91av

LIFE can be strange. Just look at narwhals, and those stick insects that resemble leaves on legs. Or consider the cockeyed squid, with its bizarrely mismatched peepers: one yellow and huge, the other tiny and blue. And yet almost nothing about life is as baffling as the lopsidedness at its core.

All biological molecules have an inherent “handedness”: they can exist in two mirror-image forms, just like your left and right hands. But for each type of molecule it uses, life on Earth prefers a single form. So much so, in fact, that their opposite numbers are rarely seen in living things.

How did life’s building blocks end up single-handed? The short answer is we don’t know. Some people have suggested that something happened in space to seed the predilection for left or right-handed molecules; others reckon it happened in shallow prebiotic pools where life is sometimes thought to have begun on Earth. Now, one researcher is claiming to have uncovered the first hints of a more convincing answer – one that could explain not only what broke life’s mirror in the first place, but also give a richer understanding of why the preference for one form of molecules has persisted over billions of years of evolution.

The answer comes not from deep space or deep time, but from the quantum nature of matter. And if the latest discoveries are anything to go by, its unexpected influence on the building blocks of life could solve the mirror mystery once and for all by revealing in fine detail why some of the most fundamental processes in biology work so beautifully.

French chemist Louis Pasteur discovered molecular “chirality” – from the Greek for “handedness” – in 1848. Working with tartaric acid crystals, he saw that some were mirror images of each other. He sorted them into left and right-handed crystals. And when he shined polarised light through them, the light emerged rotating in opposite directions. “There is no doubt,” he wrote, “that there is a grouping of the atoms of an asymmetric type that is not superposable on its mirror image.”

Not all molecules are chiral but most of the more complex ones are (see “Curious chirality”). We now know the types of molecules that make life possible tend to be exclusively right- or left-handed: the sugars that form the basis of RNA and DNA are always right-handed, for instance, whereas the amino acids that make proteins are only left-handed in nature.

“Was life’s bias initially imprinted onto organic molecules in space, before they hurtled to Earth’s surface?”

We have also learned that this “homochirality” has an essential role in helping molecules to recognise one another. When amino acids string together to make proteins, say, or molecules need to recognise each other to react or pass on a message within a cell, their handedness determines how their shapes fit together. In that sense, a meeting between wrong-handed molecules would be akin to an awkward handshake between a left and a right hand.

The question of how life became homochiral, and why it continued that way, has never been met with a satisfactory answer. Pasteur sought clues in magnetism and light before concluding he was on something of a fool’s errand. More recently, some chemists have invoked cosmic influences. They have proposed that the initial bias could have been imprinted onto organic molecules by exposure to light in space, before they hurtled to Earth’s surface as a meteorite.

This starlight idea relies on light also having a property akin to handedness: its waves can spiral clockwise or anti-clockwise as they travel. The idea is that in regions of space where the balance tips towards photons with one twist, light could have transferred the same skew onto organic starter molecules as it fell on them. “This is what we use as a chiral trigger,” says , a chemist at the University of Nice Sophia Antipolis in France. The hypothesis has been bolstered by experiments at the synchrotron particle accelerator in Paris, where Meierhenrich and his colleagues successfully imprinted the asymmetry in photons onto amino acids in simulated comet ice.

The team had ambitions for a real-world trial with the European Space Agency’s Rosetta mission, which sent a probe to comet 67P/Churyumov-Gerasimenko in 2014. The plan was to detect molecules and check for any bias in their handedness. But the rover botched its landing, settling the wrong way up so it had no chance of drilling out the complex molecules the researchers had hoped to find in the ice below. “Of course, we were a little unsatisfied,” says Meierhenrich.

Even if you could prove it, however, the idea that twisted light imposed handedness on organic molecules wouldn’t account for why the phenomenon has persisted for so long after that initial symmetry-breaking. Perhaps the most plausible scenario is one developed by at the Scripps Research Institute in California. Building on work showing how to make the genetic molecule RNA, Blackmond and her team demonstrated that spiking the starting mixture with a single-handed amino acid had a knock-on effect on the sugars, .

The implication is that life’s handedness was a fluke, a chance imbalance that got baked into biology. It created a system for fitting molecules together and it did the job. “Once you have a process that’s working, it just keeps working,” says Blackman. And that’s the best answer we have: homochirality has been conserved because it works.

There seems to be something missing, though, in the eons between the initial symmetry-breaking and life as we know it today. The complementary-shapes model of how molecules “shake hands” may not entirely explain why evolution weeded out the “wrong-handed” molecules. The trouble is that we can’t go back in time, so we’re left speculating about what happened. And attempts to fill the gap are little more than hand-waving, says Blackmond. “You get lots of people that have very strong opinions about what happened, because nobody can prove them wrong.”

A new twist

at the Weizmann Institute in Israel thinks his idea is different. His career has primarily been devoted to chemical physics and electronics, and his forays into biology start with fundamental particles. Now he has come up with a hypothesis that aspires to offer a fuller, more convincing explanation of why life is so strictly single-handed.

