GEN2018

Prominent Scientists &

Their Great Discoveries
Cecil Pong
Email: cecilpong@hsu.edu.hk

1
Introduction

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Scientific Discoveries
• How renowned scientists made their significant
discoveries
• From different fields:
• physical science
• medical science
• Life science
• The importance of creativity, team work, assiduity
and perseverance.

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In this module, we will…
• Identify some major scientific discoveries in
different fields.
• Understand the basic concepts.
• Appraise the contribution and breakthroughs of the
eminent scientists.
• Analyse the discovery journeys of the scientists.
• Evaluate how advances in one discipline might lead
to the progress of others.

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Assessment Scheme
• Class participation and discussion (10%)
• Group presentation (10%)
• In-class quizzes (40%)
• Individual final paper (40%)

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Group presentation (10%)
• Group of 5
• 15-30 minutes presentation on a topic in class
• Group 1 on topic 1, group 2 on topic 2…etc.
• Submit a powerpoint with references

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Two in-class quizzes (20% x 2)
• Duration: 30-45 minutes (Tentative)
• Composed of MC and short questions.
• Will be held at the beginning of the class.
• Don’t be late!

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Individual final paper (40%)
• Choose ONE question
• English 800-1,000 words
• The hardcopies of your paper and your VeriGuide
declaration are not required
• Footnotes (not included in the word count) but
they may not be read! Don’t put your important
points in footnotes!
• Proper citations

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 Tentative Schedule
Week L01, L02 L03 Topics Assessment
1 31-Jan 2-Feb 1) Insulin, its structure & related diagnosis
2 7-Feb 9-Feb Hormones, growth factors
3 14-Feb 16-Feb 2) Cholesterol Metabolism
4 21-Feb 23-Feb 3) Microscope & magnetic resonance imaging
5 28-Feb 2-Mar 4) Radioactivity & X-rays Group 1
6 7-Mar 9-Mar X-ray spectroscopy & crystal structure analysis Group 2
7 14-Mar 16-Mar 5) Genetics and base sequences in DNA Quiz 1 (Wk1-6)
8 21-Mar 23-Mar Biological synthesis of RNA & DNA Group 3
10 28-Mar 30-Mar Molecular structure of DNA Group 4
11 4-Apr 6-Apr 6) Immune system Group 5
12 11-Apr 13-Apr 7) Cyclic pathways of food & energy Group 6
13 18-Apr 20-Apr 8) Motion & force Quiz 2 (Wk7-12)
14 25-Apr 27-Apr Parity laws & elementary particles Group 7
15 2-May 4-May Optical fibers, laser Group 8
Final paper
(Due: 7 May)
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Prominent Scientists?
How to distinguish them?

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The Nobel Prize

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Alfred Nobel
(1833-1896)
• Born in Stockholm, Sweden.
• Chemical engineer
• His family has several distinguished
scientists:
• Maternal grandfather discovered lymph nodes
• His father, Emmanuel Nobel, self-taught father
of several inventions, including the submarine
torpedo. He taught Alfred Nobel chemistry.
• He invented a detonator to ignite
nitroglycerine (nitric acid + glycerine),
much powerful than gunpowder.

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Had became a very wealthy guy…
• Successfully refined the diverse procedures to stabilize
the product. One of the last consisted of mixing it with
kieselghur, an inert porous substance.
• The domestication of the explosive, primarily used to
loosen large masses of earth and stone, is an important
tool for civil engineering. Eg., the creation of canals and
tunnel.
• The use of dynamite – the name given to the mix of
nitroglycerine and kieselghur, was improved by Nobel
during a stay in Paris. It became widespread.
• Toward the end of the century, his invention was
manufactured by more than 80 factories in different
countries.

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How to use his fortune?
• Leave it to his heirs/successors?
• No…Nobel doubted their ability to use it properly.
• Nobel would like to use his fortune in a way that
seemed to him to be the “most profitable to humanity”:
to create a prize that would reward the most
commendable research in physics, chemistry and
medicine.
• To achieve this, he created the Nobel Foundation,
which also include a prize for the authors of the most
remarkable literature and those who strove to promote
world peace.

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The Nobel Foundation
• Some people think the creation of the foundation was a
gesture by Nobel to exonerate himself for contributing
to an industry that served war as much as peace.
• In fact, Nobel thought by giving the destructive power
to the countries as a way to dissuade those countries
from using it out of the fear of having the same weapon
turned against them (mutually assured destruction).
• After WWII, the foundation created a prize for
economics.
• Nobel died in Italy in Dec 1896, leaving an estimated
33M Kronors (about 25M USD in 2002) to his
foundation. This institution guarantees a substantial
sum of prize money to each laureate.

