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Alexander Fleming and Penicillin:
The Accidental Discovery?
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The Discovery o! $yso)yme
• n *+,, Fleming describedlyso)yme
• $yso)ymes are en)ymes
present in diverse materialssuch as tears" mucous" eggwhites etc that cause
bacteria to lyse
• -is lyso)yme research grew
out o! his interest inshowing the ine!!ectivenesso! chemical antiseptics totreat in!ection
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Fleming Disagrees
• .ased on $ister&s theory" physicians o! the time
generally believed that i! antiseptics 'illed germs
they were there!ore use!ul in treating woundin!ections
• Fleming strongly disagreed with this idea
• Fleming and his mentor" /right" argued that the
best way to treat wound in!ections was to enhance
the body&s natural immune response
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A 0evolutionary Approach to
/ound 1are• Fleming noted that"
although antiseptics 'ill
bacteria" they also 'ill
leu'ocytes o! the immune
system more rapidly than
they 'ill invading bacteria
• They recommended using
saline solution to cleansewounds instead o!
antiseptic solutions
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$yso)yme 0esearch
• Few accepted Fleming&s recommendation !or woundcare
• This re2ection !ueled Fleming&s search !orantibacterial agents and particularly his interest inlyso)yme
• $i'e leu'ocytes" lyso)yme was an endogenous way
to treat in!ections• Fleming believed that the best way to treat woundin!ections was to enhance the body&s naturalimmune response
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$yso)yme continued• n *+,, Fleming described
lyso)yme when he notedthat lyso)yme(containingmaterial would inter!ere
with the growth o! bacterial cultures
• Fleming !ound that aculture o! his own nasalmucous inhibited thegrowth o! staph cultured!rom that same mucous
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$yso)ymes continued
• Fleming was !ortunate in that the strain o!
bacteria he was culturing was particularly
sensitive to lyso)yme
• -owever" Fleming was disappointed in that
the bacteria most susceptible to lyso)yme
were those that aren&t as in!ectious inhumans
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Discovery 3 3 3
• n *+,4 a!ter returning to his lab !ollowing a twowee' vacation Fleming encountered the place in itsusual disarray
• Fleming had a inoculated a number o! petri disheswith staphylococci prior to leaving on vacation
• -e hadn&t placed them in an incubator because he'new that the staph would su!!iciently multiply overthe long vacation
• $ittle did he 'now that penicillium mold grows wellat room temperature
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Fleming&s observation• Fleming returned to his lab to
!ind many o! his culture platescontaminated with !ungus
• -e immediately started
preparing to clean all his plates but it happened that a!ormer member o! his lab wasvisiting that day
• Fleming too' some o! thecontaminated cultures to showhis visitor and that&s when henoticed the inhibition )onearound the !ungus
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Fleming&s %bservation cont3
• Fleming was not very
'nowledgeable about
!ungi but 'new thatthe mold in his dish
was a species o!
penicillin
• 5ventually determinedto be Penicillium
notatum
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Accidental?
• Fleming&s observation was made under
some accidental circumstances but clearly
made sense in light o! Fleming&s research bac'ground
• Fleming had the sophistication to reali)e
that anti(bacterial agents existed 6 this viewwas really !ueled by his bac'ground in
lyso)yme research
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The Power o! Penicillin
• t was obvious to
Fleming that penicillin
was much more power!ul than
lyso)ymes because his
crude extracts could be
diluted *777 times andstill be e!!ective in
'illing bacteria
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*+,+ Paper
• n *+,+ Fleming published a paper detailing
his discovery
• This was also a crucial moment because his
ideas reached a large audience
• .ut it wasn&t until ten years later that other
scientists began trying to use penicillin totreat clinical disease
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*+,+(*+8*
• Fleming continued to wor' on and o!! with penicillin during this time but was never able to produce it in #uantities necessary !or practicaltesting or applications
• Fleming !ound that many o! his cultures wereunstable and stopped producing mold a!ter eightdays
• nterestingly" Fleming initially conceived o! penicillin as a topical agent and did not thin' o!using it as an in2ectable or ingestible medication
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Fleming&s 0esearch• Fleming did in2ect one rabbit and one mouse with
penicillin to ma'e sure there were no ill e!!ects 9therewere none but never in2ected these animals with asimultaneous bacterial strain
• ronically" even though Fleming was an expert atadministering intravenous salvarsan to syphilis patients"he only thought o! penicillin as an external germicide
• Fleming" in his *+,+ article" compares penicillin&s
e!!ects to carbolic acid 9anti(septic !avored by $isterand his !ollowers !or treating wound in!ections
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Production Accelerates
• From ;anuary to <ay
*+=8 only =77 million
units o! penicillin had been made
• .y the time the war
ended >S companies
were ma'ing @7 billion units a month
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Awards
• Fleming and Florey
were 'nighted in *+==
• 1hain was later'nighted in *+@
• The Bobel Pri)e in
Physiology or
<edicine was awarded
to Fleming" Florey and
1hain in *+=@
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