Contributions to the biochemistry of iodine and the thyroid and related problems

In 1911 Professor Swale Vincent suggested to me that I should attempt to determine whether iodine is invariably present in the thyroid gland. Reference to the ;` first edition of his book on "Internal Secretion and the Ductless Glands" (1912) showsthat at that period the question was by no means decided. He writes (page 314) "Iodine is not invariably present in the thyroid gland ", and (page 318) "It has been stated .... that iodine is not always present in the thyroid gland, and that animals whose thyroid are devoid of iodine do not manifest any signs of ill- health."thyroid are devoid of iodine do not manifest any signs of ill- health." In a series of papers (1913 -15) 1 demonstrated that iodine is an invariable constituent of the normal thyroid gland, and investigated its distribution in mammalian tissuesand in marine species (flora and fauna). From 1915 -19 these iodine studies were interrupted by the European war. During this period Kendall completed his isolation of thyroxin, work commenced in 1911, thus taking a long step towards the solution of the problem of the function of the thyroid.In 1919 I commenced to study the effect of thyroid on growth and the hypertrophy of certain body organs. At that time experimental evidence dealing with the effect on growth was conflicting, but Hoskins had drawn attention in 1916 to the production of hypertrophy of liver, kidneys, heart, adrenals and other organs by thyroid feeding, and had shown that this was due to thyroid specifically; His work had been con firmed by Herring and others.Using young rats as test animals I was able to show that the feeding of thyroid diminished the rate of growth, and confirmed Hoskins and Herring as to the production of organ hypertrophy. The effect appeared to be greater with thyroids of greater iodine content, and since i, showed further that it was not produced by iodides (Hoskins had demonstrated that many of the other internally secreting glass were inactive from this point of view, and later I showed that parathyroids were inactive) I suggested that the double effect might be employed as a test for thyroid activity.Testing thyroxin in this way, I demonstrated that it produced, qualitatively, the same effect as desiccated thyroid tissue, but quantitatively, on basis of equal iodine content, the effect appeared to be definitely smaller. This I thought possibly due to bacterial decomposition of thyroxin in the rat's intestine. Reid Hunt, however, in 1923, demonstrated by his acetonitrile test that thyroxin, whether fed or injected, does not produce the quantitative effect of thyroid of the same iodine dose-value.During the past three years I have endeavoured to apply the growth and organ hypertrophy test more rigidly, comparing different thyroids, thyroglobulin, thyroxin, and various thyroid fractions. The results indicate that the method has definite limitations, and that a number of comparisons of each substance are necessary before reasonably definite conclusions may be drawn.I have also, from time to time, attempted to contribute to the solution of various cognate problems, as opportunity permitted.Since much of this wank is already published, and since in a field of such magnitude as the biochemistry of iodine and the thyroid the work of one individual must of necessity be closely intertwined with, and modified from time to time in its aim and extent by the published results of other investigators, I have endeavoured in the following pages to present very briefly in its proper perspective my own work in relation to the whole subject, and have added the details of this work, published and unpublished, in a series of appendices