Abstract
The Van Meter Prize Award is named for Seymour Doss Van Meter, M.D. (1865–1934), who in 1923, along with his wife, Dr. Virginia Van Meter, and “Dr. H.S. Plummer,” was one of the 26 charter members of the American Association for the Study of Goiter (AASG) (2). The AASG was incorporated as The American Goiter Association on November 23, 1959, and on October 10, 1973, its name was officially changed to The American Thyroid Association (3).
Van Meter, whose life has been chronicled by Dr. James Magner (4), was a leader in the AASG well before he conceived the award that bears his name. The year after the formation of the AASG he was selected to chair the AASG's committee on Goiter Classification and Nomenclature, probably its most important scientific endeavor of the time. The committee's report, based on consultation with “American Clinic Groups and European authorities” (2) took 5 years to complete but became an influential document in clinical practice and, even in those days, was used by insurance companies to guide their reimbursement practices. The principles of goiter classification accepted by the AASG in 1930 were anatomical and functional. Among the four classifications, goiters were stated to be either diffuse or nodular and, within those categories, nontoxic or toxic (2).
In 1929 Dr. Van Meter became President of the AASG. It is likely that his work on goiter made him uncomfortably aware of the primitive knowledge in this field. Accordingly, as detailed by the AASG's 1936 president, J. Rudolph Yung, “in 1930 and also a few subsequent years, he provided a $300 cash prize award, to be given the essayist presenting the best work on the subject of: Goiter—Especially Its Basic Cause” (2). As Yung goes on to say, “His modesty and sincere desire to avoid any semblance of personal publicity prompted him to forbid two or three officers of the Association, who were necessarily familiar with his gift, to associate his name with it in any way whatsoever. After his death, however, the Association in recognition of his sturdy qualities, his honesty of purpose, and his contribution of the original idea, honored him by continuing the contest annually and calling it the ‘Van Meter Prize Award’” (3). As the records of the AASG attest, Dr. Van Meter's request was honored during his lifetime. For example, in 1933 the citation that Anne M. Heyman, A.B., M.S., received for her study “The Bacteriology of Goiter and the Production of Thyroid Hyperplasia in Rabbits on a Special Diet,” referred only to the “Committee on Prize” (2).
While the terms of the Van Meter Prize Award have evolved over the years its intent has not. This is to recognize fresh, focused, and pioneering research in thyroid physiology. All of these attributes are contained in Dr. Shi's review (1) entitled “Dual Functions of Thyroid Hormone Receptors in Vertebrate Development: The Roles of Histone-Modifying Cofactor Complexes.” It is obvious from this title and those of other prize winners that the award is no longer confined to studies of goiter.
Though Dr. Shi's studies do not deal with goiter, they obviously are a substantial advance compared to the earliest ground-breaking research in this field that occurred during World War I when Van Meter was serving in the Medical Reserve Corps (4). Thus it was from 1914 to 1917 that several papers (5 –9) were published establishing the critical role of the hypophysis in maintaining thyroid function and tadpole metamorphosis. These relied on surgical prowess to prepare the model. Dr. Shi, in contrast, uses molecular biology to dissect components of thyroid hormone–dependent anuran metamorphosis. Current readers of the biological literature have little doubt that the transgenic methods employed by Dr. Shi and modern science mimic, in a more specific way, the early endocrine extirpation methods. “Transgenic thyroidectomy,” so to speak, is a technological tour de force. Performing a hypophysectomy on an organism only a little more than a tenth of an inch in length, as was done by Smith (7), is perhaps just as impressive.
In this issue we have chosen to present Dr. Shi's review (1) in juxtaposition with one of the important early papers dealing with thyroid dependency on the pituitary, and the dependency of tadpole metamorphoses on the thyroid. This is not only so the reader appreciates the striking advances of the past century, but also to renew the Thyroid's commitment to a historical understanding of how knowledge and concepts develop. A detailed comparison of Dr. Shi's review with earlier studies will not be attempted. Likely, it will be done better by readers. Accordingly, please see Dr. Shi's review on page 987 and Philip E. Smith's 1916 paper “Experimental Ablation of the Hypophysis in the Frog Embryo” (7) reprinted in its entirety below.* The parts most interesting to thyroidologists are presented in bold.
Special Articles
Experimental Ablation of the Hypophysis in the Frog Embryo
In the following preliminary paper the effect of the extirpation of the epithelial portion of the hypophysis upon the subsequent growth and development of tadpoles is summarized. The work was first attempted in 1914, Diemyctylus torosus being used, repeated in 1915 upon Rana pipiens, and again repeated in 1916 upon Rana boylei. In this paper the results obtained with R. boylei are reported.
