The day creationists dread — the final closure of their favourite god-shaped abiogenesis gap — moved a little closer last May, when scientists at University College London (UCL) announced that they had shown how the first RNA could have reproduced. In a selective environment with competition for resources, this would have led inevitably to ever-increasing efficiency in replication, kick-starting the whole evolutionary process and the emergence of self-organising systems (or “life”) from prebiotic precursors (or “non-life”). This is, of course, the very process that creationists insist is “impossible”, clinging to the idea that “life” is some magical essence that must be granted by a supernatural deity.
When this God-shaped gap is finally and conclusively closed — as all the others have been — creationists will need to scramble once again to reframe their beliefs and cling to whatever shrinking space remains for their god. Just as their old claim that evolution was “impossible” collapsed, to be replaced with notions of a short burst of warp-speed evolution “within kinds” after “The Flood” (and supposedly still happening today, but conveniently “guided” by God), so too will abiogenesis inevitably be rebranded as yet another process directed by divine intention — naturally, with the eventual production of (American) humans as the goal.
Progress Towards Explaining Abiogenesis. For decades, scientists have been piecing together how life could have emerged from non-life, gradually dismantling the notion that it required magic or divine intervention. Key milestones include:The announcement was published in the journal Nature Chemistry and covered in a UCL News release.
- Miller–Urey Experiment (1953): Showed that simple organic molecules such as amino acids could form spontaneously under early Earth-like conditions.
- Nucleotides and Bases (1960s–2000s): Researchers demonstrated plausible pathways for producing the building blocks of RNA and DNA from prebiotic chemistry.
- RNA World Hypothesis: Proposed that RNA, which can both store information and catalyse reactions, may have been the first self-replicating system.
- Protocells (2000s–2010s): Fatty acids and lipids shown to form simple membranes spontaneously, creating compartments where chemistry could become self-sustaining.
- Metabolism First Approaches: Evidence that cycles of chemical reactions could self-organise on mineral surfaces, providing energy and complexity before full replication.
- Recent Advances (2020s): Increasingly realistic demonstrations of RNA strands forming, copying, and evolving in laboratory conditions—such as this 2025 UCL breakthrough showing RNA reproduction.
Together, these advances outline a plausible, stepwise process by which chemistry became biology. No single “eureka moment” is required—just the gradual accumulation of evidence that natural processes can bridge the gap from prebiotic chemistry to the first living systems.
Chemists recreate how RNA might have reproduced for first time
Chemists at UCL and the MRC Laboratory of Molecular Biology have demonstrated how RNA (ribonucleic acid) might have replicated itself on early Earth – a key process in the origin of life.
Scientists believe that, in the earliest life forms, genetic material would have been carried and replicated by strands of RNA, before DNA and proteins later emerged and took over.
Yet getting strands of RNA to replicate in the lab in a simple way – i.e., that plausibly could have occurred at the outset of life – has proved challenging. RNA strands zip up into a double helix that blocks their replication. Like velcro, these are hard to pull apart and quick to stick back together, leaving no time to copy them.
In a study described in Nature Chemistry, researchers overcame this problem by using three-letter “triplet” RNA building blocks in water and adding acid and heat, which separated the double helix. They then neutralised and froze the solution. In liquid gaps between the ice crystals, they saw that the triplet building blocks coated the RNA strands and stopped them from zipping back together – allowing replication to happen.
By thawing and beginning the cycle again, repeated changes in pH and temperature – which could plausibly occur in nature – allowed the RNA to replicate over and over again, with strands of RNA long enough to have a biological function and play a role in the origin of life.
Lead author Dr James Attwater (UCL Chemistry and the MRC Laboratory of Molecular Biology) said:Replication is fundamental to biology. In one sense, it is why we are here. But there’s no trace in biology of the first replicator. Even the single-celled organism that is the ancestor of all known life, the Last Universal Common Ancestor (LUCA), is a pretty complex entity, and behind it lies a lot of evolutionary history that is hidden from us.
Our best guess is that early life was run by RNA molecules. But a big problem for this hypothesis is that we haven’t been able to get a molecule of RNA to replicate itself in a way that could have occurred before life began several billion years ago. We can’t rely on a complex enzyme to do this, as happens in biology today. It needs to be a much simpler solution. The changing conditions we engineered can occur naturally, for instance with night and day cycles of temperature, or in geothermal environments where hot rocks meet a cold atmosphere.
The triplet or three-letter building blocks of RNA we used, called trinucleotides, do not occur in biology today, but they allow for much easier replication. The earliest forms of life are likely to have been quite different from any life that we know about. The models of biological species we are trying to build need to be simple enough to have emerged from the chemistry of early Earth.
