August 06, 2010 <Back to Index>
|
Sir Alexander Fleming (6 August 1881 – 11 March 1955) was a Scottish biologist and pharmacologist. Fleming published many articles on bacteriology, immunology and chemotherapy. His best-known achievements are the discovery of the enzyme lysozyme in 1923 and the antibiotic substance penicillin from the fungus Penicillium notatum in 1928, for which he shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Walter Florey and Ernst Boris Chain. In 1999, Time Magazine named Fleming one of the 100 Most Important People of the 20th Century for
his discovery of penicillin, and stated; "It was a discovery that would
change the course of history. The active ingredient in that mold, which
Fleming named penicillin, turned out to be an infection-fighting agent
of enormous potency. When it was finally recognized for what it was — the
most efficacious life-saving drug in the world — penicillin would alter
forever the treatment of bacterial infections. By the middle of the
century, Fleming's discovery had spawned a huge pharmaceutical industry,
churning out synthetic penicillins that would conquer some of mankind's
most ancient scourges, including syphilis, gangrene and tuberculosis". Fleming was born on 6 August 1881 at Lochfield, a farm near Darvel in East Ayrshire,
Scotland. He was the third of the four children of Hugh Fleming
(1816–1888) from his second marriage to Grace Stirling Morton
(1848–1928), the daughter of a neighbouring farmer. Hugh Fleming had
four surviving children from his first marriage. He was 59 at the time
of his second marriage, and died when Alexander (known as Alec) was
seven. Fleming
went to Louden Moor School and Darvel School, and though the two before
were modest schools at best, earned a two year scholarship to Kilmarnock Academy for
his work in botany and biology. After working in a shipping office for
four years, the twenty-year-old Fleming inherited some money from an
uncle, John Fleming. His older brother, Tom, was already a physician
and suggested to his younger sibling that he follow the same career,
and so in 1901, the younger Alexander enrolled at St Mary's Hospital, Paddington, London. He qualified for the school with distinction in 1906 and had the option of becoming a surgeon. By chance, however, he had been a member of the rifle club (he had been an active member of the Volunteer Force since
1900). The captain of the club, wishing to retain Fleming in the team
suggested that he join the research department at St Mary's, where he
became assistant bacteriologist to Sir Almroth Wright, a pioneer in vaccine therapy
and immunology. He gained M.B. and then B.Sc. with Gold Medal in 1908,
and became a lecturer at St. Mary's until 1914. On 23 December 1915,
Fleming married a trained nurse, Sarah Marion McElroy of Killala, Ireland. Fleming served throughout World War I as a captain in the Army Medical Corps, and was mentioned in dispatches. He and many of his colleagues worked in battlefield hospitals at the Western Front in
France. In 1918 he returned to St. Mary's Hospital, which was a
teaching hospital. He was elected Professor of Bacteriology in 1928. After the war Fleming actively searched for anti-bacterial agents, having witnessed the death of many soldiers from septicemia resulting from infected wounds. Antiseptics killed
the patients' immunological defences more effectively than they killed
the invading bacteria. In an article he submitted for the medical
journal The Lancet during World War I,
Fleming described an ingenious experiment, which he was able to conduct
as a result of his own glass blowing skills, in which he explained why
antiseptics were killing more soldiers than infection itself during
World War I. Antiseptics worked well on the surface, but deep wounds
tended to shelter anaerobic bacteria from the antiseptic agent, and
antiseptics seemed to remove beneficial agents produced that protected
the patients in these cases at least as well as they removed bacteria,
and did nothing to remove the bacteria that were out of reach. Sir Almroth Wright strongly
supported Fleming's findings, but despite this, most army physicians
over the course of WWI continued to use antiseptics even in cases where
this worsened the condition of the patients. "When
I woke up just after dawn on September 28, 1928, I certainly didn't
plan to revolutionize all medicine by discovering the world's first
antibiotic, or bacteria killer," Fleming would later say, "But I guess
that was exactly what I did". By 1928, Fleming was investigating the properties of staphylococci.
