A cross-chiral reaction challenges our definition of life

Just like your left and right hand exist as mirror images of each other, many biological molecules have their own form of left- and right-handedness, called chirality. Our DNA, for example, is made of right-handed chiral molecules which combine to form a right-handed double helix. The left-handed version would look like its mirror image, forming a helix that spins in the opposite direction.

The thing about nature, though—it tends to pick a side. On Earth, DNA and RNA exist only in their right-handed forms. Even when scientists construct synthetic left-handed versions of these molecules, the two groups behave as if on opposite sides of a mirror, unable to interact with each other.

But what if they could? What if a molecule could reach through the mirror and interact with the reflected world on the other side? What if this set off a chain reaction that got molecules on both sides working together in ways we've never seen before?

This is precisely what scientists  have now achieved. In a study published on October 22, 2024, in the Proceedings of the National Academy of Sciences, the researchers demonstrate the first cross-chiral exponential amplification of an RNA enzyme.

Salk scientists engineered a right-handed RNA enzyme (bottom left) that can combine left-handed RNA fragments (bottom right) to create a mirror image of itself. The new left-handed RNA enzyme (top right) can then combine right-handed RNA fragments (top left) to produce more of the original right-handed enzyme, restarting the cycle of cross-chiral self-replication. Credit: Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2413668121

Using sophisticated bioengineering techniques, they produced a chemical system in which left- and right-handed versions of an RNA enzyme can effectively "reach through the mirror" and replicate each other. Through this cross-chiral self-replication, the amount of both molecules increases exponentially and indefinitely—something rarely seen outside of biology.

 NASA defines life as "a self-sustaining chemical system capable of Darwinian evolution." The researchers say this is the first evidence of a life-like chemical system that operates on both sides of the mirror of chirality.

Exponential self-replication is necessary for growth and evolution in every living system. 

Cells don't just make more of themselves; they make exponentially more of themselves, and that fast growth is what drives competition, natural selection, and evolution.

Scientists have  now shown that we can engineer forms of exponential genetic self-replication that are not yet life but are on the path to it, and are built on interactions between left- and right-handed molecules.

While cross-chiral self-replication is unlikely to occur spontaneously in nature, the discovery that it can be engineered in a laboratory setting suggests scientists could one day synthesize an artificial living system that uses both left- and right-handed molecules. This would create the opportunity to study an entirely new form of biochemical evolution, and could also lead to the development of cross-chiral therapeutics and biotechnologies.

Scientists are essentially exploring the boundaries of what biology can be, and based on this study, it seems that our definition of life doesn't have to be as narrow in the lab as it is in nature.

 Wesley G. Cochrane et al, Cross-chiral exponential amplification of an RNA enzyme, Proceedings of the National Academy of Sciences (2024). DOI: 10.1073/pnas.2413668121