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Selman Waksman: the Father of Antibiotics
The Chemical Nature of Actinomycin, an Anti-microbial Substance Produced by
Actinomyces Antibioticus
(Waksman, S. A., and Tishler, M. (1942) J. Biol. Chem. 142, 519 –528)
Selman Abraham Waksman (1888 –1973) was born in the rural Ukrainian town of Novaya
Priluka. The town and its nearby villages were surrounded by a rich black soil that supported
abundant agricultural life. Although Waksman did not do much farming as a child, the
chemistry of the fertile soil incited a curiosity in him that would eventually influence the
direction of his future endeavors.
In 1910, after completing his matriculation diploma, Waksman followed the example of
several relatives and migrated to the United States. He worked for a few years on a family
farm in New Jersey and then enrolled in Rutgers College. There he studied bacteria in culture
samples from successive soil layers, which resulted in his introduction to the actinomycetes.
These bacteria became an enduring interest that Waksman studied for both his Master’s and
Doctorate degrees and on which he would eventually become a major expert.
After receiving his doctorate from the University of California, Berkeley, in 1918, Waksman
secured a position at the Rutgers Bacteriology Department where he continued his research on
soil microflora. Several years later, a young French biologist named Rene Dubois joined his
laboratory. By 1927, Dubois was studying the one-on-one effects of soil organisms in decom-
posing cellulose and was beginning an approach that would lead to modern antibiotics. In
collaboration with Oswald Avery at the Rockefeller Institute Hospital, Dubois isolated a soil
bacterium that could attack the capsular polysaccharide of Streptococcus pneumoniae (1). This
discovery inspired Waksman to look for more pre-existing antibacterial organisms in soil
samples.
By 1940, Waksman and H. Boyd Woodruff had devised a technique for identifying natural
substances with antibacterial properties (2). The screening was done by looking for growth
inhibition zones around single colonies of systematically isolated soil microbes, grown under a
variety of culture conditions, and then testing the inhibition on specifically targeted patho-
genic bacteria.
The first true antibiotic Waksman identified was from Actinomyces antibioticus, a member
of the actinomycetes family (3). The microbe produced a substance, actinomycin, that had both
bacteriostatic and bactericidal properties. Waksman and Woodruff determined that actinomy-
cin could be separated with petroleum ether into two constituents, an orange-red colored
actinomycin A and a colorless actinomycin B. Actinomycin A had strong bacteriostatic and
bactericidal properties whereas actinomycin B displayed only bactericidal characteristics.
In the Journal of Biological Chemistry (JBC) Classic reprinted here, Waksman and Max
Tishler, who was featured in a previous JBC Classic (4), describe the nature and properties of
actinomycin A. The pair found that actinomycin is a quinine-like pigment with a molecular
formula of either C
41
H
56
N
8
O
11
,C
37
H
50
N
7
O
10
,orC
36
H
49
N
7
O
9
䡠1
2H
2
O. The compound is highly
active against various gram-positive bacteria but less active against gram-negative organisms.
Unfortunately, Waksman and Tishler also discovered that actinomycin is extremely toxic to
experimental animals and thus of little therapeutic value.
Waksman followed this initial failure with a comprehensive program of screening actino-
mycetes for their ability to produce antibacterials. He identified more than 20 new natural
THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 279, No. 48, Issue of November 26, p. e7, 2004
© 2004 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A.
Classics
A PAPER IN A SERIES REPRINTED TO CELEBRATE THE CENTENARY OF THE JBC IN 2005
JBC Centennial
1905–2005
100 Years of Biochemistry and Molecular Biology
This paper is available on line at http://www.jbc.org 101
This is an Open Access article under the CC BY license.
inhibitory substances, including streptomycin and neomycin, and proposed the now standard
term “antibiotics” for this class of natural growth inhibitors.
With his discovery of streptomycin in 1944, Waksman initiated a collaboration with Merck
and Company. Tishler led the microbiological group that developed the fermentation process
for producing bulk quantities of streptomycin. As a result of his success in developing manu-
facturing processes for products such as streptomycin, riboflavin, cortisone, vitamin B
12
, and
penicillin, Tisher eventually became the first president of the Merck Sharp & Dohme Research
Laboratory Division of Merck & Co. Inc. and remained there until 1970, running the research
programs.
Waksman patented and licensed his promising antibiotics, but rather than keeping the
money for himself, he gave 80% of his patent earnings to Rutgers University. In 1951 he
established an Institute of Microbiology in association with Rutgers, the construction of which
was completed in 1954. The institute was endowed and supported by the generous assignment
of 80% of Waksman’s streptomycin patent royalties to Rutgers. Waksman’s philanthropic
nature was further evident when he established the Foundation for Microbiology in 1951 and
assigned one-half of his 20% personal royalties for its support.
During his lifetime, Waksman received some 66 awards and 22 honorary degrees for his
scientific work. He was elected to the National Academy of Sciences in 1942. However,
Waksman’s greatest honor came when he won the Nobel Prize in physiology or medicine in
1952 “for his discovery of streptomycin, the first antibiotic effective against tuberculosis.” This
distinction earned him the title of “Father of Antibiotics” and gained him well deserved
recognition for his philanthropy and contributions to science and medicine.
1
Nicole Kresge, Robert D. Simoni, and Robert L. Hill
REFERENCES
1. Dubois, R. J. (1939) Bactericidal effect of an extract of a soil bacillus on Gram-positive bacteria. Proc. Soc. Exp.
Biol. Med.70, 1–17
2. Waksman, S. A., and Woodruff, H. B. (1940) The soil as a source of microorganisms antagonistic to disease-
producing bacteria. J. Bacteriol. 40, 581–600
3. Waksman, S. A., and Woodruff, H. B. (1941) Actinomyces antibioticus, a new soil organism antagonistic to
pathogenic and non-pathogenic bacteria. J. Bacteriol. 42, 231–249
4. JBC Classics: Fieser, L. F., Tishler, M., and Sampson, W. L. (1941) J. Biol. Chem. 137, 659 – 692
(http://www.jbc.org/cgi/content/full/278/52/e4)
5. Hotchkiss, R. D. (2003) Biographical memoir of Selman Abraham Waksman, Vol. 83, pp. 320 –343, National
Academy of Sciences, Washington, D. C.
1
All biographical information on Selman Waksman was taken from Ref. 5.
Selman Waksman. Photo courtesy of the National Library of Medicine.
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