Aurelia Butler

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,” says co-senior author Pete Schultz, the President and CEO of Scripps Research, where he also holds the L.S. “Sam” Skaggs Presidential Chair. “You can now evolve proteins continuously and precisely inside cells without damaging the cell’s genome or requiring labor-intensive steps.”
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,” says co-senior author Christian Diercks, an assistant professor of chemistry at Scripps Research. “Instead of one round of evolution per week, you get a round each time the cell divides — so it really accelerates the process.”
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,” notes Diercks. “In some cases, we saw new combinations that worked even better than those you would see in a clinic.”
But Diercks emphasizes that the study isn’t focused on antibiotic resistance per se.
“This isn’t a paper about TEM-1 β-lactamase,” he explains. “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.”
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,” says Diercks. “Because the system is customizable, you can drop in any gene and evolve it toward whatever function you need.”
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.”
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,” says Diercks. “That would open up possibilities in synthetic genomics that we’re just beginning to explore.”
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,” says Schultz. “We can now combine rational protein design with continuous evolution to discover functional molecules more efficiently than ever.”
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.
This work was supported by funding from the National Institutes of Health (grant RGM145323A). More

Immersing in virtual reality (VR) nature scenes helped relieve symptoms that are often seen in people living with long-term pain, with those who felt more present experiencing the strongest effects.
A new study led by the University of Exeter, published in the journal Pain, tested the impact of immersive 360-degree nature films delivered using VR compared with 2D video images in reducing experience of pain, finding VR almost twice as effective.
Long-term (chronic) pain typically lasts more than three months and is particularly difficult to treat. The researchers simulated this type of pain in healthy participants, finding that nature VR had an effect similar to that of painkillers, which endured for at least five minutes after the VR experience had ended.
Dr Sam Hughes, Senior Lecturer in Pain Neuroscience at the University of Exeter, led the study. He said: “We’ve seen a growing body of evidence show that exposure to nature can help reduce short term, everyday pain, but there has been less research into how this might work for people living with chronic or longer-term pain. Also, not everyone is able to get out for walks in nature, particularly those living with long term health conditions like chronic pain. Our study is the first to look at the effect of prolonged exposure to a virtual reality nature scene on symptoms seen during long term pain sensitivity. Our results suggest that immersive nature experiences can reduce the development of this pain sensitivity through an enhanced sense of presence and through harnessing the brains in-built pain suppression systems”
The study, which was funded by the Academy of Medical Sciences, involved 29 healthy participants who were shown two types of nature scene after having pain delivered on the forearm using electric shocks. On the first visit, they measured the changes in pain that occur over a 50-minute period following the electric shocks and showed how the healthy participants developed sensitivity to sharp pricking stimuli in the absence of any nature scenes. The results showed that the participants developed a type of sensitivity that closely resembles that seen in people living with nerve pain — which occurs due to changes in how pain signals are processed in the brain and spinal cord.
On the second visit, they immersed the same participants in a 45-minute virtual reality 360-degree experience of the waterfalls of Oregon to see how this could change how the development of pain sensitivity. The scene was specially chosen to maximize therapeutic effects.
In the second visit, they explored the same scene, but on a 2D screen.

They completed questionnaires on their experience of pain after watching the scenes in each case, and also on how present they felt in each experience, and to what extent they felt the nature scenes to be restorative[LV1] .
On a separate visit, participants underwent MRI brain scans at the University of Exeter’s Mireille Gillings Neuroimaging Centre. Researchers administered a cold gel to illicit a type of ongoing pain and then scanned participants to study how their brains respond.
The researchers found that the immersive VR experience significantly reduced the development and spread of feelings of pain sensitivity to pricking stimuli, and these pain-reducing effects were still there even at the end of the 45-minute experience.
The more present the person felt during the VR experience, the stronger this pain-relieving effect. The fMRI brain scans also revealed that people with stronger connectivity in brain regions involved in modulating pain responses experienced less pain. The results suggest that nature scenes delivered using VR can help to change how pain signals are transmitted in the brain and spinal cord during long-term pain conditions.
Dr Sonia Medina, of the University of Exeter Medical School and one of the authors on the study, said: “We think VR has a particularly strong effect on reducing experience of pain because it’s so immersive. It really created that feeling of being present in nature – and we found the pain – reducing effect was greatest in people for whom that perception was strongest. We hope our study leads to more research to investigate further how exposure to nature effects our pain responses, so we could one day see nature scenes incorporated into ways of reducing pain for people in settings like care homes or hospitals.”
The paper is titled ‘Immersion in nature through virtual reality attenuates the development and spread of mechanical secondary hyperalgesia: a role for insulo-thalamic effective connectivity’ and is published in the journal Pain. More

