Lessons Learned: Milestones of Toxicology! Steven G. Gilbert1 and Antoinette Hayes2! 1Institute of Neurotoxicology and Neurological Disorders and 2Pfizer Research,! Contact information: Steven G. Gilbert at [email protected] – For more information, its interactive (clickable) at www.toxipedia.org – © 2006-2010 Steven G. Gilbert!

Shen Nung Ebers Papyrus Gula 1400 BCE Homer Socrates Hippocrates Mithridates VI L. Cornelius Sulla Cleopatra Pedanius Dioscorides Mount Vesuvius 2696 BCE 1500 BCE 850 BCE (470-399 BCE) (460-377 BCE) (131-63 BCE) 82 BCE (69-30 BCE) (40-90 CE) Erupted August 24th Antiquity The Father of Egyptian records Wrote of the Charged with Greek physician, Tested antidotes Lex Cornelia de Experimented Greek 79 CE Chinese contains 110 use of arrows religious heresy observational to poisons on sicariis et with strychnine pharmacologist City of Pompeii & 3000 BCE – 90 CE Sumerian texts refer to a medicine, noted pages on anatomy poisoned with venom in the and corrupting the morals approach to human disease himself and used prisoners veneficis – law and other poisons on and Physician,wrote De Herculaneum and physiology, toxicology, female deity, Gula. This for tasting 365 herbs and epic tale of The Odyssey of local youth. Death by and treatment, founder of as guinea pigs. Created against poisoning people or prisoners and poor. Materia Medica basis for destroyed and buried spells, and treatment, mythological figure was Hemlock - active chemical modern medicine, named mixtures of substances said to have died of a toxic and The Iliad. From Greek prisoners; could not buy, Committed suicide with the modern pharmacopeia. by ash. Pliny the Elder recorded on papyrus. associated with charms, overdose. toxikon arrow poison. alkaloid coniine. cancer after creeping crab. leading to term mithridatic. sell or possess poisons. Egyptian Asp. suffocated by volcanic gases. spells and poisons.

Greek Fire Ergot Outbreak Moses Maimonides Albertus Magnus Raymundus Lullius Knights Templars Petrus de Abano The Black Death Venetian Council of Zhou Man Rodrigo & 673 CE 994 CE (1135-1204) (1193-1280) 1275 (1118-1307) (1250-1315) (1347-1351) Ten - 1419 1423 Cesare Borgia Middle Ages Ancient 40,000 died Jewish Dominican friar Ether discovered Christian military Italian scholar Bubonic & Group of Chinese explorer (1400-1500) “napalm” described by the from eating philosopher & wrote extensively by Spanish order alleged to translated pneumonic people who lost 1000s of crew Poisoned many people in Italy 476 CE – 1453 Crusaders as consisting of contaminated wheat/rye physician wrote: on compatibility chemist and be experts with Hippocrates and plague ravaged Europe carried out members from uranium for political and monetary gain. naptha, quicklime, sulphur, caused gangrene - known as Treatise on Poisons and religion and science and later called poisons. They searched for Galen to Latin. Wrote book leaving the highest number murders with poison for a exposure while mining lead Used arsenic in a concoction & saltpeter. St. Anthony’s Fire. Their Antidotes. isolated arsenic in 1250. “sweet vitriol”. the “Elixir of Life”. on poisons: De Venenis. of casualties in history. fee. in Jabiru Australia. called “La Cantrella”. Renaissance Leonardo de Vinci Pope Clement VII Paracelsus Georgius Agricola Catherine Medici William Piso Shakespeare Hieronyma Spara Catherine Monvoisin Guilia Tophania King Louis XIV (1452-1519) (1478-1534) (1493-1541) (1494-1555) (1519-1589) 1640 (1564-1616) ~1659 (LaVoisin) (1635-1719) 1682 Experimented with Died (possibly “All substances Wrote De Re Queen of France, In Brazil, From Romeo & Roman women & (1640-1680) Italian woman who supplied Passed royal decree 14th–16th bioaccumulation of murdered) after are poisons; Metallica published expert assassin, studied effects Juliet - act 5 fortune teller Accused sorcerer poison (arsenic) to wives forbidding apothecaries there is none which is not a poisons in animals eating amanita 1556. The most tested poisons of Cephaelis “Here’s to my love! O true organized wealthy wives and and convicted looking to murder their to sell arsenic or poisonous poison. The right dose Centuries and called the procedure Phalloides, (death cap) comprehensive book on on the poor and Ipecacuanha, apothecary! Thy drugs are sold them a arsenic elixir to poisoner in France. husbands. Later executed substances except to persons “passages”. differentiates a poison from a mining and metallurgy. murder their husbands. mushroom. remedy.” the sick. an emetic; treat dysentery. quick. Thus with a kiss I die.” She was burned at the stake. by strangulation. known to them.

