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Ono Pharmaceutical was founded by Ichibei Fushimiya in Osaka, Japan in 1947. Chobei Takeda started a business selling traditional Japanese and Chinese medicines in Doshomachi, Osaka. The Company changed its name to Takeda Pharmaceutical Industries The Parke-Davis Pharmaceutical company was incorporated. founded in Detroit, Michigan, by Dr. Samuel P. Duffield, a physician and pharmacist. US drug manufacturer Parke-Davis sold cocaine in various forms, including cigarettes, powder. Felix Hoffmann, a German worker for Bayer, rediscovered aspirin (acetyl salicyclic acid), the active ingredient of the willow plants (salicin). Merck chemists in Germany introduced methylene-dioxy-methamphetamine (MDMA), a euphoria-producing psychedelic. Ewing Marion Kauffman Garden City, Missouri. In 1950 he formed Marion Laboratories and sold the company to Merrell Dow in 1989. Emile Coue French pharmacist introduced a method of psychotherapy and selfimprovement based on optimistic autosuggestion. Cou discovered what later came to be known as the placebo effect

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192 Brothers Joe and Tom Longs opened their first store on Oaklands Piedmont Ave. In

8 1993 Longs acquired Bills Drugs, a 20 store chain in northern California. In 2008 Ma Longs Drugs was acquired by CVS Caremark for $2.9 billion. y Links: USA, Pharma, M&A, SF Bay Area 12 192 UCB, a Belgian drug firm, was founded by Emmanuel Janssen. 8 Links: Belgium, Pharma 194 2 De c 10 George W. Merck, former president of Merck Pharmaceutical and head of the War Research Service, requested the Chemical Warfare Service to develop a biological warfare program. Links: USA, Chemistry, Pharma, Biology

194 Swiss chemist Albert Hoffman (1906-2008) felt the first rush of LSD when a tiny 3 amount of the substance seeped onto his finger during a laboratory experiment. Ap Links: Switzerland, Pharma r 16 194 3 Ap r 19 195 5 Ap r 12 Swiss chemist Albert Hoffman, following up on an experiment on April 16, deliberately ingested .25 milligrams of LSD and soon began to feel its effects. Hallucinations continued on his bicycle ride home and lasted for some 6 hours. Links: Switzerland, Pharma The Salk Vaccine was declared safe and effective. Salk vaccine shots for polio began to be given out to school kids. The March of Dimes accomplished its mission within 20 years. Research led by Dr. Jonas Salk, of the Univ. of Pittsburgh, and supported by funds (those marching little dimes) raised annually by thousands of volunteers, resulted in the announcement that the Salk polio vaccine was "safe, potent and effective." The foundation also supported the research that led to the Sabin oral vaccine, another safe, effective polio preventative discovered by Dr. Albert B. Sabin. Following the victory over infantile paralysis, the March of Dimes turned its attention to conquering the largest killer and crippler of children: the mental and physical problems that are present at birth. Some 100 million people were given the vaccine during the 1950s and 1960s which was later found to be contaminated with the SV40 simian virus, a possible carcinogen. Links: USA, Pennsylvania, Medical, Pharma, Polio

195 McNeill Laboratories introduced Childrens Tylenol Elixir, available only by 5 prescription. No Links: USA, Medical, Pharma

v1 195 The US FDA approved the drug Propoxyphene. It was marketed as the pain killer 7 under the name Darvon and Darvocet. In 2009 an FDA advisory committee voted 1412 against continued marketing following safety concerns which linked the drug to sometimes serious and fatal heart rhythm abnormalities. In 2010 US drug makers agreed to stop marketing the drug. Links: USA, Pharma, FDA 195 Johnson & Johnson acquired McNeill Laboratories, the maker of Childrens Tylenol. 9 Links: Pharma 196 Roche's researchers in New Jersey published a report stating that Valium (Daizepam) 1 had only mild side-effects, including fatigue, dizziness and rash, but these were results based on only seven patients. Diazepam (Valium) was approved for use in 1963. In the late 1950s chemist Leo Sternbach (1908-2005) made the discovery that led to Valium while working for Hoffmann-La Roche. Links: Medical, Pharma Timeli nes A textbased site. 196 Johnson & Johnson introduced Tylenol for adults. 1 Links: Pharma 196 In California a Kansas City company opened a manufacturing plant in Merced to 1 fabricate cooling towers for industrial use. In 1969 the plant began treating the wood it used with chromium 6, arsenic and copper to combat insects and bacteria. In 1975 Baltimore Aircoil Co., a subsidiary of Merck & Co., bought the plant. In 1985 Merck sold its subsidiary and the plant to Amsted Industries. In 1986 a consultant found evidence of chromium and arsenic contamination at the site. In 1989 state regulators noted high levels of chromium 6 and arsenic in the water of a drainage pond and reported that storm water flowed from the pond into a canal running by homes in the Beachwood area of Merced. Chromium use continued until May 1991. In February 2007 the regional water board mailed notices to residents saying the plant had caused significant chromium and arsenic pollution. As of 2008 some 20 people were dead or dying of cancer in the Beachwood area. A $38 million cleanup effort was in progress. Merck and Amsted faced a lawsuit. Links: USA, California, Environment, Pharma, Cancer

