Her team reported, in a series of recent studies, that a reduced alphabet of just 10 amino acids could support the kinds of protein structures that were likely found early in life’s development, the most robust protein folds that modern life uses. She is now working on repeating these experiments with totally different amino acids.
Using biology as a guide, and chemical possibilities as a parts list, Hlouchová is probing what life may have looked like before LUCA.
Synthetic biology “opens up a whole new world where we just don’t have to rely on life that we see today,” Hlouchová said. “Did life have to happen this way, or could it have happened in different ways?” Answering the question could mean traveling ever farther away from what we might recognize as biology.
The Processes
From the start, modern life has inspired the study of life’s origins. Miller considered his experiment’s production of amino acids, a core feature of modern life, to be irrefutable evidence that life could be produced from early Earth chemistry. And more recent researchers use today’s most widespread biomolecules and processes as proxies for features early life must have had. But researchers hold varying opinions on whether, and how much, we should allow modern life to constrain our imaginations.
“It would be foolish to ignore life as a guide,” Krishnamurthy said, “but it would be even more foolish to use life as the only guide.”
Instead of focusing on the exact materials of life, some are trying to re-create its essence. The field has “been too focused on what molecules current life works with,” said Sijbren Otto, a systems chemist at the University of Groningen. It has “not looked enough at what life does.”
Life is made up of not only molecules but functions. It can replicate, it can metabolize, and it can evolve. These functions don’t necessarily need to be performed by the same molecules that life uses today.
For example, could another molecular system do what DNA does? “If you generalize the definition of a gene, you say, ‘OK, it’s a molecule that stores information,’” Otto said. A replication process generates copies of that information. While Hlouchová is looking at whether you can get to the same structure with different molecules, Otto is looking at whether you can get to the same function. In the early 2010s, he started testing whether nucleotides, the building blocks of DNA, are the only molecules that can store and pass on information.
Benzene rings are stable structures made of interlocking rings of carbon and hydrogen that are found in many biological molecules, including several amino acids. By chance, in 2010, Otto discovered that certain types of synthetically made benzene rings of the same size tended to stack neatly, like poker chips. When shaken or stirred, the growing stacks broke, which triggered the molecular edges to grow more benzene rings. This was a kind of self-replication.
The stacks of benzene rings were also, in essence, propagating information: the size of the rings. The new stacks, which Otto found could just keep growing, always contained rings of the same size. “From that moment on, we realized we stand a chance of doing evolution with these types of systems,” he said.
These chemical structures held the possibility of information storage and replication. The next step would be to induce metabolism, or to get the structures to facilitate other chemical reactions. They would also need a container to hold themselves together. Putting it all together was a dream, but one that’s gotten closer than ever in recent years.
It took Otto’s lab another 10 years to figure out how to get their self-replicating molecules to catalyze reactions other than their own replication, such as those that helped them make their own precursors. Then, in still unpublished work, they altered some of the molecules in a way that compelled the rings to form compartments that grew and divided. “It’s replicating, it’s metabolizing, it’s keeping itself together in a compartment,” Otto said. Eventually the “benzene cells” grew big enough to be seen under a microscope, he said.
But does that make them alive? The only thing they’re really missing, from a functional perspective, is the ability to evolve, Otto said. That’s where his lab is headed next. “We’re trying to make something that starts to approach life,” he said. “But it will be on a life support machine for some time to come.”
His benzene “cells” are a far cry from life as we know it. But if you can figure out conceptually how evolution could arise, Otto argued, you can reenact that mechanism, under the simulated conditions of the early Earth and with your favorite prebiotic molecules. “I think, then, you’re closer to the origin,” Otto said.
These scientists and others are probing the most fundamental aspects of life unhindered by the evolutionary journey that led from LUCA to today. They’re going beyond what genomics can tell us even about the pre-LUCA era to imaginatively reconstruct how the mechanisms and functions of life could have emerged. Despite their different tools, materials, and approaches, the common thread across the field is preserving the requirements and possibilities of evolution. Because no matter what molecules it’s built of, what makes life alive is the fact that it can adapt to a changing environment and invent new ways to survive across deep time. Its engine of change and adaptation is evolution — and re-creating it is the shared dream of chemists and biologists alike.
The Continuum
In summer 2026, a cell made headlines. Synthetic biologists had packed fatty sacs called liposomes with biological components: a DNA replication system and a set of 36 enzymes that read DNA and make proteins. They filled other liposomes with sugar, lipids, enzymes, nucleotides, and ribosomes — supply caches to send in as needed. Then they waited to see if their chemistry experiment would take on a life of its own.
After months of fussing around with a population of these proto-cells in the lab, the team started to see something: lifelike behaviors. The cells replicated their DNA, grew, and divided. And larger ones produced more daughter cells, resulting in a crude kind of natural selection. The researchers posted their results on the preprint server biorxiv.org in July. It was touted as a “stunning” step and a “breakthrough” for the field.
This synthetic cell is not a reflection of the origin of life; it had a 4-billion-year head start. It was built from biomolecular parts that are highly evolved and “disgustingly modern,” said Kate Adamala, the synthetic biologist at the University of Minnesota who led the project. But it’s the first plausible demonstration of the field’s most fundamental idea: that it is possible to take a bunch of “undeniably dead” components, she said, put them together, and create something that “starts undergoing all of those functions of life.”
Even though the cells can grow, divide, and replicate their genome, Adamala is steering clear of the word “alive.” The cell can’t feed and sustain itself; it needs constant delivery of food and ribosomes, the machinery that it needs to make proteins. But more importantly, Adamala said, it is missing true evolution.
To produce their crude version of natural selection, Adamala’s team engineered mutations into their synthetic cells that led to different growth rates. “It’s a poor man’s evolution,” she said. In true natural selection, cells would mutate, and the population would naturally gain genetic diversity. Her team had effectively built evolution in.
But still, the chemistry came together into something like biology. And it did not require some magic spark or special ingredient. The researchers had to figure out the molecular system — the relationships between known components — and then tweak them until the system worked better, and then better, and then better. Life is not an on-off-switch; it is more like a continuum. A chemical system becomes increasingly alive over time. And if you try to trace it back to a point at which it fully becomes alive, that point will likely be “arbitrary,” Otto said. This is true in the lab, and it must have been true 4 billion years ago.
