BRIEF History of endocrinology
THREE PERIODS IN HISTORICAL DEVELOPMENT OF ENDOCRINOLOGY
- DESCRIPTIVE PERIOD
- PERIOD OF ANALYTICAL ENDOCRINOLOGY
- CONTEMPORARY PERIOD/SYNTHETIC ENDOCRINOLOGY
I. DESCRIPTIVE PERIOD
- Gonads and liver were known to earliest physicians
- 1400 BC…Ayurveda documents Hindus knew that pregnancy lasts for 10 lunar months
- sealing spirits are responsible for infertility
- Contraceptive methods too hypothized in Ayurveda..
Contraceptive methods in Ayurveda
- Swallowing three year old molasses or roots of Agni tree cooked in sour rice water
- Vaginal fumigation with smoke of Neem wood or passiveness in coitus/holding breath
- Coitus obstructus or smearing of vagina with honey/ ghee or vaginal medication of rock salt dipped in oil
More from Ayurveda
- Goiter is described as GALAGANDA
- For cure of impotence and obesity administration of testicular tissue (ORGANOTHERAPY)
Ancient Chinese and Endocrinology
“THOUSANDS OF GOLD PRISCRIPTION” by SON SSU MO 695AD
- Dried placenta to improve fertility
- Abortion: a pill (oil & quick silver) fried and taken empty stomach
Ancient Chinese and Endocrinology
- The oldest reports about iodine deficiency and more specifically Goitre come from China. As much as 5000 years ago
- Nowadays it is known that people who eat a lot of seaweed do not suffer from iodine deficiency.
Ancient Egyptians and Endocinology
Ancient Egyptians and Endocinology
- Contraception: Ovariotomy were performed
- Carvings of patients with Acromegaly, Goitre and Achondroplasia have been unearthed
- Eunuchs /Castrated males in ancient times were used to guard harems
AKHENATEN (1353 BC) -ancient Egyptian ruler, Acromegalic
The skull- mummy
Cleaopatra (69 BC)
Considered to be symbol of beauty(MIDDLE AGES)
Alexandrians-III century bc-thymus
Galen -greek(AD 129 – 200) thyroid, pineal&pitutary
Bartolommeo eustachi-suprarenals-16th century
Paul langerhans (1847-1888)-insula of pancreas -1869
- 1880-Ivar Viktor Sandstorm , swedish medical student,described parathyroid
- It was the last major organ to be recognized in humans
IDEA OF A CANAL SYSTEM
17th century William Harvey describes heart as a four chambered pump that moves blood through arteries and veins, not air.
Mid 1800s idea that circulating blood carries substances from one part of the body to a distant part where the substance exerts its effect.
II. PERIOD OF ANALYTICAL ENDOCRINOLOGY
SPECIAL PHYSIOLOGY OF ENDOCRINE GLANDS : THE HORMONES
- 1766- Ruysch: Internal secretory function of endocrine organs “Haller text book of physiology”
- 1801-Le Callois.1836-T Wilkinson King: Thyroid secretion
- 1840- George Gulliver: Adrenal secretion
FIRST EXPERIMENTAL PROOF OF INTERNAL SECRETION
John hunter(1728 – 1793)-1792
Arnold Adolph Berthold ( 1 803-1 86 1 ) -1849
- Castration of cock caused atrophy of comb but this could be prevented if the testis were transplanted to another part of the body
The Great Year(1855)-Peak of Endocrinology
Concept of internal secretion-established in scientific knowledge
The great triumvirate
Claude Bernard (1813-1878 )"Father of Physiology"
1855-the glycogenic function of the liver; in the course of this he was led to the conclusion, which throws light on the causation of diabetes mellitus, that the liver, in addition to secreting bile, is the seat of an internal secretion, by which it prepares sugar at the expense of the elements of the blood passing through it
“lessons on experimental physiology”
Thomas Addison(1793-1860)“Great Man of Guys Hospital”
1855- “Constitutional And Local Effects Of Disease Of Supra Renal Capsule”
Role of internal secretion is demonstrated through anatomical observations
Addisonian anemia/pernicious anemia
Charles-Édouard Brown-Séquard(1817-1894)“Inspiration to Robert Louis Stevenson for the Character of Dr Jekyll and Mr Hyde "
1855- Demonstrated that removal of the adrenal gland resulted in death, due to lack of essential hormones.
