(10m) Spiralled light and thalidomide

An interesting discussion on the Fleming radio 1: scientists managed to create light that moves as a spiral. To know more about it, listen to the program (in Dutch). Why can this be important? What can be done with this?

 

You should also know that light is an electromagnetic radiation of a wide range of different wavelengths that results in different kinds of visible and invisible light but at the same time is also particle-like consisting of discrete packets of energy, i.e. photons, the so-called wave-particle duality. This means that light moves as a wave but only hits something in one place with a certain energy that can be sufficient to move very small things such as molecules. This is different from a wave at the beach that reaches the coast over a certain distance although also with a particular energy.

 

Possible scope of spiralled light - Thalidomide as example

Softenon with active substance thalidomide was used as an example how this light may one day be used. I've written about thalidomide before to illustrate the difficulties scientists face when they invent drugs, certainly during the early times when much less was known and legislation was almost nonexistent.

 

Why was this molecule mentioned in the program? Because now it is known that thalidomide is racemic as it has an asymmetric or chiral centre, resulting in a left (S)- and right (R)- turning enantiomer with important differences in characteristics (see Figure B).

 

Racemic - Enantiomers - Mirror molecules

Enantiomers are similar when you look to their simplified chemical structure but they have a asymmetric or chiral centre so enantiomers are mirror images of each other when you look at the real 3D molecule that can never be superimposed on each other - similar with our left and right hand that look similar but left is different from right. This difference can have major effects on how molecules behave.

An example that we know in life to illustrate this very clearly is limonene that smells like lemons when it concerns an S- (or L-) enantiomer that is a left-handed molecule and oranges when it is a R- (or D-) enantiomer that is a right-handed version of the molecule with chemical formula C10H16. A racemic mixture or racemate is when both enantiomers are present in equal amounts, either by mixing them or because they can change or racemise from one form into the other.

 

Thus, both enantiomers of thalidomide are identical in their chemical formula, i.e. C13H10N2O4, and in the second half of 1950 it was marketed for anxiety, trouble sleeping, tension and morning sickness. Thalidomide seemed very save as it didn't suppress respiration while it was not effective when people used it to commit suicide. However, while one enantiomer has positive effects, i.e. to fall asleep and against morning sickness so many pregnant women used it, the other enantiomer has a major side-effect, i.e. it affects unborn babies so children were born with abnormalities of the extremities, more specifically very short arms and legs, and other effects that could result indeed born children, the reason why it was taken from the markets in 1961. However, since 1998 it is approved in the USA as treatment of certain illnesses including leprosy and it seems it is now even on the World Health Organisation's List of Essential Medicines as treatment for multiple myeloma. But our knowledge also informs now that women can't be pregnant when they take the drug.

 

As the spiralled light consist of photons with energy, it may have the potential to separate the right and left turning molecules and thus purify the correct form that benefits humans without the form that causes harm.

 

However, in the body the R and S form can change or racemise into each other and thus it may never be possible to use thalidomide safely when for instance a pregnant woman develops multiple myeloma unless we can halt the racemisation.

 

In addition, also the degradation molecules (metabolites) play a role in the toxicity of thalidomide and this can explain why originally the toxicity wasn't seen when thalidomide was tested in certain animals as its metabolism differs between animals, the reason why now the toxicity of drugs need to be tested in different animal species to minimise the risk that drugs are not metabolized in certain animal species while they are in humans. This also shows the importance of in vitro testing in cells from many different animals and humans to know the degradation products that are formed so mainly animals that produce similar metabolites are used for in vivo testing to further reduce the numbers of animal testing.

 

Thus, I think the spiralled light may only be useful to separate the active and harmful forms of thalidomide if it is used together with something that blocks that our body turns thalidomide from the good into the bad form unless this convention is slow and sufficient amounts of the bad form are build up only after prolonged use so short acute use of the very clean active form is harmless. Still, although our body is able to eliminate the molecule, metabolites are also harmful. Thus, questions need to be answered: does everyone convert the molecule at the same speed or do differences exist due to polymorphism that may also explain the different responses to the molecule? Similar, does everyone metabolites the molecule in a similar way or do differences exist?This shows that multidisciplinary science becomes very important: a physicist may think to have a solution for a problem such as to separate good and bad molecules but a (bio)medical scientists may point to other problems that first need to be solved.