Louis Pasteur and the birth of chirality

In 1848, the revered French scientist Louis Pasteur made a remarkable discovery - some say in the bottom of a wine glass - that would help shape the future of chemistry and biology: molecules can be either left- or right-handed. It matters because this property, which is known as chirality, dictates the very structure of life itself.

But here’s the twist: life on Earth has always favoured one side or the other. Our proteins are all left handed; our DNA and the sugars we metabolise are all right handed. Why? No one knows. But now scientists are pushing the boundaries of biology by taking the first steps towards creating “mirror life” - organisms built entirely from reversed molecules: literally DNA that spirals left, and proteins that curl to the right.

The rationale for doing this is sound. It’s hoped it will advance medicine, biotechnology, and maybe even the search for alien life. But a number of world experts are worried, calling recently in a communication published in the journal Science, for a pause in research on mirror microbes. They argue that this technology could pose a grave risk to life on Earth. We’ll hear from one of those researchers later. But first, what exactly is chirality? And why does life depend on it? Phillip Broadwith, from Chemistry World, invited me out for a drink at the famous Eagle pub, in Cambridge…

Chris - Hello.

Phillip - Hi Chris, good to see you.

Chris - Yeah, likewise. You could have made it a bit warmer, Philip, but it's a nice day.

Phillip - It's lovely, but there is a reason why I've brought you here, Chris. This is the Eagle Pub in Cambridge, where James Watson and Francis Crick announced the structure of DNA, which is probably the most famous chiral molecule in the world.

And I shook your right hand with my right hand, because that's the only way it works. We could have done left to left, but that's a bit less conventional, unless you're a Cub Scout, but a right to left won't work. And we'll talk about that in a minute.

Chris - Let's get inside out the cold weather and you can tell me more about it.

Okay, right, let's put that down there. Well, we've got two nice cups of coffee. This is a pretty famous pub.

Phillip - Yeah, absolutely. So just around the corner are the Cavendish Laboratories, or the old Cavendish Laboratories, where Watson and Crick were working on the structure of DNA.

And legend has it that they came to the Eagle Pub and announced it.

Chris - You use that word chirality, and you shook my hand, right hand to right hand and said, there's only one way that can happen and chemistry is the same. You better explain what this word means.

Phillip - Well, the structure of DNA itself is a spiral, a helix, and that goes in one direction or the other. If you have a right-handed helix, it is different from a left-handed helix. It spirals the other way and they don't fit together.

They're different molecules. Lots of molecules have this property of handedness. The word chirality comes from the Greek cheir - which means hand.

And if you think of your two hands, they're mirror images of each other. They're not the same. You can't put them on top of each other and have your two thumbs over the top of each other if your hands are the same way up.

But if they're facing each other, they do. They're kind of mirror images.

Chris - And molecules are the same, are they? So if I take your hand analogy, and imagine my hand's a molecule and the fingers are different atoms stuck onto the core of the molecule, then you can have the atoms relative to each other in different places in space. They're the same molecule because they've got the same chemical formula, but it's how the atoms are arranged relative to each other, how they're stuck on effectively that gives it that one handedness or the other.

Phillip - Yeah, exactly.

If we think of the sugar that you might have put in your coffee, sugar is a handed molecule. It has left- and right-handed forms. And all of the sugars that we incorporate into our body have this same property of handedness.

Chris - How did this come to light in the first place?

Phillip - Lots of other molecules have this property as well. And what Louis Pasteur discovered was by looking at crystals of a molecule called tartaric acid or a salt of tartaric acid, like the little crystals that you might find in the bottom of a wine glass if we go on to some wine a bit later, Chris.

Chris - Wishful thinking. You better do a good job of this interview and I might think about it.

Phillip - So, he looked at these crystals of sodium ammonium tartrate and noticed by looking under the microscope that there were two different shapes of crystals that were mirror images of each other.

So, he then, very carefully, very painstakingly over hours and hours and hours took his crystals and separated them out into the left- and right-handed crystal forms and then dissolved them back up and noticed that one of those crystal forms rotated light to the left. The other one rotated light to the right.

Chris - So, literally then, you've got a situation where the handedness of the molecule makes a crystal that's asymmetric. One particular symmetry of the molecule makes a crystal that has that shape as well. And you end up with crystals that are mirror images of each other. And that's what gave the game away to Pasteur.

Phillip - Exactly right. And that's the same with our DNA with proteins. If you make them out of the same handedness of their building blocks, the individual sugars or the amino acids, then they get a handedness to their shape.

If you were to try and make them out of the opposite handedness, then you would get the mirror image overall macro shape as well.

Chris - Does this mean then that when life got started on Earth, if we go back four and a half billion years, that there were equal numbers of all of the different types of chemicals probably on the early Earth, but as life got going, it's enriched for one of them. It started using one of them or is something special going on?

Phillip - Well, we think that is right. There are meteorites that we found that have both handed forms of early molecules on them, amino acids and that kind of thing, or the precursors to life. But what we think happened is that there are a series of reactions where these molecules interact with each other and can replicate themselves.

And if you tip the balance ever so slightly towards one handedness, and then it self amplifies and makes more and more of its own handedness at the expense of the opposite, then over millions of years of evolution, as the molecules get more and more complicated, they're only incorporating this single-handedness of the molecules. And while the other molecules might exist, they're not enriched in nature in the same way.

Chris - Are they chemically identical though? So from a chemist's point of view, you're a chemist, if you did an experiment with one handedness or the other, would they have exactly the same reaction profile, etc? It's only in biological systems, they would have a different behaviour?

Phillip - Well, it depends what you're trying to interact with.

If you're trying to interact with something else that has chirality, then you will have some selectivity one way or another. So, if you think back to the Nobel Prize in Chemistry a couple of years ago for organocatalysis, asymmetric organocatalysis, with Dave McMillan and Ben List, that was all about using chiral chemistry. And it's extremely important chiral chemistry, a lot of drug molecules are chiral because we want them to interact with biological systems.

But to make those, we need to use chemical systems that are themselves chiral to impart chirality to the molecules.

Chris - What are the implications then of the fact that we have this biological world that's rooted in handedness?

Phillip - It controls how molecules interact with life.

It means that living systems tend to include one-handedness of molecules. If they include the opposite-handedness, then they might not interact with our systems in the same way. So one example is that there are bacteria that have small amounts of the opposite handedness of some amino acids on the outside of their bacterial cell walls, which makes them much, much more difficult for our immune systems to deal with because they don't see or they don't fit into the machinery that would normally chew up those molecules and help us get rid of those bacteria.