- 1856- Alfred Vulpian : discovered adrenaline /chromogen in the adrenal medulla
- 1895- Eugene Baumann: iodothyroxine as active principle in thyroid
- 1901- Takamine & Aldrich: independently isolated secretion of adrenal medulla and described chemical structure as “adrenaline”
- 1902- Bayliss and Starling isolated secretin from duodenal secretion
1905-ernest h starling
- First used the term “ endocrine/endocrinology”
- Endo= Greek adjective; inside
First to use the word hormone at royal college of physicians, in his Croonian lectures , HARMAO = GREEK VERB;HAVING PROPERTY OF STIMULATING
LAST PHASE OF “PERIOD OF ANALYTICAL ENDOCRINOLOGY”
Harvey Williams Cushing "father of modern neurosurgery".
- Discovery of the integration of glands and their regulatory process
- Pitutary gland and its regulatory actions- Harvey Cushings,Longdon-Brown
III. PERIOD OF SYNTHETIC ENDOCRINOLOGY
The connection between hormonal & nervous system: neurohumoral system
- 1918- L.Greving, 1933-Roussy & Mossinger- demonstrated nervous connections between hypothalamus and pituitary gland, olfactogonadal& opticogonadal reflex arc
- 1931- Walter Cannon: adrenaline “fight or flight response”
- 1923- John Macleod : insulin
The Connection Between Hormonal & Nervous system: Neurohumoral system
- 1904: T R Elliot- sympathetic nervous system and release of chemicals, in 1921 Cannon and Loewi termed it as adrenal hormone
- 1906-Dixon,1921-Loewi, 1929-Dale: parasympathetic nerves act through cholinergic hormone
NOSOGRAPHY OF ENDOCRINE SYSTEM
Hippocrates(460 BC – 370 BC) – disease of scyths: hypo-orchadism/climatic hypoovarism
Hypothyroidism-Earliest to studied
1850- TB Curling:
described role of thyroid in symptom complex of cretinism
- 1871- Hilton-Fagge related the Cretinoid state to a congenital inadequacy of thyroid function in early childhood.
- 1873 -Gull related dry skin, sparse hair, puffiness of the face and hands, and a swollen tongue to Myxedema, the pathological deficiency of thyroid function in adults (goiter).
- 1855-the first person to correctly connect the symptoms of what is now called ADDISON’S DISEASE to a functional deficiency of the adrenal glands
History of Endocrinotherapy
- 1889- BROWN SEQUARD: Hypodermic injection of a fluid prepared from the testicles of guinea pigs and dogs, as a means of prolonging human life
- 1890- G R M URRAY: Thyroid organotherapy
- 1921- insulinotherapy by Banting, later sex hormones, cortins, growth hormone etc
Protein of the 20th Century
- 1926- One of the first proteins to be crystallized in pure form.
- 1955 - First protein to be fully sequenced
- 1958 - First protein to be chemically synthesized in – though in insufficient quantities to be produced commercially
- 1979 – First human protein to be manufactured by way of Biotechnology
HISTORY OF INSULIN
- 1869- Paul Langerhans, a medical student in Berlin, identified some previously un-noticed tissue clumps scattered throughout the bulk of the pancreas.
- The function of the "little heaps of cells," later known as the islets of langerhans, was unknown
- Edouardluaguesse later suggested that they might produce secretions that play a regulatory role in digestion.
- Paul Langerhans' son, Archibald, also helped to understand this regulatory role.
- 1889- Oscar Minkowski in collaboration with Joseph Von Mering removed the pancreas from a healthy dog to test its assumed role in digestion.
- Several days later Minkowski's animal keeper noticed a swarm of flies feeding on the dog's urine.
