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Written by Kaushik Pandit
In the year 1855, Claude Bernard (1813-1878) showed that while the external secretion of the liver was constituted as bile, the internal secretion made blood sugar. It was Bernard who introduced the concept of ‘milieu intérieur’ or internal environment which is kept constant by several interacting, self-regulating mechanisms.
Endocrinology was recognized as a new branch of biological science mainly as a result of events which took place between about 1890 and 1905, but ideas and discoveries dating from antiquity contributed to it. As for example, experiments supporting the concept of internal secretions by the testicles were described by Aristotle (4th c. B.C.) but it matured with scientific temper by the experiments of John Hunter (18th c.) and Arnold
Berthold (19th c.).
The thyroid gland had aroused interest since antiquity. Paracelsus associated goiter with cretinism and noted its frequency in those living in mountainous areas. It was the Dutch anatomist Frederik Ruysch (1638-1731) who enunciated that the thyroid discharged substances into the bloodstream, which was later confirmed by John Simon in 1844. The life sustaining property of thyroid was confirmed by the experiments of Moritz Schiff
(1823-1896) in 1856, who showed that in experimental animals, extirpation of thyroid led to their death. The first good clinical description of myxedema was provided by William Withey Gull (1816-1890) in the year 1873, of five adult women presenting with cretinoid condition.
They were slow, sluggish, obese and puffy in face. In 1860, Bilroth introduced thyroidectomy as treatment of goiter, and his pupil Emil Theodor Kocher (1841-1917) improved on Bilroth’s technique. Working in the alpine mountain region provided him with innumerable patients. He performed more than 7000 thyroidectomies in his life; and was
awarded with Nobel prize in the year 1909 for his contributions to thyroid surgery. Kocher in a follow-up of his patients noted that a third of his operated patients developed the features described by Gull (he called it cachexia strumipriva), and inferred that myxedema was caused by thyroid deficiency. So it was not long before George Redmayne Murray (1865-1939) in 1891 reported the improvement of a forty-six year old lady with myxedema by injection of sheep thyroid extract. And in 1895 Eugen Baumen found an iodine compound in the thyroid gland, which opened the gate for controlling goiter by addition of iodine to table salt.
Such was the benefit observed in the treated patients with thyroid problems, that soon thyroid extract became the panacea for all sorts of symptoms in adults, from obesity to depression. In 1915 Edward Calvin Kendall isolated and crystallized thyroxine (also
isolated cortisone and was awarded Nobel prize in 1936) the active principle of thyroid extract, and thyroid hormone supplementation became a reality. Meanwhile, Robert James Graves (1797-1853), an astute clinician keenly interested in fevers, published a paper “a newly observed affection of the thyroid gland in females” in 1835, since known as Graves’ disease, although as we know today, this condition was first described by Caleb Hilliard Parry in 1786.
In the year 1893, George Oliver and Edward Sharpey-Schäfer (1850-1935) injected a dog with an adrenal gland extract and noted a sharp rise in blood pressure. Later in 1901, Jộkichi Takamine (1854-1922) and Thomas Bell Aldrich isolated the substance and designated it as ‘adrenaline’. Three years later Friedrich Stolz (1860-1936) synthesized the substance adrenaline (epinephrine in U.S.) and was the first hormone to be synthesized.
Walter Bradford Cannon (1871-1945) while studying the effects of autonomic nervous system coined the term ‘homeostasis’ to mean maintenance of constancy in the ‘internal environment’, as proposed by Claude Bernard by means of various chemical substances.
Thomas Addison (1793-1860), in 1849 first described what he termed as ‘melasma suprarenale’, bronzed skin associated with disease of suprarenal glands, a syndrome since known as Addison’s disease. Charles-Edouard Brown-Sequard (1817-1894, the double-hyphenated neurologist and forgotten father of endocrinology renowned for his eponymous neurological syndrome), in the year 1856 showed in animal experiments that adrenocortical
deficiency is fatal and that Addison’s disease in humans involve failure of the adrenals. William Osler in the year 1896 used adrenal extract to treat one patient of Addison’s disease.
William Bayliss (1860-1924) and Ernest Henry Starling (1866-1927, was born in Bombay) in 1902 conducted an experiment, which involved instilling hydrochloric acid into the dog
duodenum. They noted that this activity caused the pancreas to secrete pancreatic juice. They inferred that duodenum mustbe secreting a substance in the blood that reached the pancreas. They called this putative substance as ‘secretin’. In 1905, Starling adopted the term ‘hormone’ (Greek Hormao: I excite) for all such chemical messengers that move from one organ of the body to other parts of body via bloodstream regulating various body
systems.
Though the effects of castration were known since ancient times, it was only in the last century that the hormones secreted by the testes and ovaries became known. It had long been known that castrating a cock led its comb to atrophy; but in 1849 Arnold Berthold showed that if the testes were transplanted in another part of the animal’s body, this did not occur. Charles-Edouard Brown-Sequard sensationally reported to the world in 1889 that injection of extracts of pig and dog testicles led to rejuvenation. The dream of recapturing the youth seemed much near and plausible, and this formed the launching pad of such flurry of ‘scientific’ activities like ‘organotherapy’ and monkey and goat testicular implants.
