Thalidomide History

The Ever-Changing Identity of Thalidomide and its Impact on Society

The thalidomide catastrophe shocked the world and its devastating effects coupled with its high profile in the media have ensured that, despite taking place fifty years ago, it is still a mainstream topic, discussed by the general public as well as being the subject of much interest and debate in the medical world.   It was responsible for limb defects and a whole host of other abnormalities in thousands of babies born in the 1950s and early 1960s.   The effects of this tragedy have been far-reaching and the question has to be raised: how could one molecule cause so much damage?
Thalidomide, or α-phthalimidoglutarimide (derma rediscovering), is an analogue of glutamic acid.   It is a racemic mixture consisting of S(-) and R(+) enantiomers - under physiological conditions, these enantiomers readily interconvert.   It is thought that the R(+) form is responsible for the sedative effects of thalidomide via, it has been suggested, sleep receptors in the forebrain.   The S(-) enantiomer is considered to be responsible for the birth defects in the children of women who took it.1

Fig. 1: Enantiomers of thalidomide readily interconvert.1

This molecule has had many identities since its original development in 1954.   Its first intended use was as an antibiotic when Chemie Grunenthal, a small pharmaceutical company in West Germany, manufactured it by chance as part of their quest to develop an inexpensive method of producing antibiotics from peptides.   They heated phthaloyisoglutamine and produced α-phthalimidoglutarimide, coining the name ‘thalidomide’.   Disappointingly, it showed no antibiotic properties but, casting dreams of Thalidomide the Antibiotic aside, Chemie Grunenthal did not give up hope, encouraged by the fact it seemed to be harmless – they did not detect any side-effects and even the highest doses did not kill the lab animals.2  
The company’s management saw a gap in the market for a...