Student’s Edition
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Day 6
9th – 10th Grade Bellringers
Story: Penicillin
Abstract
(1)Penicillin is one of the earliest discovered and widely used antibiotic agents, derived from
the Penicillium mold. Antibiotics are natural substances that are released by bacteria and fungi
into the environment, as a means of inhibiting other organisms - it is chemical warfare on a
microscopic scale.
(2)In 1928, Sir Alexander Fleming observed that colonies of the bacterium Staphylococcus
aureus could be destroyed by the mold Penicillium notatum, proving that there was an
antibacterial agent there in principle. This principle later lead to medicines that could kill certain
types of disease-causing bacteria inside the body.
Discovering Penicillin
Much of Fleming's work focused on the search for a "wonder drug." Though the concept of
bacteria had been around since Antonie van Leeuwenhoek first described it in 1683, it wasn't
until the late nineteenth century that Louis Pasteur confirmed that bacteria caused diseases.
However, though they had this knowledge, no one had yet been able to find a chemical that
would kill harmful bacteria but also not harm the human body.
Naming the substance penicillin, Dr. Fleming in 1929 published the results of his investigations,
noting that his discovery might have therapeutic value if it could be produced in quantity. It was
not until 1939 that Dr. Howard Florey, a future Nobel Laureate, and three colleagues at Oxford
University began intensive research and were able to demonstrate penicillin's ability to kill
infectious bacteria. Using new chemical techniques, they were able to produce a brown powder
that kept its antibacterial power for longer than a few days. They experimented with the
powder and found it to be safe.
The chemical structure of penicillin was determined by Dorothy Crowfoot Hodgkin in 1945.
Penicillin has since become the most widely used antibiotic to date, and is still used for many
Gram-positive bacterial infections. A team of Oxford research scientists led by Australian
Howard Florey and including Ernst Boris Chain and Norman Heatley devised a method of massproducing the drug. Florey and Chain shared the 1945 Nobel Prize in Medicine with Fleming for
their work. After World War II, Australia was the first country to make the drug available for
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Day 6
civilian use. Chemist John C. Sheehan at MIT completed the first total synthesis of penicillin and
some of its analogs in the early 1950s, but his methods were not efficient for mass production.
Mass Production
With World War II raging in Europe and the German bombardment of England, all of England's
resources and efforts had to be placed into the war effort. Florey and Chain would be unable to
utilize any factory resources in England to experiment further with producing penicillin in
adequate amounts to be useful for large-scale usage. Also, it was feared that even if a factory
could be utilized, it was feared that all their efforts could possibly be lost if the factory was
bombed.
However, during the summer of 1941, Florey had negotiated an agreement with the Rockefeller
Foundation, which had been funding his research, to fly him and one of his assistants to the
United States to continue his work with penicillin. The United States, who was at that time a
neutral country, would enter into World War II in another few months. This gave added
incentive to the penicillin project, which became a war project and was given top priority.
Despite the efforts and resources that were being given to producing large quantities of
penicillin, it soon became obvious that Fleming's original culture would not be able to produce
enough penicillin regardless of the environment in which the fungus was grown. On March 14,
1942, the first patient was treated for streptococcal septicemia with US-made penicillin
produced by Merck & Co. Half of the total supply produced at the time was used on that one
patient. By June 1942, just enough US penicillin was available to treat ten patients.
In July 1943, the War Production Board drew up a plan for the mass distribution of penicillin
stocks to Allied troops fighting in Europe. There are many species of Penicillium, and a search
was started to find other species that could be tested for penicillin production. Eventually, one
was found, on a moldy cantaloupe in a market in Peoria, Illinois. This species would later be
identified as Penicillium chrysogeum, and would produce approximately 200 times as much
penicillin as the species used at that time.
The discovery of the cantaloupe, and the results of fermentation research on corn steep liquor
at the Northern Regional Research Laboratory at Peoria, Illinois, allowed the United States to
produce 2.3 million doses in time for the invasion of Normandy in the spring of 1944. Largescale production resulted from the development of deep-tank fermentation by chemical
engineer Margaret Hutchinson Rousseau. As a direct result of the war and the War Production
Board, by June 1945, over 646 billion units per year were being produced.
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During this period of time when mass production of penicillin was being perfected, Fleming had
little to do with penicillin. Florey did update him as to the progress being made and samples
were often sent to him, but by this time Fleming was no longer part of penicillin research.
Further Research
Scientist then began to try to increase the amount of penicillin produced by P. chrysogenum, by
irradiating it with X-rays and UV rays in order to induce mutations of this species. This
eventually lead to a mutant that produced 1000 times the amount of penicillin than Fleming's
original culture.
