- A former Nazi scientist, now working for a German pharmaceutical company synthesized a new drug. After acquiring a 20 year patent, the company began clinical trials. After two years it first appeared in a medicine called Grippex, along with several other chemicals. It was noted, however, that the drug helped with morning sickness. With this fact in mind, it was pushed out by itself on October 1st, 1957, known as Contergan, despite never having been tested on pregnant women.
Contergan was branded a "wonder drug.", advertised as being capable of helping with insomnia, coughs, colds, headaches, and of course, morning sickness. It was even said to be safe for pregnancy despite the lack of tests.
There's an advertisement for the drug from the UK. Also fucking hell, blatant sexism.
And another, under a different brand name.
It was one of the most popular drugs ever, being likened to a literal "miracle drug" all over the world. What could go wrong?
Well, in around 1961, the drug started to be connected to a series of birth defects. It was pulled from the shelves in disgrace, with up to 20,000 babies born with disfigurements. Lawsuits came, left, right, and centre. Permanent damage was caused to thousands and thousands of children due to this drug. I would go more on this - but this is a chemistry thread. So let's crack into the chemistry.
Chirality is the topic today. Look at your hands. They are made up of the same pieces and look exactly the same aside from one thing. They are mirror images of each other. No matter how much you turn them around and flip them and move them around, they are different.
This is known as chirality - if an object is different from its mirror image. Chemistry is no stranger to this - when a carbon atom has four different groups surrounding it, it is known to be a chiral centre, and thus will produce two different forms, known as enantiomers. Thalidomide, the drug the case study mentioned, is an example of a chiral substance.
Let's crack it open and take a look, shall we?
Here is thalidomide.
Now it's worth noting that each of the vertexes where two lines meet is a carbon atom, unless specified otherwise. There is also a maximum number of hydrogens bonded to each carbon atom - bearing in mind carbon wants to create four bonds. I'll draw them in for clarity.
Can you spot the chiral centre? Try taking a look. You're looking for a carbon with four different groups bonded to it.
Belo, I've marked the chiral centre. If you didn't want to look or just want to check your answer, here you go.
!
Now, with that answer some of you might be wondering where the four came from - after all the carbon is bonded to two carbons, right? Well, while you can't be blamed for thinking that, there's something else that needs to be taken into account and that is the other groups bonded to the carbon which is bonded to the chiral centre. The fact that this is a ring makes it more difficult, but due to there being distinct groups on one side that aren't on the other, you can still find chirality. I'll show a simplified diagram as well.
As you can see on the bottom, I've drawn both R and S thalidomide as being mirror images of each other. Ignore the funny dashed lines and the thick arrow, it's just trying to give depth to show the three on the bottom create a tripod-like shape. It has the same bond significance as just the straight line.
Now, back to our case study. The chirality was actually the cause for the deformations. While these two molecules are chemically identical in every single way aside from one, a change as minor as a mirrored structure can make it behave very differently pharmokinetically.
R-thalidomide, pictured on the right, did the good stuff. It was responsible for the effects that gave the medication such a popular selling point as a sedative and therefore a sleeping pill.
And then you've got S-thalidomide. Allegedly, this is the evil twin. It is a teratogen - defined as causing malformation of an embryo, which means that this enantiomer was likely responsible for the birth defects which unfortunately affected the lives of thousands of mothers and their children.
One might be forgiven for thinking that we can just separate the two, right? Wellllllll.....
Firstly, it is possible to separate enantiomers, but you can imagine it's very very difficult, and rather inefficient. But it is possible, and could be done.. if it wasn't for the next bombshell. Turns out, the enantiomers can switch to each other. So if you made a pure solution of R-thalidomide, it would eventually and slowly become a 50/50 mixture again.
From what I can gather, this transition seems to stem from the thalidomide acting as an acid and getting rid of that lone hydrogen, but it doesn't seem to be clear to anyone why that happens within the body. All we know is, there's no way to safely use this substance for that purpose.
Thalidomide, however, still has some medical applications. It was used successfully to treat Leprosy, although the WHO do not recommend it, mainly due to the presence of another drug that can work just as well. In 2006, the FDA approved its use along with another drug to treat a form of blood cancer.
However, it goes without saying, there are many precautions taken for its use that women needing to take thalidomide aren't pregnant, and are making their chances of getting pregnant as low as possible. I'd probably be fine. We had to learn the hard way, but learning from past mistakes is important, especially in the field of science. We learned to extensively test medications to ensure they are as safe as possible, among other things. And in 1961, as a result of the ongoing scandal, Germany set up a ministry of health.
Anyway, there was a lot less chemistry in this one, but the case study was really interesting to me. Several hours of work and three different days of working went into this one, so I hope this is a good read.
Thanks all.
