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Penicillin

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Emily Fox

on 29 January 2014

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Transcript of Penicillin

Penicillin
Development
into useful medicine
How does penicillin work?
Penicillin kills bacteria by interfering with its ability to create a cell wall. It manages for several bacteria within approximately half an hour. The bacteria grow in size, but cannot divide. Eventually the weak cell wall bursts or breaks, preventing it from reproducing.
Penicillin
Emily Olivia Fox
2Q, Gimnazija Bežigrad
Personal Project
Discovery
Penicillin was unintentionally discovered in September 1928, when one day scientist Alexander Fleming noticed that mould had accidentally developed on a set of culture dishes being used to grow the staphylococci germ. The dish had been left in his laboratory overnight and when Fleming returned, the Penicillium notatum mould seemed to have created a bacteria-free circle around itself by dissolving the colonies of bacteria around it. (The mould had obviously entered the dish through air). He realized that Penicillim mould, just like the human body, develops a substance (antibiotic penicillin) which is capable of destroying even some of the most deadly germs. He grew the mould in broth liquid (a growth medium) in attempt to make it useful. The liquid was just as successful against germs, also when it was diluted, but it still wasn't appropriate for injecting into the body. Fleming named the active substance penicillin.
Prof. Howard Florey
Professor Howard Florey was born in 1898 in Australia. Already at a young age he showed interest in medical research. He studied science and medicine and then got a scholarship to study at Oxford university. He became professor of Pathology at Oxford in 1935. He recruited Ernst Chain to work with him on penicillin and the rest of the team too as he was the leader.
He was vital in the development of penicillin over the whole time.
He too received a Nobel Prize in 1944 and died in 1968 in Oxford.
Ernst Chain
Ernst Boris Chain was born in 1906 in Berlin, Germany. He studied chemistry and physiology and when he was finished, worked at German institutes. In 1933 he migrated to England to escape the Nazis.
He was recruited by Howard Florey to work on his team and was vital in developing the technique of purifying penicillin to the extent of making it appropriate to be used by human beings.
He too received a Nobel Prize in 1944 and died in 1979.
Alexander Fleming
Alexander Fleming was a Scottish bacteriologist. He was born in Ayrshire, Scotland on the 6. August 1881.
At the age of 13, he moved to London and later on trained as a doctor. In 1906, he qualified and began research at St Mary's Hospital Medical School at the University of London. In 1928 he was researching on influenza. He discovered Penicillin; but he didn't come to the further stage of purifying and testing its effects against bacterial infections when injected into a living animal or patient.
He got a Nobel Prize in Medicine in 1945 and was much rewarded for his work. He died on 11 March 1955 with the nickname 'Penicillin Man'.

Alexander Fleming discovered the effects of penicillin, but didn't develop it to the extent in which it could be useful to living beings.

Mass production
Florey realized that he needed to expand production because the
drug could be an effective treatment for infection for dying infected soldiers in the war.
The Dunn School (where Florey and his team were) became a kind of factory to produce enough penicillin for trials in humans.

At first, supplies of penicillin were very limited, but by the 1940s it was taken over to America to be produced on a mass scale in penicillin factories by the American drug industry. Scientist there developed a new way of culturing penicillin, a faster way. Workers in the factories, 'penicillin girls’ were taken on to maintain production in newly designed vessels which were continuously in use. By the end of the war, Penicillin was produced at an even greater scale, also in the UK,
and was exported all over the world.
Use of Penicillin
The drug played a vital role in wartime of
World war II
. Penicillin was immensely in use on the battlefields; they had it in jars in boxes, and they injected it into the patients. It reduced the deaths among soldiers to a third of the rate of WWI.
Supplies of penicillin accompanied the troops making the D-day landings in June 1944, and the number of deaths from infected wounds dramatically reduced.

It was truly a miracle healer and saved thousands of lives of soldiers in a short time. Its outstanding success made it famous.
Timeline
Discovered by Alexander Fleming
1928
Antibiotics
A solution was to make other antibiotics like penicillin (β-lactams) with structures that are not destroyed by β-lactamase, by adding other atoms to the core of penicillin. This resulted in an ever growing family of penicillin-like antibiotics, each capable of tacking certain germs which penicillin was resistant to.

Today
Unfortunately, an increasing threat is now Methicillin-Resistant Staph aureus (MRSA) which avoids methicillin and other β-lactams by an alteration in MRSA's penicillin target-binding site.

Bacteria are constantly evolving new defenses, so treatment of bacterial infections requires a constant search for antibiotics with novel modes of action. Since the late 1940s, scientist have developed over 150 antibiotics.

Problems
Allergies
Some patients treated with penicillin end up having allergic reactions to it. Common allergic reactions to penicillin include rashes, itchy eyes, hives, and swollen face, lips or tongue.
Resistance
The inappropriate use of antibiotics (pointlessly treating viral infections with antibacterials) flooded the environment with bacteria which could resist penicillin. This is because penicillin in only treats bacterial infections.
Although penicillin was a wonder drug when discovered, some bacteria exposed to penicillin survived because they produced the enzyme β-lactamase that destroys penicillin’s structure.
It was a team at Oxford, led by professor Howard Florey and including Ernst Chain, who helped to turn Fleming's find into a usable drug.

They began to look at a range of substances that might have an effect on bacteria.
Around 1939, they came to the conclusion that penicillin was far more effective in fighting bacteria than viruses, though they still didn't have a method to extract and purify the penicillin from the Penicillium mould.

In 1940, Norman Heatley, a biochemist on the team, came up with a method called back-extraction to isolate the penicillin. They managed to transfer penicillin through liquids until it was pure enough to be held within pure water. They then extracted the pure water leaving only brown powder (penicillin).
An experiment with eight mice was performed. First lethal doses of the bacteria Streptococcus were injected into all tested mice. Half were then injected with the brown powder (penicillin). By the next morning, all the untreated mice were dead while those that had received the powder survived for days to weeks.

Ernst Chain and another member of the team then developed a successful method to make penicillin pure enough for man. The main points were in controlling the pH of the “juice,” reducing the sample’s temperature, and evaporating the product over and over (freeze-drying it). With this process, a lot of mold broth was used to produce only a tiny amount of purer penicillin.

This process was later improved by a different biochemist on the research team.
1939
Britain and France declared war on Germany
Penicillin was declared to work only against bacteria
Method of extracting penicillin developed
First effective stable form of Penicillin produced
1940
1941
First patient cured
1935
Florey became professor
at Oxford
Established the team
1943
First tested on soldiers
1944
Saved immense
amount of soldiers
(especially on D-day)
1944
Fleming, Florey and Chain
receive Nobel Prize for medicine
Mass production
New antibiotics developed
1940s+
First human test
In February 1941, penicillin was first tested on a patient. He was injected with penicillin regularly over four days, and within 24 hours he had greatly improved. But before his cure was complete, supplies of the new drug ran out. He relapsed at the beginning of March, and died two weeks later. Over other tests, penicillin was proved successful.
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