In addition to the development of this mutant, a new means of growing the mold was also
perfected. Previously, penicillin was grown in flask, the size of milk bottles, and hundreds of
bottles of Penicillium notatum were needed to produce enough penicillin for only a single
person. The new method involved growing the mold in large metal tanks, which held 25,000
gallons of nutrient, were aerated so that the mold could grow throughout the entire tank rather
than on top. Aeration was the key to growing it in such large tanks. Previously, this had not
been tried because it was known that the mold would only grow on the surface of the liquid
medium.
With this new method, production quantity began to rise. In 1943, 29 pounds were produced,
and with increases in the number of pharmaceutical companies producing penicillin, there was
a tremendous increase. By the end of the war, enough penicillin was produced to treat seven
million patients/year.
With respect to the war, the use of penicillin was immediately apparent. During World War I,
death rate from pneumonia in the American Army totaled 18%. In World War II, it fell to less
than 1%.
After World War II
One illness after another, that was tested, was cured by penicillin, which was by this time
dubbed a "wonder drug." In addition to pneumonia and blood poisoning, the major causes of
death, in hospitals, during the war, strep throat, scarlet fever, diphtheria, syphilis, gonorrhea,
meningitis, tonsillitis, rheumatic fever, and many other diseases were successfully treated with
penicillin.
Although, Fleming was the discoverer of penicillin, he was almost forgotten by the time
penicillin was being mass produced. However, he would be rescued from oblivion, in 1943,
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when he was knighted along with Howard Florey, and two years later was awarded the 1945
Nobel Prize in Physiology and Medicine along with Florey and Chain.
Though Fleming is credited for discovering penicillin, it took Florey and Chain to make it a
usable product. Fleming penicillin. On May 25, 1948, Andrew J Moyer was granted a patent for
a method of the mass production of penicillin.
Student’s Edition
Day 7
9th – 10th Grade Bellringers
Question 1
According to the author, which of these statements
was not a reason why was it important for Florey and
Chain to find the right place to produce and continue
further research on penicillin?
a. Because of the war, Florey and Chain had
limited resources in other countries outside of
the US to continue their research.
b. Florey and Chain also feared that their factory
could be bombed if located in an unsafe area.
c. The United States was a valuable ally at that
time and could greatly influence the
development of the drug.
d. Florey and Chain needed to find stronger and
more productive cultures to assist in the mass
production effort.
Answer:
Question #1 has to do with analyzing a
text’s form and meaning. What are
some things to remember about this
type of question?
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Question 2
What is the meaning of the word “colonies” in paragraph 2?
a. A country or area under the control of another country
b. A group of people living together
c. A group of organisms living together
Answer:
Question 3
From your understanding of the text, what is the purpose of this text?
a. To explain the creation, development, and significance of penicillin
b. To describe why penicillin has had such a significant impact on medicine
c. To provide a basic biography of Penicillin’s founders
Answer:
Student’s Edition
Day 8
9th – 10th Grade Bellringers
Question 1
Of the items or events listed below, which one does
the author use to illustrate the human impact of
penicillin?
a.
b.
c.
d.
The naming of the drug
World War II
Finding a factory use
The discovery of the moldy cantaloupe
Answer:
Question #1 has to do with point of
view. What are some things to
remember about this type of question?
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Question 2
Of the choices below, which fully describes the impression that the words “chemical warfare” has on the
reader?
a.
b.
c.
d.
Using the toxic properties of chemicals as a weapon to kill or injure the enemy
An industrial accident that kills or injures the enemy
Using modern weapons to hurt others
Both a and c
Answer:
Question 3
Re-evaluate the order and the organization of this excerpt. What organization technique does the
author use and why do you think he/she used it?
a.
b.
c.
d.
Chronological and Classification – to outline the development of the drug
Spatial and Descriptive – to describe the drug and how it’s made
Compare and Contrast – to compare penicillin’s development with other drugs
Logical – to prove why penicillin works
Answer:
Student’s Edition
Day 9
9th – 10th Grade Bellringers
Question 1
After reading this excerpt, what do you think the
author should have included in his or her excerpt to
establish stronger credibility of the information?
a. Use quotes from professionals who use
penicillin in their treatments
b. Provide illustrations of penicillin and drug
development
c. Incorporate citation in the excerpt to show
where the information was found
d. Give more information!!!
Answer:
Question #1 has to do with evaluating
claims and evidence. What are some
things to remember about this type of
question?
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Question 2
Why was the development of penicillin so significant?
a. Penicillin was the first antibiotic produced for the masses that would kill harmful bacteria
without harming the body.
b. Penicillin was a cheap alternative to the other forms of treatment at the time.
c. Both a and b
d. None of the above
Answer:
Question 3
Which penicillin development had the greatest impact on drug production, according to the text?
a.
b.
c.
d.
Growing mold in large metal tanks
Creating a mutant strain that produces much more penicillin
Discovering the new strain of penicillin on the cantaloupe
All of these developments had significant influences on drug production
Answer: