The Penicillin Story

The Conquest of Disease: The Penicillin Story Penicillin: why do several people share the credit for it? The discovery of penicillin was one of the major events in the history of medicine, but it took some time for people to realise how effective it was in curing diseases. In I871 the scientist Joseph Lister, by chance, noticed that the mould which grows on cheese and fruit when it goes bad can make microbes - or germs - grow weaker. He made some successful experiments on patients, but did not seem to realise fully the importance of his findings. He called the mould he used ‘penicillium’. In 1906 a young doctor, Alexander Fleming, became a research assistant at St Mary’s Hospital in London. He was working for Sir Almroth Wright, who had discovered an anti-typhoid vaccine in 1896 and had set up an innoculation department at the hospital. Both men went to France during the First World War to treat wounded soldiers and could see for themselves that there was no effective way of treating many infections. Back at St Mary’s after the war, Fleming was determined to find a better way of killing germs. In 1928 he was studying staphylococci (bacteria that make wounds go septic, or poisonous). By chance, he noticed that on a dish he had been growing germs on, near some mould, the germs were less common. He grew more of the mould, which was later developed into the antibiotic which we now know as penicillin. He discovered the mould was effective against the bacteria that caused many diseases, for example anthrax, meningitis and diphtheria and he published his discoveries, but he did not have the resources to experiment more widely. Alexander Fleming Biography (1881-1955) Major events in his life  Born in Scotland.  Qualified as a doctor from St Mary’s Medical  School, London. Began research into pioneer vaccine work.  Became a lecturer at St Mary’s, teaching medical students.  Served in WW1 as a Captain in the Army Medical Corps.  Returned to lecturing at St Mary’s. Started research into antiseptics.  After research into antibiotics and why they sometimes did more damage than good to the human body, he discovered the “body’s own antibiotic” lysozyme.  Noticed mould growing on a staphylococcus culture plate and realised the mould was  preventing the infection spreading. Named the active substance in the mould penicillin. Experimented with penicillin to show that it could cure scarlet fever, pneumonia, gonorrhea, meningitis and diphtheria.  Published his paper on penicillin but it was largely ignored.  Florey set up a team of biochemists to research penicillin and work out how it could be mass- produced. Chain worked out how to isolate and concentrate penicillin. Heatley worked out how to mass produce it.  Knighted.  Gained the Nobel Prize for Medicine along with Florey and Chain in 1945. RW PENICILLIN BOOKLET 1

How did penicillin become the world’s first effective antibiotic? Howard Florey (1898-1968) and Ernst Chain (1906-1979) Alexander FIeming discovered penicillin in 1928 but did not fully realise the drug’s potential and he did not have the necessary skills to produce any significant quantities of penicillin. No further research was carried out due to lack of funds and specialist help. Howard Florey and Ernst Chain decided to investigate Fleming’s discovery further during the 1930s and set about finding a way to turn the penicillin mould juice into a pure drug, which would be more suitable for the treatment of humans Who were Howard Florey and Ernst Chain? Florey was born in 1898 in Adelaide, Australia. He trained as a doctor and worked on a series of important discoveries at Oxford University. Chain a brilliant Jewish biochemist joined Florey’s research team after he fled to Britain from Nazi Germany. Their development of penicillin in the early 1940s led to the award of the Howard Florey Nobel Prize along with Fleming in 1945. Ernst Chain What are Florey and Chain famous for? In 1938 Howard Florey, professor of pathology at Oxford University, started work on some of the mould that Fleming had grown. Florey was an Australian doctor who had already made a number of important discoveries and was also studying natural substances that could kill bacteria. He had been impressed by an article that Fleming had published in 1929 describing the effects of penicillin. Unlike Fleming, Florey had a large research department, including Ernst Chain, a brilliant chemist who was a German Jew who had fled from Nazi persecution, and who worked closely with Florey. This work was made possible because of funding by the British government through the Medical Research Council. By 1939 Florey and Chain had begun to realise the importance of penicillin and in 1940, Florey’s team found a way of purifying penicillin which was tested first on mice and then on a patient in 1941, a policeman called Albert Alexander. The patient began to recover after receiving the drug, but unfortunately supplies ran out due to their inability to produce it in large quantities. By 1942, a number of lives had been saved using small scale production of penicillin in Oxford. Mass production of the drug was not possible without the help of the large drugs companies and British companies were already committed to fulfilling existing war time government contracts. The widespread use of penicillin was speeded up greatly by World War Two. Florey managed to persuade US drug companies to mass produce penicillin after the US entered the war in December 1941 because it could be used to treat infections caused by war wounds. The US government gave grants to drug companies who wanted to buy the expensive equipment needed to make penicillin. Mass production began in 1943 by American firms and later by British firms. In 1943 Florey went to Russia to help them to produce penicillin. By 1944 there was enough penicillin being produced to supply all the Allied armies. The price of penicillin fell and soon it was being used throughout the world to treat a range of different diseases. RW PENICILLIN BOOKLET 2

The forgotten man in the penicillin story? In 1936, Norman Heatley a brilliant young biochemist joined Florey’s team. He was to be the key individual who found a method of growing the penicillin mould more rapidly so that larger quantities could be refined and made available for experiments by Florey and Chain. In 1943, he worked with researchers in America at Pfizer to help mass produce penicillin. However the Nobel Prize can only be shared by a maximum of three people so Heatley’s crucial role went largely unrecognised in 1945. Eventually he did receive a measure of acknowledgemnt. In 1990, on the fiftieth anniversary of the first use of penicillin, the University of Oxford bestowed on Heatley the first honorary Doctor of Medicine degree in its 800-year history. And in 1998 Professor Sir Henry Harris, who succeeded Florey as Professor of Pathology at Oxford commented on the roles played by the four principal scientists responsible for penicillin: ‘Without Fleming, no Chain or Florey; without Chain, no Florey; without Florey, no Heatley; without Heatley, no penicillin.’ Mass producing penicillin in the USA during the 1940s What factors helped in the development of penicillin? • Chance: Fleming was notoriously messy and therefore didn’t bother to clean his plates which led to him making his first discovery. • Warfare: WW1 pushed Fleming into the field of antiseptics and made him look for cures to infections. WW2 meant that the British and American governments were willing to financially support Florey’s team in the development of penicillin. • Teamwork: Fleming did not have the skills or resources to work out how to extract the active ingredient in the penicillin mould into a pure concentrated form. It needed the large research team that included Florey, Chain, Heatley and a team of biochemists to move Fleming’s discovery forward into a working drug during the1940s. • Government intervention: Florey’s research team needed funding from the British government to carry out its research programme. • Industrial support: American businesses had to be financially encouraged by the American government to find a way to mass produce penicillin. RW PENICILLIN BOOKLET 3

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The Penicillin Story

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