WALT: What is penicillin? All: define penicillin Most: describe how penicillin was discovered Some: explain how to mass produce penicillin Task: What is penicillin? AQA Science © Nelson Thornes Ltd 2006  1

How do microbes kill microbes? The fungus Penicillium makes a chemical that kills bacteria. The chemical can be extracted and purified to make penicillin, a medicine that is safe for people to use and cures many bacterial diseases. Penicillin is produced in large fermenters. AQA Science © Nelson Thornes Ltd 2006  2

The story of penicillin Alexander Fleming was a scientist who studied bacteria. He was keen to find ways of killing them. In 1928, he was growing lots of bacteria known as staphylococci on agar plates. Alexander’s lab was rather untidy, and he sometimes left the lids off his plates, letting the air in. Photo: Duncan Smith/Photodisc 72(NT)

Returning from a holiday, Alexander noticed that lots of his culture plates were mouldy. A common mould that might have grown happily on a slice of bread had landed on Fleming’s plates – a stroke of luck that has saved millions of lives. Photo: Ann Fullick AQA Science © Nelson Thornes Ltd 2006  4

Fleming noticed that, although plenty of bacteria were growing on the agar, there was a clear ring around some of the mould. Something had killed the bacteria. Straight away Fleming saw that this might be important. He even labelled and saved the plates! Photo: Pfizer AQA Science © Nelson Thornes Ltd 2006  5

Fleming worked hard on his mould, which was called Penicillium notatum Fleming worked hard on his mould, which was called Penicillium notatum. He squeezed out some ‘mould juice’ which he called penicillin. But he couldn’t get much penicillin from the mould. It wouldn’t keep – even in the fridge – and he couldn’t prove it would actually kill bacteria and make people better. By 1934 Fleming gave up on penicillin and went on to do different work! AQA Science © Nelson Thornes Ltd 2006  6

Ronald Hare After Fleming stopped work on penicillin, other people carried on the story. Ronald Hare, one of Fleming’s young assistants, found that Penicillium mould grows best at quite low temperatures. AQA Science © Nelson Thornes Ltd 2006  7

Dr Cecil Paine Cecil Paine was another of Alexander Fleming’s pupils. He made a penicillin extract and was the first person to try it out on a person. A local miner got a stone in his eye and had a massive infection which was making him blind. Cecil washed the eye with his penicillin extract – and it got better. Photo: Nancy Cohen/Photodisc 46 (NT) AQA Science © Nelson Thornes Ltd 2006  8

The baby was cured and its sight was saved! Next, Cecil Paine treated a tiny baby with his penicillin wash. It had picked up an eye infection as it was born. The baby was cured and its sight was saved! Paine never published his work, but he told a new professor at the university, a man called Howard Florey. Photo: Ann Fullick AQA Science © Nelson Thornes Ltd 2006  9

Howard Florey and Ernst Chain worked at Oxford University Howard Florey and Ernst Chain worked at Oxford University. In 1938 they decided to do some work on penicillin using mice to try to get clear evidence that penicillin worked. Norman Heatley was a key man in their team. He worked out a way of making enough penicillin to try it out – and he was the man who watched over the mice as the experiment went on. AQA Science © Nelson Thornes Ltd 2006  10

The mouse experiment Eight mice were infected with bacteria which would kill them in 24 hours. Four were given penicillin. The four treated mice stayed healthy – but the other four died! Photo: Hart/Photodisc 50 (NT) AQA Science © Nelson Thornes Ltd 2006  11

Norman Heatley A human being is about 3000 times heavier than a mouse – so a lot more penicillin was needed. In 1940–1941, Norman Heatley developed some special pot vessels to grow more mould – and collect more penicillin. In just a few weeks, Norman made enough penicillin for Howard Florey to try it out on a fully grown man. Photo of Norman Heatley by Mary Krinsky AQA Science © Nelson Thornes Ltd 2006  12

