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History of endocrinology

     Endocrinology is a branch of physiology and medicine concerned with endocrine glands and hormones.

     There are three periods in historical development of endocrinology. They are:

  • Descriptive period
  • Period of analytical endocrinology
  • Contemporary period/synthetic endocrinology

 

  1.                  Descriptive period (Anatomical description)


  • Gonads and liver were known to earliest physicians
  • 1400 BC…Ayurveda documents Hindus knew that pregnancylasts 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

Infertility:

  • Dried placenta was used to improve fertility

Abortion:

  • A pill (oil & quick silver) fried and taken in empty stomach.

                              

THOUSANDS OF GOLD PRISCRIPTION” by  SON SSU MO 695AD

 

 

  • The oldest reports about iodine deficiency and more specifically Goitre come from China. As much as 5000 years ago
  • Treatment-seaweed.
  • Nowadays it is known that people who eat a lot of seaweed do not suffer from iodine deficiency.
Ancient Egyptians and Endocinology

     

     Signs of sterility:

  • If the women have spots before their eyes then it is a sign of sterility.
  • Diagnostic test for pregnancy:
  • Watermelon pounded mixed with milk of woman who has born son is given
  1. If the woman v omits- she is pregnant
  2. If only flatulence      - the woman never bear again.


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.

 

 

 


 

Statue

 

 


 

The Skull- Mummy

 

The above pictures are the statue and skull of an ancient Acromegalic Egyptian ruler Akhenaten (1353 BC).


Thyroid disease


The below pictures are of Cleaopatra (69 BC) and Ella Maria Curtis(1095) - who was considerd to be a “symbol of beauty” in the middle ages and they were suffering from thyroid disease.

 

 

 

 


Cleaopatra (69 BC)

 

 


                                                                                                          

In ancient Egyptians, Alexandrian in third century had an illness of thymus gland and Galen -Greek(AD 129 – 200) had an illness of thyroid, pineal and pitutary gland.


 

Alexandrians-III century BC

 

 Galen -Greek(AD 129 – 200)

 

Also, in 16th century, Bartolommeo Eustachi had a disease of suprarenals and in 1869 Paul Langerhans (1847-1888) had an illness insula of pancreas.


 

Bartolommeo Eustachi

 


Paul Langerhans (1847-1888)

 


In 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

  • In 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.

 

 


 

William Harvey

 

 

  1.              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 and 1836-T  Wilkinson King discovered Thyroid secretion
  • 1840- George Gulliver discovered Adrenal secretion
      First Experimental Proof of Internal Secretion:
  • The first experiment was conducted in 1792 by John Hunter (1728 – 1793) and in 1849, by Arnold Adolph Berthold (1803-1861)
  • Castration of cock caused atrophy of comb but this could be prevented if the testis were transplanted to another part of the body


 


John Hunter (1728 – 1793)

 

The great year 1855 is known as peak of endocrinology because, in that year concept of internal secretion-established in scientific knowledge by Claude Bernard (1813-1878), Thomas Addison(1793-1860), and Charles-Édouard Brown-Séquard (1817-1894). They are called as “The great triumvirate.




                                                                     “The great triumvirate”

 

Claude Bernard (1813-1878) - "Father of Physiology"


In 1855, he discovered a 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. He also wrote a book “lessons on experimental physiology.”



Claude Bernard (1813-1878)

 

Thomas Addison(1793- 1860)- “Great Man of Guys Hospital”


  • In 1855, he published his research work under the title “Constitutional And Local Effects Of Disease Of Supra Renal Capsule
  • Role of internal secretion is demonstrated through anatomical observations with regards to

  1.      Addison’s disease
  2.      Addison’s crisis
  3.      Addisonian anemia/pernicious anemia
  4.      Adrenoleukodystrophy, etc.

 

 

Thomas Addison(1793- 1860)


 

Charles-Édouard Brown-Séquard (1817-1894)- “Inspiration to Robert Louis Stevenson for the Character of Dr Jekyll and Mr Hyde"


  • In 1855, he demonstrated that removal of the adrenal gland resulted in death, due to lack of essential hormones.

 

 


Charles-Édouard Brown-Séquard (1817-1894)

 

 


  • 1856- Alfred Vulpian : discovered adrenaline /chromogen in the adrenal medulla
  • 1895- Eugene Baumann: discovered 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
  • 1904-Maurice-Adolphe Limon first used the term “endocrine/endocrinology.” Endo is a Greek adjective which means inside.
  • 1905- Ernest H Starling first used the word hormone at Royal college of physicians, in his Croonian lectures, HARMAO =Greek verb which means having property of stimulating.

 


 

Ernest H Starling

 

Last phase of “Period of analytical Endocrinology”


  • Harvey Williams Cushing who is known as "Father of Modern Neurosurgery", discovered the integration of glands and their regulatory process.
  • Harvey Cushings and Longdon-Brown discovered the regulatory actions of Pitutary gland.

 


Harvey Williams Cushing

  1. PERIOD OF SYNTHETIC ENDOCRINOLOGY- The connection between hormonal & nervous system: neurohumoral system

 

  • In 1918, L.Greving, and in 1933, Roussy & Mossinger demonstrated nervous connections between hypothalamus and pituitary gland, olfactogonadal and opticogonadal reflex arc.
  • 1931- Walter Cannon described adrenaline  as a “fight or flight response”


 Walter Cannon

 

  • 1923- John Macleod discovered insulin.

 


John Macleod

 

The Connection between Hormonal & Nervous system: Neurohumoral system:


  • In 1904, T R Elliot discovered sympathetic nervous system and release of chemicals, and in 1921, Cannon and Loewi termed it as adrenal hormone.
  • In 1906, Dixon, 1921, Loewi, and in 1929, Dale described that parasympathetic nerves act through cholinergic hormone.


Nosography of endocrine system

  • Hippocrates(460 BC –  370 BC)studied the disease of Scyths: Hypo-orchadism/Climatic Hypoovarism .

 


Hippocrates(460 BC –  370 BC)


  • In 1850, TB Curling did earliest study of Hypothyroidism and described role of thyroid in symptom complex of cretinism.

 


TB Curling

 

 

Thyroid Disease


  • 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, to the pathological deficiency of thyroid function in adults (goiter).
Hypoadrenalism


  • 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.

 

 


Thomas Addison(1793-1860)

 

History of Endocrinotherapy


  •  1889- BROWN SEQUARD discovered a 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 discovered Thyroid organotherapy.
  • 1921- insulinotherapy by Banting, later sex hormones, cortins, growth hormone etc were discovered.
     Protein of the 20th Century- Insulin

  • 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.
  • Edouard Luaguesse later suggested that they might produce secretions that play a regulatory role in digestion.
  • Paul Langerhan’s 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
  •    Established 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 then called “Pancrein”
  • Use of his techniques was patented in Romania, though no clinical use resulted.
  • 1921 -Fedrick Banting 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.
  • The below image is a picture of a young girl aged 13 years suffered 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. 

 


First diabetic patient to receive insulin

 

University of Toronto-Insulin


 


First insulin preparation

 

  • 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 was 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.

Nobel Prize


  • 1923-The Nobel Prize committee 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 is 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

 

Article written by, 

Dr. Praveen Ramachandra

                                                                                                                                                                                           MBBS, MD, DM, MRCP(UK) 
 
Web Editor: Dr. Praveen Ramachandra