1. © Copyright 2010 Robert D. Conway All Rights Reserved Who Invented It? The Controversial History of Technology and Invention http://technologyinnovation.webs.com

2. © Copyright 2010 Robert D. Conway All Rights Reserved The First Medical Miracle Millions of mothers - beginning in the middle ages Several “discoveries” which were ignored Winston Churchill and Adolph Hitler Eleanor Roosevelt and FDR Jr. Lots of medical dead ends – many of them harmful Psalm 51 Five Nobel Laureates A little girl with an infected arm

3. © Copyright 2010 Robert D. Conway All Rights Reserved References Hager, Thomas, “The Demon Under the Microscope – From Battlefield Hospitals to Nazi Labs, One Doctor’s Heroic Search for the World’s First Miracle Drug”, Harmony Books, New York, 2006 Dejauregul, Ruth, “100 Medical Milestones that Shaped World History”, Bluewood Books, San Mateo, CA, 1998 http://www.life.umd.edu/classroom/bsci424/BSCI2 23WebSiteFiles/AntibioticsHistory.htm http://germanhistorydocs.ghi-dc.org http://www.antifascistencyclopedia.com http://en.wikipedia.org/wiki/ for information on Prontosil, Salversan, childbed fever, Gerhard Domagk, Penicillin, Alexander Fleming, Joseph Lister, Paul Ehrlich and Nobel Prize controversies

4. © Copyright 2010 Robert D. Conway All Rights Reserved Childbed Fever Septicaemia contracted during or shortly after childbirth, caused by Staphylococcus and Streptococcus. Hospitals for childbirth became common in the 17th century. The first epidemic of childbed (puerperal) fever occurred in Paris in 1646. Europe and America: death rates of 20-25%, occasionally 100% 18th and 19th centuries: 6 to 9 women in every 1000 deliveries The most common cause of maternal mortality; about half of all deaths related to childbirth Puerperal fever is now rare in the West due to improved hygiene during delivery and antibiotics.

5. © Copyright 2010 Robert D. Conway All Rights Reserved Joseph Lister and Sir Almroth Wright - Antiseptics Carbolic acid on wounds reduced the incidence of gangrene; published findings 1867. Created sterile surgery: clean gloves, wash hands, instruments washed in carbolic acid, sprayed the operating theatre. Wright developed vaccines, promoted immunization for the UK Army 1902 - Wright started research department at St Mary's Hospital Medical School, London. Endorsed Alexander Fleming’s demonstration that antiseptics couldn’t stop sepsis and could cause harm Developed typhoid inoculation and measurement of protective substances in blood. Wright warned that antibiotics would create resistant bacteria

6. © Copyright 2010 Robert D. Conway All Rights Reserved Paul Ehrlich – Salversan and Chemotherapy Worked on a diphtheria serum and less toxic sleeping sickness therapy 1908 Nobel Prize for Medicine 1909 with Hata developed Salvarsan - effective against syphilis - derived from an azo dye Coined "chemotherapy" and "magic bullet" : selectively staining tissues and bacteria could deliver a toxin Research focused on the dyes not compounds attached to the dyes. Josef Klarer and Fritz Mietzsch at IG Farben created azo dyes, to repeat success of Salversan The concept of a "magic bullet" was fully realized with the invention of monoclonal antibodies Paul Ehrlich and Hata Sahachiro

7. © Copyright 2010 Robert D. Conway All Rights Reserved I.G. Farben Conglomerate of eight leading German chemical manufacturers, including Bayer, Hoechst and BASF - the largest chemical firms in the world. Dyes were a top product line Josef Klarer and Fritz Mietzsch at IG Farben created azo dyes, to repeat the success of Salversan I.G. Farben Headquarters 1931 - Frankfurt

8. © Copyright 2010 Robert D. Conway All Rights Reserved Gerhard Domagk - Sulphanamides Survived Ypres, later wounded and became an orderly in Ukraine field hospital and Russian cholera hospitals 1927 - began research at I.G. Farbenindustrie Chemists Josef Klarer and Fritz Mietzsch provided hundreds of compounds for Domagk’s biological research 1932 - discovered a red dye compound protected mice and rabbits from staphylococci and streptococci “Prontosil” – sulphanilamide - isolated 1908 by Paul Gelmo who didn’t realized its medical potential

