Imagine a pair of molecules with identical atoms and identical chemical bonds. You’d think both molecules would behave in exactly the same way, right? Not necessarily. Meet the mirror molecules, a chemical phenomenon known as chirality. This article originally appeared in the Cosmos Print Magazine, March 2025.
When British skier Alain Baxter won a bronze medal, it was a personal best for him – and a first for the UK in skiing. Baxter came third in the slalom at the 2002 Salt Lake City Winter Olympics.
But then his urine sample tested positive for methamphetamine. Three weeks later, the International Olympic Committee (IOC) had stripped him of the medal.
Baxter denied taking the illegal stimulant, saying the culprit was a Vicks inhaler he’d bought in Utah to clear his nose. Unbeknownst to him, the brand used a different substance in their US product to the UK version. While he could use the UK inhaler with impunity, the US formulation triggered a positive drug test.
The Court of Arbitration in Sport later cleared Baxter of cheating, ruling he “appears to be a sincere and honest man who did not intend to obtain a competitive advantage in the race”.
But he never got his medal back. The Court agreed with the IOC’s ruling that, whether or not he’d known he was doing it, Baxter had still used a banned substance.
The thing is, the substance inside the Vicks inhaler had an identical chemical
formula to methamphetamine. It had exactly the same atoms as methamphetamine, arranged in exactly the same chemical bonds.
All of the IOC-accredited equipment in the Salt Lake City lab would have agreed it was methamphetamine.
But it wasn’t methamphetamine. It wouldn’t have given Baxter an advantage. In the USA, you can still buy it over-the-counter in a number of inhaler brands (although Vicks themselves has since changed their recipe). Taking those inhalers won’t cause a high, or any of the addictive effects of methamphetamine. They’re recommended for children as young as 6.
The Vicks ingredient was an almost indistinguishable twin of methamphetamine: R-methamphetamine.
The difference? A simple piece of geometry.
A deeply vexing problem. An unprecedented threat.
Twin molecules
At one crucial point in the methamphetamine molecule, a single carbon atom links 4 completely different sections together.
This introduces a source of asymmetry, called ‘chirality’, into the molecule. Try and connect these 4 sections to the central atom, and you’ll discover they can be connected in 2 different ways, with one the mirror image of the other.
The molecules end up looking like a pair of hands: made of the same stuff, connected in the same way, but not interchangeable. In fact, chemists term these reflections the S form and the R form in reference to handedness – S stands for sinister, Latin for left-handed, while R is rectus (right-handed).
It’s not a distinction that’s easy to spot, chemically speaking. The molecules have all the same atoms and all the same bonds – they’re just optically different.
Given molecules are too small to see, why should optics matter? Turns out, life is full of chiral molecules. Most importantly, both DNA and 21 of the 22 amino acids that make up all the proteins in living things are chiral – only R-DNA, and mostly S-amino acids, exist naturally. So when a human encounters a chiral molecule, its symmetry suddenly matters very much.
“No one knows why our bodies got only one form of amino acids,” says Professor Ashraf Ghanem, a chemist at the University of Canberra.
While S-methamphetamine binds neatly to protein receptors in the brain, triggering the release of dopamine and other transmitters, R-methamphetamine does not.
Chemists term these symmetry twins enantiomers, or stereoisomers. And methamphetamine is far from the only substance to have enantiomers that behave differently.
Mirror effects in the body
“There’s a range of different effects if you have the wrong stereoisomer,” says Associate Professor Vinh Nguyen, a chemist at the University of New South Wales.
Take carvone molecules, which are found naturally in essential oils. They carry distinct scents – spearmint from one enantiomer, caraway from the other.
Different enantiomers have different properties. Credit: BENJAH-BMM27, JohnGollop / Getty Images, Orinoco-Art / Getty Images.
But when it comes to medicines, the difference can be much more frightening. The vast majority of pharmaceuticals are molecules designed to fit into the “active sites” of certain proteins in the human body, and these active sites are highly specific.
“The drug will be able to treat the disease because it was able to fit nicely into the active site,” says Ghanem. “If it’s not the correct form, then it will not fit, and the drug will be inactive.”
Add the wrong enantiomer to your medicine, and the best-case scenario is that it does nothing. Ibuprofen is an example of this: it’s sold as a 50-50 mixture of both enantiomers, one of which (the S-enantiomer) is 100 times better at relieving pain than the other. It’s wasteful – manufacturers are using twice as many ingredients to make the right dose of medicine – but for now, it’s cheaper to make the mixture than it is to make or separate pure S-ibuprofen.
But that’s the least harmful option.
“There’s several cases in history of drug development where the wrong stereoisomer had very different effects, sometimes severe,” says Nguyen.
The most famous example is thalidomide, which was used to treat morning sickness in the 1950s and early 60s. One form of the drug – R – has a sedative effect. But in the human body, it converted easily into the S-form, which caused disorders in developing foetuses. About 10,000 infants were born worldwide with severe limb malformation, only half of whom survived.
“Before launching any drug, now, the TGA asks companies manufacturing drugs to show us the effect of each form separately and convince us that the drug is safe in terms of chirality,” says Ghanem.
So, unless you want to do twice the amount of clinical work proving both enantiomers are safe, you need to make something enantiomerically pure. Herein lies the next problem.
Nature discriminates against chiral molecules, but chemists find it much, much harder. It’s not a random coincidence that it’s cheaper to make a mixture of ibuprofen enantiomers. That’s the default result of a chemical reaction. Nature, which has spent millions of years reinforcing its chiral purity, is the weird aberration.
If you start with symmetrical feedstocks, how can you impose asymmetry on them? How do you get the right optical property in something that’s too small to see?
