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  • AI can act exactly like a human, but we still don’t think it’s conscious

    AI can act exactly like a human, but we still don’t think it’s conscious

    Even when artificial intelligence behaves exactly like a human, people are reluctant to consider it conscious, according to a new study from Ludwig Maximilian University of Munich (LMU).

    As artificial intelligence becomes more advanced, reports of AI systems misleading users, working together, or appearing to pursue independent goals are becoming increasingly common. These behaviors often lead people to describe AI as though it can think, feel, or make decisions for itself. But does behaving like a human actually convince people that a machine has consciousness?

    New research from LMU suggests that people make a clear distinction between displaying intelligent behavior and possessing a conscious mind, even when humans and AI act in precisely the same way.

    How Scientists Tested Perceptions of AI Consciousness

    Published in the journal Cognition, the study was led by Dr. Louis Longin of LMU’s Chair of Philosophy of Mind, working alongside Dr. Bahador Bahrami, Professor Ophelia Deroy, and other researchers.

    “Whereas previous studies have typically asked general questions about whether AI actually has mental states, our study is the first to directly compare how people attribute the same mental states to AI and humans behaving in exactly the same way, under identical circumstances,” says Longin.

    “We may be using mental terms to refer to AI, but this may only be because we lack better words,” says Ophelia Deroy, philosopher and a senior author of the study. “After all, AI is trained to act and speak like a human, so these descriptions seem natural.”

    To investigate how people judge consciousness, the researchers conducted experiments involving nearly 1,100 participants. One group read brief descriptions of artificial agents that showed different levels of responsiveness to their environments. For example, some agents reacted to sounds or recognized the emotional states of others.

    Another group encountered the same situations, except the characters were described as humans rather than AI systems. Participants then evaluated how conscious or aware each character seemed to be of its surroundings.

    A Surprising Gap Between Human and AI Consciousness

    The experiments revealed that responsiveness influenced how participants judged both humans and artificial intelligence. Characters that reacted more actively to their surroundings were generally considered more conscious and more aware.

    However, a striking difference emerged when participants evaluated consciousness specifically. Even the most responsive AI was rated as less conscious than the least responsive human. In other words, identical behavior did not lead people to assign the same level of consciousness to humans and machines.

    The results changed considerably when participants were asked about awareness instead. For this characteristic, judgments of humans and AI followed largely similar patterns, suggesting that people interpret awareness and consciousness in fundamentally different ways.

    “There is a growing worry in public discussion that people will see AI behaving in a human-like way and start treating these systems as if they had human-like mental states,” says Longin, lead author of the study. “We found something much more nuanced: People are quite willing to say that an AI notices things and is aware of its surroundings. But they clearly draw a line when it comes to the term ‘consciousness’. People consistently attribute less consciousness to AI than humans — even when their behavior is identical.”

    Although people sometimes describe AI as conscious when discussing its actions, the findings indicate that they still distinguish between artificial systems and human minds.

    Why One Word Changes How We Perceive AI

    The researchers believe the difference between consciousness and awareness offers an important insight into how people understand artificial intelligence.

    Awareness is a relatively neutral term that can describe an agent’s ability to detect and respond to information in its environment. Consciousness, however, carries deeper implications about subjective experience and what it means to have an inner mental life.

    Because awareness focuses more directly on observable behavior, people appear comfortable applying it to both humans and AI. Consciousness carries a different meaning, leading people to judge the two much less similarly.

    The findings also highlight why the language used to discuss artificial intelligence matters, particularly as AI systems become increasingly capable of producing convincing human behavior.

    “Our study teaches us lessons for how we communicate about AI,” says Bahador Bahrami, who is also a senior author of the study and an expert in social neuroscience. “Companies and journalists often reach for hyped descriptions of AI models, and credit them with intentions, plans, or even moral conscience and hesitation. What our study shows is that everyday judgments are much more discriminating: People do not simply put AI and humans on the same mental scale. But the boundary also depends on which terms we use. For more neutral descriptors such as ‘awareness’, the distinction can largely disappear. That makes our choice of language important.”

  • X-Chromosome Gene Linked to Increased Autism Diagnosis in Males

    X-Chromosome Gene Linked to Increased Autism Diagnosis in Males

    Researchers at Baylor College of Medicine, the Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital, and collaborating institutions have identified new genetic candidates that help explain why autism is diagnosed about four times more often in boys than it is in girls. The study, involving tests in induced pluripotent stem cell (iPSC)-derived neurons (iNeurons), revealed that small changes in the gene MECP2 on the X chromosome might help explain part of this difference.

    Huda Zoghbi, MD, Distinguished Service Professor at Baylor, director of Duncan NRI, and a Howard Hughes Medical Institute investigator, is senior and corresponding author of the team’s published paper in The American Journal of Human Genetics, titled “A massively parallel reporter assay of MECP2 cis-regulatory elements reveals genetic candidates for male-biased autism.” In their paper, the team concluded, “These findings suggest noncoding MECP2 variants can cause idiopathic, male-biased autism and provide a framework for uncovering regulatory variants in other X chromosome neurodevelopmental genes that may contribute to autism’s missing heritability.”

