22 January 2015

The story of penicillin

Penicillin gave the allies a secret weapon during the Second World War and was soon being mass produced. Here we look at the history of this 'miracle drug'.

By Andrew Butterworth

3D illustration of Penicillium katerynakon showing spores conidia and conidiophore

The most famous fungus?

I am one of Kew's new Library Graduate Trainees and as part of my role I am required to work in the Jodrell Library which is located alongside Kew's Fungarium. An estimated 1.25 million specimens of dried fungi are housed in the Fungarium and it is considered one of the oldest, largest and most important mycological reference collections in the world.

Penicillin is a group of antibiotics derived from Penicillium fungi and interestingly I recently discovered some early photographs taken by Jean Straker of the drug being produced in the late 1940s by one of the UK's major pharmaceutical companies: Boots. Meanwhile though returning to penicillin, I decided to use the early photos as a starting point for a look into the history of the drug and how it was later mass produced.

The discovery of penicillin

"I had a clue that here was something good, but I could not possibly know how good it was."

- Sir Alexander Fleming in his speech upon receiving the Nobel Prize for Medicine, at the Nobel Banquet in Stockholm, December 10, 1945 with Ernst B. Chain & Sir Howard Florey.

The story of penicillin actually began in 1929 with Alexander Fleming, a doctor and researcher at St. Mary's Hospital, London. Returning to his basement laboratory at the hospital after having been on holiday, he found an unwashed petri dish in which mould had been contaminated by streptococcus. Significantly, Fleming realised that the white ‘halo,’ surrounding the mould was killing off this common infectious bacterium, an important discovery. However, as crucial as this moment was, revisionists have now placed Fleming as one of the many scientists who discovered the ‘wonder drug’ but failed to realise its full potential. This view is supported by an experiment Fleming conducted where he added penicillin extract to blood in a test tube. It seemed inactive but this was because he had failed to isolate the penicillin correctly.

Fleming published his discovery but it ultimately fell to others to further develop the uses of the drug, an aim which was soon to be driven forward by the extraordinary circumstances created by the Second World War. It was Australian scientist Howard Florey (1898-1968), German biochemist Ernst Chain (1906-79) and Norman Heartley (1911-2004) that led Boots Pure Drug Company to further experiments with penicilin as part of the British war effort.

Making penicillin work

On Saturday 25 May 1940 Chain and Florey conducted an experiment on 8 mice, and after the drug had proven successful they turned to human trials. Sadly early patients like Albert Alexander did pass away, but this was only because Chain and Florey had not learnt how to extract enough penicillin for an extensive dose. It was Heatley who re-engineered the process to create a surperior yield.

The Second World War led to the Therapeutic Research Corporation being created which comprised leading British drug companies including Boots, British Drug Houses, Glaxo Laboratories, May and Baker, and the Wellcome Foundation. The group's aim was to share new discoveries so that no single company could monopolise development of a particular drug. At the time the focus was on wartime medicine, developing new drugs and maintaining supply collaboratively. However, Jonathan Liebenau documents how the British companies were unsurprisingly very cautious about collaborating or passing information between each other.

It was the Americans through the centralised control of the Northern Regional Research Laboratory in Peoria Illinois, Pfizer and also their Universities who gained better results. In 1943 Mary Hunt (who later became known as 'Mouldy Mary') found a golden mould growing on an American Cantaloupe (Penicillium chrysogenum). A number of experiments took place and researchers discovered that if Mary's mould was exposed to X-rays, a mutant penicillium strain was produced that further increased the quantity of antibiotic compound to 1,000 times more than Fleming’s example. These successes had a signicant impact which meant that by 1945 more than 1 million people had been treated with the drug as opposed to less than 1000 in early 1943.

As Boots was a pioneer in the manufacture of penicillin during the war, it wanted to continue the success of the ‘miracle drug’ through mass production.

Dr. Florey's dilemma

"I am now accused of being partly responsible for the population explosion ... One of the most devastating things that the world has got to face for the rest of this century."

- Dr. Howard Florey as quoted in What on Earth Evolved? 100 Species that changed the world by Christopher Lloyd, p.315. 

Many would see penicillin as a great success, however Florey became so sensitive about the population issue that he dedicated much of his later research into developing improved methods of contraception. Yet as much as Florey found his association with penicillin uncomfortable, he was placed on the $50 note, for 22 years, as the most noted Australian scientist.

"Without Fleming, no Florey or Chain, without Chain no Florey, without Florey, no Heatley, without Heatley no penicillin."

- Sir Henry Harris in a BBC TV programme entitled Breaking the Mould, aired July 2009.

Although revisionists have dismissed Fleming, Sir Henry Harris' quote really explains why Fleming, Florey and Chain where given the Nobel Prize for Medicine in 1945. Antibiotic sales today are estimated at more than £6 million a year, and without the amazing knowledge gained from mycology the world would be a very different place.

Andrew Butterworth

- Library Graduate Trainee -

Further reading

Bedoyere, Guy de la, The Discovery of Penicillin: Modern Milestones in Modern Science. (London, 2005)

Brown, Kevin, Penicillin Man: Alexander Fleming and the Antibiotic Revolution (Stroud, 2004)

Bud, Robert, Penicillin: Triumph and Tragedy. (Oxford, 2007)

Clark, Ronald W., The Life of Ernst Chain: Penicillin and Beyond. (London, 1985)

Kavaler, Lucy., Mushrooms Moulds and Miracles. (London, 1967)

Lax, Eric, The Mould in Dr Florey’s Coat: The Remarkable True story of the Penicillin Miracle. (London, 2004)

Liebenau, Jonathan, ‘The British Success with Penicillin, Social Studies of Science,’ Vol. 17, No. 1 (Feb., 1987), pp. 69-86.

Lloyd, Christopher, What on Earth Evolved? 100 Species that changed the world. (London, 2009), p. 314-15.

Phillips, Simon, ‘Jesse Boot and the rise of Boots the Chemists,’ The Pharmaceutical Journal, Vol. 269, No. 7228, (Dec. 21/28, 2002), p. 925-928.

Reader’s Digest, The 20th Eventful Century: Milestones of Medicine. (London, 2000)

Stone, Tevor, and Darlington, Gail, Pills potions poisons: How drugs work. (Oxford, 2000), p. 254.

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