“It has been a challenge in organic synthesis for a long time,” says Nguyen.
Pure asymmetry
One way to get a pure enantiomer is to make a mixture of both forms, and separate them. A common way to do this is chromatography: filling a tube with a chiral substance that will stick to only one enantiomer, and flushing the mixture through it.
“That will cost a lot of operating time, solvents and materials,” says Nguyen.
This technique can also help to identify enantiomers. In 2002, the IOC had access to chiral chromatography equipment at a Californian lab, but they denied Baxter’s request to use it on his sample.
A neater way is to make something chirally pure in the first place.
“From the beginning, you can use a catalyst that can differentiate between R and S, and you will make only one of the drugs,” says Ghanem.
Start with a catalyst – something that triggers a chemical reaction, without being used up itself – and you can turn a tiny bit of chirality into a lot of chirality. Ghanem and colleagues have seen commercial success with this technique, making a catalyst that yields Ritalin. The catalyst – under patent – is now in the hands of multinational company Merck.
Historically, chemists have turned to transition metals like palladium to form the basis of these catalysts. The metal atoms have the right sort of structure to accommodate other molecules coming together and reacting in their presence. But nature’s provided a carbon-based solution: enzymes.
“Enzymes are these really big proteins, with a lot of hydrophobic [water-repelling] pockets and some sort of active site to catalyse reactions,” says Nguyen.
“The reagents have to get inside that pocket, and then bind to those active sites, to react with each other better.”
Ghanem and colleagues have used enzymes to get to the chiral molecules they want.
Nguyen’s team, meanwhile, is interested in combining the best of both worlds with a technique called organocatalysis. It relies on small, carbon-based molecules that can mimic the active sites of enzymes and the structure of metals to trigger reactions.
“Essentially, simplify everything and use what we know about the other catalytic interactions to bring it together onto this small organic framework,” says Nguyen.
“It uses all the advantages of the other two fields. But then [it doesn’t] have to deal with bulky, complicated molecules, or transition metals, which are kind of toxic and hard to handle – and expensive, sometimes.”
A new kid on the block at only a few decades old, organocatalysis promises to be safer and more efficient than both its predecessors.
Many of the catalysts used are derived from nature themselves.
“A bunch of the original organocatalysts are actually amino acids,” says Nguyen. “So they have stereochemistry already built in, and it’s quite easy to isolate them and use them to then coordinate or interact with other organic molecules.”
Nguyen’s interested in making all of this synthesis greener – using sunlight as a source of power to trigger reactions, and figuring out ways to make the reactions happen in water. Carbon-based molecules generally require polluting and expensive carbon-based solvents to dissolve properly, so water-based reactions could clean industry up dramatically.
“There’s a lot of things that we can use from nature, but human creativity is unlimited,” says Nguyen.
The risk of an evil twin
There’s nothing inherently life-giving about a left-handed protein. The S designation itself is an arbitrary one, dreamt up by mid-century chemists, just so they could distinguish between enantiomers without resorting to drawing diagrams. There have even been boons to medicine from reversing natural chirality, and making right-handed proteins or left-handed DNA.
“These mirror molecules are really intriguing as a new category of potential drugs, because they are not recognised by the body – by degradative enzymes or the immune system,” says Professor Michael Kay, a biochemist at the University of Utah, USA.
“[Mirror] drugs could have very desirable properties in terms of very long half-life, low cost, infrequent administration – things like that.”
Professor Michael Kay, a biochemist at the University of Utah, USA. Credit: Courtesy of Professor Michael Kay.
But Kay, who does research on these therapeutic drugs, is concerned the work could go too far. In December, he was part of an interdisciplinary group of researchers who co-authored a stark warning in Science.
Their concern was the possible creation of “mirror life” – entire organisms created from the opposite enantiomers to ordinary life. It’s feasible, the researchers suggested, to make bacteria with right-handed amino acids and left-handed DNA.
We can’t make mirror bacteria yet. Every chiral part of the organism would need to be made from scratch, and the researchers think we’re at least a decade of hard work away from such a feat.
“This is not an imminent threat. It’s not science fiction either,” says Kay.
The problem is that if mirror bacteria escaped the lab, it could make all previous pandemics look minor.
Most of the nutrients bacteria live on aren’t chiral, so mirror life would have no problem replicating. But the things that control bacterial numbers – phages, antibiotics, other microbes, immune system proteins – they’re all chiral.
“Since almost all of the immune system has this chiral requirement, you would have something that could escape many different aspects of immunity all at one time,” says Kay.
The effect would be deleterious – not just to humans, but to every living organism. The world would have no natural defences against these bacteria, and the researchers are sceptical that we could build artificial defences strong enough.
Mirror life should never be made, concluded Kay and his colleagues – any pharmaceutical or scientific benefits are not worth the risk.
The good news is that there’s plenty of time to put rules in place, so that mirror proteins and other molecules can be studied, without any risk someone might make a whole bacterium. The group is inviting wide discussions this year to start developing these rules.
“This is not something that somebody could work on in their garage, away from a regulatory infrastructure,” says Kay.
Nor are they totally slamming the door. “We do want to be humble in that we don’t know everything,” says Kay. It’s possible – albeit very unlikely, he thinks – that some new insight could render mirror life safer.
But chirality has been a source of medical disasters in the past, and for now, all the evidence suggests that mirror bacteria would be far worse.
Chirality was a trivial matter for the IOC, which denied Baxter’s medal on the grounds that it had banned all methamphetamine. But for chemists, the distinction matters. An R or an S could be the difference between life and death.
We are getting better and better at choosing the symmetries of molecules. Will these choices lead to something beneficial – or sinister? For now, it’s not quite clear. We see in a mirror – dimly.