Electrons are negatively charged particles that glue atoms and molecules together, and their movements govern chemical reactions. Like photons, they have an intrinsic angular momentum or “spin”, roughly akin to rotation in one direction or the other. Naaman realised this property might have something to do with molecular handedness in the 1990s, when German physicists shot electrons at vaporised molecules from the camphor tree family. They noticed an imbalance in the spins of electrons transmitted by the molecules: electrons spinning in one direction passed more easily through left-handed molecules, while electrons with the opposite spin passed more easily through right-handed molecules.

The asymmetry was tiny but when Naaman did a similar experiment with amino acids, aligning them neatly on a surface rather than scattering them in a vapour, he saw a larger effect. “The truth is, I was sort of excited for the effect,” he says. “But I didn’t understand its implication.”

Naaman began to join the dots when he fired electrons at other chiral molecules, including DNA. Here he saw how electrons passing through the screw-like length of a right-handed DNA helix are filtered so that most of those popping out the other end have the same spin. This wasn’t just a small sway. “It was a huge number,” says Naaman. “It was beyond 60 per cent, which was really surprising.”

The effect, now known as chiral-induced spin selectivity (CISS), made a splash, albeit primarily for its potential in spintronics, a branch of electronics geared towards manufacturing high-speed computing devices. And although eyebrows were raised initially, it is no longer in any doubt. “Naaman and others have done a lot of experiments and it always seems to work,” says , an astrophysicist at Harvard University. Naaman has since demonstrated it in proteins too.

In the past few years, Naaman has also begun to sketch out . First, he thinks, it provides a more complete picture of how biological molecules recognise each other. Naaman suggests that electrons moving through chiral molecules as they approach each other create charge differences across the molecules that can help them align and stick together. In two screw-shaped molecules, for instance, because the electrons are negatively charged, their movement results in a pile-up of negative charge at one end of each screw, attracting the opposite – more positively charged – end of the other molecule. Without this, Naaman says, the theoretical strength of interactions is too weak compared with what is measured. It is what is missing, he believes, from the standard lock-and-key view of biological recognition.

What’s more, Naaman argues that the CISS effect can explain another fundamental aspect of life, namely why biological processes requiring electrons to be shuttled through chains of molecules work so flawlessly. The extremely high efficiency of the oxygen-generating step in photosynthesis – the chemical reaction that plants use to trap the energy of sunlight in sugars – has long puzzled biologists. Naaman argues that chiral proteins act as conductors for the electrons transported in this process, ensuring they don’t get stuck, a situation that could destroy the protein. The CISS effect could thus account for why “in the photosystem, every electron that starts to move gets to the end, which is very surprising”, says Naaman. Sure enough, when he and his team tracked electrons through one of the main protein clusters involved in photosynthesis, they found .

“If this effect explains why the engines of biology work so beautifully, it can tell us why life’s handedness has been conserved”

Reverse spin

Electron transport isn’t just important in photosynthesis. It is also key to respiration, part of the energy making process across all forms of life. If the CISS effect is what makes these two engines of biology work so beautifully, as Naaman contends, it might just complete our understanding of why homochirality has been conserved – even if it doesn’t explain why life lurched left for amino acids and right for sugars. “I don’t think we have an answer for why this specific chirality,” he says. “But I have an answer to the question why chirality. Because chirality helps in many processes, like recognition and electron transfer. So in that sense, it explains why there is a reason for evolution to be homochiral.”

For others, this relationship isn’t so clear-cut. “This link to biology is very interesting,” says at Imperial College London. “But I think it’s uncertain whether CISS has a fundamentally important role.” When it comes to the electron-transport processes that fuel life, he argues, we can’t assume improved efficiency in chiral molecules was what drove biology to be homochiral – it could just be a consequence of how things already were.

But Naaman’s claim on the origin of homochirality goes further. Last year, he and his colleagues demonstrated the existence of a , in which electrons with a certain spin filter the handedness of molecules during a chemical reaction, rather than the other way around. The implication is that it could it have been electrons, rather than photons in starlight, that shattered life’s mirror in the first place by imprinting handedness on the molecules that first gave rise to life.

Meierhenrich says the proposal fits with his own thinking. “The underlying idea is not too different,” he says. “In our case, they are photons and in this case, they are electrons that give the chiral information.” He adds that his team have “some ideas” along these lines, although it has yet to identify a definite source for asymmetric electrons in space.

For his part, Sasselov is cautious about Naaman’s most recent results. But he takes them seriously enough to want to test the idea himself. “Biased electrons should introduce a chiral selectivity in the molecules, so this is exactly what I’m trying to do in the lab,” he reveals. “I’m working with one of Ron Naaman’s former students and we’re using a very highly sensitive new technique to actually try this. We haven’t tried it yet, so I don’t know what we’ll find… but if it works, it will be great.”

Naaman thinks electron spins offer a “more probable mechanism” for the smashing of life’s symmetry than photons in starlight, and yet he has been reluctant to say as much in any peer-reviewed journal. His 2019 paper is ostensibly for chemists, making no explicit references to life. “We are really pushing things and, as you can imagine, we face resistance,” he says.

It certainly looks like he is onto something. But Naaman is probably wise to wait for support. When you are a chemical physicist wading into biology, you don’t want to take everyone on single-handedly.