BRIEF History of endocrinology

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BRIEF History of endocrinology

• Iendocrinology.com

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THREE PERIODS IN HISTORICAL DEVELOPMENT OF
ENDOCRINOLOGY

• DESCRIPTIVE PERIOD
• PERIOD OF ANALYTICAL ENDOCRINOLOGY
• CONTEMPORARY PERIOD/SYNTHETIC ENDOCRINOLOGY

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I. DESCRIPTIVE PERIOD
Anatomical description

• Gonads and liver were known to earliest
  physicians
• 1400 BCAyurveda documents Hindus knew that
  pregnancy lasts for 10 lunar months
• sealing spirits are responsible for infertility
• Contraceptive methods too hypothized in
  Ayurveda..

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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

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More from Ayurveda

• Goiter is described as GALAGANDA
• For cure of impotence and obesity administration
  of testicular tissue (ORGANOTHERAPY)

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Ancient Chinese and Endocrinology

• infertility

• 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

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Ancient Chinese and Endocrinology

• 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.

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Ancient Egyptians and Endocinology

• Signs of sterility women having spots before
  their eyes
• Diagnostic test for pregnancy watermelon pounded
  mixed with milk of woman who has born son is
  given
• a) if the woman vomits- she is pregnant
• b) if only flatulence - never bear again

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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

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AKHENATEN (1353 BC) -ancient Egyptian  ruler,
Acromegalic

• Statue

• The skull- mummy

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Thyroid disease

• Cleaopatra (69 BC)

• Considered to be symbol of beauty(MIDDLE AGES)

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Ancient Europeans

• Alexandrians-III century bc-thymus

• Galen -greek(AD 129 200) thyroid,
  pinealpitutary

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Ancient Europeans

• Bartolommeo eustachi-suprarenals-16th century

• Paul langerhans (1847-1888)-insula of pancreas
  -1869

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• 1880-Ivar Viktor Sandstorm , swedish medical
  student,described parathyroid
• It was the last major organ to be recognized in
  humans

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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.

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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

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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

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The Great Year(1855)-Peak of Endocrinology

• Concept of internal secretion-established in
  scientific knowledge

The great triumvirate
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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

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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
• Addisons disease
• Addisons crisis
• Addisonian anemia/pernicious anemia
• Adrenoleukodystrophy, etc

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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.

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• 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

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20th Century

• 1905-ernest h starling

• 1904-maurice-adolphe limon

• 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 VERBHAVING PROPERTY OF STIMULATING
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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

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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

WALTER CANNON
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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

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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

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

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HYPOADRENALISM

• 1855-the first person to correctly connect the
  symptoms of what is now called ADDISONS
  DISEASE to a functional deficiency of the adrenal
  glands

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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

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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

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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 Langerhans' son, Archibald, also helped to
  understand this regulatory role.

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• 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.

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• 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. .

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• 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.

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• 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

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• 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

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• 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

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•  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.

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•  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. 

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University of Toronto-Insulin
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• 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.

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• 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.

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Nobel Prize

• 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

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Nobel Prize

• 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.

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Banting and Best's laboratory where insulin was
discovered
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Banting and Best in the laboratory where insulin
was discovered
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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
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