The male sex hormone ‘androsterone’ was isolated by a German chemist Adolf Butenandt (1903-1995) in 1931, and synthesized by Leopold Ruzicka in 1934. Soon after, the Dutch scientist Ernst Laquer succeeded in isolating pure hormone from the ground-up testicles of bull and designated it ‘testosterone’. Isolation of female sex hormone was much more
difficult. Edgar Allen and Edward Adalbert Doisy (1893-1986, the recipient of Nobel prize in 1943 for his work on vitamin K) in 1929 isolated the female sex hormone estrone (they called it oestrin) from urine of pregnant women. And estradiol and estriol were discovered in 1933. Progesterone was discovered a year later from corpus luteum. Synthetic progesterone was prepared from diosgenin sourced from Mexican yam (incidentally, cortisone and testosterone were also synthesized from the same Mexican yam later on) in the 1940s. In 1951, Luis Miramontes synthesized the first synthetic progestagen, norethisterone. The potential of this substance in contraception was quickly understood, and in 1957, norethynodrel was introduced in U.S. as the first oral contraceptive pill.
The location and anatomy of the pituitary gland at the base of the brain was known since quite a long time, though its function was a mystery till the end of nineteenth century. In
1886, Pierre Marie (1853-1940) described a disease characterised by prognathism, overgrowth of hands and feet, and Oskar Minkowski (1858-1931) noted that in ‘acromegaly’ pituitary is enlarged, and later on Woods Hutchinson inferred that pituitary was the likely source of growth hormone in the body. In 1909, Henry Hallett Dale (1875-1968) isolated the hormone oxytocin from the posterior pituitary. Various experiments suggested that anterior pituitary has effects on many other glands of the body, and Walter Langdon-Brown described pituitary as the ‘leader of the endocrine orchestra’.
Harvey Cushing (1869-1939), an outstanding neurosurgeon of his time, and avid researcher and biographer, described in 1906 relationship between pituitary tumors and sexual infantilism. And in 1932 he described a clinical syndrome named ‘hypophysial basophilism’, since known as Cushing’s disease. The brain (hypothalamus) as the source of hormones was first described by Roger Guillemin (1924-present), Andrew Schally (1926-present) and ushered in the era of neuroendocrinology (and for which they were awarded with Nobel prize in the year 1977).
Diabetes was known to humanity since antiquity. And discovery of its description in an Egyptian papyrus of 1550 B.C. by Georg Ebers testifies to its long history. But the first clear
description of diabetes emanated from Hindu physicians in the sixth century B.c., who clearly differentiated it (diabetes mellitus or Madhumeha) from other causes of polyuria and sugary urine, like Udakameha (watery urine disease, i.e. diabetes insipidus) and Ikshumeha (cane sugar disease; i.e. renal glycosuria). They also gave a clear description of two types of diabetes, one which occurs in the young, characterised by a lean constitution, dehydration, increased thirst and polyuria and is due to a genetic defect and the other is characterised by stout built, increased appetite and due to injudicious way of life- quite reminiscent of today’s classification of diabetes into type 1 and type 2.
The modern western description of the disease came from Aretaeus of Cappadocia in the second century, who also baptized the disease as ‘diabetes’ (Greek, meaning siphon). And the English physician Thomas Willis (1621-1675, of the Circle of Willis fame) added the term mellitus (derived from Latin root for ‘honey’, c.f. madhumeha) to distinguish it from diabetes insipidus. In the year 1776 Mathew Dobson (?-1784) described diabetes as a disease with increased sugar in the serum. In 1788, Thomas Cowley reported that diabetes may follow damage to pancreas. In 1869, Paul Langerhans (1847-1888) observed the special cells in the pancreas which bears his name, but he could not fathom the function of the same. In 1889, Oskar Minkowski and Joseph von Mering (1849-1907) removed a dog’s pancreas and found it developed diabetes.
Edward Sharpey-Schäfer (1850-1935) determined that the substance needed for carbohydrate metabolism was produced in the Islets of Langerhans, and named the substance ‘insuline’ after the Latin insula (island). Isolation of the active principle of the islets was elusive, and after many attempts, Frederick Grant Banting (1891-1944) and Charles Herbert Best (1899-1978) in the year 1921, with the help of John Macleod (1876-1935) and James Collip (1892-1965) isolated insulin from a dog’s pancreas and saved the life of the pancreatectomized dog by infusing insulin, heralding a new era in endocrine therapy. On 11th January 1922, they injected for the first time a human being almost dying of diabetes (Leonard Thompson by name) with the pancreatic extracts and the boy survived. What followed was history and they were aptly and promptly awarded Nobel prize in the year 1923 for their seminal work and the epoch making discovery (Banting and Macleod were awarded Nobel prize, which they shared with Best and Collip respectively).
Rosalyn Yallow (1921-present) discovered the technique of measuring extremely low concentration of substances in the plasma (for example hormones) by radioimmunoassay. And the hormone which on which this measurement technique was developed was insulin,
and she was awarded Nobel prize in the year 1977 for this seminal contribution in the advancement of science.
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