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The discoveries that we
will look at…

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Discoveries related to:
1. The treatment of diabetes
2. The regulation of cholesterol metabolism and familial
high blood cholesterol
3. Microscope and magnetic resonance imaging
4. Radioactivity
5. Genetics
6. Immune system
7. Cyclic pathways related to food and energy in plant
and animal life
8. The physical world

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 1. Discoveries related to
the Treatment of Diabetes
• Pancreatic insulin
• The structure of hormone insulin
• Diagnosis based on insulin level in blood
• Mechanism of hormones
• Brain hormones that control the secretion of the
pituitary gland
• Growth factors (eg. epidermal growth factor) and
its role in cancer development

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The Discovery of
Pancreatic Insulin

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 Exocrine secretion
A

Banting, Frederick Grant

Wirsung channel
Langerhans islets

(1891-1941)
The pancreas. It is both an endocrine (insulin and
glucagon) and an exocrine gland (digestive enzymes).
• Born in Alliston, Canada.
Insulin and glucagon regulate carbohydrate metabolism
and are produced by clusters of endocrine cells named
• The youngest son.
islets of Langerhans.
Frede
• His father was a farmer.
• He started in the general arts program- at 247Victoria
- College.
Failed his first year, applied to join the medical program in
1912.
• In August 1914, he attempted to enter the army, then again
in October, but was refused due to poor eyesight.
• Banting successfully joined the army in 1915.
• He graduated in Dec 1916. His class has been accelerated
due to the need for more doctors into the army.
• Nobel Laureate in Physiology/Medicine 1923 with John
McLeod, for the discovery of insulin.
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What is insulin?
• A kind of hormone.
• A peptide hormone (shorter amino acid
chain than protein hormones) produced
by beta cells of the pancreatic islets
encoded in humans by the INS gene.
• The main anabolic hormone of the body,
regulating the metabolism of
carbohydrates, fats and protein, by
promoting the absorption of glucose
from the blood into liver, fat and
skeletal muscle cells.
• Glucose production by the liver is
regulated by the concentrations of
insulin in the blood.

21
The pancreas
• An organ of the digestive
system and endocrine
system.
• The endocrine System is a
messenger system with
feedback loops of the
hormones released by
internal glands of an
organism directly into the
circulatory system, to
regulate target organs.
Endocrine System
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Banting’s Research
• Began in 1920 after the recovery from serious
wounds sustained on the Allied front in France.
• Look for the cause of sugar diabetes.
• A disease in which sugar levels in blood become very
high results in a slow but certain death.
• But before that…

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Diabetes has something to do
with the pancreas…
• It had been known for some time that removal of
the pancreas led to similar symptoms.
• Suspected pancreas produced a hormone capable
of regulating blood sugar levels.
• In 1901, Edward Albert Sharpey-Schaefer and other
researchers worked out that diabetes could be
caused by the lack of a substance produced by
specialized cells discovered in the pancreas by Paul
Langerhans, a German histologist.

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Banting wondered…
• Is it possible to extract that substance (insulin) from
the pancreas?
• Difficulty: to obtain sufficient quantity of insulin.
• Banting contacted McLeod who ran a research lab
in Canada for help.
• Collaborate with Charles Best, a young Canadian
physiologist under McLeod’s lab.

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How to test the insulin (the
pancreatic extracts)?
• How to ensure the procedure wouldn’t harm the
diabetic patients?
• Banting and Best first injected themselves with the
pancreatic extracts!

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The first therapeutic test
• was done in January 1922, on a 14 year-old diabetic
patient.
• A few days later, using a more purified insulin on
the same adolescent.
• How to obtain?
• James B. Collip, McLeod’s assistant, established a way to
obtain insulin in a highly purified form and in much
larger quantity.
• Results: A short time later, the young man’s sugar
concentrations in blood and urine decreased. The
treatment seemed successful.

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The Nobel Prize went to…
• Banting and McLeod!
• However, Banting was very unhappy.
• He felt sad because his colleague, Best, had not been
jointly awarded.
• Banting recognized Best’s invaluable contribution.
• On the other hand, he felt McLeod had not been a great
help in the discovery of insulin.
• As a result, Banting refused to accept the award!
• In the end, Banting was persuaded to accept it and
shared the prize money with Best.
28
 very of insulin. McLeod specialized in th
bolism and headed a research la
Canada
vised B

McLeod, John James Richard gave hi

borator
did not

(1876-1936)
and wa
tance to
and B
effort, s
in-sulin

• Scottish physiologist he at la
membe
B. Colli
• Got Nobel Prize for Medicine (1923), along with Banting, for his
John McLeod

work leading to the discovery of insulin.

• Specialized in the carbohydrate metabolism
• Headed a research laboratory in Toronto.
• Although he supervised Banting’s research and gave him a
previous collaborator, Charles Best, he did not like Banting and
didn’t help him in full effort.
• After years of efforts, the B&B team succeeded in extracting
insulin from pancreas, McLeod finally decided to add a member
to their team (James Collip) in order to isolate insulin chemically.
• Although he “free-rode” on Banting for the Nobel Prize, he
shared his portion of the prize money with Collip.

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Banting’s death
• Banting died in an air accident on his way to the
Ministry of Health of the Canadian Army. The plane
crashed over Scotland.
• After Banting’s death, Best took charge of the
laboratory in Toronto.

