Thalidomide was first developed by CIBA, a Swiss pharmaceutical company in the early 1950s, and subsequently introduced as Contergan by Chemi Grunenthal. The drug was initially advertised as a sedative which would allow users to undergo a deep sleep in the absence of a hangover and with a reduced risk of developing drug dependency. At the time, basic testing was done on the drug, and it was considered not to have any toxic effects on humans. However, unlike today’s level of rigorous testing, the drug was not analyzed for any potentially dangerous teratogenic effects. In the 1950s, scientists did not know that the effects of a drug could be passed through the placental barrier and harm a foetus in the womb, so the use of medications during pregnancy was not strictly controlled. And in the case of thalidomide, no tests were done involving pregnant women. As the drug was traded under so many different names in 49 countries, it took five years for the connection between thalidomide taken by pregnant women and the impact on their children to be made. A UK Government warning was not issued until May 1962. One reason why researchers and doctors were slow to make this connection was due to the wide range of changes to foetal development. Limbs, internal organs including the brain, eyesight and hearing could all be affected.The first time the link between thalidomide and its impact on development was made public in a letter published in The Lancet from an Australian doctor William McBride, in 1961. The drug was formally withdrawn by Chemie Grünenthal on 26 November 1961 and a few days later, on 2 December 1961, the UK distributors followed suit. However, it remained in many medicine cabinets under many different names. In the few short years that thalidomide was available, it's estimated that over 10,000 babies were affected by the drug worldwide. Around half died within months of being born. The thalidomide babies who survived and their families live with the effects of the drug. The Thalidomide Society was formed in 1962 by the parents of children affected by the drug thalidomide. The original aim of the Society was to provide mutual support and a social network as well as to seek compensation. In 1972, a highly publicised campaign led by the Sunday Times newspaper helped to secure a further settlement for children affected by thalidomide in the UK. Thalidomide forced governments and medical authorities to review their pharmaceutical licencing policies. As a result, changes were made to the way drugs were marketed, tested and approved both in the UK and across the world. One key change was that drugs intended for human use could no longer be approved purely on the basis of animal testing. And drug trials for substances marketed to pregnant women also had to provide evidence that they were safe for use in pregnancy.

1. The Thalidomide tragedy
Prepared by: Ms. Kajal Pradhan
Assistant professor
M.Pharm. (Pharmaceutics)

2. What is Thalidomide?
 Thalidomide was first developed by CIBA, a Swiss pharmaceutical company in
the early 1950s, and subsequently introduced as Contergan by Chemi Grunenthal.
 The drug was initially advertised as a sedative which would allow users to
undergo a deep sleep in the absence of a hangover and with a reduced risk of
developing drug dependency. At the time, basic testing was done on the drug, and
it was considered not to have any toxic effects on humans.
 However, unlike today’s level of rigorous testing, the drug was not analyzed for
any potentially dangerous teratogenic effects.

4. Thalidomide and Congenital Mutations
 In the 1960s, two medical professionals; Dr Widukind Lenze and Dr
William McBride, observed an association between the use of
thalidomide in expecting mothers and congenital malformations.
 Once publicized, these findings were further backed by several cases
across the globe with a reported 10,000 children thought to have been
born with phocomelia.

5. Across the cases of patients, a range of abnormalities
was noted including:
 Phocoemelia - a congenital deformity whereby the hands and feet
are bound to the child’s trunk, absent or grossly underdeveloped;
 Disfigurements of the ear;
 Ocular abnormalities;
 Facial palsies
 Internal organ damage
 Congenital heart disease.

7. THALIDOMIDE AND PREGNANCY:
 In the 1950s, scientists did not know that the effects of a drug could be passed
through the placental barrier and harm a foetus in the womb, so the use of
medications during pregnancy was not strictly controlled. And in the case of
thalidomide, no tests were done involving pregnant women.
 As the drug was traded under so many different names in 49 countries, it took
five years for the connection between thalidomide taken by pregnant women and
the impact on their children to be made. A UK Government warning was not
issued until May 1962.
 One reason why researchers and doctors were slow to make this connection was
due to the wide range of changes to foetal development. Limbs, internal organs
including the brain, eyesight and hearing could all be affected.

8.  Later, they found that the impact on
development was linked to when during
pregnancy the drug was taken, and effects
only occurred between 20 and 37 days
after conception. After that, thalidomide
had no effect on the foetus.
 Another reason why it took so long to
establish the link to thalidomide was that
some of the damage caused by the drug
was very similar to certain genetic
conditions that affect the upper or lower
limbs.

9. Defects caused by Thalidomide

10. THE THALIDOMIDE SCANDAL
 The first time the link between thalidomide and its impact on development was
made public in a letter published in The Lancet from an Australian doctor
William McBride, in 1961.
 The drug was formally withdrawn by Chemie Grünenthal on 26 November 1961
and a few days later, on 2 December 1961, the UK distributors followed suit.
However, it remained in many medicine cabinets under many different names.
 In the few short years that thalidomide was available, it's estimated that over
10,000 babies were affected by the drug worldwide. Around half died within
months of being born. The thalidomide babies who survived and their families
live with the effects of the drug.

11.  The Thalidomide Society was formed in 1962 by the parents of children affected
by the drug thalidomide. The original aim of the Society was to provide mutual
support and a social network as well as to seek compensation.
 In 1972, a highly publicised campaign led by the Sunday Times newspaper helped
to secure a further settlement for children affected by thalidomide in the UK.
 Thalidomide forced governments and medical authorities to review their
pharmaceutical licencing policies. As a result, changes were made to the way
drugs were marketed, tested and approved both in the UK and across the world.
 One key change was that drugs intended for human use could no longer be
approved purely on the basis of animal testing. And drug trials for substances
marketed to pregnant women also had to provide evidence that they were safe for
use in pregnancy.


12.  The easy, over-the-counter access to thalidomide prompted many countries to
improve their classification and control of medicines. In the UK the 1968
Medicines Act, passed as a result of the thalidomide scandal, made distinctions
between prescription drugs, drugs only available in pharmacies and drugs available
for general sale.
 The Yellow Card Scheme was set up for doctors to share previously unknown side
effects of medications they prescribed. The Scheme has now widened so anyone
can report a side effect.

13. References
 A Leslie Florence, ‘Is Thalidomide to Blame?’, British Medical Journal, 2
(1960), p 1954.
 https://www.sciencemuseum.org.uk/
 T Stephens and R Brynner, Dark Remedy: The Impact of Thalidomide and
its Revival as a Vital Medicine, 2001.
 The Insight Team of the Sunday Times, Suffer the Children: The Story of
Thalidomide, 1979.
 https://www.news-medical.net/health/History-of-Thalidomide.aspx
• Kim, J. H.; Scialli, A. R. (2011). Thalidomide: The Tragedy of Birth Defects
and the Effective Treatment of Disease. Toxicological Sciences, 122(1), 1–
6. doi:10.1093/toxsci/kfr088