196 Cytosine, produced under the brand name Tabex, was first marketed in Bulgaria. It 4 was produced by the Bulgarian pharmaceutical company Sopharma AD and became widely available in the Formerly Socialist Economies of Europe (FSE). The cytisine derivative varenicline was approved in 2006 as a smoking cessation drug. Links: Bulgaria, Pharma, Smoking 196 The US Food and Drug Administration issued a report calling birth control pills safe, 9 despite a slight risk of fatal blood-clotting disorders linked to the pills. Se Links: USA, Pharma, FDA p4 196 Valium was the most prescribed medicine in the US. Leo Sternbach (d.2005) of Roche 9 Holding AG helped develop the drug. 199 Links: USA, Pharma 2

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197 The US FDA approved lithium medication for manic depressives. 0 Links: USA, Pharma, FDA 197 India introduced process patents which allowed innovators to protect the way they 0 made drugs, rather than the molecules themselves. Links: India, Pharma 197 Earl W. Sutherland Jr. (1915-1974), US pharmacologist, won the Nobel Prize in 1 Medicine for his discoveries concerning the mechanisms of the action of hormones. Oc Links: USA, Nobel Prize, Pharma t 197 Rohypnol was first marketed as a sleeping pill. It was 10 times more powerful than 5 Valium. Links: USA, Medical, Pharma 198 Extra-Strength Tylenol capsules laced with cyanide claimed the first of seven victims 2 in the Chicago area. As of 2008 the case remained unsolved. Se Links: USA, Chicago, Pharma p 29

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198 Marc Lappe (1942-2004), toxics expert, authored Germs That Wont Die: Medical 2 Consequences of the Misuse of Antibiotics. Links: USA, Microbiology, Pharma, Books 198 The sleeping pill Halcion, made by Upjohn Pharm., was OK'd by the FDA. It later 2 displayed side effects such as anxiety, behavior changes, and abnormal thinking. Dosage was reduced and label warning were added and it was banned by Britain in 1991. Links: USA, Pharma, FDA 198 In the US capsules of Tylenol laced with cyanide killed 7 people. This brought about a 2 major effort in safe sealing methods by consumer companies. Links: USA, Pharma 198 Austrian Dietrich Mateschitz (b.1944), who had become aware of "tonic drinks" while 2 traveling in Asia, got the idea for the Red Bull energy drink business while sitting at the bar in the Mandarin Hotel in Hong Kong. In the 1970s T.C. Pharmaceuticals of Thailand, founded by Chaleo Yoovidhya, had formulated an energy drink prototype called Krathing Daeng, or Red Bull in English. Mateschitz and Yoovidhya started selling the drink in Austria in 1987. Links: Austria, Hong Kong, Thailand, Pharma 198 3 Ja n4 US Congress amended the Federal Food, Drug and Cosmetic Act with the Orphan Drug Act (P.L. 97-414). Additional orphan drug amendments were passed in 1984, 1985 and 1988. Links: USA, Pharma, FDA

198 Amgen Inc. developed the hormone drug erythropoietin (EPO). In 1989 it was 3 approved for the treatment of anemia in patients with end-stage kidney disease. Links: USA, Medical, Pharma, BioTech 198 Nasalcrom, a prescription drug for allergies made by Fisons PLC, was approved by the 3 FDA to be marketed by Rhone-Poulenc Rorer. It was first approved in the US for bronchial asthma in 1968 under the name Intal and in 1996 it was approved for over the counter sale by McNeil Consumer Products, a division of Johnson & Johnson. Links: USA, France, Pharma, FDA

