Like many young children, was fascinated by the history of life and wanted to dig up dinosaurs when he grew up. But life doesn’t always go to plan, and he ended up becoming not a palaeontologist in the field, but a chemist in the lab. Still, maybe that wasn’t such a departure from his childhood dream. Thanks to a surprise discovery, his work would take him closer than any fossil ever could to the heart of one of the most profound questions about life on Earth.
In 2010, Otto stumbled upon some of the first synthetic molecules that could self-replicate. Since then, he has been trying to coax them into states that look intriguingly like life. “We’ve been building on them to make them do more and more lifelike things – not only replicate, but also metabolise and evolve,” he says.
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That simple chemicals can behave in this way is startling enough. But recently, Otto’s experiments have also offered tentative evidence that life may best be described as a novel state of matter, an idea proposed by , a chemist at Ben-Gurion University of the Negev in Israel. “It’s a bridge that brings the physical and the biological worlds together,” says Pross.
The hope is that studying the physical processes that underpin life may explain how it originated and illuminate its nature. Already the results are suggesting that Darwinian evolution may be just one facet of a more general evolutionary principle that also applies to the non-living world. In which case, researchers argue, evolution may have begun before life did.
You may think you have an intuitive sense of whether something is alive. But the search for a clear-cut, scientific definition of life in all its diversity has long been fraught. A decade ago, biologist Edward Trifonov tried to and found no fewer than 123. In this chaotic definitional chorus, he identified two universal features: self-replication and evolution. Despite these common themes, the definition of life remains stubbornly slippery.
Scientists’ ideas about what life is are often tangled up in their theories of how it began. Traditionally, origin of life researchers tend to fall into one of two camps, says astrobiologist at Carnegie Science in Washington DC. The first and oldest camp is the genetics-first camp, sometimes also called replication-first or information-first. In this view, the formation of self-replicating molecules like DNA or RNA was the defining moment in life’s origin. The second camp argues life started with metabolism; that is, the networks of chemical reactions that break down and build up the stuff of life.
Both of these origin stories smuggle in their own definitions of life. Information-first theories define life in genetic terms as chemical systems that replicate and evolve, while proponents of metabolism-first theories define life more like an engine that burns chemical fuels to keep on running. “These conceptions for what life even is in the first place are very different from one another, which is, I think, at the heart of why there are so many heated debates in the origins of life field,” says Wong.
To try to make sense of this muddle, Pross set aside the specific chemical details of life’s origin and focused on fundamental principles that could bridge chemistry and biology. Starting in 2003, he developed an idea he calls dynamic kinetic stability (DKS), which paints life as a new state of matter. And it tells a different origin story – one that might be called “evolution-first”. Pross argues that Darwinian evolution can be reduced to a deeper kind of evolutionary behaviour obeyed by living and nonliving matter alike: it’s not survival of the fittest, but survival of the stable. “The ultimate logical principle of nature is that things that persist, persist, and things that don’t, don’t,” says Pross.
This might seem painfully obvious, but it suggests a different kind of stability from that with which chemists and physicists usually work. In thermodynamics, the framework that describes how heat, energy and work relate to each other, the stability of a state is determined by its energy. Higher-energy states are less stable than lower-energy ones, and the non-living world evolves in one direction: down the energetic slope, towards equilibrium – at which point there is no net flow of material or energy between the system and its surroundings. Balls roll downhill, not uphill, and they stay put once they reach the bottom if left alone. “Chemists do most things at equilibrium or in systems that go there. It’s the default,” says Otto.
Evolution can begin in systems that we wouldn't normally consider to be alive
If the energetic landscapes of the real world were smooth slopes, everything would slide to equilibrium and nothing interesting would ever happen again. But it’s not that simple: systems can get stuck in local valleys uphill from true equilibrium. When that happens, chemical reactions become incredibly slow. This is called kinetic stability, and it’s why woodpiles don’t spontaneously combust and why diamonds are “forever” even though, thermodynamically, they are uphill of graphite.
But life defies both kinds of stability. For life, whether it’s resting at the bottom of a mountain or stuck in a high-altitude ditch, standing still means death. “Life is a dynamic system. It is never in equilibrium, says Wong.”
Dynamic kinetic stability
It is this refusal to comply with the usual thermodynamic order of things that has long made life so indigestible for the physical sciences. Pross made biology easier to swallow by divorcing the concept of stability from static states. Stability of the dynamic kinetic sort isn’t about sitting at the bottom of the hill, but about consuming energy and material to stay on top of it. Like the paradoxical ship of Theseus, systems in such a state persist by changing. Left alone, the ship would eventually fall apart and into equilibrium. But supplied with a steady flow of new parts and the energy to assemble them, it can be maintained. “That regime of formation versus breakdown is the norm in biology, but it has been the exception in chemistry for most of its history,” says Otto.
The idea that systems can sometimes, somehow, maintain themselves out of equilibrium isn’t entirely new. In his 1944 book What is Life?, physicist Erwin Schrödinger pointed out that life maintains itself far from equilibrium by dissipating energy. Later, in 1977, physical chemist Ilya Prigogine won the Nobel prize in chemistry for his work on the thermodynamics that allows complex physical systems like hurricanes to self-organise. Pross’s insight was to : specifically, he turned to kinetic rate laws, which describe how quickly reactions occur. “[DKS] is a very useful framework because it’s a lot more concrete than Darwinian evolution,” says Otto.
Pross argues that kinetic rate laws are crucial to understanding why life persists. In one sense, this all boils down to probability: if there is a lot of something now, it is more likely to exist a moment from now. Bacteria are a good example of this logic. Individually they are rather easy to kill, but there are a lot of bacteria. If even one survives, it can make a million copies of itself by dividing just 20 times. For E. coli, that would take about 6 hours.
