Transcript History of endocrinology

Iendocrinology.com
I.
DESCRIPTIVE PERIOD
II.
PERIOD OF ANALYTICAL ENDOCRINOLOGY
III.
CONTEMPORARY PERIOD/SYNTHETIC
ENDOCRINOLOGY
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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..
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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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Goiter is described as GALAGANDA
For cure of impotence and obesity
administration of testicular tissue
(ORGANOTHERAPY)
INFERTILITY
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Dried placenta to
improve fertility
Abortion: a pill (oil &
quick silver) fried and
taken empty stomach
“THOUSANDS OF GOLD
PRISCRIPTION” BY SON SSU MO
695AD
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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.
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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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
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 EUSTACHISUPRARENALS-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
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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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
JOHN HUNTER(1728 – 1793)1792
ARNOLD ADOLPH BERTHOLD (
1 803-1 86 1 ) -1849
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Castration of cock
caused atrophy of comb
but this could be
prevented if the testis
were transplanted to
another part of the body
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
1.
Addison’s disease
2.
Addison’s crisis
3.
Addisonian
anemia/pernicious anemia
4.
Adrenoleukodystrophy, etc
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
1904-MAURICE-ADOLPHE
LIMON
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1905-ERNEST H STARLING
First used the term “
endocrine/endocrinolo
gy”
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
HARVEY WILLIAMS CUSHING "FATHER OF
MODERN NEUROSURGERY".
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Discovery of the
integration of glands
and their regulatory
process
Pitutary gland and its
regulatory actionsHarvey
Cushings,LongdonBrown
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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
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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
HIPPOCRATES(460 BC –
370 BC) – DISEASE OF
SCYTHS: HYPOORCHADISM/CLIMATIC
HYPOOVARISM
HYPOTHYROIDISMEARLIEST TO STUDIED
1850- TB Curling:
described role of
thyroid in symptom
complex of
cretinism
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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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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
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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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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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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-yearold 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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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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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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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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