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Alexander Fleming and Penicillin:

The Accidental Discovery?

Treating Syphilis
Fleming had published on this topic and was
considered an expert at administrating salvarsan
If fact, Fleming made quite a bit of extra income
treating members of the London Arts community
for syphilis
Often, artists would give him paintings as payment
for his services
Flemings background in administering salvarsan
exposed him to the ill-effects of substances that
interfere with natural host defense processes

The Discovery of Lysozyme


In 1922 Fleming described
lysozyme
Lysozymes are enzymes
present in diverse materials
such as tears, mucous, egg
whites etc that cause
bacteria to lyse
His lysozyme research grew
out of his interest in
showing the ineffectiveness
of chemical antiseptics to
treat infection

Fleming Disagrees
Based on Listers theory, physicians of the time
generally believed that if antiseptics killed germs
they were therefore useful in treating wound
infections
Fleming strongly disagreed with this idea
Fleming and his mentor, Wright, argued that the
best way to treat wound infections was to enhance
the bodys natural immune response

A Revolutionary Approach to
Wound Care
Fleming noted that,
although antiseptics kill
bacteria, they also kill
leukocytes of the immune
system more rapidly than
they kill invading bacteria
They recommended using
saline solution to cleanse
wounds instead of
antiseptic solutions

Lysozyme Research
Few accepted Flemings recommendation for wound
care
This rejection fueled Flemings search for
antibacterial agents and particularly his interest in
lysozyme
Like leukocytes, lysozyme was an endogenous way
to treat infections
Fleming believed that the best way to treat wound
infections was to enhance the bodys natural
immune response

Lysozyme continued
In 1922 Fleming described
lysozyme when he noted
that lysozyme-containing
material would interfere
with the growth of
bacterial cultures
Fleming found that a
culture of his own nasal
mucous inhibited the
growth of staph cultured
from that same mucous

Lysozymes continued
Fleming was fortunate in that the strain of
bacteria he was culturing was particularly
sensitive to lysozyme
However, Fleming was disappointed in that
the bacteria most susceptible to lysozyme
were those that arent as infectious in
humans

Discovery . . .
In 1928 after returning to his lab following a two
week vacation Fleming encountered the place in its
usual disarray
Fleming had a inoculated a number of petri dishes
with staphylococci prior to leaving on vacation
He hadnt placed them in an incubator because he
knew that the staph would sufficiently multiply over
the long vacation
Little did he know that penicillium mold grows well
at room temperature

Flemings observation
Fleming returned to his lab to
find many of his culture plates
contaminated with fungus
He immediately started
preparing to clean all his
plates but it happened that a
former member of his lab was
visiting that day
Fleming took some of the
contaminated cultures to show
his visitor and thats when he
noticed the inhibition zone
around the fungus

Flemings Observation cont.


Fleming was not very
knowledgeable about
fungi but knew that
the mold in his dish
was a species of
penicillin
Eventually determined
to be Penicillium
notatum

Accidental?
Flemings observation was made under
some accidental circumstances but clearly
made sense in light of Flemings research
background
Fleming had the sophistication to realize
that anti-bacterial agents existed this view
was really fueled by his background in
lysozyme research

The Power of Penicillin


It was obvious to
Fleming that penicillin
was much more
powerful than
lysozymes because his
crude extracts could be
diluted 1000 times and
still be effective in
killing bacteria

1929 Paper
In 1929 Fleming published a paper detailing
his discovery
This was also a crucial moment because his
ideas reached a large audience
But it wasnt until ten years later that other
scientists began trying to use penicillin to
treat clinical disease

1929-1931
Fleming continued to work on and off with
penicillin during this time but was never able to
produce it in quantities necessary for practical
testing or applications
Fleming found that many of his cultures were
unstable and stopped producing mold after eight
days
Interestingly, Fleming initially conceived of
penicillin as a topical agent and did not think of
using it as an injectable or ingestible medication

Flemings Research
Fleming did inject one rabbit and one mouse with
penicillin to make sure there were no ill effects (there
were none) but never injected these animals with a
simultaneous bacterial strain
Ironically, even though Fleming was an expert at
administering intravenous salvarsan to syphilis patients,
he only thought of penicillin as an external germicide
Fleming, in his 1929 article, compares penicillins
effects to carbolic acid (anti-septic favored by Lister
and his followers for treating wound infections)

Production Accelerates
From January to May
1943 only 400 million
units of penicillin had
been made
By the time the war
ended US companies
were making 650
billion units a month!

Awards
Fleming and Florey
were knighted in 1944
Chain was later
knighted in 1965
The Nobel Prize in
Physiology or
Medicine was awarded
to Fleming, Florey and
Chain in 1945