Researchers have successfully demonstrated a spectrometer that is orders of magnitude smaller than current technologies and can accurately measure wavelengths of light from ultraviolet to the near-infrared. The technology makes it possible to create hand-held spectroscopy devices and holds promise for the development of devices that incorporate an array of the new sensors to serve as next-generation imaging spectrometers.
“Spectrometers are critical tools for helping us understand the chemical and physical properties of various materials based on how light changes when it interacts with those materials,” says Brendan O’Connor, corresponding author of a paper on the work and a professor of mechanical and aerospace engineering at North Carolina State University. “They are used in applications that range from manufacturing to biomedical diagnostics. However, the smallest spectrometers on the market are still fairly bulky.
“We’ve created a spectrometer that operates quickly, at low voltage, and that is sensitive to a wide spectrum of light,” O’Connor says. “Our demonstration prototype is only a few square millimeters in size – it could fit on your phone. You could make it as small as a pixel, if you wanted to.”
The technology makes use of a tiny photodetector capable of sensing wavelengths of light after the light interacts with a target material. By applying different voltages to the photodetector, you can manipulate which wavelengths of light the photodetector is most sensitive to.
“If you rapidly apply a range of voltages to the photodetector, and measure all of the wavelengths of light being captured at each voltage, you have enough data that a simple computational program can recreate an accurate signature of the light that is passing through or reflecting off of the target material,” O’Connor says. “The range of voltages is less than one volt, and the entire process can take place in less than a millisecond.”
Previous attempts to create miniaturized photodetectors have relied on complex optics, used high voltages, or have not been as sensitive to such a broad range of wavelengths.
In proof-of-concept testing, the researchers found their pixel-sized spectrometer was as accurate as a conventional spectrometer and had sensitivity comparable to commercial photodetection devices.
“In the long term, our goal is to bring spectrometers to the consumer market,” O’Connor says. “The size and energy demand of the technology make it feasible to incorporate into a smartphone, and we think this makes some exciting applications possible. From a research standpoint, this also paves the way for improved access to imaging spectroscopy, microscopic spectroscopy, and other applications that would be useful in the lab.”
The paper, “Single pixel spectrometer based on a bias-tunable tandem organic photodetector,” is published in the journal Device. First author of the paper is Harry Schrickx, a former Ph.D. student at NC State. The paper was co-authored by Abdullah Al Shafe, a former Ph.D. student at NC State; Caleb Moore, a former undergraduate at NC State; Yusen Pei, a Ph.D. student at NC State; Franky So, the Walter and Ida Freeman Distinguished Professor of Materials Science and Engineering at NC State; and Michael Kudenov, the John and Catherine Amein Family Distinguished Professor of Electrical and Computer Engineering at NC State.
The work was done with support from the National Science Foundation under grants 1809753 and 2324190, and from the Office of Naval Research under grant N000142412101. More