Albert Alexander was a 43-year-old policeman who was dying of a blood infection. Florey and Chain gave him penicillin for five days. Albert recovered well until the penicillin ran out. Florey and Chain tried everything – they even collected spare penicillin from Albert’s urine but it was no good. The infection came back and Albert died. AQA Science © Nelson Thornes Ltd 2006  13

Florey and Chain collected more penicillin Florey and Chain collected more penicillin. They were determined to succeed. This time they tried their penicillin on a 15-year-old boy who had an infection after an operation. He was completely cured. AQA Science © Nelson Thornes Ltd 2006  14

By 1941, Europe was in the grip of the Second World War By 1941, Europe was in the grip of the Second World War. Thousands of soldiers were dying from infected wounds and infectious disease. Photo: Ann Fullick Potentially, penicillin could save thousands of lives – but the scientists still couldn’t make enough of it. AQA Science © Nelson Thornes Ltd 2006  15

British laboratories and factories were busy with the war effort. Howard Florey had contacts in America, so the scientists took their mould to the United States where some of the large chemical companies helped them to make penicillin on a big scale. Photo: Pfizer AQA Science © Nelson Thornes Ltd 2006  16

‘Mouldy Mary’ Penicillium notatum is slow growing and produces little penicillin. When Mary Hunt, a member of the US team, brought in a mouldy melon she found on a market stall it gave them a breakthrough – a new and better form of Penicillium! Photo: Ann Fullick AQA Science © Nelson Thornes Ltd 2006  17

Chain, Fleming and Florey all got a Nobel prize for their work. Photo: Pfizer Sir Alexander Fleming opening Pfizer’s new UK factory to make penicillin in 1954 The number of people dying from diseases caused by bacteria in countries like Britain and America dropped dramatically. Everyone thought the battle against bacteria had been won! AQA Science © Nelson Thornes Ltd 2006  18

Penicillin Production B3 3.5 What does the penicillin fungus need to grow?  Pfizer Ltd AQA Science © Nelson Thornes Ltd 2006  19

This is Penicillium – the fungus that produces penicillin, the first of the antibiotic ‘wonder drugs’. Antibiotics kill bacteria without harming humans. Penicillin has saved many, many millions of lives since it was discovered – and treated millions of minor infections as well.  Alan Silverside AQA Science © Nelson Thornes Ltd 2006  20

As a fungus, Penicillium cannot photosynthesise As a fungus, Penicillium cannot photosynthesise. A solution containing corn liquor (containing sugar), nitrate fertilisers and yeast extract is added to the fungus in a giant tank or fermenter. This provides all of the required nutrients, and fermentation begins.  Pfizer Ltd AQA Science © Nelson Thornes Ltd 2006  21

Temperature, oxygen concentration and pH are controlled in the fermenter. Large paddles swirl the medium around to keep everything well mixed. Over the next 140 hours the fungus will grow and start to produce penicillin. AQA Science © Nelson Thornes Ltd 2006  22

After about 140 hours roughly 30% of the mixture will be drained off and fresh nutrient added. The material that has been drained off is passed to a separator. Why wait until 140 hours before this is done? AQA Science © Nelson Thornes Ltd 2006  23

The separator acts a bit like a spin-dryer – a vacuum draws mixture onto a rotating drum. The drum is porous so the dissolved penicillin passes through into the centre while the fungal filaments are stuck on the outside. These filaments are removed by a blade as the drum rotates.  Pfizer Ltd AQA Science © Nelson Thornes Ltd 2006  24

The filtered liquid with the dissolved penicillin is treated with potassium salts. This precipitates the penicillin out of solution. This precipitate can then be collected by filtering and the powder produced can be as high as 99.5% pure penicillin. NOAA AQA Science © Nelson Thornes Ltd 2006  25

Penicillin and the other antibiotics which have been discovered are some of the most useful medicines we have. Doctors all over the world prescribe them to save patients from the effects of bacterial disease. AQA Science © Nelson Thornes Ltd 2006  26