Dr James Atwater, first author.
MRC Laboratory of Molecular Biology
Cambridge Biomedical Campus, Cambridge, UK. And UCL Department of Chemistry, London, UK.
While the paper focuses solely on the chemistry, the research team said the conditions they created could plausibly mimic those in freshwater ponds or lakes, especially in geothermal environments where heat from inside the Earth has reached the surface.
However, this replication of RNA could not occur in freezing and thawing saltwater, as the presence of salt interferes with the freezing process and prevents RNA building blocks from reaching the concentration required to replicate RNA strands.
While a high concentration of RNA can also occur through evaporation, for instance a puddle evaporating in hot temperatures, RNA molecules are unstable at higher temperatures and more likely to break down, the researchers said.
Life is separated from pure chemistry by information, a molecular memory encoded in the genetic material that is transmitted from one generation to the next. For this process to occur, the information must be copied, i.e. replicated, to be passed on.
Dr Philipp Holliger, lead author
MRC Laboratory of Molecular Biology
Cambridge Biomedical Campus, Cambridge, UK.
The origin of life does not likely lie with RNA alone, but is thought to have emerged out of a combination of RNA, peptides (short chains of amino acids that are the building blocks of proteins), enzymes, and barrier-forming lipids that can protect these ingredients from their environment.
Several researchers at UCL are uncovering clues about how life began. In recent years, a team led by Professor Matthew Powner (UCL Chemistry) has demonstrated how chemistry could create several of the key molecules of life’s origin, including nucleotides (the building blocks of RNA and DNA) and amino acids and peptides (the building blocks of proteins), from simple molecular building blocks likely abundant on the early Earth.
Publication:
AbstractFor creationists who understand the science well enough, each step towards explaining abiogenesis represents another retreat for their god. They have long claimed that life cannot arise from non-life, insisting that it requires a miraculous spark bestowed by a deity. Yet every advance in prebiotic chemistry shows how natural processes could bridge that supposed impossibility.
RNA replication is considered a key process in the origins of life. However, both enzymatic and non-enzymatic RNA replication cycles are impeded by the ‘strand separation problem’, a form of product inhibition arising from the extraordinary stability of RNA duplexes and their rapid reannealing kinetics. Here we show that RNA trinucleotide triphosphates can overcome this problem by binding to and kinetically trapping dissociated RNA strands in a single-stranded form, while simultaneously serving as substrates for replication by an RNA polymerase ribozyme. When combined with coupled pH and freeze–thaw cycles, this enabled exponential replication of both (+) and (−) strands of double-stranded RNAs, including a fragment of the ribozyme itself. Subjecting random RNA sequence pools to open-ended replication yielded either defined replicating RNA sequences or the gradual emergence of diverse sequence pools. The latter derived from partial ribozyme self-replication alongside generation of new RNA sequences, and their composition drifted towards hypothesized primordial codons. These results unlock broader opportunities to model primordial RNA replication.
Main
Life on Earth relies on the faithful copying of its genetic material—replication—to enable heredity and evolution. This process is thought to have begun with the templated polymerization of activated mono- or oligonucleotide building blocks by chemical replication processes1,2,3 and later by RNA-catalysed RNA replication4,5,6,7. In its simplest form, RNA replication comprises the copying of (+) and (−) strands into complementary (−) and (+) daughter strands. For replication to proceed further, the double-stranded RNA replication products (duplexes) must again be dissociated into single-stranded RNAs, and these must be copied before they reanneal (Fig. 1a).
Fig. 1: Triplet substrates alleviate strand reannealing during RNA replication.
a, The strand separation problem: the high energetic barrier of strand separation and speed of strand reannealing jointly inhibit RNA replication cycles. b, RNA strand copying by polymerization of trinucleotide triphosphates (triplets) upon a RNA template, catalysed by a TPR (a polymerase ribozyme using trinucleotide triphosphates as substrates, structure from ref. 21). Below, substrates for synthesis of the AD RNA duplex. Individual strands (A+ and A-) are shown hybridized to their complementary primers and triplets. c, TPR-catalysed RNA polymerization using 0.1 µM AD duplex or individual strands (A+, A-) as templates, showing product A- (top, fluorescein channel) and A+ (bottom, Cy5 channel). ‘AD acidified’ was pre-incubated in 2.5 mM HCl, and neutralized before reactions were frozen to initiate RNA polymerization (−7 °C for 48 h). Observed percentages of primer extended by >1 triplet, or reaching full length, are given after subtraction of levels in no-template controls (/). d, Effect of delaying ribozyme and triplet/primer addition after neutralization of the acidified AD template upon the percent of primers extended. Curve fitting indicates that AD reanneals with a t1/2 of 0.7 µM−1 min−1 (black circles, n = 3). Addition of triplets immediately upon AD neutralization (red squares, n = 3) essentially abolishes strand reannealing. ND, not detected. e, Revised scheme of an RNA replication cycle driven by triplet substrate inhibition of strand reannealing.
