Sir Alexander Fleming

The Scottish bacteriologist Sir Alexander Fleming (1881-1955) is best known for his discovery of penicillin, which has been hailed as "the greatest contribution medical science ever made to humanity."

Alexander Fleming was born on Aug. 6, 1881, at Lochfield, Ayrshire, one of the eight children of Hugh Fleming, a farmer. Nature, which he considered his first and best teacher, developed his power of observation and taught him to apply his powers of reasoning to what he observed and to act in accordance with his observations. Like many Scots who were forced to leave their native land for better career opportunities, Fleming, at the age of 13, left for London, where he lived with his brothers. He attended lectures at the Polytechnic School and worked for 4 years in a shipping office. In 1901 an uncle left Fleming a legacy that enabled him to study medicine, and he entered St. Mary's Hospital Medical School in Paddington, later a part of the University of London.

In 1906 Fleming received his licentiate from the Royal College of Physicians. He chose a career in bacteriology and immediately joined the Inoculation Department, now the Wright-Fleming Institute, where he spent his entire career. He assisted Sir Almroth Wright, the originator of vaccinotherapy (therapeutic inoculation for bacterial infection) and the first doctor to use antityphoid vaccines on human beings. Fleming's research at this time primarily involved the use of Paul Ehrlich's Salvarsan in the treatment of syphilis. In 1908 Fleming passed his final medical examinations, winning the Gold Medal of the University of London. He was awarded the Cheadle Medal for his thesis "Acute Bacterial Infections," which foreshadowed the line of work he followed throughout his life.

During World War I Fleming served in the Royal Army Medical Corps, specializing in the treatment of wounds by antiseptics. He noticed that phagocytosis (the ingestion and destruction of infectious microbes by the cells) was more active in war wound infections than in ordinary wound infections, and he advised surgeons to remove all necrotic tissue as soon as possible. He observed that antiseptics not only did nothing to prevent gangrene but actually promoted its development by destroying leukocytes. Although Fleming's later discoveries have overshadowed this work, some authorities believe that he never conceived anything more perfect or ingenious than these brilliant experiments by which he demonstrated the danger to human tissues of incorrectly administered antiseptics.

In 1915, while on leave, Fleming married Sarah Marion McElroy, an Irish nurse who operated a private nursing home in London. The couple had one son, Robert.

Lysozyme Research

In 1921, the year he became assistant director of the Inoculation Department at St. Mary's, Fleming discovered that nasal mucus, human tears, and, especially, egg whites contain a chemical substance with marked bactericidal properties. Inasmuch as it lysed (dissolved) microbes and had the properties of an enzyme, Fleming called it lysozyme. Élie Metchnikoff believed that bodily secretions removed microbes by mechanical rather than chemical means, an opinion held in 1921 by most bacteriologists. Fleming now challenged this view, but his work met a cold reception. Between 1922 and 1927 he published five more articles on lysozyme: he proved that antiseptics then in use, even in much weaker solutions than necessary to fight septicemia, would destroy leukocytes, and that "whereas egg white … has no destructive effects on the leukocytes, it has considerable inhibitory or lethal effect on some of the bacteria."

Discovery of Penicillin

The leitmotiv of Fleming's career was his search for a chemical substance which would destroy infectious bacteria without destroying tissues or weakening the body's defenses. In 1928 an accidental observation, which was a direct result of his apparently disorderly habit of not discarding culture plates promptly, led to the fulfillment of his goal. Fleming noted that on a culture plate of staphylococci a mold (Penicillium notatum) which had been introduced by accidental contamination had dissolved the colonies of staphylococci—an example of antibiosis. He found that the broth containing the bactericidal substance (penicillin) produced by the mold was unstable and rapidly lost its activity. Furthermore, it could not be used for injections until freed from foreign protein. Clearly, a method of extraction and concentration of the crude substance was required. Fleming had no chemist or biochemist on his staff, and he encouraged others to attempt the task.

In 1935 Howard W. Florey, an Australian experimental pathologist, and Ernst B. Chain, a Jewish chemist who had fled from Nazi Germany, came to Oxford University, where in 1939 they took up Fleming's work on penicillin. By employing the relatively new technique of lyophilization, Florey and Chain isolated the drug in completely purified form, which was a million times more active than Fleming's crude substance of 1928, and in 1940 they published the results of their successful treatment of infected white mice. A completely successful test involving a human being was not accomplished until 1942 because of the limited supply of the drug. By 1943 factories in England and the United States were producing penicillin on a large scale, and it became available for military use. By 1944 the miracle drug became available for civilian use.

Fleming never collected royalties on penicillin. In 1945 he received the Nobel Prize in physiology or medicine and toured the United States, where he was hailed as a hero. American chemical firms collected $100,000 and presented it to him in gratitude for his contribution to medical science. He refused to accept the money personally but used it for research at St. Mary's.

In 1946 Fleming became director of the Institute, a position he held until 1955. In 1951 he was elected rector of Edinburgh University. His wife had died in 1949, and in 1953 he married Amalia Coutsouris-Voureka, a Greek medical worker who had come to London in 1946 to work with him. Fleming died on March 11, 1955, and was buried in the crypt of St. Paul's Cathedral in London. According to André Maurois, "No man, except Einstein in another field, and before him Pasteur, has had a more profound influence on the contemporary history of the human race."