Devonshire Colic John Jones Richard Meade Carl Wilhelm Percivall Pott Felice Fontana Friedrich Serturner Francoise Magendie Fowler’s Solution Pierre Ordinaire Mateu J.B. Orfila 1700’s 1701 (1673-1754) Scheele (1742-1760) (1714-1788) 1767 (1783-1841) (1783-1855) 1786-1936 1797-1915 (1787-1853) Devonshire, English doctor wrote In 1702, wrote A Swedish apothecary British physician Italian chemist and Isolated an alkaloid Discovered emetine Potassium arsenite Created elixir Considered the father 1700s England. High The Mysteries of Opium Mechanical and chemist, who recognized physiologist who From opium poppy and studied effects solution prescribed using absinthe of modern toxicology. incidence of lead Reveal’d described many Account of Poisons discovered oxygen, coal-tar caused was the first to study in 1803. He named of strychnine & as a general tonic popularized and sold by Henry In 1813 he published colic drinking treatments of opium, but also dedicated to poisons snakes, barium, chlorine, cancer of the scrotum in venomous snakes. Discovered it Morphine after Morpheus, the cyanide. Called and used from about Pernod. Absinthe was used by Traite des Poisons, the father of contaminated cider. withdrawal and addiction. animals and plants. manganese, and chimney sweeps. Chimney that viper venom affects blood. Greek god of dreams. 1786 to 1936. Used Vincent Van Gogh; banned in which described the symptoms of hydrogen cyanide. Sweepers Act of 1788. experimental pharmacology. by Charles Darwin? 1915, subject of Degas. poisons.

Thomas de Quincey James Marsh Robert Christison Claude Bernard Ascanio Sobrero Theodore G. Wormley Joseph Caventou & Arsenic Act 1851 Louis Lewin Emil Fischer Constantine Fahlberg (1785-1859) (1794-1846) (1797-1882) (1813-1878) (1812- 1888) (1826-1897) Pierre Pelletier Required arsenic to be colored (1854-1929) 1852-1919 Saccharin - 1879 with soot or indigo to prevent English writer Chemist Toxicologist at French Italian chemist, in Wrote the first German Constantine Fahlberg 1820 “accidental” poisoning. 1800s became addicted Developed and perfected the University of physiologist 1847 discovered American book pharmacologist discovered saccharin to opium in early Marsh test for arsenic. The Edinburgh wrote Treatise on studied the effects nitroglycerin, a dedicated to Friedrich Gaedcke studied and classified while working in the 1800’s and improved Marsh test used laboratory of Ira Poisons in 1829; invented of carbon monoxide and powerful explosive poisons in 1869 French pharmacists isolated 1855 Isolated hallucinogenic plants, published Confessions of an forensically for first time in poison harpoon for whaling curare. Influenced by and vasodilator. Alfred Nobel entitled: Microchemistry of cocaine from alcohols and other Remsen (right) Opium Eater in 1821. 1840 trial of Marie Lafarge. quinine from bark of Cinchona Isolated the stimulant caffeine in 1879. that contained prussic acid. Francoise Magendie. was his student. Poisons. tree in back of their pharmacy. Erythroxylon coca. psychoactive compounds. from plant extracts in 1895.

Upton Sinclair Pure Food and Chemical Warfare A U.S. Prohibition Geneva Protocol Ginger Jake 1929 Hawk's Nest Gerhard Schrader Elixir Sulfanilamide Albert Hofmann Marijuana Tax Act (1878-1968) Drugs Act - 1906 Reality 1915 1919-1933 1925 Alcoholic tonic produced Incident 1927-1935 (1903-1990) 1937 1938 1937 Published Harvey Washington German Law that made Banned use of illegally during prohibition Hundreds of black German Chemist Food Drug & Lysergic acid Federal criminal 1900-1930s The Jungle Wiley, M.D. (1844- chemist Fritz the production chemical weapons. adulterated with TOCP workers die from accidentally (LSD) synthesized offense to possess, 1930). Law prevents Cosmetic Act in 1905. Haber (1868-1934) and sale of Updated in 1993 produced OPIDN acute silicosis while made nerve agents; sarin, tabun, in the Sandoz produce, or dispense production or trafficking (Jake Leg), 1938 Chronicled the unsanitary of mislabeled, adulterated developed blistering agents alcoholic beverages as the “Chemical Weapons digging tunnel for a soman, and cyclosarin while Laboratory (now hemp. Non-medical 100 die, diethylene conditions in meat packing or poisonous foods, drugs, used in WWI; chlorine and illegal but very profitable. Convention” to include affecting 50,000 hydroelectric project developing insecticides 1938; Novartis). In 1943 Hoffman use prohibited in California (1915) industry in Chicago. medicines, and liquors. cyanide gases. agents used in WWII. glycol as a vehicle. and Texas (1919). banning production. adults. for Union Carbide. tested LSD on himself.