The operation was most successfully carried out upon approximately 3 mm. larvae, at which time the tail-bud is forming and the stomadeum can be detected. At that stage the epithelial hypophysial invagination can be accurately determined from the pit that it forms, or from its location between the protuberance of the forebrain and the stomadeum, and can be removed without injury to the adjacent brain. This epithelial ingrowth was removed with some neighboring epithelium. The wound healed within three hours, less than 1 per cent. of the larvae disintegrating after the operation. About 200 larvae of the 3 mm. stage were operated upon, the hypophysis being successfully removed in over 60 per cent. of the cases. Approximately 30 per cent. of those animals in which the gland was extirpated did not give reliable results in the rate of growth as the mouth was wholly or partially removed thus interfering with feeding. For checks, unoperated specimens and those in which the ablation of the gland was unsuccessfully attempted were available. The operated animals and checks were kept in boiled water for five days and then transferred to a frog tank where they were in an essentially normal environment.
The hypophysis-free animals grew more slowly than the normal controls. No hypophysectomized animals reached the size of the largest checks and the averages of the two show a noticeable difference. On June 6 the operated but not hypophysectomized animals had an average length of 40–43 mm., the hypophysis-free animals averaging 33–35 mm. A ratio such as this prevailed throughout their growth. The ratio of body to tail length is the same in the two classes, the differences in size being uniform for all parts of the animal.
Differences in color began to be noticeable at an early stage. From then on the contrast in pigmentation between the hypophysectomized animals and the checks was striking. Those animals without a hypophysis had a slightly darkened silvery appearance of almost uniform character; however, the dorsal side was more pigmented than the ventral. These are referred to as albinos. The checks were a brown-black color often showing a mottling. This color difference was more noticeable over the body than on the tail, but was evident in both regions and was the most striking feature up to the time when the hind legs began to appear in the checks. Sections show that in the albinos the epidermis is pigment-free while that of the checks is filled with it. The subcutaneous pigment is present in the albino in as great a quantity if not greater than in the normal animal. The retinal pigment appears to be the same in both.
The hind leg buds appear, normally, when the tadpole has reached a length of 25–27 mm. In the albino the hind limb buds appear but slightly later than in the checks or when they are from 26–28 mm. in length. From this stage on, however, the hind limbs in the hypophysectomized animals grow but little if at all, although their total length increases at a rate but slightly under the normal one. For instance in 28 mm. checks the hind legs average 1.0 mm.; in 30 mm. checks 2.0 mm.; in 38 mm. checks 4.0 mm. In the albinos of each of the above sizes and ages the hind legs were 0.1 mm. long. The above is in accord with Adler (’14),† who found that the removal of the hypophysis in a 20 mm. stage inhibited the growth of the hind legs.
Sections of the albino and normal animals show striking contrasts in the organs. Of the specimens yet sectioned none described above as albino or hypophysectomized have had a trace of the anterior lobe of the hypophysis present. Thus it is certain that the entoderm has not the intrinsic power to form a hypophysis, but that if it enters into the formation of the gland at all it must be considered as a tissue inclusion which may become changed through its adaptability into glandular parenchyma, a conclusion previously drawn by the writer Smith (’14).‡ Comparison with the checks shows that the infundibulum undergoes structural modifications, although the saccus vasculosus, as far as determined, appears to be normal. In the checks that region of the diencephalon which rests against the pars glandularis is of considerable thickness, having in addition to the ependyma a rudimentary pars nervosa. Caudad to this the wall is formed almost entirely of ependyma. In the hypophysectomized animals the pars nervosa is reduced throughout most of its extent to an ependymal layer. Small localized thickenings may occur but nothing corresponding to the normal animal.
An examination of the gonads shows significant size differences between the normal and albino specimens. In the hypophysectomized animal the development of the sex glands is apparently much retarded and the size correspondingly reduced.
The author in a later and more complete account will describe any changes which may be found in the other endocrine glands and treat of the progressiveness of the changes noted.
Footnotes
Acknowledgments and Notes
Grateful acknowledgment and thanks are made to Ms. Barbara R. Smith, Executive Director of the ATA, for her analysis and retrieval of archival material concerning the AASG and Dr. Seymour Van Meter. Some information for references 3–6 was obtained from Spaul (
). Some early journal names are no longer in use or may now be used by other journals.
*
Reproduced with permission and with credits to Science Journal and New Scientist (Lacon House, 84 Theobald's Road, London, WC1X8NS,
‡
Smith, P.E., “The Development of the Hypophysis of Anima calva,” Anat. Rec., Vol. 8, 1914.