Transcript The discovery and development of Penicillin

FLEMING,
FLOREY AND
CHAIN:
THE DISCOVERY AND
DEVELOPMENT OF
PENICILLIN
What is Penicillin?
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Penicillin is an antibiotic.
‘Antibiotic’ literally means ‘against life’ –
but antibiotics only kill life that is harmful
to living creatures, i.e. bacteria.
A bacterial infection is caused by millions
of tiny bacteria that are trying to survive
and multiply in the body. An antibiotic
attacks and kills these bacteria.
Before the development of penicillin, many
people suffered and died from bacterial
infections that are no longer considered
dangerous today.
So did Fleming actually discover
penicillin?
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Penicillin is made from a mould called
penicillium. This mould was first
discovered in the early 19th century by
John Sanderson who found that very
little grew near it.
In the 1880s, Joseph Lister noted these
observations and wrote to his brother to
say that he intended to try penicillin on
infected wounds.
Lister successfully treated a nurse with
an infected wound with penicillin, but
did not leave any notes on the case
and apparently did not continue his
research in this area.
Who was Alexander Fleming?
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Alexander Fleming was born
in Ayrshire, Scotland, in 1881.
He was the son of a farmer.
When he was 13, he moved
to London to live with his
older brother.
After graduating from the
University of London, he
became a bacteriologist at
St. Mary’s Hospital in the city.
The great re-discovery of penicillin!
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It was in the laboratory of St. Mary’s Hospital in 1928 that Fleming
rediscovered the properties of penicillin. This source comes from a
biography, The Life of Sir Alexander Fleming, written in 1963. It
describes when Fleming was visited by his friend, Pryce.
‘Fleming was in his little laboratory as usual, surrounded by
innumerable dishes. The cautious Scot disliked being separated from his
cultures before he was quite sure there was nothing more to be learned
from them... Fleming took up several old cultures and removed the lids.
Several of the containers had been contaminated with mould... ‘As soon as
you uncover a culture dish,’ he said to Pryce, ‘something tiresome is sure to
happen. Things fall out of the air.’
Suddenly he stopped talking, then, after a moment’s observation,
said... ‘That’s funny...’ On the cultures at which he was looking there was a
growth of mould, as on several of the others, but on this particular one, all
around the mould, the colonies of staphylococci had been dissolved...’
So what did the mould look like?
The mould Penicillium Notatum, shown growing in a Petri dish, and in close-up
How had it got into Fleming’s dish?
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On investigation, Fleming found that penicillin bacteria had got
on to the dish, perhaps blown into his lab through an open
window. The penicillin was killing the staphylococci.
Whether the account we just read it how it really happened, we
cannot be sure – even Fleming’s own accounts of how it
happened varied! Does that matter?
The important point is that Fleming identified the mould and saw
its significance – that penicillin could be applied to or injected
into areas where there were penicillin-sensitive microbes .
However, Fleming did not have the facilities or the support to
develop and test his idea that penicillin could fight infection.
Think!
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Why is Fleming usually thought of as the discoverer
of penicillin?
Why do you think that so many people observed
the power of penicillin but did not develop it as a
cure?
Florey and Chain
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It was the Second World War which
finally brought about the successful
development of penicillin.
In the 1930s two Oxford scientists,
Howard Florey and Ernst Chain,
became interested in Fleming’s 1929
paper on penicillin.
In 1939 they assembled a team of
pathologists, chemists and
biochemists, and three days after
the outbreak of war Florey asked
the British government for money to
fund the team’s research into
penicillin.
Howard Florey (left) and
Ernst Chain.
Do you think this was a good
time for Florey to approach
the government for money
into this kind of research?
Why?
The development of penicillin
Stage 1:Growing the penicillin
This was a combination of the latest freeze-drying technology and some much more traditional
equipment: thousands of milk bottles (in which to grow the bacteria), milk churns, a dog bath and a
hand pump! From this, the team were able to gather a few grams of pure penicillin.
Stage 2: Testing penicillin on animals
There was enough penicillin to test it on eight mice. They were injected with a deadly
bacteria (streptococci). Four of the mice were then given penicillin. 24 hours later the
mice which had not been injected with penicillin were dead. Those who had been
injected were healthy.
Stage 3: The first human trial of penicillin
By 1941 the team had enough penicillin to test it on a human. The patient had terrible abscesses
which had spread from his mouth to his scalp, eyes, arm and even his lung. He was going to die –
there was nothing to lose by trying penicillin. After four days of treatment he was much improved
and was sitting up in bed – penicillin worked. However, they did not have enough, and after five
days the supply ran out – the patient relapsed and died.
Production continues... but not in great quantities!
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Although this first patient still died, it was clear that
penicillin was a powerful drug. Production remained
painfully slow, but as new batches were produced, two
more patients were successfully treated.
In August 1942, Fleming himself used penicillin to
successfully treat a friend who had meningitis.
But the war was producing thousands of casualties –
penicillin needed to be mass produced if lives were to
be saved.
Steps to Successful Mass Production
June 1941:
Florey travels
to US to try to
get drug
companies to
develop
penicillin – not
much interest.
December
1941:
US enters the
war
After WW2:
Penicillin made
available for
civilian use.
1942:
US government
gives $80 million
to 4 drug
companies to
find a way to
mass produce
penicillin.
1943: Mass
production began.
Penicillin first used
by British army in
North Africa.
1945: US Army
using 2 million
doses of
penicillin a month
June 1944:
Enough penicillin
is available to
treat all the
casualties of DDay.
How important was penicillin?
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It is estimated that without
penicillin, another 12-15
per cent of wounded
Allied soldiers would
have died of infections.
Penicillin also roughly
halved the average time
the Allied wounded spent
in hospital.
How important was penicillin?
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Penicillin was a miracle drug when
it was first developed. It could treat
a wide range of infections and
diseases, including streptococcus,
scarlet fever, syphilis and
gonorrhoea.
In 1945, Fleming, Florey and Chain
were jointly awarded the Nobel Prize
for Medicine for their work on
penicillin.
Penicillin – why then?
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On your own slide, draw a spider chart which shows
the different factors which influenced the discovery
of penicillin.
It should help you to think about why penicillin was
finally mass produced in 1942-1945, and not
before.
Try to link any factors which you think are interconnected.
So which factor was most important?
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Do you think any one factor was particularly
important to the development of penicillin?
Who do you think deserves the credit for the
discovery of penicillin?