    “Autism is a common, heritable neurodevelopmental trait that affects how a person communicates, interacts with others, and experiences the world, and is characterized by altered social interactions and restricted, repetitive behaviors or interests,” Zoghbi explained. “It is diagnosed about four times more in male individuals than in female individuals, suggesting sex-specific factors may increase male vulnerability,” the researchers added in their paper.

    In the current study, the researchers drew from their long experience with gene MECP2, which is on the X chromosome and has been associated with neurodevelopmental conditions, including autism. “We tested the idea that the predominance of autism in males could be explained in part by mild mutations in an X chromosome gene’s regulatory regions,” commented Rebecca Meyer-Schuman, PhD, a postdoctoral associate in the Zoghbi lab. “Females might be protected from such a mild mutation because of their second X chromosome, but males, who have only one copy, would be more vulnerable. The regulatory regions are like dials that control whether a gene will be expressed and by how much. And what better place to start looking at these regulatory regions than the gene MECP2, where brain health depends on how much of the gene is expressed, and where mutations can cause neurodevelopmental disorders that include autism.”

    Previous murine studies by Zoghbi lab and others have taught researchers that MECP2 produces a Goldilocks protein, meaning that it must maintain a “just right” concentration or activity level for a healthy brain. Having too little—about 50% or less of the normal levels—leads to Rett syndrome, and having twice the normal levels causes a different neurodevelopmental condition called MECP2 duplication syndrome. “Both loss-of-function and gain-of-function variants lead to severe neurodevelopmental conditions—Rett syndrome (MIM: 312750) and MECP2 duplication syndrome (MDS; MIM: 300260[intellectual developmental disorder, X-linked, syndromic, Lubs type (MRXSL)]), respectively,” the authors commented. “Because MECP2 is on the X chromosome, hemizygous male individuals have a more severe phenotype than heterozygous female carriers with the same variant.”

    Meyer-Schuman also noted, “Previous studies in mice also showed us that milder changes in MECP2 levels, for instance reducing the expression by 30% or increasing it by 50%, do not cause the more severe features of Rett syndrome or MECP2 duplication syndrome like seizures or motor problems, but lead to autism-like behaviors.”

    For their current study the team used a massively parallel reporter assay (MPRA) to screen the regulatory regions of the MECP2 gene in induced pluripotent stem-cell (iPC)-derived neurons. “This allowed us to identify and manipulate the regulatory regions and determine what kinds of changes would alter their function,” Meyer-Schuman said. The researchers also screened MECP2 regulatory regions in autistic individuals and tested the genetic variants they identified using the MPRA assays.

    “We identified two regulatory regions where male autistic individuals inherited a variant from their unaffected mother that altered regulatory activity,” Meyer-Schuman said. “One of these variants reduced MECP2 expression by approximately 30% in human neurons, a magnitude that produces social deficits, hyperactivity and anxiety-like characteristics in mice. As predicted by the mouse model, this individual was diagnosed with autism and ADHD but had none of the defining characteristics of Rett syndrome.”

    In their paper, the authors commented that their work supports a broader hypothesis that altered dosage or expression of sex chromosome genes are a major source of the male bias observed in autism. Zoghbi added, “These findings, a result of integrating human and animal studies, suggest that MECP2 regulatory variants can contribute to male-biased autism and reveal just the tip of the iceberg, providing a framework for uncovering regulatory variants in other X chromosome neurodevelopmental genes that may contribute to autism’s missing heritability.”

  • Enodia Therapeutics Inks Pfizer Deal to Develop Sec61-Targeting Small Molecules

    Enodia Therapeutics Inks Pfizer Deal to Develop Sec61-Targeting Small Molecules

    Biotechnology firm Enodia Therapeutics has announced a research collaboration and licensing agreement with pharma giant Pfizer to discover and develop small molecule inhibitors of Sec61, using Enodia’s proprietary platform. 

    Under the terms of the agreement, Enodia will perform discovery activities to screen, optimize, and develop Sec61 inhibitor candidates against multiple collaboration targets. Following the collaboration term, Pfizer will be responsible for all clinical, manufacturing, regulatory, and commercial activities. Furthermore, Enodia will receive an upfront payment and is eligible for future research, development, and sales milestone payments, as well as tiered royalties on net sales, bringing the total potential value to more than $500 million.

    Enodia develops novel small-molecule therapies for targeted protein degradation using its platform, which is designed to identify small molecules that enable selective Sec61 translocon modulation, a novel approach to inhibit disease-driving proteins when they are synthesized and before pathological effects occur. To date, the company has built a broad chemical space that spans multiple Sec61 inhibitor families and is supported by biological datasets including proteomics and cryo-EM data as well as tailored cell-line libraries. 

