How penicillin was massively produced during World War


Alexander Fleming was a young Scottish doctor who, after being horrified by the great mortality caused by shrapnel wounds infected during World War I, decided to look for a new antiseptic.

Alexander Fleming.

Alexander Fleming.

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One summer day in 1928, when he returned from vacation, he discovered that staph crops had been contaminated with a fungus. This was later identified as Penicillium notatum, and the antibacterial substance it secretes was called penicillin.

The discovery would have been a mere laboratory curiosity if many other scientists had not worked to produce the new product with sufficient purity and on a large scale to give rise to the antibiotic we all know today.

So far comes the story that many people know, but how was it possible to get penicillin out of the laboratory and start producing it on a large scale?

Howard Florey

Howard Florey

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First we have to move from London to Oxford, to the laboratory of Howard Florey and Ernst Chain. There the surface fermentation method was developed, first in reused milk bottles and then in containers designed for this purpose.

For animal studies and the clinical trial they needed to purify about 500 liters of culture broth a week. This incredible work was done by a group of women, the calls "penicillin girls", they charged £ 2 a week.

In February 1941 the first human test was done. Policeman Albert Alexander had scratched his mouth while pruning rose bushes and had developed an infection in the face and lungs. He recovered in a few days, but ended up dying because the antibiotic reserves ran out.

Ernst Chain

Ernst Chain

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As World War II prevented further research in Europe, English pharmaceutical companies ceded their results to the Government of the United States. It was very important to produce enough penicillin for the Allied troops, since the Germans already used sulfamide.

Howard Florey took penicillin samples to Andrew Moyer, a researcher at the Department of Agriculture, in Illinois. In a few weeks he proposed improvements in the process, mainly replacing the surface crop with a fermentation with submerged culture.

Who would have experience in submerged crop fermentation in the United States? Jasper Kane and John McKeen worked at Pfizer, the main producer of citric acid in deep fermenters. As the war prevented bringing citrus from Italy, a way of synthesizing citric acid with microorganisms was devised. There was a great demand for this product because of the already buoyant sugary drinks industry.

Within 6 months, and despite the limitations of the war, Pfizer developed a plant with 14 fermenters of 28,500 liters each. So much reaction volume was needed because only 4 grams of penicillin were produced per 10 liters of broth, and more than 60% of them were lost during purification.

Bioreactor for penicillin production.

Bioreactor for penicillin production.

Wikipedia

Using increasing reactors, strains of greater productivity and better recovery methods, in five years the production of penicillin was multiplied by 800.

For all these reasons, Fleming, Florey and Chain were awarded the Nobel Prize in Medicine in 1945. In the same ceremony, Fleming himself warned us of the danger of generating resistance to antibiotics due to their indiscriminate use.

Dorothy Hodgkin

Dorothy Hodgkin

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There is also a female protagonist in this story. The crystallographer Dorothy Hodgkin was awarded a few years later with the Nobel Prize in Chemistry for determining the structure of many biomolecules, among others, that of penicillin.

Only a few weeks after the industrial penicillin process was about, one of the most famous operations of World War II took place: the Normandy Landings. In the first 24 hours 150,000 allied soldiers landed in France. Everyone had a dose of penicillin in their medical kit to use if they were injured.

Penicillin campaign.

Penicillin campaign.

Wikipedia

In this way the dream that Fleming had had, 25 years before, also in France was fulfilled. By the way, one of the landing barges of the English army was piloted by the officer Alec Guinness, who three decades later would interpret in the Star Wars Episode IV to Jedi teacher Obi-Wan Kenobi.

Penicillin became a luxury product in war-torn Europe, as its use was reserved for Allied troops. To show the movie The third man (1949), with a script by Graham Greene, in which a black market of adulterated penicillin is portrayed in Vienna.

The third man

The third man

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We had to wait until the end of the war, and already in the 50s in Spain, for penicillin to reach the market massively.

Today Fleming's discovery, attributed to serendipity, is undervalued. But, as Thomas Jefferson said, "the harder I work, the luckier I am."

This article was originally published in The Conversation. You can read the original here.

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