2 Overview :In 1937, at the dawn of the antimicrobial era, 105 people died after ingesting a sulfanilamide preparation known as Elixir Sulfanilamide .A subsequent investigation showed that the lethal agent was not the sulfanilamide itself but rather its diluent—diethylene glycol.The 1938 Federal Food, Drug and Cosmetic Actwas passed by the U.S. Congress and signedinto law by President Franklin DelanoRoosevelt.
3 The Development of Elixir Sulfanilamide : In 1932, Gerhard Domagk made the importantdiscovery that a chemical, prontosil, protectedagainst certain types of bacterial infections in mice .Subsequent investigations showed that prontosil was metabolized to the active agent para- aminobenzenesulfonamide, also known as sulfanilamide .
4 About this time, the S.E. Massengill Company of Bristol, Tennessee, founded by Samuel E. Massengill ( ), also began to produce sulfanilamide.A solution of sulfanilamide had not been previously available because of the lack of an appropriate vehicle.Harold Watkins, Massengill's chief chemist, was assigned the task of finding the right diluent.
5 After investigating several possible solvents, Watkins formulated a raspberry-tasting pink preparation.The concoction was called Elixir Sulfanilamide despite the lack of ethanol.Toxicity of the individual ingredients or the finished product was never tested.Diethylene glycol
6 By early September 1937, 240 gallons of Elixir Sulfanilamide had been manufactured by the Massengill Company.One of the major points of delivery of the drug was Tulsa, Oklahoma.
7 On 2 October 1937, an editorial appeared in JAMA warning against an overzealous embrace of sulfanilamide.Six patients from Tulsa had unexpectedly died from renal failure after ingesting Elixir Sulfanilamide.
8 The AMA then sent a telegraph to Dr The AMA then sent a telegraph to Dr. Massengill, requesting the composition of the elixir.Massengill released this proprietary information but urged that it be kept strictly confidential.
9 Massengill Company sent out 1100 telegrams requesting the return of the elixir. Researchers began to search for the etiologic agent.Investigation focused primarily on the diluent —diethylene glycol.
10 Diethylene Glycol :Is a condensation product of ethylene glycol production.Before the elixir disaster, only two studies had been done on the toxicity of diethylene glycol.In 1931 by Von Oettingen and Jirouch.In early 1937 by Haag and Ambrose.
11 Enter the Food and Drug Administration : By mid-October 1937, news of the Tulsa deaths reached the offices of the FDA.Walter Campbell, the chief of the FDA, immediately ordered a massive investigation.The legal grounds for action on the partof the FDA were limited.
12 The 1906 regulations were enforced by the Bureau of Chemistry in the Department of Agriculture. In 1930, this unit became known as the FDA.Under the 1906 law, in cases of suspected adulteration, drugs were tested for strength and purity.The Elixir Sulfanilamide lackedethanol.
13 The Epidemic :Three hundred fifty-three patients received Elixir Sulfanilamide during a 4-week period in the fall ofThere were 105 deaths and 248 survivors, for a case fatality rate of 30%.The earliest clinical symptoms were nausea and vomiting.Later symptoms included manifestations of renal failure.
14 THE EFFECTSLETHARGYDROWSINESSCOMAFACIAL PARALYSIS
15 Congressional Action : In November 1937, both Houses of theU.S. Congress passed resolutionsrequesting a full investigation into thetragedy.Legislation to revise the 1906 regulations had been considered by Congress.On 1 December 1937, Senator Royal S. Copeland of New York, introduced Senate Bill S
16 The 1951 Humphrey-Dunham Drug Prescription Act codified these trends. One consequence of the regulations was the increasing practice of requiring prescriptions for the dispensing of certain drugs.The 1951 Humphrey-Dunham Drug Prescription Act codified these trends.Despite the vast improvements of the 1938 law, significant regulatory limitations remained.Prescription needed
17 Aftermath of Diethylene Glycol Mass Poisonings : Dr. Massengill pleaded guilty to 112 counts of adulteration and misbranding and paid a fine of $26,100.The chemist Watkins committed suicide.Gerhard Domagk was awarded the 1939 Nobel Prize for Medicine.suicideFineMassengillWatkins
18 Recent Diethylene Glycol Mass Poisonings : In 1969, an epidemic of fatal renal failure occurred among seven children in Cape Town, South Africa.In another diethylene glycol-mediated catastrophe, 14 unexpected deaths from renal failure occurred at a hospital in Bombay, India, in 1986.Most recently, at a Nigerian hospital in1990, 40 children ranging in age from 6months to 23 months died unexpectedlyfrom renal failure
19 Other Glycols, Other Mass Poisonings : Recently, Cantarell and colleagues reported a case series from Spain of five patients with extensive burn injuries being exposed to diethyelene glycol.Today, ethylene glycol poisoning is a much more common problem.In 1993, more than 3500 human exposures to ethylene glycol were reported.Propylene glycol, considerably less toxic than ethylene or diethylene glycol.
20 Conclusion :The legacy of the Elixir Sulfanilamide tragedy was the successful passage of the 1938 Federal Food, Drug, and Cosmetic Act (FDCA).The 1938 regulations has prevented similar misadventures from occurring in the United States.The relationship between the pharmaceutical industry and the government and its effect on the practice of medicine were significantly changed by this event.
21 References :Okuonghae HO, Ighogboja IS, Lawson JO, Nwana EJ. Diethylene glycol poisoning in Nigerian children. Ann Trop Paediatr. 1992; 12:235-8.Calvery HO, Klumpp TG. The toxicity for human beings of diethylene glycol with sulfanilamide. South Med J. 1939; 32:Jackson CO. Food and Drug Legislation in the New Deal. Princeton, NJ: Princeton University Press; 1970:Domagk G. Ein beitrag zur chemotherapie der bakteriellen infektionen. Deutsche Med Wochenschr ; 61:250-3.