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Health, Law and Bioethics 2014
By: Ana Granadeiro
 The release of thalidomide in the 1950s and 1960s led to the world’s most
publicised pharmaceutical disaster.
 Thalidomide was invented in the early 1950s by scientists working for a German
pharmaceutical company Chemie Grünenthal, who believed the drug could
succeed as a sleeping pill and sedative and it was marketed in 1957, first in
Germany and then throughout Europe.
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Thalidomide first entered the
German market in 1957 as an
over-the-counter
remedy,
based on the maker’s safety
claims. They advertised their
product as “completely safe”
for
everyone,
including
mother and child, “even
during pregnancy,” as its
developers “could not find a
dose high enough to kill a rat.”
By 1960, thalidomide was
marketed in 46 countries, with
sales nearly matching those of
aspirin.
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 Australian obstetrician Dr. William McBride
discovered that the drug also alleviated
morning sickness. He started recommending
this off-label use of the drug to his pregnant
patients, setting a worldwide trend.
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 McBride began to associate this so-called harmless compound with severe birth defects in the
babies he delivered. The drug interfered with the babies normal development, more than 10,000
children in 46 countries were born with deformities such as phocomelia as a consequence of
thalidomide use.
 Other effects included deformed eyes and hearts, deformed alimentary and urinary tracts, blindness
and deafness.
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 It took some time before the increasing number of babies being born with
malformations was connected with thalidomide, despite the existence of reports of
birth defects associated with the drug.
 Initially he phenomenon was
blamed on nuclear weapon testing and lack of
healthy nutrition and behavior of the mothers.
 When a German newspaper published that 161 babies were adversely affected by
thalidomide, marked he beginning of the end, leading the makers of the drug to
finally stop distribution within Germany. Other countries followed and, by March of
1962, the drug was banned in most countries where it was previously sold.
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The British pharmaceutical company The Distillers Company (Biochemicals) Ltd, who marketed
thalidomide under the brand name Distavel throughout the United Kingdom, Australia and New
Zealand.
Their advertisement claimed that: "Distavel can be given with complete safety to pregnant women
and nursing mothers without adverse effect on mother or child...Outstandingly safe Distavel has been
prescribed for nearly three years in this country."
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 Chemie Grünenthal approached Smith, Kline & French (SKF), with a request to
market and distribute the drug in the United States, however said marketing and
distribution of the drug were denied by the FDA.
 FDA inspector Frances Kelsey considered the application for thalidomide
contained incomplete data on its safety and effectiveness. Chemie Grünenthal
applied for its approval 6 more times, through different distributors and
manufacturers, and 6 more times Frances Kelsey refused.
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 Clinical trials were not under supervision nor needed aproval by the FDA at the
time, which resulted in about 2,5 million doses being distributed in the United
States.
 Smith, Kline and French and other pharmaceutical companies conducted animal
tests and ran clinical trials of the drug in the United States involving about 20,000
people, including pregnant women.
 A total of 17 children in the United States were born with thalidomide-induced
malformations.
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 FDA inspector Frances Kelsey, who prevented the drug’s
approval within the United States was praised as a hero
and received the President's Award for Distinguished
Federal Civilian Service by John F. Kennedy.
 The tragedy surrounding thalidomide helped motivate
profound changes in the FDA. By passing the KefauverHarris Drug Amendments Act in 1962, legislators
tightened restrictions surrounding the surveillance and
approval process for drugs to be sold in the United
States, requiring that manufacturers prove they are both
safe and effective before they are marketed.
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 The procedures for drug testing at that time were much less rigid and therefore the
tests on thalidomide revealed no teratogenic effects. The tests in rodents, which
metabolized drugs differently than humans do, did not show problems. Later, the
same tests were performed in rabbits and primates, which produced the same
horrible effects that he drug caused in human fetuses.
 The drug was never tested on pregnant animals to check the effect on the embryos,
and no follow-up was made to see what effect the drug had had on the children of
pregnant women who had taken it once the drug was on the market.
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 The
need for the testing and approval of the toxins in certain
pharmaceutical drugs became more important after the disaster.
 Thalidomide brought changes in the way drugs are tested, what type of
drugs are used during pregnancy, and increased the awareness of potential
side effects of drugs.
 The negative effects of thalidomide also led to the development of more
structured drug regulations and control over drug use and development.
 Kefauver Harris Amendment (U.S.)
 Directive 65/65/EEC1 (E.U.)
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 In 1968, a large criminal trial began in Germany, charging several Grünenthal officials
with negligent homicide and injury. After Grünenthal settled with the victims in April
1970, the trial ended in December 1970 with no finding of guilt.
 In 2011, a class action commenced against Chemie Grünenthal and the British
company The Distillers Company (Biochemicals) Ltd, who marketed thalidomide under
the brand name Distavel throughout the United Kingdom, Australia and New Zealand on
behalf of Australians born between January 1, 1958 and December 31, 1970. The lead
plaintiff in the court case was Ms Lynette Rowe, a victim of thalidomide who was born
without arms and legs.
 On July 18, 2012 it was announced that Ms Rowe had settled her case (believed to be) in
the millions of dollars, opening the way for class action victims to receive further
compensation.
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 For a long time, thalidomide was associated with one of the
most horrific medical accidents of history. Slowly new
studies began being made regarding thalidomide
treatments for diseases like cancer or leprosy.
 Was found useful in treating diseases such as lupus,
relieving symptoms of HIV patients, decreased risk of bone
marrow transplant rejection and rheumatoid arthritis,
thalidomide is today indicated in about 60 treatments.
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by: Ana Granadeiro
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