PES Trivia, at Your Fingertips
These tidbits were originally published in our 2016 President’s newsletters.
December 2016 – submitted by Walter Miller
Bioassays for lactogenic and somatogenic activities were described in the 1930’s, but it took another 40 years to show that GH and Prl are distinct hormones. Frantz and Kleinberg showed that primate GH’s have low lactogenic activity via sensitive bioassays based on prolactin’s ability to induce differentiation and milk secretion in cultured mouse breast tissue (Science 170:7745, 1970). Clinical observation suggested GH and Prl were distinct: men with acromegaly and high serum hGH had very low lactogenic activity; patients with galactorrhea lacked acromegaly; women with GH deficiency had normal lactation post-partum. Niall’s group reported prolactin’s amino acid sequence, ending the debate (Red Progr Horm Res 29:387-416, 1973); distinct, but related GH and Prl genes were cloned in the late 1970s.
November 2016 – submitted by Walter Miller
Nathan B. Talbot (1909-94) created one of America’s first pediatric endocrine programs at the Massachusetts General Hospital (MGH) in 1942. He published a textbook of pediatric endocrinology in 1952, preceded only by Lawson Wilkins’ 1950 text. Talbot’s early work centered on adrenal steroids, refining the colorimetric assay of corticosteroids (J Biol Chem 160:535, 1945) and describing the growth-inhibitory effects of cortisone (NEJM 254:636, 1956). He first described what was later termed ‘the maternal deprivation syndrome’ (NEJM 236: 783, 1947) and with his fellow, Juan Sotos, described cerebral gigantism (NEJM 271:109, 1964). When Talbot became Chief of Pediatrics at MGH (1962-77), he designated John D. Crawford (1920-2005) as chief of pediatric endocrinology (1963-90), who grew the program to international prominence.
October 2016 – submitted by Walter Miller
Stress can inhibit growth. Talbot at MGH reported poor growth secondary to grief or maternal rejection (Am J Dis Child 72:450, 1946; NEJM 236: 783, 1947). Twenty years later, Powell, Brasel and Blizzard at Johns Hopkins expanded on these observations, calling it the ‘maternal deprivation syndrome,’ characterized by ravenous appetite, foraging from garbage cans, drinking from toilets and disordered sleep cycles (NEJM 276:1271, 1967). With Raiti, they noted transiently failed secretion of growth hormone with rapid growth when the child was removed from the dysfunctional environment (NEJM 276:1279, 1967). Such ‘reversible GH deficiency’ in children >2yo is now distinguished from true maternal deprivation syndrome in infancy; both disorders highlight the interactions of stress, hormones and behavior.
September 2016 – submitted by Walter Miller
Cushing syndrome results from glucocorticoid excess from any source, whereas Cushing Disease results from ACTH-producing pituitary adenomas. Harvey Cushing (1869-1939) famously described his eponymous disorder as “The Basophil Adenomas of the Pituitary Body and Their Clinical Manifestations: Pituitary Basophilism” (Bull Johns Hopkins Hosp 50:137-195, 1932), but failed to appreciate the role of the adrenal. Fuller Albright correctly deduced that ‘hyperadrenocorticism’ caused Cushing syndrome, hypothesizing that ‘’those patients with Cushing’s syndrome, who do not have adrenal cancer, have hyperadrenocorticism because of over-production of some pituitary corticotropic hormone’ (J Clin Endocrinol 1:375-384, 1941). ACTH was purified and sequenced by CH Li (Nature 176 687–689, 1955) and shown to derive from a large precursor (POMC) by Nakanishi (Nature 278 423–427, 1979)
August 2016 – submitted by Walter Miller
The most important discovery in biology since the discovery of cells by Robert Hooke (1665) was the discovery that DNA is the genetic material. Watson and Crick famously discovered the double helical structure and base-pairing of DNA (Nature 171:737, 1953; Nature 171:964, 1953), but credit for the discovery that DNA conveyed genetic information belongs to Oswald T. Avery (1877-1955). Frederic Griffith reported in 1928 that the pneumococcal serotypes could be ‘transformed’ by dead bacteria. Avery, MacLeod and McCarty showed that the transforming fraction was DNA (prepared by ethanol precipitation, still used today), and not proteins (J Exp Med 79:137, 1944). Avery is arguably the most deserving medical scientist not to receive a Nobel Prize, despite multiple nominations.
