Independently of Bartholin and Rudbeck, George Joyliffe (1621-58) observed the lymphatics. He communicated his discovery to Glisson early in 1652 and the latter included an account in the above work (Cap. xxxi). See No. 972. Includes a description of “Peyer’s patches”, the lymphoid follicles in the small intestine which have an important role in typhoid. They were first described by J. N. Pechlin (1644-1706) in his De purgantium medicamentorum facultatibus exercitatio nova (1672).

Nuck’s name has been attached to the glands and duct described by him.

Hewson gave the first complete account of the anatomical peculiarities of the lymphatics. He divided the lymphatics into two groups – superficial and deep. He described the leucocytes as derived from the lymphatic glands and thymus.

"Hewson's studies of the lymphatics are models of skill and ingenuity. He studied them in vitro and in vivo (observing them through a hand‐held magnifying glass in the web of a frog's foot). Disproving the current theory, he showed that the lymphatics are not part of the blood system, that nodes are stopping stations along lymphatic vessels and that every cavity of the body, and not just the lacteals of the small intestine, is drained by the lymphatic system. He demonstrated the absorptive properties of the lymphatics by injecting a dye or noxious substance into experimental animals and then demonstrating it in the lymphatics in a distant part of the body. It was this theory – that the lymphatics, and not just the intestinal lacteals, are a vast and highly effective absorption system – that brought him into conflict with Monro secundus (Wintrobe, 1980).

"Hewson went further, suggesting that noxious agents could enter the body via the lymphatics. ‘The axillary glands are likewise frequently observed to swell in consequence of cancers in the breast and it is found of no use to extirpate the breast itself unless the affected glands can likewise be removed; for otherwise the cancerous tumour of the glands may renew the disease.’ (Hewson, 1774a).

"This work inevitably led him to study further the villi of the gut and their lacteals. He demonstrated how villi in the small intestine differed from those in the colon, and then went on to compare the lacteals of fish, amphibians and turtles (Hewson, 1774b)." (Derek Doyle, "William Hewson (1739-74): the father of haematology", British Journal of Haematology, April, 2006).

With Hunter and Hewson, Cruikshank laid the foundation of modern knowledge concerning the lymphatics. He was Dr. Johnson’s physician and William Hunter’s assistant.

Mascagni, Professor of Anatomy at Siena, made several discoveries regarding the lymphatics. His beautiful atlas contained 41 engravings of the lymphatics and gained him lasting fame. He had previously published a Prodrome, in French, 1784; this contained only four plates.

Noll advanced the theory that lymph is formed by the diffusion of fluids from the blood through the vessel walls into the surrounding tissues.

Histology of the lymphatics. His drew the illustrations.

“Recklinghausen’s canals”, the lymph canaliculi.

Notable for its illustrations.

“Waldeyer’s tonsillar ring”, the lymphoid ring of the nasopharynx.

Wharton described the duct of the submaxillary salivary gland (“Wharton’s duct”). He described the thyroid more accurately than his predecessors, naming it. He also described “Wharton’s jelly” of the umbilical cord (pp.243-44). Wharton explained the role of saliva in mastication and digestion, but provided erroneous explanations for the functions of the adrenals and thyroid. Adenographia gave the first thorough account of the glands of the human body, which Wharton classified as excretory, reductive, and nutrient. He differentiated the viscera from the glands and explained their relationship. Wharton was one of the few physicians to remain in London during the plague of 1666.

De Bordeu first conceived the idea of internal secretion by his hypothesis that every organ, tissue, and cell discharges into the blood products which influence other parts of the body. His work was published in a collective volume by three physicians from his family: Antoine de Bordeu, Théophile de Bordeu, and François de Bordeu. Théophile's Analyse médicinale du sang appeared as part six of the book (pp. 346-588). In the first edition he was not specifically credited as author. Digital facsimile from Google Books at this link.

Like de Bordeu, and more definitely, Legallois anticipated the conception of internal secretions. He surmised from the identity in composition of all varieties of arterial blood and the diversity of venous blood in different parts of the body, that this diversity is acquired, in each case from the loss of some substance from the organ from which the vein proceeds.

Cooper, the most popular surgeon in London during the early part of the 19th century, was connected with both Guy’s and St. Thomas’s Hospitals. Among his best works is his description of the thymus; he described the “reservoir” of the thymus as lined by smooth mucous membrane and running spirally, not straight, through the gland.

