Rosa Rubicondior: Refuting Creationism - Scientists Create An 'Evolution Engine' Based on The Theory of Evolution

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Scientists build an “evolution engine” to rapidly reprogram proteins | Scripps Research
In a groundbreaking stride for synthetic biology, researchers at Scripps Research have unveiled T7-ORACLE, a revolutionary platform that functions as an “evolution engine,” accelerating protein evolution thousands of times faster than in nature. Published in Science on 7 August 2025, this system enables continuous, hypermutated protein evolution inside E. coli, providing a transformative leap over traditional methods that require laborious, week-long cycles of DNA modification and testing (scripps.edu).

Unlike conventional directed evolution, which works in stop-start fashion, T7-ORACLE embeds an orthogonal T7 replisome — a virus-derived DNA replication machine—into bacteria. This replisome copies only a special plasmid carrying the gene to be evolved and does so at an error rate about 100,000 times higher than the host’s own DNA polymerase. With each bacterial division—roughly every 20 minutes—this system produces an enormous variety of mutant gene versions.

Selection is built into the process by linking the protein’s desired property to the bacterium’s survival or a measurable output. If the goal is to create an enzyme with a new function, the bacteria are grown under conditions where only those producing a beneficial version can thrive, allowing natural selection to occur at high speed. Alternatively, variants can be screened for specific traits—such as binding strength or fluorescence—and the best performers isolated. In both cases, the familiar Darwinian mechanism of mutation and selection drives the improvement, just as it does in nature.

Creationists often leap on examples like this to declare, “See! It took intelligence to make it work!” — missing the point entirely. The role of scientists here is like that of a farmer planting seeds: they set up the conditions, but they do not design each mutation or dictate which variants survive. Those outcomes arise from the same blind, automatic process of mutation and selection that occurs in nature. Building a racetrack does not create the laws of motion; it simply gives you a place to watch them in action.

Schematic of the T7-ORACLE system. The genome is maintained by the non-mutagenic host replisome (gray), while an orthogonal T7 replisome (red) maintains only a dedicated plasmid (OR) at 100,000-fold elevated mutation rate.

Credit: Scripps Research

Far from undermining the Theory of Evolution, this system is a direct application of it. The fact that scientists can harness and accelerate these natural processes does not mean evolution needs intelligence to operate in the wild—any more than a wind tunnel “proves” that air cannot flow without engineers. Human design here lies only in setting up conditions and choosing the desired outcome; the step-by-step emergence of improved proteins still follows the same blind, undirected rules that have shaped life for billions of years. The “evolution engine” is not replacing evolution with intelligent design—it is evolution, sped up and brought under observation.

The Genetic Algorithm. A genetic algorithm is a problem-solving method inspired by biological evolution. It’s especially useful for generating original designs where the solution space is too large or complex for straightforward calculation.

Initial population – Start with a set of random designs.
Evaluate fitness – Test how well each design performs against a goal.
Selection – Keep the best-performing designs.
Crossover – Combine features from two or more designs to create new ones.
Mutation – Introduce small random changes to explore new possibilities.
New generation – Replace the old population with the improved designs.
Repeat – Continue until the goal is reached or progress plateaus.

Like natural evolution, the process requires no foresight: improvement emerges from the repeated cycle of variation and selection. In engineering, genetic algorithms have been used to evolve novel antenna shapes, optimised circuit layouts, and even aerodynamic vehicle profiles—designs often surprising to human engineers.

Scientists build an “evolution engine” to rapidly reprogram proteins
A new platform developed at Scripps Research enables fast, scalable protein evolution—opening the door to new therapies and diagnostics, and to predicting resistance mutations across many disease areas.
In medicine and biotechnology, the ability to evolve proteins with new or improved functions is crucial, but current methods are often slow and laborious. Now, Scripps Research scientists have developed a synthetic biology platform that accelerates evolution itself—enabling researchers to evolve proteins with useful, new properties thousands of times faster than nature. The system, named T7-ORACLE, was described in Science on August 7, 2025, and represents a breakthrough in how researchers can engineer therapeutic proteins for cancer, neurodegeneration and essentially any other disease area.

This is like giving evolution a fast-forward button. You can now evolve proteins continuously and precisely inside cells without damaging the cell’s genome or requiring labor-intensive steps.

