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Journal of The Association of Physicians of India ■ Vol. 63 ■ September 2015
Pioneers in Infectious Diseases
Pioneers in Antimicrobial Chemotherapy
Neha Gupta1, Camilla Rodrigues2, Rajeev Soman3
“I
f we are not careful, we soon
will be in the post-antibiotic
era, and for some patients and some
microbes we are already there”Tom Friedan
witnessed the death of many
soldiers from sepsis resulting
from infected wounds. By 1927,
Fleming had been investigating the
properties of staphylococci.
Antibiotics revolutionized
medicine in the 20 th century. The
era of antibacterial chemotherapy
began in 1907 with the discovery
of arsphenamine, first synthesized
b y A l f e r d B e r t h e i m a n d Pa u l
Ehrlich in 1907, used to treat
syphilis. The first systemically
active antibiotic, Prontosil was
discovered in 1933 by Gerhard
Domagk, for which he was awarded
the 1939 Nobel Prize.
“When I woke up just after dawn
on September 28, 1928, I certainly
didn’t plan to revolutionise all
medicine by discovering the
world’s first antibiotic, or bacteria
killer,” “But I suppose that was
exactly what I did.” – Alexander
Fleming.
Fleming’s accidental discovery
and isolation of penicillin in
September 1928 marked the start
of modern antibiotics. It was a
discovery that changed the course
of history and saved millions of
lives.
Sir Alexander
Fleming (1881-1955)
Sir Alexander Fleming was a
Scottish bacteriologist and Nobel
Prize winner, best known for
his discovery of penicillin along
with Ernst Chain and Howard
Florey. He wrote many articles on
bacteriology, immunology, and
chemotherapy. He also discovered
the enzyme lysozyme in 1923.
F o l l o w i n g W o r l d Wa r I ,
F l e m i n g a c t i ve l y s e a r c h e d f o r
anti-bacterial agents, having
He was already well-known
from his earlier work, and had
developed a reputation as a brilliant
researcher, but his laboratory was
often untidy. On 3 September 1928,
Fleming returned to his laboratory
having spent August on holiday
with his family. Before leaving,
he had stacked all his cultures
of staphylococci on a bench in
a corner of his laboratory. On
returning, 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
s t a p h yl o c o c c i c o l o n i e s f a r t h e r
a wa y w e r e n o r m a l , f a m o u s l y
remarking “That’s funny”. Fleming
showed the contaminated culture
to his former assistant Merlin Price,
who reminded him, “That’s how
you discovered lysozyme.”Fleming
grew the mould in a pure culture
and found that it produced a
substance that killed a number
of disease-causing bacteria. He
identified the mould as being from
the Penicillium genus, and, after
some months of calling it “mould
ju ice ”, named t he sub st ance it
released penicillin on 7 March 1929.
He investigated its positive antibacterial 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 Gramnegative bacteria, for which he
was seeking a cure at the time. It
also affected Neisseria gonorrhoeae,
which causes gonorrhoea although
this bacterium is Gram-negative.
Fleming also discovered very early
that bacteria developed antibiotic
r e s i s t a n c e w h e n e ve r t o o l i t t l e
penicillin was used or when it
was used for too short a period.
Fleming cautioned about the use
of penicillin in his many speeches
around the world. He cautioned
not to use penicillin unless there
was a properly diagnosed reason
for it to be used, and that if it were
used, never to use too little, or for
too short a period, since these are
the circumstances under which
bacterial resistance to antibiotics
develops.
Selman Abraham
Waksman (1888 –1973)
Selman Abrahman Waksman
was a Jewish-Ukrainian-American
inventor, biochemist and
microbiologist whose research
into organic substances—largely
into organisms that live in soil—
Associate Consultant Infectious Diseases, Medanta- The Medicity; 2Consultant Microbiologist and Chairperson
Infection Control, 3Consultant Physician and infectious Diseases Specialist, PD Hinduja National Hospital and
MRC, Mumbai, Maharashtra
1
Journal of The Association of Physicians of India ■ Vol. 63 ■ September 2015
credit for the discovery leading
to litigation and out of court
settlement.
Waksman had been studying
the Streptomyces family of organism
since his college student days and
had, for a time, been studying the
organism Streptomyces griseus.
Streptomycin was isolated
from S. griseus and found
effective against tuberculosis by
o n e o f Wa k s m a n ’ s g r a d u a t e
students, Albert Schatz.
The bacteria which produced
the antibiotic streptomycin was
discovered by Schatz in the
farmland outside his lab, and
tested by him. Waksman, however,
e ve n t u a l l y c a m e t o c l a i m s o l e
not being permitted by law to
accept the Nobel Prize.)
Prontosil had a relatively broad
effect against Gram-positive cocci,
but not against enterobacteria. The
discovery and development of this
sulfonamide drug opened the era
of antibacterials and more research.
Domagk’s work on sulfonamides
eventually led to the development
of the antituberculosis drugs
thiosemicarbazone and isoniazid,
which helped to curb the epidemic
of tuberculosis which swept Europe
after World War II.
and their decomposition promoted
the discovery of Streptomycin, and
several other antibiotics. Waksman
coined the term antibiotics which is
widely used today.
Waksman’s team discovered
more than 15 antibiotics. Two of
these, streptomycin and neomycin,
have found extensive application
in the treatment of numerous
infectious diseases. Streptomycin
was the first antibiotic that
could be used to cure the disease
tuberculosis.
91
References
Gerhard Johannes Paul
Domagk (1895–1964)
Gerhard Johannes Paul Domagk
was a German pathologist and bacteriologist. He is credited with the
discovery of first sulfonamide and
first commercially available
antibacterial, Prontosil, for which
he received the 1939 Nobel Prize
for Medicine.
He was forced by the Nazi regime
to refuse the prize and was arrested
by the Gestapo for a week. (This
was because the Nazi-critical Carl
von Ossietzky had won the Nobel
Peace Prize in 1935, which had
angered the German government
and resulted in German nationals
1.
Brown, K. (2004). Penicillin Man: Alexander
Fleming and the Antibiotic Revolution. 320
pp. Sutton Publishing. ISBN 0-7509-3152-3.
2.
Hare, R. The Birth of Penicillin, Allen and
Unwin, London, 1970
3.
Diggins, F. The true history of the discovery of
penicillin by Alexander Fleming Biomedical
Scientist, March 2003, Institute of
Biomedical Sciences, London. (Originally
published in the Imperial College School
of Medicine Gazette)
4.
Pringle, Peter (June 11, 2012). “Notebooks
Shed Light on a Discover y, and a
Mentor’s Betrayal”. The New York Times.
Retrieved June 11, 2012.
5.
Mistiaen, Veronique (November 2,
2002). “ Time, and the great healer.”.
London: The Guardian. Retrieved April
13, 2010. The story of streptomycin –
of scientific triumphs, all-too-human
scientists and a long quest for justice – lies
somewhere between these two men.
6.
Domagk Biography at nobelprize.org
7.http://en.wikipedia.org