to the rest of the body. 

 The relative nature of the process, the fact that the thyroid 

 is in balance with other tissues, is well shown by various facts 

 concerning geographical races of frogs on the one hand, and 

 the effects of temperature on the other. Adler, for instance (2), 

 took three lots of eggs of the same species of frogs, one from 

 the Adriatic, one from the plains of Germany, and one from 

 the high Alps, and let them all develop at the same tempera- 

 ture. The Alpine larvae metamorphosed first, those from the 

 Adriatic last ; and the difference in metamorphosis-time was 