Pete R. Schultz, co-author
President and CEO of Scripps Research
Department of Chemistry and Skaggs Institute for Chemical Biology
The Scripps Research Institute, La Jolla, CA, USA.

Directed evolution is a laboratory process that involves introducing mutations and selecting variants with improved function over multiple cycles. It’s used to tailor proteins with desired properties, such as highly selective, high-affinity antibodies, enzymes with new specificities or catalytic properties, or to investigate the emergence of resistance mutations in drug targets. However, traditional methods often require repeated rounds of DNA manipulation and testing with each round taking a week or more. Systems for continuous evolution—where proteins evolve inside living cells without manual intervention—aim to streamline this process by enabling simultaneous mutation and selection with each round of cell division (roughly 20 minutes for bacteria). But existing approaches have been limited by technical complexity or modest mutation rates.

T7-ORACLE circumvents these bottlenecks by engineering E. coli bacteria—a standard model organism in molecular biology—to host a second, artificial DNA replication system derived from bacteriophage T7, a virus that infects bacteria and has been widely studied for its simple, efficient replication system. T7-ORACLE enables continuous hypermutation and accelerated evolution of biomacromolecules, and is designed to be broadly applicable to many protein targets and biological challenges. Conceptually, T7-ORACLE builds on and extends efforts on existing orthogonal replication systems—meaning they operate separately from the cell’s own machinery—such as OrthoRep in Saccharomyces cerevisiae (baker’s yeast) and EcORep in E. coli. In comparison to these systems, T7-ORACLE benefits from the combination of high mutagenesis, fast growth, high transformation efficiency, and the ease with which both the E. coli host and the circular replicon plasmid can be integrated into standard molecular biology workflows.

The T-7 ORACLE orthogonal system targets only plasmid DNA (small, circular pieces of genetic material), leaving the cell’s host genome untouched. By engineering T7 DNA polymerase (a viral enzyme that replicates DNA) to be error-prone, the researchers introduced mutations into target genes at a rate 100,000 times higher than normal without damaging the host cells.

This system represents a major advance in continuous evolution. Instead of one round of evolution per week, you get a round each time the cell divides—so it really accelerates the process.

Assistant Professor Christian Diercks, co-senior author
Department of Chemistry and Skaggs Institute for Chemical Biology
The Scripps Research Institute, La Jolla, CA, USA.

To demonstrate the power of T7-ORACLE, the research team inserted a common antibiotic resistance gene, TEM-1 β-lactamase, into the system and exposed the E. coli cells to escalating doses of various antibiotics. In less than a week, the system evolved versions of the enzyme that could resist antibiotic levels up to 5,000 times higher than the original. This proof-of-concept demonstrated not only T7-ORACLE’s speed and precision, but also its real-world relevance by replicating how resistance develops in response to antibiotics.

The surprising part was how closely the mutations we saw matched real-world resistance mutations found in clinical settings. In some cases, we saw new combinations that worked even better than those you would see in a clinic, [but] this isn’t a paper about TEM-1 β-lactamase. That gene was just a well-characterized benchmark to show how the system works. What matters is that we can now evolve virtually any protein, like cancer drug targets and therapeutic enzymes, in days instead of months.

Assistant Professor Christian Diercks.

The broader potential of T7-ORACLE lies in its adaptability as a platform for protein engineering. Although the system is built into E. coli, the bacterium serves primarily as a vessel for continuous evolution. Scientists can insert genes from humans, viruses or other sources into plasmids, which are then introduced into E. coli cells. T7-ORACLE mutates these genes, generating variant proteins that can be screened or selected for improved function. Because E. coli is easy to grow and widely used in labs, it provides a convenient, scalable system for evolving virtually any protein of interest.

This could help scientists more rapidly evolve antibodies to target specific cancers, evolve more effective therapeutic enzymes, and design proteases that target proteins involved in cancer and neurodegenerative disease.

What’s exciting is that it’s not limited to one disease or one kind of protein. Because the system is customizable, you can drop in any gene and evolve it toward whatever function you need.

Assistant Professor Christian Diercks.