This exponential runaway is the “incredible kinetic power” of molecules that can copy themselves, says Pross. Unfettered, a self-replicating reaction is its own worst enemy: without anything to stop them, E. coli cells would quickly overrun the planet, consume everything and then die in equilibrium. But if the rate of birth is balanced by death, replicating populations can linger high on the energetic slope instead of sliding down it. Individual organisms die, but life as a whole is far older than most rocks on the surface of Earth.
In theory, what is true for E. coli should be true for self-replicating molecules, too. In chemical systems, self-replication balanced by destruction should produce a DKS state with the kinetic power to resist falling into equilibrium. And once the system is in such a state, Pross’s guiding principle of “survival of the stable” should favour replicators that maintain that stability. In fact, Pross has , in a process that looks a lot like what happens in evolution when multiple species compete for finite resources.
Dynamic kinetic stability could even explain why evolution seems to drive life towards ever-increasing diversity and complexity. Generally speaking, that’s because increasing DKS doesn’t have a final destination the same way that increasing thermodynamic stability does. If you climb out of a crater, you could end up anywhere along the rim, but going the other way always lands you at the bottom. “Make a system in this dynamic state, make it replicative, and I’m telling you, it’ll move in the direction of greater complexity,” says Pross.
But are any of these ideas testable? That is where Otto comes into the story. In 2010, he was studying questions around how proteins work. Along the way, he . These molecules can react with each other to form rings that stack themselves into tube-like structures. And these tubes then spur more of the original molecules to form into further tubes. It took many years for Otto and his team to perfect the art of working with and studying these molecular wonders. But as they did so, they realised these were the perfect tools for exploring principles that might transcend the specific biological components of life on Earth.
Chemical ecologies
Otto’s team began experimenting with balancing the kinetics of “birth” and “death” to keep the replicators far from equilibrium. Once Pross had coined DKS, Otto finally had a name – and a useful set of equations – for what they’d been working with.
Armed with the DKS framework, in 2021, Otto’s team validated one of Pross’s key predictions: that . To do it, they experimented with two different-sized replicators made of the same building blocks – a sort of primitive ecosystem with two “species” in competition for the same resource. These replicators were subject to chemical decay at different rates. The smaller replicator multiplied faster, but the bigger replicator better resisted chemical attack, so it stuck around for longer. Taken together, these birth and death processes struck a balance that favoured the bigger, more complex replicator. While it formed a stable population, the smaller replicator went extinct. In other words, survival of the stable drove the system out of equilibrium and towards complexity.
Otto’s experiment was the first time that anyone had used DKS to propel synthetic chemical replicators towards complexity. But there was more to come. In 2024, Otto’s team showed that similar systems can . This says that two species can’t occupy the same ecological niche. For instance, two species of finches living on the same island and eating the same food can’t co-exist, so these species must develop different feeding strategies if both are to survive. Similarly, in Otto’s chemical systems, trios of competing replicators that would usually drive each other extinct could co-exist if endowed with different preferences for chemical building blocks.
The results suggest a new answer to the question of how inanimate chemistry becomes biology. “You need some kind of evolutionary dynamics,” says , a physicist at Memorial Sloan Kettering Cancer Center in New York state who . In other words, evolution can begin in systems that we wouldn’t normally consider to be alive. This means that, as Pross says, life wasn’t evolution’s beginning but rather its product – a chemical system that had climbed up and away from equilibrium in a DKS state . Pross describes the kinetics that push towards complexity as a “driving force”.
However, while Pross argues that dynamic kinetic stability should drive increasing complexity over time, this argument is qualitative: no one has yet figured out how to measure the growth of complexity in DKS systems. There is also no widely accepted definition of complexity, and it is not clear that ever-increasing complexity really is a hallmark of life. After all, certain cave fish have lost their eyes and bacteria slim down their genomes when they can get away with it.
Origins of awareness
So where does that leave Pross’s ideas around DKS states? Well, thanks to Otto’s experiments, we can say for sure that non-living systems can evolve towards complexity. That has vindicated one of Pross’s key predictions. Beyond that, it remains unclear just how influential the idea will be. It is a new language for revealing the nature of life, but it remains unclear if it will lead to further insights.
There are already ideas that build on Pross’s work that may end up being more useful. Inspired in part by Pross, Wong and his colleagues devised an alternative framework based on the more rigorously defined rather than nebulous concept of “complexity”. They’ve proposed that in evolving systems functional information always increases over time, as they accumulate information about how to persist in their environments. For instance, a bird’s wing implicitly contains lots of information about aerodynamics and Earth’s atmosphere. And unlike complexity, functional information still goes up even when evolution simplifies organisms – if that simplification helps it persist in its environment.
For Pross, though, DKS states have a lot more to give. One of the key lessons he takes from the hypothesis is that life can never be considered in isolation. In fact, this has led him to a radical thought: he interprets the dependence of DKS systems on their environments as a kind of primitive awareness. “That dependence, to me, is the beginning of a mental dimension,” he says. “Once you’re aware of an outside, you start to become aware of yourself.”
Ascribing awareness to chemical systems is controversial, to say the least. , a neurogeneticist at Trinity College Dublin in Ireland who studies the evolution of agency, is sceptical that cognition should be reduced to chemistry this way. “It’s absolutely right to think of living organisms as this persisting pattern of dynamic chemical processes at one level,” he says. “But that doesn’t mean everything the organism does is usefully understood at that level.”
Pross still argues that mental processes must ultimately be understood as physical processes – so where better to start than dynamic kinetic stability? “Mind doesn’t just sort of float in the air. It has to emerge from a physical system,” he says. “The door to resolving that mystery has just opened.”
