This presentation highlights on an important discovery i.e. Penicillin antibiotics by Sir Alexander Fleming.

1. DISCOVERY OF PENICILLIN
Note:- The information in this power point presentation is
Collected from different sources and only Edited by:-
Dr. Vishal S. More, Amrutvahini College of pharmacy,
Sangamner

2. DISCOVERY OF PENICILLIN
Dr. Vishal S. More,
Assistant Professor,
Dept. of Pharmaceutical Chemistry,
Amrutvahini College of Pharmacy, Sangamner.

3. Alexander Fleming and Penicillin:
The Accidental Discovery

4. A Clinical Case
• A 48 year old policeman
presents to Urgent Care
with a small cut on his
face after shaving
• The cut is slightly red and
draining a small amount of
pus
• Before the 1940s this
small, infected cut could
lead to a swift death

5. The Discovery of Penicillin: One of
the Most Important Events in
Medical History
• For the first time, doctors had a way to treat
infections and miraculously save lives
• Prior to the discovery of penicillin patients
often died from trivial injuries or infections
• Today in the United States, deaths by
infectious bacterial diseases are one-
twentieth what they were in 1900

6. Prior to Penicillin
• Physicians had little ability to help patients
suffering from infection Physicians could only
watch and wait hoping a patient’s immune
system could topple an infection

7. 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.

8. Chemical Antiseptics
The idea of using chemical
antiseptics to kill germs was a
revolutionary idea of the late 19th
century popularized by “Joseph
Lister”
Lister was a Scottish surgeon,
influenced by Pasteur, who
believed that germs caused
infection Lister (1827-1912)

9. Fleming Disagrees
Based on Lister’s 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
body’s natural immune response

10. A Revolutionary Approach to
Wound Care
• Fleming and Wright 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

11. Discovery . . .
• In 1928 after returning to his lab following a two
week vacation Fleming encountered the place in
its usual disarray
• Fleming had inoculated number of petri dishes
with Staphylococci prior to leaving on vacation
• He hadn’t placed them in an incubator because he
knew that the Staphylococci would sufficiently
multiply over the long vacation
• Little did he know that penicillium mold(fungus)
grows well at room temperature

12. Fleming’s 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 that’s when he
noticed the inhibition zone
around the fungus

13. Fleming’s observation
Penicillium colony
Staphylococci undergoing lysis
Normal staphylococci colony

14. Fleming’s Observation
• Fleming was not very knowledgeable about
fungi but knew that the mold in his dish was a
species of penicillin
Eventually
determined to
“Penicillium notatum”

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

16. The Power of Penicillin
• It was obvious to Fleming
that penicillin was much
more powerful than
lysozymes because crude
extracts could be diluted
1000 times and still be
effective in killing
bacteria

17. Fleming, Florey and Chain
Alexander Fleming Howard Walter Florey Ernst Boris Chain

18. Florey, Chain Research
• Soon after beginning his
research, Chain discovered
that penicillin was not an
enzyme but a molecule
• He got the fact that
penicillin was a very
unstable molecule
• Chain was able to freeze-
dry the penicillin and
produce a stable brown
powder
• Tested on mice, a huge
dose proved safe

19. Mass Production of Penicillin
• Penicillin production began in Britain on a small scale
in 1941
• The British government encouraged the development
of a number of small production facilities at this time.
Large scale companies could easily be bombed by
German war planes.

20. 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

21. Infections and World War
• During WWI the death
rate from pneumonia
in the US Army
totaled 18%
• During WWII the
death rate fell to less
than 1%

22. Awards
• The Nobel Prize in
Physiology or Medicine
was awarded to Fleming,
Florey and Chain in
1945

23. Modern Day Treatments
• A 48 year old policeman
presents to Urgent Care
with a small cut on his
face after shaving
• The cut is slightly red and
draining a small amount of
pus
• Today-
Prescribe antibiotic

24. • The biosynthesis of Penicillin was dependent
upon growth of Penicillium notatum and
Penicillium chrysogenum
The name Penicillium
comes from Penicillus =
brush and this is based on
the brush-like appearance
of the fruiting structures

25. Chemistry

26. • In 1958 the basic nucleus 6-Animo
penicillanic acid was isolated and it became
possible to synthetically produce a range of
Penicillins
• The Thiazolidine ring fused to a Beta-lactam
ring to form 6-Amino penicillanic acid
(6-APA) upon which the antibacterial activity
depends
• The substitution on the N-acyl group
determines the individual penicillin
characteristics

28. “One sometimes finds, what one is not
looking for. When I woke up just after dawn
on September 28, 1928, I certainly didn't
plan to revolutionize all medicine by
discovering the world's first antibiotic, or
bacteria killer. But I suppose that was
exactly what I did”.
-Sir Alexander Fleming

30. By 1927, Fleming had been investigating the
properties of staphylococci. He was already well
known from his earlier work, and had developed a
reputation as a brilliant researcher. In 1928, he
studied the variation of Staphylococcus aureus
grown under natural condition, after the work of
Joseph Warwick Bigger, who discovered that the
bacterium could grow into a variety of types
(strains).
SEQUENCE OF EVENTS IN PENICILLIN
DISCOVERY

31. On 3 September 1928, Fleming returned to his
laboratory having spent a holiday with his family at
Suffolk. Before leaving for his holiday, he inoculated
Staphylococci on culture plates and left them on a
bench in a corner of his laboratory.
On his return, Fleming noticed that one culture was
contaminated with a fungus, and that the colonies of
staphylococci immediately surrounding the fungus had
been destroyed, whereas other staphylococci colonies
farther away were normal, famously remarking "That's
funny".