Investigation of the secretory and trophic nerves of glands. Heidenhain considered all secretory phenomena to be intracellular, rather than mechanical, processes.

Bayliss and Starling developed the theory of hormonal control of internal secretion.

Starling constructed a general scheme of the “hormones” as he named the internal secretions. This is the first appearance of the word, which was suggested by W. B. Hardy.

Biedl showed that the adrenal cortex is essential for life. His classic work shows the rapid development of the knowledge concerning endocrinology. In 1890 there were few publications dealing with internal secretion, but Biedl, in the second edition of his book, 1913, was able to include a bibliography of 8,500 items. The 4th edition (1922) includes an exhaustive bibliography. An English translation appeared in 1912.

Observation of the effect of strong emotions on gastrointestinal motility (No. 1029) led Cannon to examination of the sympathetic nervous system and its emergency function. Cannon showed the close connexion between the endocrine glands and the emotions.

King, sometimes referred to as the “father of endocrinology”, antici-pated the endocrine action of the thyroid.

Owen was the first to describe the parathyroids, which he observed in his dissection of a Great Indian Rhinoceros that had lived at the Zoological Society of London from 1834 to 1849.  See B. Modarai, A. Sawyer, & H. Ellis, "The Glands of Owen," Journal Royal Society of Medicine 97 (2004) 494-495.

Remak, Owen, and Virchow had previously noted the presence of what may have been parathyroids; the first systematic account of them was given by Sandström. An English translation of this paper appeared in Bull. Inst. Hist. Med., Baltimore, 1938,6, 192-222; a translation was also published in book form at Baltimore, 1938.

From his experimental work Horsley produced evidence to support the view that myxoedema, cretinism and operative cachexia strumpriva are all due to thyroid deficiency.

First successful experimental hypophysectomy; two dogs survived five and six months respectively after this operation.

Gley re-discovered the parathyroids and later came across Sandström’s description (see No. 1127). Gley seems to have been the first to understand their real significance; his work showed the necessity of the parathyroids for the maintenance of life.

Demonstration of the presence of iodine in organic combination in the thyroid. Baumann isolated an iodine-containing compound (“Thyrojodin”). The biochemical research stimulated by this work led eventually to the discovery of thyroxine. Second paper is written with E. Roos.

Isolation of a globulin afterwards named thyroglobulin.

Kendall isolated in crystalline form the thyroid hormone “thyroxine” on Christmas Day, 1914.

The acetonitril test was introduced by Hunt in 1905 (J. biol. Chem., 1, 33) and later modified by him. It shows the activity of thyroid preparations to be proportional to their iodine content.

Hanson isolated the first really potent parathyroid extract.

Isolation of parathormone, the active principle of the parathyroids.

Collip’s “parathormone”. He showed that it raises the calcium level in para-thyroidectomized dogs.

Harington showed that thyroxine is a derivative of tyrosine, and he gave its formula as C₁₅H₁₁O₄NI₄.

Synthesis of thyroxine.

Loeb and Aron (No.1138.2) demonstrated the thyroid-stimulating hormone (TSH) in the anterior pituitary.

Simultaneously with Loeb (No. 1138.1) Aron demonstrated the thyroid-stimulating hormone (TSH) in the anterior pituitary.

Discovery of the second thyroid hormone, triiodothyronine. Digital facsimile from PubMedCentral at this link.

With E. C. Cameron, B. A. Cheney, A. G. F. Davidson, and K. G. Henze.

Eustachius is credited with several anatomical discoveries, among them the tensor tympani muscle and the Eustachian tube, published in his chapter entitled De auditus organis. In the last respect, however, he was anticipated by Alcmaeon, about 500 BCE. Eustachius was the first to describe the chorda tympani as a nerve. Plate VIII illustrates the “Eustachian valve”, the valvula venae cavae in the right auricle. Eustachius recognized the thoracic duct in the horse and even detected some of its valves. His work on this structure was forgotten until Aselli’s description of the lacteals. This work includes first description of the adrenals. Several of the plates deal with the structure of the kidney.

Basing his work on the dissection of fetuses and newborn children, Eustachi was the first to study the teeth in any considerable detail. In his Libellus de dentibus attached to this work he provided an important description of the first and second dentitions and described the hard outer tissue and soft inner structure of the teeth. He also attempted an explanation of the problem of the sensitivity of the tooth’s hard structure. The Libellus has a separate title page dated 1563. It was reprinted with German translation, Wien, Urban & Schwarzenberg, 1951. It was translated into English by Joan H. Thomas and edited and introduced by David A. Chernin and Gerald Shlklar as as A little treatise on the teeth. The first authoritative book on dentistry (1563) (Canton, MA, 1999). Eustachi’s illustrations of the teeth were first published in his Tabulae anatomicae, edited by Giovanni Maria Lancisi (No. 391). For further information, including a discussion of the states of the Opuscula, see the entry at HistoryofInformation.com at this link.

