FLEMING, FLOREY AND CHAIN:

THE DISCOVERY AND DEVELOPMENT OF PENICILLIN

Edexcel IGCSE Lesson 5

What is Penicillin?

Penicillin is an antibiotic. Antibiotic literally means against life but antibiotics only kill life that is harmful to living creatures, i.e. bacteria. A bacterial infection is caused by millions of tiny bacteria that are trying to survive and multiply in the body. An antibiotic attacks and kills these bacteria. Before the development of penicillin, many people suffered and died from bacterial infections that are no longer considered dangerous today.

So did Fleming actually discover penicillin?

Penicillin is made from a mould called penicillium. This mould was first discovered in the early 19th century by John Sanderson who found that very little grew near it. In the 1880s, Joseph Lister noted these observations and wrote to his brother to say that he intended to try penicillin on infected wounds. Lister successfully treated a nurse with an infected wound with penicillin, but did not leave any notes on the case and apparently did not continue his research in this area.

Who was Alexander Fleming?

Alexander Fleming was born in Ayrshire, Scotland, in 1881. He was the son of a farmer. When he was 13, he moved to London to live with his older brother. After graduating from the University of London, he became a bacteriologist at St. Marys Hospital in the city.

The great re-discovery of penicillin!

It was in the laboratory of St. Marys Hospital in 1928 that Fleming rediscovered the properties of penicillin. This source comes from a biography, The Life of Sir Alexander Fleming, written in 1963. It describes when Fleming was visited by his friend, Pryce.
Fleming was in his little laboratory as usual, surrounded by innumerable dishes. The cautious Scot disliked being separated from his cultures before he was quite sure there was nothing more to be learned from them... Fleming took up several old cultures and removed the lids. Several of the containers had been contaminated with mould... As soon as you uncover a culture dish, he said to Pryce, something tiresome is sure to happen. Things fall out of the air. Suddenly he stopped talking, then, after a moments observation, said... Thats funny... On the cultures at which he was looking there was a growth of mould, as on several of the others, but on this particular one, all around the mould, the

So what did the mould look like?

The mould Penicillium Notatum, shown growing in a Petri dish, and in close-up

How had it got into Flemings dish?

On investigation, Fleming found that penicillin bacteria had got on to the dish, perhaps blown into his lab through an open window. The penicillin was killing the staphylococci. Whether the account we just read it how it really happened, we cannot be sure even Flemings own accounts of how it happened varied! Does that matter? The important point is that Fleming identified the mould and saw its significance that penicillin could be applied to or injected into areas where there were penicillinsensitive microbes . However, Fleming did not have the facilities or the support to develop and test his idea that penicillin could

Think!

Why is Fleming usually thought of as the discoverer of penicillin? Why do you think that so many people observed the power of penicillin but did not develop it as a cure?

Now read your textbook, pp42 43 to see how penicillin came to be developed.

Florey and Chain

It was the Second World War which finally brought about the successful development of penicillin. In the 1930s two Oxford scientists, Howard Florey and Ernst Chain, became interested in Flemings 1929 paper on penicillin. In 1939 they assembled a team of pathologists, chemists and biochemists, and three days after the outbreak of war Florey asked the British government for money to fund the teams research into

Howard Florey (left) and Ernst Chain.

Do you think this was a good time for Florey to approach the government for money into this kind of research? Why?

The development of penicillin

Stage 1:Growing the penicillin This was a combination of the latest freeze-drying technology and some much more traditional equipment: thousands of milk bottles (in which to grow the bacteria), milk churns, a dog bath and a hand pump! From this, the team were able to gather a few grams of pure penicillin.

Stage 2: Testing penicillin on animals There was enough penicillin to test it on eight mice. They were injected with a deadly bacteria (streptococci). Four of the mice were then given penicillin. 24 hours later the mice which had not been injected with penicillin were dead. Those who had been injected were healthy.
Stage 3: The first human trial of penicillin By 1941 the team had enough penicillin to test it on a human. The patient had terrible abscesses which had spread from his mouth to his scalp, eyes, arm and even his lung. He was going to die there was nothing to lose by trying penicillin. After four days of treatment he was much improved and was sitting up in bed penicillin worked. However, they did not have enough, and after five days the supply ran out the patient relapsed and died.

Production continues... but not in great quantities!

Although this first patient still died, it was clear that penicillin was a powerful drug. Production remained painfully slow, but as new batches were produced, two more patients were successfully treated. In August 1942, Fleming himself used penicillin to successfully treat a friend who had meningitis.

But the war was producing thousands of casualties penicillin needed to be mass produced if lives were to be saved.

Steps to Successful Mass Production

June 1941: Florey travels to US to try to get drug companies to develop penicillin not much interest. December 1941: US enters the war
1942: US government gives $80 million to 4 drug companies to find a way to mass produce penicillin. 1943: Mass production began. Penicillin first used by British army in North Africa.

After WW2: Penicillin made available for civilian use.

1945: US Army using 2 million doses of penicillin a month

June 1944: Enough penicillin is available to treat all the casualties of DDay.

How important was penicillin?

It is estimated that without penicillin, another 12-15 per cent of wounded Allied soldiers would have died of infections. Penicillin also roughly halved the average time the Allied wounded spent in hospital.

How important was penicillin?

Penicillin was a miracle drug when it was first developed. It could treat a wide range of infections and diseases, including streptococcus, scarlet fever, syphilis and gonorrhoea.
In 1945, Fleming, Florey and Chain were jointly awarded the Nobel Prize for Medicine for their work on penicillin.

Penicillin why then?

On your own slide, draw a spider chart which shows the different factors which influenced the discovery of penicillin. It should help you to think about why penicillin was finally mass produced in 1942-1945, and not before. Try to link any factors which you think are inter-connected.

So which factor was most important?

So can we answer our question why was penicillin mass produced in 1942-1945 and not before?

Do you think any one factor was particularly important to the development of penicillin? Who do you think deserves the credit for the discovery of penicillin?

Homework
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What is penicillin? What part did chance play in the discovery of penicillin? How did war influence the development of penicillin? How did governments help in the mass production of penicillin? What other factors were important in the development of the drug? Why was penicillin mass produced in 1942-1945 and not before? Who deserves most of the credit for Penicillin? Add the major steps in the discovery/development of penicillin to your ongoing timeline.