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Start Fleming and the Difficult Beginnings of Penicillin: Myth and Reality
06 August 2018

Fleming and the Difficult Beginnings of Penicillin: Myth and Reality

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The story of the discovery of penicillin in 1928 by the Scottish physician Alexander Fleming at St. Mary’s Hospital in London is one of the most popular in the history of science. The plot is novelistic: Fleming forgets a petri dish containing bacterial culture on which, by chance, a fungus grows; he returns from his summer holidays in Suffolk and, eureka, he’s credited with the scientific discovery of the century. The episode is also the most cited example of serendipity or accidental discovery.

The story of Alexander Fleming (6 August 1881 – 11 March 1955) and penicillin has been told a thousand and one times, to such an extent that in 1985 the specialist in infectious diseases Harold Neu wondered in the magazine JAMA: “Do we really need another book on Alexander Fleming?” However, the book that Neu was referring to put a twist on the classical view, since in Alexander Fleming: The Man and the Myth (Hogarth Press, 1984), the haematologist Robert Gwyn Macfarlane offered a revisionist version that minimises Fleming’s achievement.

Alexander Fleming in his laboratory at St Mary’s, Paddington, London. Source: Imperial War Museums

The truth is that the details surrounding the discovery cannot be summarized without offering a distorted view of reality. In contrast to the stories that begin with Fleming and his famous petri dish, the bigger picture actually goes further back, much beyond September 1928: various sources cite the use of moulds from antiquity to heal wounds. The first scientific observation that bacteria did not grow in the presence of the fungus Penicillium is attributed to the British physiologist John Scott Burdon-Sanderson in 1870, almost 60 years before Fleming’s finding. In later decades, scientists like Joseph Lister, John Tyndall, Louis Pasteur and others in Italy, France and Belgium, observed and studied this same phenomenon.

A reward for tenacity

So, Fleming was not the first to discover the antibacterial properties of the Penicillium fungus. And although it can be argued that none of those pioneering observations founded a continuous and fruitful line of research, basically, the same can be said of Fleming’s studies, which produced “mould juice” of little use because of the instability of the penicillin. When Fleming published his work in 1929, he mentioned “its possible use in the treatment of bacterial infections,” but above all he stressed that it was “certainly useful” as a merely technical tool to separate in culture resistant bacteria from those sensitive to penicillin.

Sample of penicillium mould presented by Alexander Fleming to Douglas Macleod, 1935. Credit: Science Museum London.

In spite of everything, it would not be fair to limit Fleming’s work to a fortunate stroke of serendipity; rather, it was a chance reward for tenacity. As a bacteriologist, he had spent decades looking for antibacterial substances to overcome the problems of the available antiseptics. In his previous work he had identified lysozyme, an enzyme present in the nasal discharge of a patient with a cold that seemed to inhibit the growth of bacteria. “Even without penicillin, Fleming would have been more than just a footnote in the history of medical microbiology,” says Kevin Brown, curator of the Alexander Fleming Laboratory Museum in St. Mary’s, to OpenMind. “Underlying this was a solid background in scientific thought and method.”

But the lack of success with penicillin led him to lose interest. His work went unnoticed and for ten years no one knew of his discovery, which was put on a shelf by its own discoverer. In the review of Macfarlane’s book, published in 1984 in Medical History, Norman Heatley wondered if Fleming was a great scientist. “In the view of the present reviewer the answer must be No,” he wrote. The importance of that judgment lies in who its author was: Heatley was a member of the group from the Radcliffe Infirmary Hospital, Oxford that succeeded in purifying penicillin to make it the medicine that would save millions of lives.

María Jesús Santesmases, an historian of science from the Centre for Human and Social Sciences of the Spanish National Research Council (Spain), and author of several works on the history of penicillin, including the book The Circulation of Penicillin in Spain: Health, Wealth and Authority (Palgrave Macmillan, 2018) tells OpenMind that “Fleming was a good scientist.” Santesmases clarifies that the role of Fleming was limited to “the detection of the activity of an agent that he couldn’t isolate.”

New ways of doing science

It was by chance that the Oxford group, captained by Howard Florey and Ernst Boris Chain, learned about the work published a decade earlier by Fleming. That’s where the coincidences ended and the real scientific process began. As the historian of medicine Bill Bynum wrote in 2007 in The Lancet: “The discovery was old science, but the drug itself required new ways of doing science.”

Howard Florey at his desk at the Sir William Dunn School of Pathology in Oxford.  Source: Imperial War Museums

That new science employed fresh methods and a concept of teamwork far removed from the primitive image of the solitary scientist. “The Oxford group was essential, both Chain’s biochemical expertise and all the accumulated wisdom of Florey and the work of many people,” says Santesmases, who especially highlights the work of women such as Ethel Florey, Jane Orr-Ewing and Margaret Jennings. Another woman, pathologist Mary Barber, detected the first resistant microbes. It is said that in 1940, when Fleming read the first papers from the Oxford group, he phoned Florey to arrange a meeting. When Chain learned of Fleming’s next visit, he commented: “Good God! I thought he was dead.”

Ernest Chain undertakes an experiment in his office at the School of Pathology at Oxford University. Source: Imperial War Museums

The process of the purification and production of penicillin was long and laborious. In 1941, for the first time, it was administered to a patient, the Oxford police officer Albert Alexander, who had contracted a serious infection on his face—apparently not by the scratch of a rose thorn, as is said, but by a cut suffered during a German bombing. With the scant penicillin available and its rapid elimination in the urine, Florey lamented that it was like “trying to fill the bathtub with the plug out.” The researchers collected Alexander’s urine and took it by bicycle to the laboratory to extract the drug, but lost the race against the infection and Alexander died.

It was the collaboration of the governments of the United Kingdom and the USA that led to the mass production of penicillin as a strategic objective during World War II. In 1945, Fleming, Chain and Florey received the Nobel Prize for Medicine, leaving the rest of the team unrecognised. In popular memory, the compelling story of serendipity would make Fleming the hero. But as Santesmases points out, “heroic visions help very little to understand the history of science, and the science itself.”

Javier Yanes

@yanes68

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