Diabetes and the discovery of insulin in 1920
by Frederick Banting and Charles Best, Toronto, Canada
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Type I diabetes mellitus
(lack of insulin; le miel = honey)
• Symptoms: always hungry and thirsty,
glucose in urine, tired, blurred vision,
extreme weight loss.
• Prognosis: slow, painful death, delayed
by low carbohydrate diet.
• Reason: digestion by carbohydrases converts
all the eaten carbohydrate to glucose, and 100%
is absorbed from the small intestine to the blood.
But, in the absence of insulin, the cells are unable
to take up (and use) the glucose for respiration.
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Excess unused glucose accumulates in the blood and is
flushed by the kidneys out into the urine, using lots of water
and making the patient constantly thirsty.
Dogs whose pancreas had been cruelly removed
survived a long time on a diet of small molecules that did
not need to be digested before being absorbed into the blood
stream. But the dogs turned diabetic (sweet urine).
Hypothesis: the pancreas produces something that
is lacking in diabetics.
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Blocking the
pancreatic duct using
a ligature stopped
the flow of digestive
enzymes (amylase,
lipase, and the
protease trypsin) to
the small intestine.
But the dogs did not
become diabetic.
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Hypothesis: the
pancreas secretes an
unknown substance
(insulin) directly to the
blood.
Search for insulin: pancreas was mashed up and
the soluble extract was injected into dogs that were
made diabetic by removing the pancreas.
Result: the pancreas extract did not cure diabetic
dogs.
Explanation: the hormone insulin is a protein that
was digested (destroyed) by the trypsin (proteinase)
from the pancreas.
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Observation: ligated
pancreas lost the ability
to produce trypsin.
Hypothesis: active
insulin can be isolated
from ligated pancreas.
Prediction: injecting
“insulin” into the blood
should reduce the level
of blood sugar in
diabetic dogs.
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Sterilising the pancreas extract before
injection into the bloodstream
• Meat extract is full of bacteria and possibly also
viruses
• Insulin is destroyed by boiling
• Bacteria can be filtered out using sintered glass
filters
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It worked!
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It also worked for humans, but they
very quickly produced a serious
allergic reaction against the pancreas
extract from the dogs.
Only when insulin was purified (i.e.
everything but insulin was removed)
could it be given repeatedly to
humans.
Only minute quantities of insulin could
be prepared from tied up dog
pancreas.
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Later, larger quantities of insulin were produced from foetal calf
pancreas that had not matured to produce trypsin.
Insulin was always in short supply, and diabetes increased.
• Calf insulin is slightly different in its amino acid sequence from
human insulin. Because of this it does not work perfectly in
humans, and it may even be destroyed by our immune system
(like a pathogen in a vaccinated person).
Insulin from animals was also feared to transmit mad cow
disease and dangerous viruses.
USA
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Just when the world was running out of calf insulin, it became
possible to produce
• human insulin
•
guaranteed free of disease
•
in unlimited quantities
by putting the human gene for insulin into a
harmless bacterium by
genetic modification.
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Transplanting a pancreas from another person does not seem
possible, but In the future, it may become possible to re-
grow a functioning pancreas from your own stem
cells.
• Such a replacement pancreas would be accepted by your
body without the need to take unpleasant and expensive
immuno-suppressant drugs.
• A replacement pancreas would control the level of blood
glucose better than is currently possible with insulin
injections; i.e. blood glucose homeostasis would be better
regulated.
• The fertilised egg is the ultimate stem cell because it has the
potential to develop into every type of specialised body cell
(e.g. nerve cell, muscle cell etc.).
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The total number of people in this world
with diabetes is projected to rise from
171 million in 2000 to
366 million in 2030
= 4% of the population
doubling in 30 years!
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Questions about the discovery of insulin
1.
2.
Who discovered insulin?
When was insulin discovered?
3.
4.
5.
6.
7.
Why are untreated diabetics hungry even after they have eaten pasta?
Why does the blood glucose level increase in diabetics? (2 reasons)
How could dogs survive without a pancreas and what diet should they be given?
Why did ligature of the pancreatic duct not make the dogs diabetic?
Why was insulin, the chemical substance, so difficult to discover?
8.
9.
Why does insulin need to be injected into the blood stream?
What needed to be done before animal insulin could be used for humans?
Explain why.
10. How could insulin preparations be sterilised (made free of bacteria and viruses)
to prevent harmful bacteria being introduced into the blood (blood “poisoning”)?
11. What was the source of insulin before the advent of genetically modified (GMO),
insulin producing bacteria.
12. Would you prefer insulin made naturally by animals to GMO insulin? List
advantages and disadvantages of both.
13. What would happen if we could no longer use insulin from GMO bacteria?
14. Should stem cell research be allowed? Give arguments for and against.
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Dorothy Hodgkin 1910-1994
Sir John Leman Grammar School,
Beccles, Suffolk.
Universites: Oxford and Cambridge
1964 Nobel prize for developing protein
crystallography and determining the
position in 3d of every single atom in the
hormone insulin.
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