32. Fleming showed the contaminated culture to his
former assistant Merlin Pryce, who reminded him,
"That's how you discovered lysozyme." He identified
the mould as being from the genus Penicillium. He
suspected it to be P. chrysogenum, but a colleague
Charles J. La Touche identified it as P. rubrum.
(It was later corrected as P. notatum and then
officially accepted as P. chrysogenum; but finally in
2011, it was resolved as P. rubens.)
The laboratory in which Fleming discovered and
tested penicillin is preserved as the Alexander
Fleming Laboratory Museum in St. Mary's Hospital,
Paddington.

33. Fleming grew the mould in a pure culture and
found that the culture broth contained the
antibacterial a substance.
He investigated its positive anti-bacterial effect on
many organisms, and noticed that it affected
bacteria such as staphylococci and many other
Gram-positive pathogens that cause scarlet fever,
pneumonia, meningitis and diphtheria, but not
typhoid fever or paratyphoid fever, which are
caused by Gram-negative bacteria, for which he
was seeking a cure at the time.

34. It also affected Neisseria gonorrhoeae, which
causes gonorrhoea, although this bacterium is
Gram-negative. After some months of calling it
"mould juice" or "the inhibitor", he named the
substance it released penicillin on 7 March 1929.
Fleming published his discovery in 1929, in the
British Journal of Experimental Pathology, but little
attention was paid to his article. Fleming continued
his investigations, but found that cultivating
Penicillium was quite difficult, and that after having
grown the mould, it was even more difficult to
isolate the antibiotic agent.

35. Fleming's impression was that because of the
problem of producing it in quantity, and because
its action appeared to be rather slow, penicillin
would not be important in treating infection.
Fleming also became convinced that penicillin
would not last long enough in the human body
(in vivo) to kill bacteria effectively. Many
clinical tests were inconclusive, probably
because it had been used as a surface antiseptic.

36. In the 1930s, Fleming's trials occasionally
showed more promise, but Fleming largely
abandoned penicillin work, leaving Howard
Florey and Ernst Boris Chain at the Radcliffe
Infirmary in Oxford to take up research to
mass-produce it, with funds from the U.S. and
British governments.
They started mass production after the bombing
of Pearl Harbor. By D-Day in 1944, enough
penicillin had been produced to treat all the
wounded in the Allied forces.

37. Thank you

38. PENICILLIN DISCOVERED
It all started with a mold that developed on a staphylococcus culture plate.
Since then, the discovery of penicillin changed the course of medicine and
has enabled physicians to treat formerly severe and life-threatening illnesses
such as bacterial endocarditis, meningitis, pneumococcal pneumonia,
gonorrhea and syphilis. Sir Alexander Fleming, a Scottish researcher, is
credited with the discovery of penicillin in 1928. At the time, Fleming was
experimenting with the influenza virus in the Laboratory of the Inoculation
Department at St. Mary’s Hospital in London. Often described as a careless
lab technician, Fleming returned from a two-week vacation to find that a
mold had developed on an accidentally contaminated staphylococcus culture
plate. Upon examination of the mold, he noticed that the culture prevented
the growth of staphylococci. An article published by Fleming in the British
Journal of Experimental Pathology in 1929 reads, “The staphylococcus
colonies became transparent and were obviously undergoing lysis… the
broth in which the mold had been grown at room temperature for one to two
weeks had acquired marked inhibitory, bactericidal and bacteriolytic
properties to many of the more common pathogenic bacteria.”

39. Fleming described the colony as a “fluffy white mass which rapidly
increases in size and after a few days sporulates” and changes color
from dark green to black to bright yellow. Even in the early
experimentation stages, penicillin had no effect against gram-
negative organisms but was effective against gram-positive bacteria.
Published reports credit Fleming as saying: “One sometimes finds
what one is not looking for. When I woke up just after dawn on Sept.
28, 1928, I certainly didn’t plan to revolutionize all medicine by
discovering the world’s first antibiotic, or bacteria killer. But I guess
that was exactly what I did.”
Though Fleming stopped studying penicillin in 1931, his research
was continued and finished by Howard Flory and Ernst Chain,
researchers at University of Oxford who are credited with the
development of penicillin for use as a medicine in mice.

40. Widespread use of Penicillin
Penicillin made a difference during the first half of the 20th century.
The first patient was successfully treated for streptococcal
septicemia in the United States in 1942. However, supply was
limited and demand was high in the early days of penicillin.
Penicillin helped reduce the number of deaths and amputations of
troops during World War II. According to records, there were only
400 million units of penicillin available during the first five months
of 1943; by the time World War II ended, U.S. companies were
making 650 billion units a month. To date, penicillin has become the
most widely used antibiotic in the world.
– by Katie Kalvaitis

41. References:
•Fleming A. On the antibacterial action of cultures of a penicillium,
with special reference to their use in the isolation of B.
influenzae. British Journal of Experimental Pathology.
1929;10:226-236.
•Haven KF. Marvels of Science: 50 Fascinating 5-Minute Reads.
Connecticut: Libraries Unlimited; 1994:182.