July 2016 – submitted by Walter Miller
In 1865, Luigi De Crecchio, a forensic pathologist in Naples, described the autopsy of Giuseppe Marzo, who lived as a man and had Tanner IV genitalia, but had female internal reproductive organs and massively enlarged adrenals (Il Morgagni 7:151, 1865). De Crecchio dismissed the adrenal hyperplasia as being unrelated, and considered that Marzo had a disorder of puberty. De Crecchio interviewed people who knew Marzo to understand his life, emphasizing his social difficulties functioning as a male. This first report of congenital adrenal hyperplasia illustrates that despite advances in the endocrinology and genetics of CAH, the psycho-social aspects have advanced less. A complete translation and discussion of De Crecchio’s paper was published last year by Delle Piane et al. (Endocrinology 156:1210, 2015).
June 2016 – submitted by Arlan Rosenbloom
Since the first demonstrations that purified GH from human pituitaries possesses lactogenic activity in 1961, efforts had been made to isolate a human prolactin separate from GH. Frantz and Kleinberg reported their highly sensitive bioassay differentiating GH and prolactin in unextracted human plasma in Science in 1970 (Prolactin: evidence that it is separate from growth hormone in human blood. 170:745-7)
May 2016 – submitted by History Committee
‘Sex chromatin’;, first described by ML Barr (Nature 163:676, 1949), became known as the ‘Barr body’; and was used to establish sex via buccal smear cytology. Independent studies by Mary Lyon (Nature 190:372, 1961) and by Mel Grumbach & Akira Morishima (Acta Cytologica 6:46, 1962) showed that sex chromatin was an inactivated X chromosome. Grumbach’;s paper, contributed to the proceedings of a Symposium on Sex Chromatin, is listed as having been received on October 25, 1960, but publication was delayed for over a year. Morishima, Grumbach and Taylor showed that the inactivated X replicated after the active one (PNAS 48:756, 1962). Inactivation of an X chromosome became known as ‘Lyonization’;, in part because no one could say ‘Grumbachianization’;.
April 2016 – submitted by History Committee
The growth promoting activity of crude anterior pituitary extract was first reported in 1921, by Evans and Long from the University of California (Anat Record 21:62-63). They injected the extract into the peritoneal cavity of 38 rats, at an undisclosed frequency beginning at 14 days of age. The animals were followed for 60 days with weight measurements every five days. Weight at 75 days for the experimental animals was 228 g and for the littermate controls 183 g. Twenty-four years later Li and associates (including Evans) isolated and characterized the hormone responsible for this effect (J Biol Chem 159:353-366).
March 2016 – submitted by History Committee
That chlorothiazide could increase the urine concentration of normal subjects in the midst of a sustained water diuresis was reported in 1958 (Laragh et al. Effect of chlorothiazide on electrolyte transport in man JAMA 166:145-152). The effective application of this observation to 2 subjects with diabetes insipidus, one central and one nephrogenic, was described the following year in Nature (Crawford JD, Kennedy GC: Chlorothiazide in diabetes insipidus. 183:891-2).
February 2016 – submitted by History Committee
In 1958, before the development of radioimmunoassay for GH, Laron and colleagues evaluated 3 siblings with marked growth retardation from a recently immigrated consanguineous Yemenite Jewish family. When GH assay became available in 1963, the children were found to have, apparently paradoxically, elevated GH levels, reported in 1966. (Z. Laron, A. Pertzelan, S. Mannheimer. Genetic pituitary dwarfism with high serum concentration of growth hormone. A new inborn error of metabolism? Isr. J. Med. Sci., 2, pp. 153-155)
January 2016 – submitted by History Committee
The initial attempt to determine the frequency of congenital adrenal hyperplasia (CAH) in the US was by Child, Grumbach, and Van Wyk in 1956 (Virilizing adrenal hyperplasia; a genetic and hormonal study. JCI 1956; 35:213-222). Assuming that all CAH came to Hopkins, and comparing to all live births from Maryland during the years the patients were born, they estimated the frequency of 1/67,000. Using a comparable assumption for the referral area to the University of Wisconsin, Rosenbloom and Smith calculated a minimal incidence of 1/15,000 live births (Lancet 1966;1:660), very similar to subsequent incidence rates based on infant screening programs.