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However, RNA duplexes of functional lengths and concentrations (for example >25 nucleotides (nt), 100 nM) behave as essentially inert, ‘dead-end’ products due to their remarkable stability (with melting temperatures approaching the boiling point of water)8. Furthermore, even when dissociated into individual, single-stranded RNAs, such strands reanneal on timescales (seconds to minutes) that are shorter than the typical time needed for copying reactions (hours to days) either by non-enzymatic processes or by polymerase ribozymes1. Thus, RNA replication cycles under standard conditions are both kinetically and thermodynamically disfavoured (Fig. 1a).
This so-called ‘strand separation problem’1 is aggravated by the comparative chemical instability of RNA. This precludes duplex dissociation under harsh conditions. High temperatures degrade RNA templates and ribozyme catalysts, particularly in the presence of divalent cations such as Mg2+(which boost ribozyme activity but accelerate RNA fragmentation by transesterification)9. Furthermore, the strand separation problem worsens with increasing lengths of RNA duplexes, which become progressively harder to dissociate, more vulnerable to degradation and more prone to reannealing.
A range of different approaches have been tried to overcome this fundamental barrier to open-ended RNA replication. Acidic pH can protonate the N1 of adenine and N3 of cytosine, disrupting base-pairing and destabilizing RNA duplexes10. Coupled with wet/dry cycles or ionic gradients in a thermophoretic setting, this has been shown to promote duplex melting and RNA assembly, and enable nucleic acid amplification by proteinaceous enzymes11,12,13,14. Furthermore, highly viscous solvents can slow RNA reannealing sufficiently for long (32 nt) substrates to be ligated15,16. Alternatively, strand-displacement syntheses can circumvent full duplex dissociation by the progressive addition of ‘invader’ oligonucleotides complementary to the non-templating strand17, or by the buildup of conformational strain on circular RNA templates18. Nevertheless, the scope of RNA-catalysed RNA replication cycles has been limited to polymerization of mononucleotides on primers flanking a 4-nt region assisted by denaturants19, or the templated ligation of up to three polynucleotide substrate segments14,20. However, general RNA replication and open-ended evolution requires the replication of longer sequences (able to encode a phenotype) via the polymerization of building blocks short enough to allow free sequence variation.
In this Article we describe an approach that unlocks both the replication of longer RNA sequences and enables free sequence variation in replicating RNA pools. Our approach leverages an unexpected capacity of trinucleotide triphosphate (triplet) substrates to stabilize dissociated RNA strands. This can be coupled to cycles of pH, temperature and concentration to drive open-ended RNA replication by a polymerase ribozyme that utilises triplet substrates.
Fig. 2: Freeze–thaw/pH cycling allows iterative cycles of RNA replication.a, Schematic of conflicting conditions required for RNA strand separation (left) and triplet polymerization (right). b, Physicochemical cycling workflow that integrates strand separation and polymerization conditions. pH switching results in a build-up of KCl, and serial dilution allows continued cycling by resetting KCl concentrations and restoring ribozyme and triplet substrate levels. c, Iterative replication of the model RNA duplex AD and its constituent strands in replication buffer (4 nM template, substrates and primers from Fig. 1b). Also shown (for comparison) are a single-cycle eight-day polymerization reaction (1 × 8 days), and four-cycle reactions undergoing twofold dilution (4 ÷ 2) followed by an extra cycle (5). Full-length primer extension yields are expressed as percentages relative to the starting template. To compare efficiencies in the diluted 4 ÷ 2 and five cycle reactions, their yields should be doubled (×2).
