Full text - The American Association of Immunologists

Celebrating
100 Years
Nobel Laureates of AAI
Sir Alexander Fleming, F.R.C.S.
(1881–1955)
Alexander Fleming, F.R.C.S., AAI ’14, was
awarded the 1945 Nobel Prize in Physiology or
Medicine jointly with Ernst Boris Chain and
Sir Howard Walter Florey “for the discovery
of penicillin and its curative effect in various
infectious diseases.”1
Scientific Accomplishments
The story of penicillin’s discovery has long been
mythologized as one of the most fortuitous “accidents” in the history of medicine.2 Chance,
no doubt, played a large role, but, as the British Medical Journal pointed out at the time of
Fleming’s death, all of humanity has benefitted
from the fact that this particular accident was
observed by the “prepared mind” of Alexander
Fleming in September 1928.3 Upon returning
from vacation to his laboratory at St. Mary’s
Hospital, Fleming found that one of the staphylococcus cultures he had left out was contaminated by fungus. Fleming noted that a ring had
formed around the fungus in which staphylococci did not grow. Curious, he began culturing
the fungus, which he identified as Penicillium
notatum, and called the antibacterial substance
it produced “penicillin.”
After months of observation, Fleming discovered that penicillin continued to inhibit the
growth of bacteria even when diluted up to 800
times. Moreover, unlike the antiseptics in use
at the time, penicillin appeared to be nontoxic
to animals, a property that led him to believe
it might be used as a topical treatment to fight
infection in humans. He reported these findings
in the British Journal of Experimental Pathology in 1929, but the paper was largely ignored.4
Although he continued to cultivate Penicillium
and provided samples to other laboratories,
Fleming primarily used penicillin in the lab as
a filtrate to isolate penicillin-insensitive from
penicillin-sensitive bacteria in mixed cultures
and did not pursue its use as a therapeutic. That
line of investigation was left to Chain and Florey
at the Department of Pathology at the University of Oxford.
While surveying the literature on naturally produced antibacterial substances in
1938, Chain ran across Fleming’s 1929 paper,
which, according to him, “had been forgotten
completely in the vast mass of scientific literature.”5 Intrigued by Fleming’s findings, in July
1939, Chain and Florey began working with a
sample of Penicillium that Fleming had given
one of their Oxford colleagues one decade before. Chain, a biochemist, succeeded in purifying penicillin in early 1940, and he and Florey
reported its therapeutic value on mice later that
year and on human volunteers in early 1941.7
That summer, Florey promoted the drug in the
United States, and, by early 1942, American
pharmaceutical companies were mass producing penicillin for distribution to Allied soldiers
Celebrating
100 Years
during the Second World War. By war’s end, the
supply was large enough to use the drug in the
treatment of civilians. Together, Fleming, Chain,
and Florey had discovered and developed the
first antibiotic, providing physicians with what
was colloquially called the “wonder drug” in the
1940s and 1950s for its ability to effectively treat
previously fatal bacterial infections.
Prior to his discovery of penicillin, Fleming
had already enjoyed a successful career as an
immunologist. Working under the guidance of
Almroth Wright (AAI ’14) in the Department of
Inoculation at St. Mary’s Hospital in London,
Fleming established himself as a highly capable
research scientist. His earliest accomplishments
included making two improvements on methods for testing and treating syphilis. He simplified the Wassermann test so that it could be
performed using a small blood sample derived
from a finger prick rather than a vein. He also
described an improved technique for treating
syphilis patients with Salvarsan, or “606,” the
notoriously difficult-to-administer antisyphilis
drug developed by Paul Ehrlich.8
More than just a technician who improved
upon others’ ideas, Fleming made many discoveries in his own right. While working at a
makeshift laboratory in France during the First
World War, Fleming and Wright demonstrated
that the antiseptics used by surgeons in the field
were more harmful than helpful: they were often more effective at killing the body’s infectionfighting leukocytes than infection-causing bacteria. Thereafter, Fleming began searching for a
nontoxic antibacterial substance, and, by November 1921, he had found one. Examining cultures of his own nasal mucus that he had made
two weeks prior while suffering from a common
cold, Fleming discovered that, although bacteria
had formed colonies on parts of his cultures,
they had not grown in or directly near the mucus. He coined the term “lysozyme” to describe
the enzyme in mucus capable of inducing bacteriolysis and soon detected its presence in human
tissues and secretions, including saliva and tears
and, later, in egg whites.9 Although lysozyme’s
antibacterial properties proved considerably
weaker against bacteria other than the airborne
Micrococcus lysodeikticus that had colonized
Fleming’s cultures, he had nevertheless opened
a new field in immunological research and
renewed hopes about the possibility of finding a
nontoxic antiseptic. Once penicillin was proven
to be such a substance, Fleming devoted himself
to furthering research on the drug and promoting its use.10
Because penicillin has saved countless lives,
Fleming has been elevated to heights that few
scientists reach. Upon Fleming’s death, French
Biologist Jean Rostand stated, “The world has
lost its greatest scientific benefactor since Pasteur.”11 The British Medical Journal concurred,
calling Fleming “one of the immortals of medical history.”12 Even world leaders recognized
Fleming’s accomplishments. While at the Potsdam Conference on postwar settlement in July
1945, U.S. President Harry Truman declared
that Fleming was one individual to whom “the
whole world owes a debt of gratitude difficult to
estimate.”13
Biography
Born into a large farm family in Lochfield,
Scotland, on August 6, 1881, Fleming was the
youngest of eight children. After demonstrating
scholarly promise early on, he left home at the
age of 13 to live with an older brother in London
to increase his educational opportunities. There,
he attended Regent Street Polytechnic for three
years before economic hardship forced him to
leave school and work as a clerk for a shipping
company. When he turned 20, Fleming received
an inheritance from an uncle and decided to use
this sum to attend medical school at St. Mary’s
Hospital. After completing his coursework at
the top of his class in 1906, he began working as
a research assistant under Wright, head of the
Inoculation Department at St. Mary’s. Fleming
Celebrating
100 Years
received his M.B., B.S. in 1908 and, unsure of
his career path, prepared for the Fellowship
of the Royal College of Surgeons exam while
continuing to work in the Inoculation Department. Although he passed the exam and was
accepted as a fellow in 1909, he chose to stay in
Wright’s laboratory and pursue research rather
than become a practicing surgeon.
