III. TECHNOLOGY MILESTONES IN HEALTH AND MEDICINE III.6. Anti-infective Drugs Salvarsan and Prontosil Paul Ehrlich, the German bacteriologist, studied arsenic compounds for their anti-bacterial properties and invented Salvarsan in 1909 as a successful treatment for the fatal, sexually transmitted disease, syphilis. This strategy was followed by other researchers to find active compounds for combating infectious diseases. The first sulfa drug, Prontosil, which was formerly used as a textile dye, was discovered in 1932 as chemists searched for an antibacterial drug that could cure the deadly streptococcal infection, a common cause of chronic pneumonia. This discovery was so important that the German biochemist Gerhard Domagk received the 1939 Nobel Prize in medicine for his work in this area. The active antibacterial agent of Prontosil was later discovered to be sulphanilamide. Many other antibiotics were then created from this agent, including Sulphapyridine in 1938. The sulfa drugs were dramatically successful in reducing the mortality rate of lobar pneumonia in the 1940s, and saved the lives of millions. Their importance declined only with the advent of the Penicillin era. Penicillin In 1928, the Scottish bacteriologist, Alexander Fleming, discovered a potent substance that could kill bacteria, which he isolated from a naturally occurring mold (Penicillium notatum). Penicillin, a drug based on this natural substance, was created during a massive wartime project in 1943; it dramatically reduced infection and amputation among injured soldiers in the American and British armies throughout World War II. This natural Penicillin was so expensive and rare that it had to be recycled from the urine of the treated patients. Chemists attempted a new method of synthesis: to artificially manufacture the natural substance on which the drug was based. The chemical structure of penicillin was determined by the British researcher, Dorothy Crowfoot Hodgkin in the 1940s, enabling its synthesis. By 1957, several pharmaceutical companies synthesized and commercially produced this drug. Their success heralded the beginning of the modern era of antibiotic therapy. Zidovudine (AZT) Zidovudine (AZT) was approved in the United States for the treatment of Human Immunodeficiency Virus (HIV) infection in 1987. This drug was first synthesized in 1964, but proved ineffective as a cancer chemotherapeutic. It was abandoned until 1986, when its activity against retroviruses was discovered by an American research group. AZT and related nucleoside drugs inhibit viral replication by targeting specific viral enzymes. Because of the rapid development of HIV’s drug resistance, first demonstrated with AZT, mono-drug therapy can no longer Prontos il Penicillium notatum Zidovudi ne Alexand er Fleming Gerhard Domagk Streptoco ccus bacteria Zidovudine crystals