9. © Copyright 2010 Robert D. Conway All Rights Reserved Gerhard Domagk Domagk cured his daughter from near fatal streptococcal infection but omitted it in his report on the drug Waited until 1935 to publish when clinical results were available from two German hospitals European clinical success of Prontosil 1936 – Prontisil saves FDR Jr. 1939 - Domagk awarded Nobel Prize in Medicine for the first drug effective against bacterial infections. Nazi regime prevented acceptance; Gestapo arrests Domagk. Extended his work on sulphonamides with Klarer and Mietzsch

10. © Copyright 2010 Robert D. Conway All Rights Reserved Alexander Fleming - Penicillin WWI - British Army Medical Corps; demonstrated why anti-septics were ineffective and harmful to patients – Sir Almroth Wright endorsed his work. 1928 - researching staphylococci; noticed a mold contamination killed staphylococci cultures. 1929 - Named the mold product penicillin 1929 publication ignored. Cultivating the mold and isolating the antibiotic was extremely difficult. Clinical tests inconclusive, but some trials were encouraging Abandoned penicillin in 1940

11. © Copyright 2010 Robert D. Conway All Rights Reserved Penicillin After Pearl Harbor the US and UK governments fund research by Howard Florey and Ernst Chain to produce penicillin in quantities and develop medicines. By D-day they made enough penicillin to treat all the wounded allied forces.

12. © Copyright 2010 Robert D. Conway All Rights Reserved Sulpha vs. Penicillin At Casablanca in Jan. 1943 the German bombing campaign is agreed 1943 – Allies bomb IG Farben at Wuppertal where Gerhard Domagk developed sulfa drugs Dec. 1943 - Churchill becomes ill at Carthage Churchill is saved by sulphonamides. UK papers credit the British discovery of penicillin, rather than sulpha which was developed in Germany.

13. © Copyright 2010 Robert D. Conway All Rights Reserved I.G. Farben 1941 - builds a synthetic rubber factory in Monowitz (Poland) near Auschwitz. About 28,000 camp inmates made available as laborers die Farben works at Wuppertal bombed in 1943 as part of the air battle of the Ruhr Leading supplier of the war economy, profited from Nazi exploitation of forced labor A company partly owned by IGF supplied death camps with poisonous gas Zyklon B. 1945 – Allies occupy I.G. Farben building in Frankfurt which becomes the headquarters of American forces in Germany 1947-48 company decision-makers charged in the Nuremberg trials

14. © Copyright 2010 Robert D. Conway All Rights Reserved Post WWII 1945 – Alexander Fleming, Howard Florey and Ernst Boris Chain shared the Nobel Prize in Physiology or Medicine. 1947 - Gerhard Domagk received his 1939 Nobel Prize – but not the money Winston Churchill lives until 1965. FDR Jr. has five marriages, five children and lives until 1988

15. © Copyright 2010 Robert D. Conway All Rights Reserved Gerhard Domagk Extended his work on sulphonamides with Klarer and Mietzsch Domagk developed chemotherapy for tuberculosis which helped curb the post-WWII European tuberculosis epidemic Continued research and teaching until his death in 1964

16. © Copyright 2010 Robert D. Conway All Rights Reserved Sulpha vs. Penicillin Fleming did not discover penicillin. Decades before scientists and physicians had studied its medicinal characteristics Fleming noted Psalm 51: "Purge me with hyssop and I shall be clean". Fleming learned from Charles Thom - who helped Fleming identify the mold - that penicillium notatum was first recognised by Westling, a Swedish chemist, from a specimen of decayed hyssop Alexander Fleming Gerhard Domagk

17. © Copyright 2010 Robert D. Conway All Rights Reserved Sulpha and Penicillin vs. Resistant Bacteria Sulfonamides can cause kidney stones and changes in bone marrow. Sir Almroth Wright (1861-1947) warned that antibiotics would create resistant bacteria. Genetic mutation in bacteria create resistant strains. These result from antibiotic use in medicine and veterinary medicine. The greater the duration of exposure the greater the risk of the development of resistance. Despite a push for new antibiotic therapies there has been a continued decline in the number of newly approved drugs. Antibiotic resistance therefore poses a significant problem.