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 that
had immediately surrounded it had been destroyed, whereas other
colonies further away were normal. Fleming showed the contaminated
culture to his former assistant Merlin Price who said "that's how you
discovered lysozyme." Fleming identified the mould that had contaminated his culture plates as being from the Penicillium genus, and — after some months' of calling it "mould juice" — named the substance it released penicillin on 7 March 1929. He
investigated its positive anti-bacterial 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 Gram-negative 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 published his discovery in 1929, in the British Journal of Experimental Pathology, but
little attention was paid to his article. Fleming continued his
investigations, but found that cultivating penicillium was quite
difficult, and that after having grown the mould, it was even more
difficult to isolate the antibiotic agent. Fleming's impression was
that because of the problem of producing it in quantity, and because
its action appeared to be rather slow, penicillin would not be
important in treating infection. Fleming also became convinced that
penicillin would not last long enough in the human body (in vivo)
to kill bacteria effectively. Many clinical tests were inconclusive,
probably because it had been used as a surface antiseptic. In the
1930s, Fleming’s trials occasionally showed more promise, and he continued, until 1940, to try to interest a chemist skilled enough to further refine usable penicillin. Fleming
soon abandoned penicillin, and not long after Florey and Chain took up
researching and mass producing it with funds from the U.S and British
governments. They started mass production after the bombing of Pearl
Harbor. When D-day arrived they had made enough penicillin to treat all
the wounded allied forces. Ernst Chain worked
out how to isolate and concentrate penicillin. He also correctly
theorised the structure of penicillin. Shortly after the team published
its first results in 1940, Fleming telephoned Howard Florey,
Chain's head of department to say that he would be visiting within the
next few days. When Chain heard that he was coming he remarked "Good
God! I thought he was dead". Norman Heatley suggested
transferring the active ingredient of penicillin back into water by
changing its acidity. This produced enough of the drug to begin testing
on animals. There were many more people involved in the Oxford team,
and at one point the entire Dunn School was involved in its production. After
the team had developed a method of purifying penicillin to an effective
first stable form in 1940, several clinical trials ensued, and their
amazing success inspired the team to develop methods for mass
production and mass distribution in 1945. Fleming
was modest about his part in the development of penicillin, describing
his fame as the "Fleming Myth" and he praised Florey and Chain for
transforming the laboratory curiosity into a practical drug. Fleming
was the first to discover the properties of the active substance,
giving him the privilege of naming it: penicillin. He also kept, grew
and distributed the original mould for twelve years, and continued
until 1940 to try to get help from any chemist who had enough skill to
make penicillin. Sir Henry Harris said in 1998: "Without Fleming, no
Chain; without Chain, no Florey; without Florey, no Heatley; without
Heatley, no penicillin."
Fleming's accidental discovery and isolation of penicillin in September 1928 marks the start of modern antibiotics. Fleming also discovered very early that bacteria developed antibiotic resistance whenever too little penicillin was used or when it was used for too short a period. Almroth Wright had
predicted antibiotic resistance even before it was noticed during
experiments. 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. The popular story of Winston Churchill's father's paying for Fleming's education after Fleming's father saved young Winston from death is false. According to the biography, Penicillin Man: Alexander Fleming and the Antibiotic Revolution by Kevin Brown, Alexander Fleming, in a letter to his friend and colleague Andre Gratia, described this as "a wondrous fable." Nor did he save Winston Churchill himself during World War II. Churchill was saved by Lord Moran, using sulphonamides, since he had no experience with penicillin, when Churchill fell ill in Carthage in Tunisia in 1943. The Daily Telegraph and the Morning Post on 21 December 1943 wrote that he had been saved by penicillin. He was saved by the new sulphonamide drug, Sulphapyridine, known at the time under the research code M&B 693, discovered and produced by May & Baker Ltd, Dagenham, Essex – a subsidiary of the French group Rhône-Poulenc. In a subsequent radio broadcast, Churchill referred to the new drug as "This admirable M&B." It
is highly probable that the correct information about the sulphonamide
did not reach the newspapers because, since this drug had been a
discovery by the German laboratory Bayer and the UK was at war with
Germany at the time, it was thought better to raise British morale by
associating Churchill's cure with the British discovery, penicillin. Fleming's first wife, Sarah, died in 1949. Their only child, Robert Fleming, became a general medical practitioner. After Sarah's death, Fleming married Dr. Amalia Koutsouri-Vourekas, a Greek colleague at St. Mary's, on 9 April 1953; she died in 1986. In 1955, Fleming died at his home in London of a heart attack. He was cremated and his ashes interred in St Paul's Cathedral a week later. |