Presented by:
•Abhijit Pal
•Amit Atre
•Amrita Puranik
•Amrita Kulkarni
•Anjali Iyer
 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 Act
was passed by the U.S. Congress and signed
into law by President Franklin Delano
Roosevelt.
 In 1932, Gerhard Domagk made the important
discovery that a chemical, prontosil, protected
against certain types of bacterial infections in mice .
 Subsequent investigations showed that prontosil was
metabolized to the active agent paraaminobenzenesulfonamide, also known as sulfanilamide .
 About this time, the S.E. Massengill Company of Bristol,
Tennessee, founded by Samuel E. Massengill (1871-1946),
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.
 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
 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.
 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.
 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.
 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.
 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.
 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 part
of the FDA were limited.
 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 lacked
ethanol.
 Three hundred fifty-three patients received Elixir
Sulfanilamide during a 4-week period in the fall of
1937.
 There 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.
DROWSINESS
COMA
LETHARGY
FACIAL PARALYSIS
 In November 1937, both Houses of the
U.S. Congress passed resolutions
requesting a full investigation into the
tragedy.
 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. 3073.
 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
 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.
Fine
Massengill
Watkins
suicide
 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 in
1990, 40 children ranging in age from 6
months to 23 months died unexpectedly
from renal failure
 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.
 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.
 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; 32:1105-9.
 Jackson CO. Food and Drug Legislation in the New
Deal. Princeton, NJ: Princeton University Press; 1970:15174.
 Domagk G. Ein beitrag zur chemotherapie der
bakteriellen infektionen. Deutsche Med Wochenschr.
1935; 61:250-3.