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The Discovery of
Insulin Structure

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Sanger, Frederick (1918-2013)
• Born in Rendcombe, England.
• Son of a physician.
• Graduated from Cambridge University in 1943
• A biochemist who has won twice the Nobel Prize
for Chemistry!
• 1958 for methods of amino acid sequencing
• 1980 with Walter Gilbert & Paul Berg for a method of
nucleic acid sequencing

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• After graduation, Sanger worked at
University’s famous molecular
biology laboratory (Francis Crick,
James Watson, Max Perutz worked
in the same lab.!).
• Determine not only the amino acid
composition of a protein, but also
the sequence of amino acid in the
protein chain. Eg. Insulin consists
two polypeptide chains, one of 21
and the other of 30 amino acids.

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Paper Chromatography
• Developed by Archer Martin
and Richard Synge.
• An analytic method used to
separate coloured chemicals or
substances.
• Made it possible to determine
the proportion of each amino Paper Chromatography
acid in a given protein.

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Sanger’s research
• Sanger chose to focus on insulin.
• A pancreatic extracts isolated by Banting
25 years earlier.
• After eight years of hard work, he
managed to reconstruct a insulin
containing 51 amino acids + two small
chains linked by disulfide bonds.
• With today’s technology, it takes no
more than a few days to sequence a
protein of this size. However, at that
time, it was a very difficult task,

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Sanger’s achievement
• He was able to demonstrate in 1953 that:
• A protein has a precise but non-repetitive sequence.
• It implied that the sequence information required to
produce such molecules must be encrypted somewhere,
somehow, genetically.
• Sanger has opened up the later possibility to the
discovery of such genetic code.

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The Development of
Diagnosis of Diabetes

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Yalow, Rosalyn
(1921-2011)
• Born in New-York City, New York.
• American medical physicist.
• Graduated from Hunter College in New York City in
1941.
• Obtained her Ph.D. in physics at the University of
Illinois in 1945.
• Won the Nobel Prize for Medicine in 1977, along
with Andrew V. Schally and Roger Guillemin, for
development of the technique of
radioimmunoassay (RIA).

38
Radioimmunoassay (RIA)
• Yalow’s first research was collaborated with
Solomon Berson. She has headed the Solomon
Berson Research Laboratory since 1973.
• A technique that can detect very small quantities of
substances such as hormones in biological
preparations.
• RIA is an immunoassay that uses radiolabeled
molecules in a stepwise formation of immune
complexes.

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RIA method
• Usually used to measure antigen concentrations, eg.
hormone level in blood.
• The method uses antibodies that recognize their
targets. It is very precise and able to detect
quantities as low as one thousandth of a billionth
of a gram, has benefited the development of
endocrinology.
• First applied in determining insulin concentration in
the blood of diabetics, but also in diagnosis of
thyroid diseases.

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How does it work?
• To perform RIA, a known quantity of an antigen is made
radioactive by labelling it with gamma-radioactive
isotopes of iodine.
• Antigen is a molecule that can be bind to a specific antibody
or T-cell receptor.
• The labelled antigen is mixed with a known amount of
antibody for that antigen. As a result, the two bind to
one another.
• A sample of serum from a patient containing an
unknown quantity of that same antigen is added. This
caused the unlabelled (cold) antigen from the serum to
compete with the raiolabelled (hot) antigen for
antibody binding sites.

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• As the concentration of "cold" antigen is increased,
more of it binds to the antibody, displacing the
radiolabelled variant, and reducing the ratio of
antibody-bound radiolabelled antigen to free
radiolabelled antigen.
• The bound antigens are then separated and the
radioactivity of the hot(bounded) antigen
remaining is measured using a gamma counter.

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43
RIA procedures
1. Specific antibodies of known concentration are fixed in
the microtitre well.
2. A known amount of hot antigens is then added to the
well.
3. Washed carefully to remove any unbound antigens
4. At this point, the radioactivity of the well will be
maximum.
5. Unlabeled antigens are then added to the well.
6. The unlabeled antigens will bind to the antibodies and
there will be free labeled antigens in the well.
7. Again washed carefully to remove the free labeled
antigens.
8. Radioactivity of wells is then measured by gamma-
counter.

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Discussion
• What is the meaning of a big award and prize
money?
• What does it take to get one?
• What would you do if you have won a Nobel Prize?

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Next week…
• Mechanism of hormones
• Brain hormones that control the secretion of the
pituitary gland
• Growth factors (eg. epidermal growth factor) and
its role in cancer development

46
References:
• Lehninger, A., Nelson, D. L. & Cox, M. M. (1993).
Principles of biochemistry. New York: Worth
Publishers.
• Leroy, F. (2003). A century of Nobel prizes recipients:
chemistry, physics, and medicine. New York: Marcel
Dekker.
• Symons, A. (2000). Nobel laureates, 1901-2000.
London: Polo Pub.
• Thompson, G.. (2012). Nobel prizes that changed
medicine. London: Imperial College Press.
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