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Text File | 1996-01-29 | 11.3 KB | 226 lines

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Fleming shared a Nobel prize with Ernst Chain and Howard
Florey for discovering and developing penicillin, the first of
the antibiotics which were to transform the medical practice
of the twentieth century. It was in 1928 at St Mary's
Hospital, London, that Fleming noticed that a mould had
contaminated a culture of staphylococci, bacteria that cause
skin and other infections. The mould seemed to have
produced something that had attacked the bacteria. Fleming
concluded that the unidentified substance, which he named
penicillin, could be used to inhibit the growth of sensitive
bacteria. Unfortunately, the chemists he approached were
unable to purify the material, and it was not until a decade
later that the idea of administering penicillin to treat
infections was taken up vigorously by Florey and Chain (a
refugee from Hitler's Germany). In a project led by Florey,
Chain together with Norman Heatley succeeded at last in
extracting and purifying penicillin. It was shown to be
dramatically effective in curing certain bacterial infections.
In 1941, because demand far exceeded the output of their
Oxford laboratory and because British industry was being
disrupted by bombing, Florey and Heatley visited the US to
get help in mass-producing it. Before leaving Britain they
smeared the linings of their coats with spores of the
penicillin fungus, which could be recovered later should the
cultures at Oxford be lost after a German invasion
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On the outbreak of war in 1914  Fleming went to France as a
captain in the R.A.M.C.  He worked in Sir Almroth Wright's
laboratory in the Casino at Boulogne and received a mention
in dispatches.  At the end of the war he returned to St.
Mary's as assistant to Sir Almroth Wright and was also
appointed lecturer in bacteriology in the medical school.  He
subsequently became director of the department of
systematic bacteriology and assistant director of the
inoculation department.  For some years he acted as
pathologist to the venereal disease department at St. Mary's
and was also pathologist to the London Lock Hospital.  In
1928 he was appointed Professor of Bacteriology in the
University of London, the post being tenable at St. Mary's.
He retired with the title emeritus in 1948, but continued at
St. Mary's as head of the Wright-Fleming Institute of Micro-
Biology.  Though last year he formally handed over the reins
to Professor R. Cruikshank, he continued his own research
work there and only the day before yesterday was at the
institute discussing plans for the lecture tour in the Middle
East he had been asked to undertake by the British Council.

Fleming's first notable discovery, that of Iysozyme, was made
in 1922.  He had for some time been interested in antiseptics
and in naturally occurring antibacterial substances.  In
culturing nasal secretion from a patient with an acute cold he
found a remarkable element that had the power of dissolving
bacteria.  This bacteriolyte element, which he also found in
tears and other body fluids, he isolated and named Iysozyme.

Penicillin was discovered in 1928 when Fleming was engaged
in bacteriological researches on staphylococci.  For
examination purposes he had to remove the covers of his
culture plates and a mould spore drifted on to a plate.  After
a time it revealed itself by developing into a colony about
half an inch across.  It was no new thing for a bacteriologist
to find that a mould had grown on a culture plate which had
lain on the bench for a week, but the strange thing in this
particular case was that the bacterial colonies in the
neighbourhood of the mould appeared to be fading away.
What had a week before been vigorous staphylococcus
colonies were now faint shadows of their former selves.
Fleming might have merely discarded the contaminated
culture plate but fortunately his previous research work on
antiseptics and on naturally occurring antibacterial
substances caused him to take special note of the apparent
antibacterial action of the mould.

He made sub-cultures of the mould and investigated the
properties of the antibacterial substance.  He found that
while the crude culture fluid in which the mould had grown
was strongly antibacterial it was non-toxic to animals and
human beings.  The crude penicillin was, however, very
unstable and was too weak and too crude for injection.  Early
attempts at concentration were not very successful, and after
a few tentative trials its clinical use was not pursued,
although it continued to be used in Fleming's laboratory for
differential culture.  The position in 1929 was that Fleming
had discovered and named penicillin, had investigated its
antibacterial power, and had suggested that it might be
useful as an antiseptic applied to infected lesions.  Attempts
to produce a concentrated extract capable of clinical
application were not successful and had been abandoned.  In
the light of later knowledge Fleming's original paper of 1929
was remarkable.  It covered nearly the whole field, realized
most of the problems and made considerable progress in
solving them.  The resuscitation of penicillin as a
chemotherapeutic agent was due to the brilliant work of Sir
Howard Florey and his colleagues at Oxford, notably Dr. E.B.
Chain.
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SIR Alexander Fleming, the discoverer of penicillin,
delivering the first of a series of lectures arranged by the
British Council to medical men from Britain and the United
States at Nottingham yesterday, spoke of the probability that
before long penicillin will be used efficaciously through the
mouth, that it will appear in chemists' shops in the form of
gelatine lozenges for throat affections, and that it might even
form the base for some face powders because of its beneficial
effects on impetigo.

