Bio 3 - Microbiology - Antibiotic production

Penicillin is one of the best known medicines in the world. It has revolutionised medicine since it was manufactured

In 1928, Alexander Fleming was a young researcher at St mary's medical school, London. He left some of the plates on which he was culturing bacteria uncovered near an open window. When he remembered to look at them, he found bacteria growing on the surface of his dishes as he expected. But Fleming also noticed spots of mould growing, and around them were clear areas of agar. The bacteria were no longer growing. Whatever had blown in and started growing on the plates was producing a chemical which had killed the bacteria

Fleming found that the microorganism which had invaded his Petri dishes was a common mould called Penicillium Notatum. He set about trying to extract the substance which killed bacteria but found it almost impossible with the technology available at the time

He managed to get a tiny amount and used it to treat an infected wound. He called his extract Penicillin. But it was very difficult to extract, and very unstable once he got it. So he decided he wouldn't be able to get useful amounts of it from his mould. He saved his cultures and moved on from the research.

During WW2 the need for a drug to kill bacterial infections became ever more urgent. Howard Florey and Ernest Chain were working at Oxford University in a desperate search to find an antibacterial drug. They turned to Flemings mould and finally manages to extract enough penicillin to show what it could do.

After successful animal trials, they tried to save the life of a London Policemen who was dying of a blood infection. The dying man made an amazing recovery. However the supply of penicillin ran out, the infection came back and the man died

More months of work produced enough penicillin to save the life of a boy with a bacterial infection. But what was needed was enough of the drug to treat thousands of wounded soldiers. British factories were dedicated to the war effort, so Chain and Florey turned to the american pharmacuetical industry for help in developing a manufactoring process

More months of work produced enough penicillin to save the life of a boy with a bacterial infection. But what was needed was enough of the drug to treat thousands of wounded soldiers. British factories were dedicated to the war effort, so Chain and Florey turned to the american pharmacuetical industry for help in developing a manufactoring process

Flemings original mould was incredibly difficult to grow in large cultures. Then a mould growing on a melon in a market was found to yield 200 times more penicillin than the orginal. Whats more, it grew relatively easily in deep tanks, making large scale

The production of penicillin did not stop with the end of the war. We now use modern strains of Penicillium mould which give even higher yields. We grow the mould in a sterilised medium. It contains sugar, amino acids, mineral salts and other nutrients. The medium is called corn steep liquor. It is a waste product from the food industry.

We use huge 10,000dm^3 fermenters which have strong paddles to keep stirring the broth. Thats because the penicillen mould needs lots of oxygen to thrive. Sterile air is blown in to provide the oxygen. We control the temperature by a cooling jacket which surrounds the fermenter.

During the first 40 hours of fermentation the mould grows rapidly, using up most of the nutrients in the broth. It is only after most of the nutrients have gone that the mould begin to make penicillin. This is why there is a 40 hour lag period from the start of fermentation to the start of the production of penicillin. We have to provide it enough food to allow its mould to grow. Then limit the supplies so that it produces the penicillin we need.

Over a period of about 140 hours broth is removed regularly and small amounts of nutrients are added. This allows us to get the maximum yield of the drug, which is then extracted from the broth. It is purified and turned into medicines - almost 30000 tonnes a year!