On October 1, 1957, a new over the counter drug called Thalidomide was introduced in West Germany by the pharmaceutical company Chemie Grünenthal GmbH. It was originally used as a mild sleeping pill, and was declared safe for everyone, including pregnant women. It was later found to cure morning sickness during pregnancy. Thousands of women used it and it seemed to work well until, later the next year, thousands of infants were born with severe birth defects. They ranged from brain damage to deformed limbs.
Image source: Otis Historical Archives National Museum of Health and Medicine. - NCP14053, CC BY 2.0,
source: Luciana Christiante
Doctors noticed the surge in such birth defects cases but they couldn't guess what was causing it. Then, Widukind Lenz and William McBride, noticed that all the mothers of these babies had taken Thalidomide! In 1961, Lenz proved the link between Thalidomide and the birth defects and the drug was withdrawn. During those times, drug testing rules weren't as strict as they are now. The only test that it had undergone was that even extremely high doses of Thalidomide didn't kill rats. The tests didn't include looking at its effects during pregnancy. This resulted in thousands of deaths. Later, there were reports of nerve damage in limbs after long term use. The USA were spared of much of this disaster thanks to FDA pharmacologist Frances Oldham Kelsey, who didn't allow it to be used in USA, and was awarded the President's Award for Distinguished Federal Civilian Service from President John F. Kennedy for blocking sale of thalidomide in the United States.
Even though scientists knew thalidomide was causing the birth defects, they couldn't know why. At that time, it was not known that Thalidomide is chiral, i.e. there exists two versions of the molecule which behave differently according to their structure.
In chemistry, a molecule is called chiral when its mirror image is not superimposable on the original molecule. The pair of molecules are called as enantiomers of each other. It is something like our hands. You cannot superimpose one hand on the other however you rotate them because they aren't identical. Even if you tried to superimpose them by pressing your palms together, you would realize that one has palm side up and the other has the back of the hand side up. By superimposing, I mean you have to place your hands/ the molecules in such a way that both of them look identical. For example, Bromochlorofuoromethane is chiral while Dichlorofluoromethane is not, as shown in the image below.
image source
This means that even though the composition is the same, they are two different molecules with different properties! The best example for this is methamphetamine. The (R)-enantiomers is legal and used as vasodilators and commonly available over the counter as nasal decongestants like the Vicks Vapor Inhaler. This is completely non-addictive and is non-psychoactive. However the (S)-enantiomer, commonly known as meth or crystal meth, is illegal and causes euphoria and addiction.
Image source: self
In the case of Thalidomide, the R enantiomer helped with the morning sickness, while the S enantiomer caused the birth defects. The medicines sold till then contained a mixture of both of them. When the researchers discovered this, they considered the isolation of the R enantiomer, so that it could be continued as a treatment for morning sickness. But they found out that, the S enantiomer could react with the chemicals inside the human body and flip into the s enantiomer! This meant that even a 100% pure R-Thalidomide would still cause birth defects in the babies. If you are interested on how Thalidomide causes the birth defects, read this. I didn't include this because it is way too technical.
image source
However, 4 decades later, in 1998, the FDA approved Thalidomide for use in the USA for treatment of leprosy and in certain cases of cancer. You can read about this here. Care is taken to prescribe it to only those who aren't pregnant. Events like this caused the laws for testing medicines to be made stringent for the good.
References
- Thalidomide- Wikipedia
- Thalidomide - sciencemuseum.org.uk
- Chirality - Wikipedia
- Chirality and Stereoisomers - Chemistry Libre Texts
- Thalidomide–A Notorious Sedative to a Wonder Anticancer Drug
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