DDT – 1939 2,4-D – 1946 Minimata Japan Poison Control Journal of Tox. & Thalidomide Society of Toxicology Alice Hamilton Rachel Carson Occupational Safety U.S. EPA Recognized as Developed during (1950’s) Centers 1953 App. Pharmacology (1959-1960’s) 1961 (1869-1970) (1907-1964) & Health Act 1970 1970 insecticide by the Swiss WW II at British Minimata Bay First, Chicago 1959 Drug prescribed Founded Pathologist and Scientist lead Act passed on December Established to 1940-1960s scientist Paul Hermann Rothamsted contaminated 1953, second Adopted by to pregnant women for March 4, 1961, first female faculty crusade against the use of 29, 1970 to ensure every consolidate federal research, on Müller, who was awarded Experimental morning sickness induced with mercury by chemical at Duke SOT until 1981 first formal member at Harvard dichlorodiphenyltrichloroethane worker a safe and healthful monitoring, standard-setting the 1948 Nobel Station, by J.H. Quastela industry. Thousands adults birth defects. Medical School. Associated (DDT) a pesticide and University, when SOT meeting held April 15, 1962 workplace. and enforcement activities to Frances Kelsey persistent organic pollutant. Prize in Physiology and sold commercially in and children were poisoned NC in 1954, and third founded Fundamentals of (9 founders, 183 worksite chemical hazards ensure human & environmental from eating fish contaminated of FDA blocked with disease. Studied effects Carson several books including and Medicine. 1946. Used to control opened in Boston 1955. Applied Toxicology. charter members). protection. Banned in 1972. broadleaf plants. with methyl mercury. approval in U.S. of lead & rubber on workers. Silent Spring published 1962.

Mr. Yuk Iraq – Mercury Bangladeshi 1970s First Modern Love Canal Disaster IUTOX 1980 Times Beach 1983 Bhopal Disaster Chernobyl Accident Tokyo Subway Sarin Vioxx (1999-2004) 1971 1971 Arsenic poisoning Toxicology 1978 International Union of Dangerous levels of dioxin Dec. 3, 1984 April 26, 1986 Gas Attack 1995 A nonsteroidal anti-inflammatory, Toxicology Symbol adopted Pink- Tubewells, August 7, 1978 discovered in Times Beach, Accidental release The Chernobyl Members of religious group COX-2 selective inhibitor for Textbook American Board 1970-2006 by the Pittsburgh Poison colored drilled to US President MO. EPA orders 40 metric tons of nuclear power plant Aum treatment of osteoarthritis, 1975 of Toxicology (ABT) the town produced by Merck & Co. Center at The Children’s seed grain coated with a provide clean Jimmy Carter methyl isocyanate accident produced a Shinrikyo Louis J. Casarett declared Love Canal a federal 1979 First exam Aug. 1980 evacuation and from a Union plume of radioactive and voluntarily Hospital in 1971. Used to mercury fungicide was drinking water, are - released sarin & John Doull edited, emergency. 42 million pounds Academy of makes it a Carbide Indian pesticide plant debris over the withdrawn because educate children and parents tragically consumed by contaminated by arsenic gas in 5 places about poisons and to prevent Toxicology: The Basic of over 200 chemicals Toxicological Superfund site. in heart of city resulted in the Ukraine, Eastern in Tokyo subway, killing of risk of heart Iraqis tragically affecting resulting in millions of contaminated Love Canal, killing thousands, and injured Europe, Scandinavia, UK and accidental poisonings. Science of Poisons, in 1975. Sciences (ATS) All residents gone 12 and injuring 6,000. attack & stroke. over 40,000 people. people harmed. disrupting many lives. 1981 by 1985. 100s of thousands. eastern USA.