Fleming remained at St. Mary’s for the entirety of his career, absent from the hospital only
during the First World War, when he served
as a captain in the Royal Army Medical Corps
along with Wright and the rest of the Inoculation Department at a makeshift army laboratory
in Boulogne, France. Upon Wright’s retirement in 1946, Fleming became director of the
department, which was renamed the WrightFleming Institute in 1947, following Wright’s
death. Fleming also taught bacteriology at the
hospital’s medical school from 1920 to 1948. In
December 1954, he retired from his directorship
of the institute, although he continued to visit
the laboratory regularly until his death.
Fleming died of a heart attack at his home in
London on March 11, 1955, at the age of 73. His
ashes were interred at St. Paul’s Cathedral.14
Awards and Honors
Fleming was a fellow of the Royal Society (1943)
and an honorary fellow of the Royal College of
Physicians (1944), Royal College of Physicians
of Edinburgh (1945), and the Royal Society of
Edinburgh (1947). He was also an honorary
foreign member of several national academies,
including the French Académie Nationale de
Médecine and the Pontifical Academy of Sciences (1946).15
In addition to the Nobel Prize, Fleming’s honors and awards include the John Scott Award
of the City of Philadelphia (1944), the Cameron
Prize of the University of Edinburgh (1945), the
Moxon Medal of the Royal College of Physicians
(1945), the Albert Medal of the Royal Society
of Arts (1946), the Honorary Gold Medal of the
Royal College of Surgeons (1946), the Medal for
Merit awarded by the U.S. President (1947), and
the Gold Medal of the Royal Society of Medicine
(1947). He was knighted by King George VI in
1944 and named a commander in the French
Legion d’Honneur the following year.
1 “The Nobel Prize in Physiology or Medicine 1945—Summary,” Nobelprize.org, http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/.
2 The historical record concerning the discovery and development of penicillin is replete with conflicting details. The account that
follows is based primarily on F. W. E. Diggins, “The True History of the Discovery of Penicillin: With Refutation of the Misinformation in the Literature,” British Journal of Biomedical Science 56, no. 2 (1999): 83–93; L. Colebrook, “Alexander Fleming.
1881–1955,” Biographical Memoirs of Fellows of the Royal Society 2 (1956): 117–27;.and E. P. Abraham, “Howard Walter Florey,
Baron Florey of Adelaide and Marston, 1898–1968,” Biographical Memoirs of Fellows of the Royal Society 17 (1971): 255–302.
3 “Sir Alexander Fleming, M.D., D.Sc. F.R.C.P., F.R.C.S., F.R.S.,” Obituary, British Medical Journal 1, no. 4915 (1955): 732.
4 A. Fleming, “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 10 (1929): 226–36.
5 “Fleming and Two Co-Workers Get Nobel Award for Penicillin Boon,” New York Times, 26 October 1945, 21.
6 Diggins, “True History of the Discovery of Penicillin,” 89.
7 E. Chain, H. W. Florey, A. D. Gardner, N. G. Heatley, M. A. Jennings, J. Orr-Ewing, and A. G. Sanders, “Penicillin as a Chemotherapeutic Agent,” Lancet 236, no. 6104 (1940): 226–28; E. P. Abraham, E. Chain, C. M. Fletcher, A. D. Gardner, N. G. Heatley,
M. A. Jennings, and H. W. Florey, “Further Observations on Penicillin,” Lancet 238, no. 6155 (1941): 177–89.
8 L. Colebrook, “Alexander Fleming,” 118.
9 A. Fleming, “On a Remarkable Bacteriolytic Element Found in Tissues and Secretions,” Proceedings of the Royal Society,
Series B 93 (1922): 306–17.
10 L. Colebrook, “Alexander Fleming,” 120–23.
11 “Alexander Fleming, Discovered Penicillin,” Washington Post, 12 March 1955, 22.
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100 Years
12 “Sir Alexander Fleming,” British Medical Journal, 732.
13 “Truman Hails Fleming for Penicillin Drug,” New York Times, 26 July 1945, 17.
14 “Fleming, Pioneer in Penicillin, Dies,” New York Times, 12 March 1955, 19; “Alexander Fleming, Discovered Penicillin,”
Washington Post, 12 March 1955, 22.
15 “Sir Alexander Fleming,” British Medical Journal, 733.
Photo: Library of Congress, Prints & Photographs Division, Portrait of America Collection