Experts say quantum computing is the future of computers. Unlike conventional computers, quantum computers leverage the properties of quantum physics such as superposition and interference, theoretically outperforming current equipment to an exponential degree.
When a quantum computer is able to solve a problem unfeasible for current technologies, this is called the quantum advantage. However, this edge is not guaranteed for all calculations, raising fundamental questions regarding the conditions under which such an advantage exists. While previous studies have proposed various sufficient conditions for quantum advantage, the necessity of these conditions has remained unclear.
Motivated by this uncertainty, a team of researchers at Kyoto University has endeavored to understand the necessary and sufficient conditions for quantum advantage, using an approach combining techniques from quantum computing and cryptography, the science of coding information securely.
Specifically, the team focused on interactive protocols called inefficient-verifier proofs of quantumness, which allow a verifier without a quantum computer to interact with a quantum prover and verify that it indeed possesses quantum computational power. In their study, the team demonstrated that the existence of these proofs depends on the existence of a certain cryptographic primitive called a one-way puzzle.
By integrating these methods, the team introduced a novel framework uniting the seemingly unrelated concepts of quantum advantage and cryptographic security. As a result, the team was able to completely characterize quantum advantage for the first time.
“We were able to identify the necessary and sufficient conditions for quantum advantage by proving an equivalence between the existence of quantum advantage and the security of certain quantum cryptographic primitives,” says corresponding author Yuki Shirakawa.
The results imply that when quantum advantage does not exist, then the security of almost all cryptographic primitives — previously believed to be secure — is broken. Importantly, these primitives are not limited to quantum cryptography but also include widely-used conventional cryptographic primitives as well as post-quantum ones that are rapidly evolving.
The established equivalence between quantum computing and cryptography also provides a stronger cryptographic foundation for future experimental demonstrations of quantum advantage, as well as for ongoing theoretical investigations in the field.
“Quantum advantage is a highly expected and actively studied concept, but it is still not fully understood. Our study represents a significant step toward a deeper understanding of this property,” says Shirakawa.
The team expects that future research will extend characterization to other types of quantum advantage and lead to a more general theoretical framework. More

Jadarite has been likened to Superman’s ‘kryptonite’ based on their similar chemical compositions. It was discovered in the Jadar Valley of Serbia and officially recognized as a new mineral in 2006. Whilst lacking any actual superpowers, jadarite has great potential as an important resource of lithium and boron.Kryptonite’s twin on Earth Described as ‘Earth’s kryptonite twin’, jadarite is a rare and fascinating mineral that quickly caught the attention of scientists and Superman fans alike.
The mineral was discovered by exploration geologists from Rio Tinto in 2004 in the Jadar Valley of Serbia. Its chemical composition is exactly like the fictional kryptonite right out of the comic books — with a few differences. Where kryptonite glows green and weakens superheroes, jadarite offers immense potential for Earth’s energy transition away from fossil fuels.
A new mineral on the scene
Jadarite was identified by Rio Tinto geologists during exploration drilling and didn’t match any known mineral at the time. After analysis by the Natural History Museum in London and the National Research Council of Canada, it was officially recognised as a new mineral in 2006.
Jadarite is a “sodium lithium boron silicate hydroxide” mineral, coincidentally the same scientific name written on a case containing kryptonite stolen by Lex Luther from a museum in the film Superman Returns.

While the film version of kryptonite contains fluorine and glows an eery green, the chemical formula of the real version is LiNaSiB₃O₇(OH) and is a much less supernatural dull white — though it does fluoresce a pinkish-orange under UV light.
Super in its own right
Michael Page, a scientist with Australia’s Nuclear Science and Technology Organisation (ANSTO), said that the mineral is ‘super’ in its own right.
“While lacking any supernatural powers the real jadarite has great potential as an important source of lithium and boron,” Michael said.
“In fact, the Jadar deposit where it was first discovered is considered one of the largest lithium deposits in the world, making it a potential game-changer for the global green energy transition.”
ANSTO is one of the three supporting agencies of the Australian Critical Minerals R&D Hub, alongside Geoscience Australia and CSIRO, hosted by CSIRO. One of the Hub’s key missions is to better connect Australia’s R&D ecosystem, including Australian industry, to enable access and utilization of critical minerals to strengthen Australia’s value chain domestically and across the globe.
The work that ANSTO does has a significant focus on how these critical minerals, such as jadarite, can be utilised to support Australian industry in a commercial capacity.
“At ANSTO, we work with industry to develop process solutions for many critical elements including lithium, and the challenges posed by a new type of mineral resource are very exciting,” Michael said.
ANSTO has produced battery grade lithium chemicals from many different mineral deposits, such as spodumene, lepidolite and even jadarite, ensuring that Australian miners receive the support they need to meet the challenges of the energy transition. More