Among the conditions for which penicillin could be used were
septic wounds, diphtheria, anthrax, pneumonia, gas gangrene,
and tetanus.  Penicillin could stop the spread of a carbuncle
in two days, and it was the ideal antiseptic, because it was
non-poisonous and it was impossible to overdose a patient
with it.

For a number of years one of the difficulties was the keeping
of the product and preventing it from becoming inert, but
American chemical engineers had overcome the difficulty of
mass production and were now producing it in 12,000-gallon
tanks.
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The circumstances in which the weapon of penicillin was
forged for the armoury of medical science were recalled in
London yesterday when a presentation was made at St.
Mary's Hospital Medical School to Sir Alexander Fleming of a
pair of silver George III sauce tureens to mark the twenty-
fifth anniversary of the discovery.  The presentation was
made by the Duke of Edinburgh on behalf of the Medical
School, with which Sir Alexander Fleming has a long
association.

Sir Alexander Fleming, in his response, expressed his
continuing amazement that the presence on one of his culture
plates of a minute spore of mould, half the size of a blood
corpuscle, had resulted in the creation of a large industry
employing thousands of people in most of the important
countries in the world.  The methods of preparation had been
so developed since that it was now manufactured by the ton,
quite pure and so cheap that it was economical to feed it to
young pigs and chickens.

"I was the lucky one to be chosen to notice the happening
that eventually led to penicillin, but would I ever have
noticed it but for my previous work in association with my
master, Sir Almroth Wright?" he said.  "When the first war
came we worked in Boulogne and saw thousands of septic
wounds for which we could do little.  The work then done in
Wright's laboratory in Boulogne and in the inoculation
department of St. Mary's Hospital was good work in which I
am proud to have taken part."

The Duke of Edinburgh accepted from Sir Alexander Fleming
a medallion in which was mounted a specimen culture of the
mould with which all penicillin was made until about 1943.

LORD VERULAM, president of the council of St. Mary's
Hospital Medical School, referred to the forthcoming
celebrations of the centenary of the school, and said its
struggles and achievements would be described in a book.
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In the history of medicine, moments of revelation are
disappointingly few. Less separates us from the horrors of
the nineteenth century then we might wish, or half believe.
Take away public hygiene and antibiotics, and we would soon
find ourselves struggling against a resurgence of infectious
diseases, as helpless to save our children from an early death
as were our great-grandparents.

Yet penicillin, the drug that really did work a miracle, is
barely half a century old. Alexander Fleming, who made the
original discovery, died forty years ago, in March 1955: his
Nobel Prize for medicine, shared with Howard Florey and
Ernst Chain, was awarded fifty years ago, in 1945, at the end
of the war that had proved penicillin such a lifesaver.

The discovery of penicillin is a tale so often told that it has
now fallen prey to the revisionists. They assert that the
greater credit is due to the Oxford team of Florey, Chain and
Norman Heatley, rather than to Fleming, and that only
tireless efforts of  St Mary's, Paddington, ensured that
Fleming emerged primus inter pares. A search through the
archives lends them some support for when The Times first
offered an editorial opinion of the merits of penicillin, on
August 27, 1942, no credit was given to its discoverer. But
the ink was barely dry before we were publishing a letter
from the eminent pathologist Sir Almroth Wright of St Mary's
caricatured by Bernard Shaw as Sir Colenso Rigeon in The
Doctor's Dilemma awarding the laurel wreath to Fleming. "He
is the discoverer of penicillin and was the author of the
original suggestion that this substance might prove to have
important applications in medicine," Sir Almroth asserted.

What cemented Fleming's claim in the public mind were the
circumstances of the discovery: a culture plate left out in the
laboratory, an open window, the happy accident of
contamination by the mould Penicillim notatum. Fleming
deduced that some substance from the mould was killing
mature staphlococci, a mistake as it later turned out.
Penicillin acts only against growing bacteria, which means
that Fleming's plate must have been contaminated with
mould before the bacteria were inoculated on to it.

Yet the fact remains that Fleming did notice something
strange, and drew the right conclusions. He failed to isolate
the active agent, and tentative clinical trials produced no
evidence of penicillin's wonderful properties. Not until the
Oxford workers took up the hunt a decade later was the drug
proved the life-saver of the century; and even they had to
give best to the United States when mass-production was
required. In fact, it is now known that another researcher,
Cecil Paine, had given crude penicillin to patients in Sheffield
several years earlier, but had never published his results.

What this proves is that scientific discovery is seldom as
straightforward as it seems. Luck, instinct, and the prepared
mind are needed to make sense of confusion; and sometimes
even the greatest discoveries lie around waiting for
somebody with the wit to pick them up. This is as true today
as it was half a century ago: we need both Flemings and
Floreys if we are to keep the darkness at bay.