Moreover, T7-ORACLE works with standard E. coli cultures and widely used lab workflows, avoiding the complex protocols required by other continuous evolution systems.
The main thing that sets this apart is how easy it is to implement,” adds Diercks. “There’s no specialized equipment or expertise required. If you already work with E. coli, you can probably use this system with minimal adjustments.

Assistant Professor Christian Diercks.

T7-ORACLE reflects Schultz’s broader goal: to rebuild key biological processes—such as DNA replication, RNA transcription and protein translation—so they function independently of the host cell. This separation allows scientists to reprogram these processes without disrupting normal cellular activity. By decoupling fundamental processes from the genome, tools like T7-ORACLE help advance synthetic biology.

In the future, we’re interested in using this system to evolve polymerases that can replicate entirely unnatural nucleic acids: synthetic molecules that resemble DNA and RNA but with novel chemical properties. That would open up possibilities in synthetic genomics that we’re just beginning to explore.

Assistant Professor Christian Diercks.

Currently, the research team is focused on evolving human-derived enzymes for therapeutic use, and on tailoring proteases to recognize specific cancer-related protein sequences.
The T7-ORACLE approach merges the best of both worlds. We can now combine rational protein design with continuous evolution to discover functional molecules more efficiently than ever.

Pete R. Schultz.

In addition to Diercks and Schultz, authors of the study, “An orthogonal T7 replisome for continuous hypermutation and accelerated evolution in E. coli,” are Philipp Sondermann, Cynthia Rong, Thomas G. Gillis, Yahui Ban, Celine Wang and David A. Dik of Scripps Research.

Publication:
Christian S. Diercks et al.
An orthogonal T7 replisome for continuous hypermutation and accelerated evolution in E. coli. Science 389, 618-622 (2025). DOI:10.1126/science.adp9583

Abstract
Systems that perform continuous hypermutation of designated genes without compromising the integrity of the host genome can substantially accelerate the evolution of new or enhanced protein functions. We describe an orthogonal DNA replication system in Escherichia coli based on the controlled expression of the replisome of bacteriophage T7 (T7-ORACLE). The system replicates circular plasmids that enable high transformation efficiencies and seamless integration into standard molecular biology workflows. Engineering of T7 DNA polymerase yielded variant proteins with mutation rates of 1.7 × 10−5 substitutions per base in vivo—100,000-fold above the genomic mutation rate. We demonstrated continuous evolution using the T7 replisome by expanding the substrate scope of TEM-1 β-lactamase and increasing activity 5000-fold against clinically relevant monobactam and cephalosporin antibiotics in less than 1 week.

Christian S. Diercks et al.
An orthogonal T7 replisome for continuous hypermutation and accelerated evolution in E. coli. Science 389, 618-622 (2025). DOI:10.1126/science.adp9583

© 2025 American Association for the Advancement of Science.
Reprinted under the terms of s60 of the Copyright, Designs and Patents Act 1988.

For creationists, the Scripps “evolution engine” presents an uncomfortable reality. It doesn’t just confirm that the mechanisms of evolution—mutation, selection, and adaptation—work exactly as biologists have always described; it demonstrates them happening at breakneck speed in a controlled environment. In other words, it strips away the “too slow to see” excuse and makes evolutionary change observable within hours or days. That is not good news for any ideology that insists such change is impossible.

The inevitable creationist counter-claim will be that because scientists designed the system, it somehow proves “Intelligent Design.” But that argument is as flawed as claiming that building a weather station proves that storms are designed. Scientists here have not replaced evolution with intelligence; they have set up the conditions in which evolution’s natural processes—random mutation and non-random selection—can be watched and measured. The “design” is in the apparatus, not in the outcomes, which emerge unpredictably and without guidance, just as they do in nature.

This is, in fact, the opposite of a vindication for Intelligent Design. T7-ORACLE works precisely because it harnesses the principles of Darwinian evolution, not because it bypasses them. If Intelligent Design’s premise were correct—that complex new functions require foresight and purposeful engineering—then the system would simply generate noise without producing any useful results. Instead, it reliably evolves novel proteins with improved functions, in direct confirmation of evolutionary theory.

Creationists can close their eyes, but the evidence now runs not only through the fossil record and comparative genetics, but also in petri dishes—proof, in real time, that evolution works exactly as science predicts. The only thing evolving faster than these proteins is the creativity of creationists in finding new ways not to look at the evidence.

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