Digital facsimile of the 1563 edition from the Internet Archive at this link.

Brown-Séquard found that excision of both adrenals in animals invariably proved fatal, thus determining their indispensability. He also believed that they had an antitoxic influence upon the blood. His experimental work was of great importance in the development of our knowledge of the internal secretions.

Vulpian discovered adrenaline in the adrenal medulla.

These workers demonstrated the existence of a pressor substance (adrenaline) in the adrenal medulla. Preliminary communications regarding the above appeared in the proceedings of the Physiological Society, J. Physiol., 1894,16, p. i-v; 1895,17, p. ix-xiv.

Abel and Crawford further investigated the pressor substance of Oliver and Schäfer calling it “epinephrine”.

Isolation of adrenaline.

Independently of Takamine, Aldrich succeeded in isolating adrenaline in a crystalline form. He gave it the formula C₉H₁₃NO₃. Adrenaline was the first hormone to be isolated.

Synthesis of adrenaline.

Cortical hormone first obtained.

First practical method of preparing an extract of the active agent of the adrenal cortical hormone. It was named cortin until it was recognized that there are several active agents in the secretion.

Together with H. L. Mason, B. F. McKenzie, C. S. Myers, and G. A. Koelsche, Kendall reported the isolation in crystalline form of cortin ('C₂₀H₃₀O₅)'

Isolation of nine closely related steroid hormones from adrenal cortical extracts; one of these was Compound E (C₂₁H₂₈O₅) which in 1939 was renamed cortisone. With H. L. Mason, C. S. Myers, and W. D. Allers. See also the same journal, 1936,114, 613; 116, 267.

Isolation of Compound F, identical with Kendall’s Compund E. See No. 1151.

Isolation of Compound Fa, identical with Compounds E and F. "In the mid-1930s Edward Kendall and Tadeus Reichstein succeeded in isolating and analyzing the composition of a number of similar hormones derived from the adrenal cortex. These became the basis for cortisone preparations that, with input from Kendall and Philip Hench, were used at the end of the 1940s to treat rheumatoid arthritis and other inflammations."

In 1950 Reichstein shared the Nobel Prize in Physiology or Medicine with Kendall and Hench "for their discoveries relating to the hormones of the adrenal cortex, their structure and biological effects."

Isolation of corticosterone. With E. Laqueur, T. Reichstein, R. W. Spanhoff, and I. E. Uyldert.

With U.S. von Euler and U. Hamberg. See also fuller account in Acta physiol. scand., 1950, 20, 101-8. Noradrenaline was independently isolated by B. F. Tullar, Science, 1950, 109, 536-7.

Isolation of aldosterone. With S. A. Simpson and J. F. Tait.

Synthesis of cortisone by Woodward and colleagues. With F. D. Taub, K. Heusler, and W. M. McLamore.

Important description of the pituitary.

Vassale and Sacchi showed water and mineral metabolism to be affected by hypophysectomy.

Paulesco found that the removal of the anterior pituitary had fatal results, while removal of the posterior lobe had negative results.

Oxytocic action of posterior pituitary injection.

First experimental evidence of the relationship between the pituitary and the reproductive system; demonstration that hypophysectomy causes genital atrophy. 

See No. 3896.

Aschner was able to keep his hypophysectomized dogs alive indefinitely. He found that they developed genital hypoplasia.

Gaines demonstrated the action of the pituitary in lactation.

Evans and Long discovered the growth hormone of the anterior pituitary, showing that continued injections of an anterior pituitary extract produced an acceleration in the growth-rate of laboratory animals.

Smith was able to induce precocious sexual maturity in mice and rats by the implantation of pituitary tissue.

Pituitary tissue implanted in the immature mouse was found by these writers to cause precocious sexual maturity. Thus they showed that the activity of the gonads is maintained by the anterior lobe of the pituitary.

Isolation of the gonadotrophic hormone of the anterior pituitary (Prolan A & B).

Isolation of vasopressin and oxytocin. With T. B. Aldrich, I. W. Grote, L. W. Rowe, and E. P. Bugbee.

