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Alexander Fleming (1881-1955)

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Vita

   * b. 1881, Darvel, Ayrshire, Scotland
   * Intermediate MB, 1904, London University
   * MRCS, LRCP, 1906, London University (one notch below M.D., but
     qualifies one as a physician)
   * Staff, St. Mary's Hospital, London
   * Professor of Bacteriology, St. Mary's Hospital, University of London,
     1938
   * Fellow of the Royal Society, 1943
   * Knighted, 1944
   * Nobel Prize in Physiology or Medicine, 1945, shared with Howard Florey
     and Ernst Chain

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Synopsis

Fleming was born to a Scottish farming family. He left home with his brother
for London; Robert became an oculist, "Alec" went to medical school. He
became associated with St. Mary's Hospital, the youngest of London's
teaching hospitals, and remained there for his entire career. He worked with
Almroth Wright, a major advocate of vaccines who developed vaccines for many
microbial diseases and was keenly interested in the immune system. Wright
became head of the newly created "Inoculation Department" at St. Mary's, an
essentially autonomous entity within the hospital. The Inoculation
Department was financially self-supporting, on the basis of the vaccines
they developed, sold, and treated patients with.

During World War I, Fleming was one of Wright's primary assistants in a
major effort to combat the rampant infections and septicemia in British
soldiers' wounds. Physicians had only recently accepted Lister's protocols
for antiseptic surgery and assumed that since germs caused infection and
antiseptics killed germs, that antiseptics must cure infections. Wright and
Fleming argued conversely that the leukocytes of the immune system were the
body's most important line of defense against infection and that most
antiseptics killed leukocytes more rapidly than they killed bacteria. The
best treatment for infection, they said, was simply washing with copious
saline. Few physicians, however, could believe this advice, which seemed to
go against the latest and most profound advances in surgical technique for
many years.

In 1921 Fleming discovered lysozyme. A culture of his own nasal mucus (he
had a cold) inhibited the growth of Staphylococcus cultured from that same
mucus. Though he first thought it was bacteriophage, he soon realized it was
a chemical present in the mucus and that it was a protein. He found that it
was present in mucus from healthy noses, and as well in tears. Egg white
contained high activity for lysozyme. The strain of bacteria he was
culturing happened to be particularly sensitive to lysozyme; this was the
first of two major chance events in Fleming's career. The weak
concentrations of lysozyme Fleming was using, however, prevented him from
seeing the broad antibiotic properties of lysozyme, and tthe broader medical
applications of this discovery went unappreciated for years, by Fleming and
everyone else at the time.

The lysozyme work grew out of his interest in showing the ineffectiveness of
chemical antiseptics to treat infection; like leukocytes, lysozyme was an
endogenous way for the body to treat infection and demonstrated to Fleming
the verity of Wright's conclusion that the best treatment was to enhance the
body's own natural immune responses. The lysozyme work further stimulated
Fleming's interest in antimicrobial agents. This work paved the way for the
discovery of penicillin a few years later.

Fleming loved to play, both in the laboratory and out. He always loved
snooker and golf and had many whimsical variants on the rules. In the lab he
made "germ paintings," in which he would draw with his culture loop using
spores of highly pigmented bacteria, which were invisible when he made the
painting, but when cultured developed into brightly colored scenes. He
followed what Max Delbruck would later call the "principle of limited
sloppiness." Fleming abhorred a tidy, meticulous lab; he left culture dishes
lying around for weeks and would often discover interesting things in them.
Though the story has been told in many sometimes conflicting ways, something
like this resulted in the discovery of penicillin. He seems to have left a
culture dish lying on the lab bench and then gone away on vacation. When he
returned a few spores of an unusual mold had germinated on the plate. When
he cultured the bacteria on the plate he found that they grew up to within a
few centimeters of the mold, but there were killed. A crude extract of the
mold was then shown to have antibacterial properties. Fleming made this
discovery in 1928 and by 1929 had named it penicillin (he was told by a
colleague that the mold was a type of Penicillium and "penicillozyme" must
have seemed cumbersome).

Fleming continued to use penicillin in his lab but not with any great
enthusiasm and certainly not to the exclusion of many other projects. He
never developed it into a clinically useful compound, though in 1929 he
suggested that it might have important clinical applications. Because he was
a bacteriologist and not a chemist, Fleming did not attempt to purify
penicillin. He seems to have run into a dead end with penicillin and so
during the 1930s, though he kept it in his lab, he did not do much with it.
In the late 1930s Australian Howard Florey came to London to work with
Charles Sherrington. He worked on lysozyme for a while and then became
interested in penicillin. It was Florey, with Chain and other of his group
that developed penicillin into a clinincal antibiotic. They did this during
1940-41. Fleming, Florey, and Chain shared the 1945 Nobel Prize in
Physiology or Medicine.

Fleming became world-famous for penicillin, and was rightly acknowledged as
the father of modern antibiotics, but Florey was just as rightly miffed at
being denied much of the credit for creating the powerful medical tool we
now know. Evidence does not suggest that Fleming deliberately denied Florey
his due credit, but Fleming's peculiar, dry sense of humor seems to have
caused him not to deny even the wildest attributions to him.

The most striking thing about Fleming is his sense of play. He used to say
he "played with microbes." His inventive mind and nimble fingers allowed him
to play all sorts of games and kept his mind and his lab open to sponteneity
and, perhaps, serendipity. He was also a keen observer and knew how to seize
on an anomaly rather than ignoring it. MacFarlane's account, while at times
quite Whiggish and somewhat teleological, attempts, generally successfully,
to demythologize Fleming. When he asks whether Fleming was a "genius" and a
"great man," MacFarlane answers with a qualified "maybe." MacFarlane, a
clinical pathologist from Oxford, seems unaware of the debate among the
social constructivists and the positivists. He seems quite positivistic in
his own views about science, and yet he fully acknowledges the nonrational
quality in Fleming's science, as well as the strong social/cultural/personal
components of his success.

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References

   * Gwyn MacFarlane, Alexander Fleming: The man and the myth, Oxford:
     Oxford University Press, 1985.


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Nathaniel C. Comfort