Further Reading

Discussions of Fleming's life and work can be found in John D. Ratcliff, Yellow Magic: The Story of Penicillin (1945); Laurence J. Ludovici, Fleming, Discoverer of Penicillin (1952); Lloyd G. Stevenson, Nobel Prize Winners in Medicine and Physiology, 1901-1950 (1953); John Rowland, The Penicillin Man: The Story of Alexander Fleming (1957); and, André Maurois, The Life of Sir Alexander Fleming, Discoverer of Penicillin (1959; trans. 1959). □

Sir Alexander Fleming

1881-1955

Scottish Bacteriologist

Alexander Fleming discovered penicillin, a "wonder drug" that ushered in the era of antibiotics. This new weapon against bacterial disease offered hope in fighting many infections that could not be treated effectively in the past. Together with Sir Howard Walter Florey (1898-1968) and Ernst Boris Chain (1906-1979), Fleming was awarded the Nobel Prize in 1945. In addition to penicillin, he also discovered lysozyme, an antibacterial agent found in tears and saliva.

Fleming was born on August 6, 1881, on a farm in Lochfield, Ayrshire, Scotland. He began his education in Scotland and then went on to London, where he received his medical degree in 1906 from St. Mary's Hospital Medical School at the University of London. He lectured there until World War I, during which he served in the Army Medical Corps. After the war he returned to St. Mary's, and in 1921 identified lysozyme. He was appointed a professor in 1928.

That same year, Fleming was experimenting with the staphylococcus bacteria, and had the good luck to have one of his culture plates contaminated by a mold called Penicillium notatum. Around the mold, there was a ring in which no bacteria grew. Further experiments confirmed that the effect was due to a substance produced by the mold, and it not only inhibited the growth of many types of bacteria, it killed existing growth. The effect was specific to Penicillium notatum; other molds did not work the same way.

Fleming called the active substance penicillin. He diluted it hundreds of times, and it was still effective. He showed that, unlike harsh antiseptics such as phenol, penicillin did not destroy white blood cells. He injected it into animals without negative effects. He published the results of his experiments in 1929, suggesting that the substance might have therapeutic uses, but the mold extract was too perishable to allow extensive tests. Penicillin was largely neglected for a decade.

In 1939, the sulfanilomide derivatives, or sulfa drugs, were introduced by the Italian pharmacologist Daniel Bovet (1907-1992). Sulfa was effective against streptococcus and other disease-causing bacteria, and saved many lives during World War II. However, it was somewhat toxic, tending to cause kidney damage if not used very carefully. Its promise, coupled with the needs of the war, interested researchers in finding other valuable medicines with fewer toxic effects.

It was at this point that Chain and Florey obtained a sample of Fleming's Penicillium notatum culture. Isolating the active substance, penicillin, they were able to purify it so that it was more stable and produce it in larger quantities. Then they performed clinical trials that demonstrated its effectiveness for use as an antibiotic. Like sulfa, penicillin was employed in what amounted to a massive field trial during World War II.

Honors soon followed for all three men. In addition to the Nobel Prize, Fleming was elected a Fellow of the Royal Society in 1943 and knighted in 1944. In 1948, he became emeritus professor of bacteriology at the University of London. He died in London on March 11, 1955.

SHERRI CHASIN CALVO

Fleming, Sir Alexander

Alexander Fleming (1881-1955) was one of three men who discovered and developed the first antibiotic, penicillin. Fleming was born on a farm in Scotland and worked in a shipping company as a youth. He hated the work, however, and when he received a small inheritance from a relative, he used it to go to medical school. Initially he worked for Almroth Wright, who believed strongly in the effectiveness of vaccinations to prevent disease. But Fleming thought there might be other ways to treat infections.

During World War I (1914-1918), Fleming was further inspired by the problems of wounded soldiers. Immunizations did nothing to stop the bacterial infections which tended to attack the wound sites. Fleming was determined to find a "magic bullet" substance that could destroy these invading bacteria. In 1922, he discovered that the body actually has enzymes in tears and mucus (slimy secretions) that, though weak, can kill certain bacteria very quickly.

In 1928 Fleming was still working on the properties of various bacteria when a little bit of luck led to his most important discovery. Fleming had left some microbes (bacteria samples) in dishes in his lab; he had also left the window open. Mold spores from outside landed in the dish and miraculously dissolved the bacteria. Fleming identified the mold as "Penicillium notatum," and he named the substance that actually killed the bacteria "penicillin." While Fleming proved that penicillin was not poisonous to animals, he did not have the means to actually synthesize (artificially create) a pure form of it to use in experiments. The practical purification of penicillin was the later achievement of Howard Walter Florey (1898-1968) and Ernst Boris Chain (1906-1979). Fleming, Horey, and Chain shared the 1945 Nobel Prize in medicine for their combined research with penicillin.

After receiving the Nobel Prize, Fleming spent the rest of his career doing research at the Wright-Fleming Institute. Because of Fleming's momentous discovery, many previously incurable diseases are now easily treated, and the average human life span has been significantly increased.

Fleming, Sir Alexander (1881–1955) Scottish bacteriologist, discoverer of penicillin. In 1922, Fleming discovered lysozyme, a natural antibacterial substance found in saliva and tears. During research on staphylococci in 1928, Fleming noticed that a mould, identified as Penicillium notatum, liberated a substance that inhibited the growth of some bacteria. He named it penicillin; it was the first antibiotic. Howard Florey and Ernst Chain refined the drug's production and it was first produced commercially in 1941. In 1945, Fleming, Florey and Chain shared the Nobel Prize in physiology or medicine.

Fleming, Sir Alexander (1881–1955) British bacteriologist, born in Scotland. He studied medicine at St Mary's Hospital, London, where he remained all his life. In 1922 he identified lysozyme, an enzyme that destroys bacteria, and in 1928 discovered the antibiotic penicillin. He shared the 1945 Nobel Prize for physiology or medicine with Florey and Chain, who first isolated the drug.