When the first spark of life emerged on a young, ocean-covered Earth some four billion years ago, it didn’t happen at once. The process was slow and drawn out over eons, with lifeless chemicals slowly behaving more and more like living things, until they actually were living. One of the most confounding pieces of that puzzle has been how the building blocks of life—RNA and amino acids—first connected. Now, scientists believe they’ve recreated that primordial connection in the lab.
In a landmark study published in Nature on August 28, 2025, a team of chemists led by Professor Matthew Powner at University College London (UCL) has shown how amino acids, the molecular bricks of proteins, could have spontaneously linked to RNA under realistic early-Earth conditions. The feat provides a long-sought clue about the origins of life and may help bridge a fundamental mystery in biology.
“Life relies on the ability to synthesize proteins — they are life’s key functional molecules,” said Powner in a UCL press release. “Understanding the origin of protein synthesis is fundamental to understanding where life came from.”
Chicken-and-egg proteins
Life’s chemistry is full of paradoxes. Proteins are vital for nearly every task inside a cell, yet they’re made by ribosomes, elaborate molecular machines built from both proteins and RNA. The instructions for making proteins come from DNA and are delivered by RNA. But that raises a puzzling question: how could the first proteins have formed if they’re needed to build the very machinery that makes them?
For decades, scientists have argued over the competing “RNA world” and “metabolism first” hypotheses, trying to solve this chicken-and-egg problem. The former suggests that life began with self-replicating RNA, which only later recruited proteins. The latter proposes that primitive metabolic reactions, powered by high-energy molecules like thioesters, came first.
In Powner’s study, these two worlds meet. Using simple, biologically relevant thioesters (organic sulfur compounds also found in modern metabolism) his team demonstrated a spontaneous and selective reaction: amino acids binding to RNA in water, at neutral pH, with no enzymes required.
The team used thioesters derived from pantetheine, a sulfur-bearing compound and the active core of coenzyme A, which is present in every living cell today. This molecule helped link amino acids like arginine, glycine, and alanine to RNA strands, mimicking the very first steps of protein synthesis.
“Our study unites two prominent origin-of-life theories,” Powner explained, “the ‘RNA world’ and the ‘thioester world’.”
Chemistry Without Life
Of course, proving this is far from trivial.
It’s one thing to imagine ancient molecules combining in some forgotten pool and it’s another to make that chemistry happen in a modern lab with no enzymes, no living cells, and quite a bit of guesswork.
In the new study, researchers crafted aminoacyl-thiols, simple activated amino acids that prefer to react with RNA over anything else in the mix. They did this in plain water, under neutral pH—conditions thought to resemble the small, shallow ponds on early Earth.
“We have achieved the first part of that complex process, using very simple chemistry,” said Powner. “The chemistry is spontaneous, selective, and could have occurred on the early Earth.”
Remarkably, these special molecules, called aminoacyl-thiols, ignored other common chemicals around them—even ones they would normally react with. Instead of forming random chains, they focused on attaching to a specific spot on RNA. That spot happens to be the exact same place where proteins begin to form in cells today.
That level of selectivity had never been achieved in water before. Previous attempts used harsh chemicals that fell apart quickly or created unhelpful side reactions.
The First Protein Assembly Line
In biology today, ribosomes read strands of RNA and build proteins by linking amino acids one by one. This process begins with a molecule called transfer RNA (tRNA), which carries an amino acid at one end and matches a genetic code at the other. To prepare tRNA, cells use enzymes to attach amino acids precisely at the 2′,3′-diol position on the molecule—a step called “aminoacylation.”
But those enzymes didn’t exist in the early days of life.
“Understanding how nucleotide-controlled peptide biosynthesis could have first emerged is a notable gap in our understanding of life,” the authors wrote.
Their new results suggest a chemical alternative to enzymes. By carefully testing different amino acids and RNA sequences, the team showed that thioesters not only prefer RNA but also specifically target the correct location on the molecule. This means that, even in the chaotic soup of early Earth, nature may have found a way to start building the first proteins—without enzymes, ribosomes, or cells. The process didn’t need any extreme conditions, either.
The reactions demonstrated by Powner’s group didn’t require extreme heat, volcanic vents, or complex molecules. They happened in ordinary water. But the key was concentration—these reactions likely wouldn’t work in the vast ocean. Instead, the researchers propose they could have occurred in ponds or other enclosed settings where compounds could accumulate.
Interestingly, they found that freezing the reaction mixture enhanced the aminoacylation process. As the water formed ice, it excluded solutes into small liquid pockets called eutectic phases, increasing their local concentration. This suggests that cold environments, maybe even icy pools, may have been ideal cradles for life’s origin.
This matters in more than one way. Understanding these early steps informs everything from biotechnology to astrobiology. If life could begin this way on Earth, it might also begin elsewhere, like in the icy plumes of Enceladu sor in the subsurface oceans of Europa, for instance. But for now, Powner and his team are looking inward, into the early times of Earth, when chemistry first turned into biology.
“There are numerous problems to overcome before we can fully elucidate the origin of life,” said Powner. “But the most challenging and exciting remains the origins of protein synthesis.”
