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BMJ. 2007 May 19; 334(7602): 1059.
PMCID: PMC1871770
Review of the Week

Penicillin and a series of fortunate events

Reviewed by Allen F Shaughnessy, director of curriculum development, Tufts University family medicine residency at Cambridge Health Alliance, Cambridge, MA, USA

Penicillin: Triumph and Tragedy. Robert Bud. Oxford University Press, £30, pp 330. ISBN 978-0-19-925406-4. Rating: ****.

The story of penicillin takes in a dirty Petri dish, a refugee chemist, and a few human tears, finds Allen F Shaughnessy

Like an impromptu relay race, a series of fortunate events and unlikely connections between the right people with the right knowledge in the right places gave the world penicillin. We owe our antibiotic armamentarium to a dirty Petri dish in Alexander Fleming's laboratory, a German refugee chemist, a rotten melon, and the rising popularity of soft drinks. And the whole process, in a sense, started with a few human tears.

Penicillin: Triumph and Tragedy, by medical historian Robert Bud, traces the development of penicillin from a chemical stumbled on by accident to an idea, or perhaps an ideal, that has led to a social revolution.

This development began in 1929 when Fleming noticed a zone of inhibition around a colony of Penicillium mould on an agar plate of Staphylococcus. The story almost ended there, for Fleming could not simply siphon off the juice produced by the Penicillium mould and inject it into infected patients.

The research needed to isolate the responsible chemical compound was stalled for years. It wasn't until eight years later that Ernest Boris Chain, a German expatriate chemist, developed a method of producing a stable powder form.

After tests on only a handful of mice, the first “safety trial” was performed: a single dose given to a woman dying from cancer. The first clinical trial was performed on an infected patient, a policeman who developed septicaemia after a minor cut.

Police constable Alexander improved dramatically with each penicillin injection—until supplies ran out and he succumbed. His initial response encouraged further testing in five patients, four of whom had miraculous recoveries.

Mould grows only on surfaces, and about 500 agar plates were needed to produce treatment for a single patient. Large scale production took penicillin to the cornfields of the Midwest of America, where the technology was developed to grow moulds without needing sterile plates the size of football fields.

Sparked by the high demand for use as flavouring agents in the newly popular carbonated beverages, moulds producing citric acid and lactic acid were being grown in the Midwest on a large scale. Botanists in Peoria, Illinois, had developed a method of “deep fermentation,” in which continuous aeration and agitation of the medium created a virtual surface for the growth of mould.

Having found a method of mass production that could be adapted to penicillin production, the researchers searched for a more productive strain of the Penicillium mould. In yet another strange twist, after a worldwide search, this better strain was found on a melon in a local market in Peoria.

Soon, production of penicillin had grown exponentially, from the 40 mg first isolated by Chain in 1937 to four tonnes of pure drug produced in 1945. News—and then use—of penicillin grew rapidly. The first commercial production plant was opened by Pfizer. Germany, the ancestral home of brewing and fermentation, was among the countries that were developing methods of producing penicillin.

The triumph of antibiotics allowed other medical technologies to take off. “Antibiotics supported surgeons, who were now confident they could manage infection and were routinely carrying out more ambitious operations. Cancer therapists could also reduce the immunity of patients without the worry of infection,” writes Bud.

On the other hand, the availability of antibiotics allowed for sloppiness in medical care: “Whereas before strict hygiene had been seen as essential to the avoidance of disaster, now a little less rigour was sometimes afforded. A Harvard professor warned in 1963 that the rapid growth in antibiotic use was due not just to clinical need, but also to understaffing, ignorance, and poor diagnosis.”

Not much has changed today, with the implicit mottos in medicine of “when in doubt, antibioticise,” and “broader [spectrum] is better.” After all, how many children reach their fifth birthday without taking antibiotics for at least a week?

The tragedy of penicillin, according to the author, occurred when penicillin the chemical became penicillin the promise—offering hope, wellness, and freedom from pain and disease that would far outrun its therapeutic ability. As Bud points out, “Penicillin is so closely associated with ‘strong medicine', scientific triumph, social improvement, and reliability that the very writing of a prescription gives hope to the patient and a sense of power to the doctor.”

Penicillin: Triumph and Tragedy, is a fascinating overview of the development and marketing of penicillin. It will have too much detail for some readers. The book is extensively referenced and annotated, and the notes and bibliography comprise 95 of the 318 pages.

And what was the role of tears? In the years before noticing the antibacterial activity of Penicillium, Alexander Fleming had investigated the antiseptic properties of human tears. This experience led him to retrieve the mouldy plate from the rubbish because the mould might have produced a substance similar to the germ killing lysozyme he had identified in human tears. This insight resulted in countless lives saved and also transformed Pfizer, a small chemical company originally specialising in the production of citric acid for soft drinks, into the pharmaceutical powerhouse it is today.

There is an implicit motto in medicine of “when in doubt, antibioticise,” and “broader spectrum is better”


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