198 The Green Cross Corp., a major Japanese pharmaceutical firm, was later accused of 3 having sold unheated blood products at this time even after learning that they could infect people with the AIDS virus. In 1996 prosecutors raided their offices. Drug company executives, Renzo Matsushita (79), Takehiko Kawano (69) and Tadakazu Suyama (72) pleaded guilty in 1997 and began prison terms in 2000. Links: Japan, AIDS, Pharma 198 Ajay Piramal (29) took over as head of the family business following the sudden death 4 of his brother. Under his leadership the Piramal Group evolved from a textile centric business to a USD 2 billion conglomerate with diversified business interests across pharmaceuticals, packaging, financial services and real estate. In 2012 Piramal moved into health care services and acquired Decision Resources, a Massachusetts fir, that analyzes and crunches data on drugs and treatments. Links: India, Pharma 198 6 Fe b 17 Johnson and Johnson, maker of Tylenol, announced it would no longer sell over-thecounter medications in capsule form, following the death of a woman who had taken a cyanide-laced capsule. Links: USA, Pharma Timeli nes A textbased site. 198 A fire in a Sandoz factory in Basel left 30 tons of chemicals in the Rhine. 6 Links: Switzerland, Pharma No v1 198 Thrifty Drugs under Leonard H. Straus (d.1998) merged with Pacific Lighting. The 6 Thrifty Corp. had 555 drugstores and the Big Five sports equipment chain. Links: USA, Pharma, M&A 198 7 Ma r 20 The Food and Drug Administration approved the sale of AZT, a drug shown to prolong the lives of some AIDS patients. Jerome Horwitz of the Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine first synthesized AZT in 1964 under a US National Institutes of Health (NIH) grant. It was developed by Burroughs-Welcome (later part of GlaxoSmithKline). Links: USA, Microbiology, AIDS, Pharma, FDA

198 7 De c 29 198 8 Ja n 21

The antidepressant drug Prozac was allowed to go on the market. It was based on fluoxetine, which increases serotonin levels in the brain by preventing the cells that that produce serotonin from reabsorbing it too quickly. It was discovered by Dr. Ray W. Fuller (1936-1996), Dr. David Wong and Dr. Bryan Molloy of Eli Lilly. Links: USA, Pharma, Brain Retin-A got a boost when a study published in the Journal of the American Medical Association said the anti-acne drug could also reduce wrinkles caused by exposure to the sun. Links: USA, Medical, Pharma, Sun

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198 8 Oc t 26 A French pharmaceutical company, Roussel Uclaf, announced it would halt worldwide distribution of RU-486, a pill to induce abortions, because of "an outcry of opinion at home and abroad." The French government ordered the company to reverse itself two days later. Links: France, Medical, Pharma

198 A French pharmaceutical company that manufactured the abortion pill RU-486 8 announced it would resume distribution on command of the French government. Oc Links: France, Medical, Pharma t 28 198 Eli Lilly launched Prozac (Fluoxetine), an anti-depressant. The US FDA had approved 8 it on Dec 29, 1987. Links: USA, Pharma, FDA 198 SmithKline Beckman merged with Beecham Group PCL of Britain to create the 9 worlds 2nd largest drug company. Links: Britain, USA, Pharma 198 Merck Corp. announced the discovery of the 3-dimensional structure of the enzyme 9 protease. It was seen as a promising target for attacking the virus that causes AIDS. Links: AIDS, Pharma, BioTech

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199 The US federal government approved the use of the drug AZT to treat children 0 infected with the AIDS virus. Ma Links: USA, AIDS, Pharma y3 199 In Nigeria 109 children died after taking paracetamol laced with a compound similar to 0 diethylene glycol and also used in engine coolants. Links: Nigeria, Pharma, Kids 199 George Sperti (91), inventor of Preparation H, died. 1 Links: USA, Ohio, Pharma Ap r 29 199 Cor Therapeutics went public and raised $15 million. In 1998 it received partial FDA 1 clearance for Integrillin, an anti-clotting drug. Ju Links: USA, Medical, Pharma n 27 199 Imperial Chemical Industries (ICI) of Britain split into two parts, ICI, a chemicals 1 company, and Zeneca, a bioscience and drug company. Links: Britain, Pharma 199 Ewing Marion Kauffman (b.1916) founder of Marion Laboratories (1950) and the 3 Ewing Marion Kauffman Foundation (1966), died. Au Links: USA, Missouri, Pharma g1 199 Depo-Provera, an injectable drug for birth control, was released in the US. 3 Links: USA, Pharma 199 Sanofi-Aventis of France introduced its Ambien sleeping pill to the US. 3 Links: USA, France, Pharma

199 Bjorgolfur Bjorgolfsson (26) left Iceland and started a soft-drink company in St. 3 Petersburg, Russia. He later expanded into brewing, banking, telecommunications and discount pharmaceuticals. By 2006 his stake in the Iceland-based Actavis Group was valued at $1 billion, making him Icelands first billionaire. Links: Russia, Pharma, Iceland, Telecom, Cola 199 The US FDA approved Risperdal, made by Johnson & Johnson, to treat schizophrenia 3 and bipolar disorder in adults. In 2006 approval was expanded to help treat autism in children. Links: USA, Medical, Pharma Timeli nes A textbased site.