- On testing the urine they found –sugar
- Establishing for the first time a relationship between the pancreas and diabetes.
- 1901- Eugene Opie, established the link between the Islets of Langerhans and diabetes
- ”Diabetes mellitus … is caused by destruction of the islets of Langerhans and occurs only when these bodies are in part or wholly destroyed. .”
- 1906- George Ludwig Zuelzer was partially successful treating dogs with pancreatic extract but was unable to continue his work.
- Between 1911 and 1912- E L Scott at the university of Chicago used aqueous pancreatic extracts and noted a slight diminution of glycosuria but was unable to convince his director of his work's value; it was shut down.
- 1919- Israel Kleiner demonstrated similar effects at Rockfellar university, but his work was interrupted by WW I and he did not return to it.
- 1921 - Nicolae Paulescu, a professor of physiology at the university of medicine and pharmacy in Bucharest was the first one to isolate insulin
- called “Pancrein”
- Use of his techniques was patented in Romania, though no clinical use resulted
- 1921 -Fedrickbanting meet JJR MacLeod, who supplied Banting with a lab at the University of Toronto, an assistant (medical student Charles Best), and 10 dogs, then left on vacation during the summer of 1921.
- Their method was tying a ligature (string) around the pancreatic duct, and, when examined several weeks later, the pancreatic digestive cells had died and been absorbed by the immune system, leaving thousands of islets.
- They then isolated an extract from these islets, producing what they called ”isletin” (what we now know as insulin), and tested this extract on the dogs.
- Banting and Best were then able to keep a pancreatectomized dog alive all summer because the extract lowered the level of sugar in the blood
- December 1921- Macleod invited the Biochemist James Collip, to help with this task, and, within a month, the team felt ready for a clinical test
- January 11,1922, Leonard Thompson, a 14-year-old diabetic who lay dying at the Toronto general hospital, was given the first injection of insulin. However, the extract was so impure that Thompson suffered a severe allergic reaction, and further injections were canceled.
- Over the next 12 days, Collip worked day and night to improve the ox-pancreas extract, and a second dose was injected on the 23rd. This was completely successful, not only in having no obvious side-effects, but in completely eliminating the glycosuria sign of diabetes.
- young girl aged 13 years suffering from diabetes. She weighs just 45lbs and her chances of surviving for much longer are very, very poor. She was one of the first patients to be treated with insulin extracted from the pancreases of slaughtered cattle.
University of Toronto-Insulin
- spring of 1922- Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the preparation remained impure.
- The drug firm Eli Lilly and company had offered assistance not long after the first publications in 1921, and they took Lilly up on the offer in April.
- November,1922- Lilly made a major breakthrough, and were able to produce large quantities of highly refined, 'pure' insulin. Insulin was offered for sale shortly thereafter.
- 1950’-The amino acid structure of insulin was characterized in the 1950's and
- 1977-the first genetically-engineered human insulin was produced in a laboratory in 1977 by Genentech using E. Coli.
- 1982-Partnering with Genentech , Eli Lilly went on in 1982 to sell the first commercially available human insulin under the brand name Humulin.
- 1923-The Nobel Prize committee in 1923 credited the practical extraction of insulin to a team at the University of Toronto and awarded the Nobel Prize to two men; Frederick Banting and JJR Macleod.
- Banting, insulted that Best was not mentioned, shared his prize with Best, and Macleod immediately shared his with James Collip.
- The patent for insulin was sold to the University of Toronto for one dollar
- The primary structure of insulin was determined by British molecular biologist Frederick Sanger.
- 1958-It was the first protein to have its sequence be determined. He was awarded the 1958 Nobel prize in Chemistry for this work.
Banting and Best's laboratory where insulin was discovered
Banting and Best in the laboratory where insulin was discovered
Student assistant Charles H. Best and Frederick G. Banting are standing on the roof of the medical building with one of the diabetic dogs used in their experiments with insulin
Slide 49 Slide 50
BOOKS ON HISTORY OF ENDOCRINOLOGY