Demonstration of the existence of a pituitary lactogenic hormone (prolactin).

Houssay’s depancreatized hypophysectomized dog. This work led to Houssay’s demonstration of the importance of the anterior pituitary in sugar metabolism. See also Endocrinology, 1931,15, 511-23.

In 1947 Houssay shared the Nobel Prize in Physiology or Medicine "for discovery of the part played by the hormone of the anterior pituitary lobe in the metabolism of sugar."

Isolation of an impure “adrenotropic hormone” containing adrenocorticotropic principle. With E. M. Anderson and D. L. Thomson.

With R. W. Bates and S. W. Dykshorn.

Includes an extensive bibliography.

Anterior pituitary diabetogenic hormone.

Choh Hao Li and colleagues isolated of the interstitial cell stimulating (luteinizing) hormone. 

Choh Hao Li and colleagues Isolated pure adrenocorticotropic hormone (ACTH) from sheep pituitary glands. 

Isolation of ACTH from swine pituitaries. 

Choh Hao Li and colleagues isolated the anterior pituitary growth hormone. 

By Choh Hao Li and colleagues. 

Synthesis of oxytocin. With C. Ressler, J. M. Swan, C. W. Roberts, P. G. Katsoyannis, and S. Gordon.

In 1955 Vigneaud was awarded the Nobel Prize in Chemistry "for his work on biochemically important sulphur compounds, especially for the first synthesis of a polypeptide hormone."  

See also No. 1175.4.

Synthesis of vasopressin. With D. T. Gish and P. G. Katsoyannis.

Berthold showed that transplantation of a cock’s testes to another part of the body prevented atrophy of the comb, the usual sequel to castration. He was thus the first to prove the existence of an internal secretion. English translation in Bull. Hist. Med., 1944, 16, 399-401.

Brown-Séquard injected into himself a testicular extract in order to bring about rejuvenation. He reported much benefit but his advocacy of this method evoked scepticism and criticism, although it stimulated research on internal secretion, being perhaps the first employment of “male sex hormone”. Further papers on this subject were published by Brown-Séquard in the same journal, 1889, 5 sér., 1, 739-46; 1890, 2, 201-08, 443-57, 641-48; and 1891, 3, 747-61.

Isolation of spermin from the testis.

Knauer implanted ovaries into immature or castrated animals, producing development of sexual characteristics, thus demonstrating the existence of an ovarian hormone.

In their classic paper on the mammary gland, these workers attributed its changes during pregnancy to the fetus.

First definite description of the cyclical changes in the endometrium, which were shown to be a normal physiological process.

The vaginal smear test for estrus; it demonstrates the histological changes occurring in the vagina during the menstrual cycle.

Isolation of the active principle of the ovarian hormone (oestrin). More detailed account in J. biol. Chem., 1924, 61, 711-23.

Test for recognition of the estrus hormone.

This paper marks the beginning of modern knowledge of the menstrual cycle. Allen showed that uterine bleeding occurs as a withdrawal effect when estrogen ceases to act on the endometrium.

Discovery of the estrogenic activity of male urine. With E. Dingemanse, P. C. Hart, and S. E. de Jongh.

McGee prepared the first active male hormone extract from the lipoid fraction of bull testes. His paper includes a preliminary account of the capon-comb test. See No. 1191.

Discovery of the corpus luteum hormone, progesterone.

Funk and Harrow obtained crude active male hormone extracts from male urine.

Isolation of pregnanediol.

C. R. Moore, T. F. Gallagher, and F. C. Koch were the first to obtain a potent testicular extract containing the male sex hormone, androsterone, later obtained in crystalline form by Butenandt. They also gave a detailed account of the capon-comb test for the assay of the male hormone.

Collip’s anterior-pituitary-like (A-L-P) factor.

First isolation of a pure crystalline hormone (estrone). Preliminary communication in Amer. J. Physiol., 1929, 90, 329-30.

Crystalline estriol obtained.

The male sex hormone, androsterone, was isolated in crystalline form by Butenandt.

In 1939 Butenandt received half of  the Nobel Prize in Chemistry "for his work on sex hormones." The other half was awarded to Leopold Ruzicka "for his work on polymethylenes and higher terpenes." See No. 1201.

Second edition, 1935.

Second edition, 1939, with C. H. Danforth and E. A. Doisy.

Estriol obtained from placental tissue.

First use of estrogenic hormone for the treatment of amenorrhea in ovariectomized women, with production of the typical cyclical endometrial changes.