Antibiotics

• magic bullet- Salvarson 606

  1909 Paul Ehrlich. cured syphilis but also killed patients
• magic bullet- Prontosil


  1932 Gerhard Domagk. bright red dye that killed bacteria in mice. bacteriostatic- prevent bacteria from multiplying in the body e.g. blood poisoning
• further sulphonamides


  active ingredient - coal tar. e.g. M&B 693. cured diseases such as pneumonia & scarlet fever
• Penicillin- Alexander Fleming


  streptococci & staphylococci not affected by antiseptics when deep in body. 1st world war- Fleming was sent to France to study infected wounds of soldiers. 1928- returned from holiday, saw staphylococci had disappeared around mould. used mould to treat colleague's eye infection. 1929- wrote about findings in a medical journal. could not extract active ingredient
• Penicillin- the dream team


  Howard Florey- Professor of Chemistry at Oxford. Ernst Chain- refugee biochemist from Nazi Germany. Norman Heatley- biologist
• Chain's knowledge and contribution

  read Fleming's papers. knew of Ancient Greek's using mouldy cheese for antibacterial purposes & Chinese using mouldy soya beans. took 2 years to isolate the active ingredient of Penicillium Notatum, by freezedrying. very difficult and produced tiny amount
• testing the effectiveness of Penicillin

  infected 8 mice with streptococcus bacteria. 4 mice treated with Penicillin & 4 untreated. 4 treated mice survived.
• issues with production


  struggled to produce Penicillin, factories preoccupied with manufacturing weapons and supplies for the war. lacked funding due to insufficient proof of progress. requested £600, received £25
• mould manufacturing process


  grow fungus for 20 days at 24 degrees then concentrate the broth in cold conditions.
• effect of the Blitz

  shelters were built to bury the lab equipment in an emergency. sense of urgency!
• Heatley's contribution


  back extracted Penicillin into water. constructed a chemical extraction plant which could extract more and better Penicillin
• human trial 1- Albert Alexander


  county police constable chosen as he was dying from a bacterial infection (48h life expectancy). given 200 mg. temperature decreased from 103 degrees to normal
• supply issues in the human trial

  had a very small amount so extracted penicillin back out of Alexander's urine but lost more and more of the active ingredient each time so he died
• importance of human trial 1

  showed it could be given over a period of at least 5 days with a positive effect. now understood they needed a much larger quantity to clear up infections
• human trial 2- Johnny Cox

  staphylococcus bacteria behind left eye- verge of death. penicillin completely destroyed infection but Cox still died as an artery had burst (death = unrelated to penicillin)
• mass production (America)


  Florey and Heatley travelled to America (took samples of mould and Lancet article about successful human trials) in order to convince American doctors of penicillin's importance.
• significance of Pearl Harbour


  (Japan bombed America.) America became involved in the war so took penicillin seriously
• human trial 3- Anne Miller


  30 yr old mother caught throat infection from 1 of 3 kids. about to die. from 3pm to 5am temp went from 105 degrees to normal. she survived! showed penicillin could completely cure a dying patient
• universal credit for Fleming

  Lord Beaverbrook (patron of St Mary's) was an owner of the Daily Express and leads a press campaign claiming Fleming to be fully responisble for Penicillin's discovery & development.
• war's affect on Penicillin's production

  2nd highest priority in America after the atom bomb. HUGE advantage for the allies as Germany did not have Penicillin. saved 300,000 lives in last stages of the war. [every D-day soldier had vial of penicillin in case of injury?]
• the US' impact on penicillin production

  Pearl Harbour brought America into the war. penicillin became 2nd priority behind atom bomb. several pharmaceutical companies e.g. MERCK & Pfizer involved in production. in prep for D-day 21 US companies produced 2.3 mill doses
• the war's affect on penicillin

  D-day to end of war: 2 mill lives saved. Germany did not have penicillin. wait time for treatment = 14 h- long enough for infection in wounds
• factor: government


  (American!!!) $80 million government grant to pharmaceutical companies. without US gov's intervention, penicillin would have had little to no impact on war
• factor: luck


  Fleming's discovery (finding mould spores had landed on petri dish by chance while on hols) Pasteur- "chance favours the prepared mind"
• factor: war


  Fleming- researched infection in 1st WW. 2nd WW- incentive for new medical treatments. sense of urgency. enabled mass production of penicillin. lead to factor of gov
• factor: science/industry


  technology (microscopes, petri dishes, agar jelly etc.). factories= necessary for mass production
• factor: individual genius


  finding the active ingredient. Heatley- improvised extraction machine without sufficient materials or funding. human trials
• Dorothy Hodgkins


  scientist at Oxford uni. 1945. mapped the chemical structure of penicillin using X-ray crystallography. v useful as it could now be modified to treat other bacteria
• John Sheehan


  chemist. 1957. created a chemical copy of penicillin so it could then be altered to target certain diseases
• NHS


  not until 1948 with establishment of the NHS that penicillin became available for free to the public
• major turning point


  successful & effective (TB cure was fresh air!). childbirth = safer (chance of death in labour = 40 times lower than 60 years ago). surgery = safer. previously incurable STI's are now treatable. saved countless lives during war
• limitations


  not the first (Prontosil). some bacteria have now become resistant. only available to everyone after NHS. required work of others (Dorothy Hodgkins) to enable penicillin to treat multiple bacteria