Source data
Fig. 3: Open-ended exponential amplification of RNA.a, Design of replication substrates and scheme for iterative replication of an N17 RNA random-sequence library. To start, library template LibN17 was mixed at 8 nM in replication buffer (including 0.9 mM KCl and 20 nM TPR) together with 20 nM each of the indicated primers (FITCrep, Cy5rep, pppGUAGC, pppGGACC) and 12 nM each of all 64 triplets (pppNNN). b, FITCrep extension products from this reaction analysed at each five-cycle interval before threefold serial dilution. c, Quantification of overall amplification of ‘(3)n + 5’-register products in b, calculated as the fold increase in band intensity versus five cycles, multiplied by reaction dilution versus five cycles. Exponential fits yielded the per-cycle amplification efficiencies described in the text. d, Reactions set-up as in a, but seeded with 0.8 nM of both strands of one emergent RNA duplex sequence from a–c (Rep(1–4)+ with Rep(1–4)−, detected in the sequencing of each product population of the final reactions in b) as a template, using their constituent triplets as substrates (middle lane: triplets from all four sequences but no template). e, Cycling as in a of 0.8 nM of both strands of one clone (shown here beneath its substrates) without dilution. Average strand copy numbers (filled orange circles, FITC strand; open blue circles, Cy5 strand; comprising full-length and starting template) are shown for three independent reactions per cycle (transparent circles). Dotted lines are exponential curves fitted up to four cycles (x): FITC strand = e0.38x, R2 = 0.997; Cy5 strand = e0.20x, R2 = 0.984.
Source data
Fig. 4: Ribozyme-catalysed replication of a fragment of itself.a, 3D structural model21 (left) of the TPR catalytic subunit with the γ+ segment highlighted in red. Right, sequences of the γD duplex and its constituent strands γ+ and γ-, shown with primer and triplet substrates. b, γ+ and γ- synthesis during replication of single strands and duplex. The triplets (0.2 µM each) and primers (0.1 µM each) shown in a were polymerized by the TPR (20 nM) on the indicated templates (2 nM each) in replication buffer across one or two denaturing acid cycles (polymerization: 24 h at −7 °C). Per-template yields of primer reaching full length are shown; two cycles yielded more product than a single cycle with equivalent total incubation time in ice (1 × 2 days). c, Iterative replication cycling of reactions (set-up as in b, with 0.6 mM starting KCl) with no template or 4 nM γD duplex (concentrated to ~1.8 µM in the eutectic phase). The eutectic phase concentrations of products reaching full-length were inferred from gel densitometry. Averages are shown of three independent reactions (transparent data points) set up for each cycle number. γ+ from γD template, filled red circles; γ- from γD template, open blue circles; γ+ or γ- products from no γD template, red/blue dashed crosses.
Source data
Fig. 5: Emergence and amplification of RNA pools during primer-free triplet-based replication cycling.a, All 64 RNA triplets (pppNNN, 0.1 µM each) ± 20 nM N20 random-sequence RNA template seed were subjected to iterative cycles of replication and dilution in replication buffer (with 20 nM TPR and 1.8 mM KCl, but no primers). b, RNAs present at different replication cycles (up to 73) were visualized with an intercalating dye. Both the intensity and length of the RNA products increased during cycling, despite serial dilution. c, Estimated conversion of the total triplet substrate pool into the RNA products. The amount of triplets needed to constitute calculated RNA product yields was expressed as a percentage of the replenished triplet substrates (Extended Data Fig. 10). d, In silico ‘translation’ using a reduced codon set applied to the sequenced, unseeded 73-cycle synthesis products (red), compared to a simulated pool of random sequences with matching lengths but unbiased codon composition (grey). For each sequence, the longest stretch of family box codons is counted to show the maximum potential length of any encoded peptide using only a primordial genetic code. e, A population of sequenced products from the unseeded 73-cycle reaction (left) shows high ribozyme sequence complementarity, absent in a simulated pool of randomized RNAs of identical composition (right). Data are coloured by the classification in f (Extended Data Fig. 9 shows the criteria used); sequences with homology to the ribozyme (+) strand are plotted separately (Supplementary Fig. 8). f, Changes in proportions of sequence classes in 9–27-nt products from unseeded reactions during amplification. g, As cycling progresses, the G–C base composition of sequences classed as having no ribozyme homology increases (data from N20-seeded reactions shown). h, Mapping of ribozyme-homologous parts of 9–27-nt products from unseeded amplification reactions to the (+) and (−) strands of the TPR subunits 5TU and t1. Peak heights reflect the fraction of products homologous to that site, scaled by the product intensity in the corresponding gel lane in b. Products with homology to multiple locations on one or both strands were randomly assigned to one. Note the prior emergence and buildup of (−)-strand TPR homology products, followed by (+)-strand products (templated from (−)-strand products).
Source data
What makes this particularly awkward is that their argument relies on the “god of the gaps”: wherever science has not yet explained something, they insert divine intervention. But the gaps only ever shrink, never grow. As experiments like UCL’s RNA reproduction study accumulate, the mystery of life’s origins looks less like a miracle and more like chemistry in action.
In effect, science is showing that no supernatural explanation is required—just the right molecules, conditions, and time. For creationists, that means one less refuge for their dwindling, gap-dwelling deity.
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