    “Enodia has built a broad platform that enables selective Sec61 translocon modulation, a novel approach to inhibit disease-driving proteins while preserving essential physiological functions,” said Yves Ribeill, PhD, Enodia’s CEO. “We look forward to collaborating with Pfizer, combining their deep expertise and clinical resources with our approach for precisely targeting pathological proteins to bring forth potential new medicines.”

    Earlier this year, Enodia announced that it had purchased assets from Kezar Life Sciences’ Sec61-based discovery and development program. At the time, Enodia said that the acquisition helped advance its understanding of Sec61 selectivity mechanisms. The company also said that insights from Kezar’s programs would further strengthen Enodia’s core focus on Sec61-driven selectivity for targeted protein degradation. Under the terms of the purchase agreement, Kezar received an initial upfront payment totaling $1 million, and was expected to receive future payments upon achievement of certain development, regulatory and commercialization milestones. 

  • The Top 10 Questions Shaping the Future of Optogenetic Biomanufacturing

    The Top 10 Questions Shaping the Future of Optogenetic Biomanufacturing

    Maximilian Hoerner
    Maximilian Hoerner, PhD

    The emergence of increasingly complex biologics such as multi‑specific antibodies, cytokines, fusion proteins, and other structurally demanding modalities has exposed the limits of conventional bioprocessing. Many of these molecules are difficult to express at commercially viable yields, and their quality attributes can be highly sensitive to the cellular environment. As a result, productivity, consistency, and cost remain major constraints across the industry.

    Traditional cell line development (CLD) relies on constitutive promoters that drive static expression throughout development and production. Because production is always on, cells must divide and manufacture protein simultaneously, even when the product is burdensome or toxic. While this model worked relatively well for easy-to-express monoclonal antibodies, it does not work well for next-generation biologics, where the inherent trade-off between higher specific productivity and rapid cell growth, both competing for the same cellular resources, is increased. Light‑controlled gene expression using optogenetics is emerging as a credible alternative.

    This article explores the ten most important questions facing optogenetic biomanufacturing as it moves from proof‑of‑concept demonstrations toward mainstream adoption in modern bioprocessing.

    1. What is optogenetics, and why is it relevant to biologics manufacturing?

    Optogenetics uses light‑responsive proteins to control specific cellular functions. In biomanufacturing, the key application is regulating gene expression with light instead of relying on constitutive promoters or chemical inducers. When light‑controlled gene expression systems are engineered into production cell lines, illumination at defined wavelengths can switch expression on, off, or to intermediate levels.

    This is important because it introduces a fundamentally different control modality. Conventional systems provide static expression, whereas optogenetics enables dynamic, reversible, and tunable control. As biologics become more complex and more sensitive to expression conditions, having a way to precisely modulate transcription directly, rather than perturbing the entire cell by modulating process parameters such as temperature, will become increasingly valuable.

    2. What core limitation in biologics manufacturing does light‑based control address?

    The main limitation is the inherent competition between cell growth and protein production. In constitutive systems, cells must divide and manufacture protein at the same time, drawing on the same finite pool of metabolic resources. This creates a structural trade‑off: clones that produce strongly have a slow doubling time and/or do not grow to viable densities, while clones that grow well often produce only modest titers. This trade‑off becomes much more pronounced for challenging molecules such as multi‑specific antibodies, cytokines, and fusion proteins that are aggregation‑prone or place a significant burden on the host cell.

    Optogenetics addresses this by separating the growth and production phases. Cells can grow in an uninduced, low-burden state and then transition into a productive state upon illumination. As light acts directly on transcriptional regulators in a dose-dependent manner, expression can be tuned precisely rather than modulated indirectly through temperature shifts or coarsely and irreversibly by chemical induction. Chemical inducers can also negatively affect cell performance through off-target effects and are difficult to remove during downstream processing, which has limited their adoption in mammalian biomanufacturing. The direct, tunable control by light also enables more deliberate modulation of pathways that influence critical quality attributes such as post-translational modifications (PTMs), which is increasingly important for complex biologics and biosimilars.

    3. How does optogenetic light exposure work, and is it safe for cells and media?

    Optogenetics uses light as an informational cue rather than an energy source. Because photoreceptors respond to brief, low-intensity pulses and stay “on” for a tunable period of time before reverting to the off state, optogenetic systems can maintain precise control without continuous or high-power illumination.

    The wavelengths used in bioprocessing are in the visible range and non-ionizing, operating well under established phototoxicity thresholds. At these levels, light does not harm cells or DNA, nor does it disrupt cellular physiology. Although certain media components are known to be light-sensitive, the illumination used for optogenetic induction has not shown detrimental effects on cellular performance.

    4. What is the impact of optogenetics on lab operations?

    Optogenetic workflows use standard lab equipment with the addition of illumination devices compatible with existing infrastructure, such as plates, shake flasks, or bioreactors. The main operational difference occurs during pool generation and single-cell cloning, where cells must remain uninduced. This is achieved by working under “safe light” conditions, visible wavelengths that do not activate the specific optogenetic system but allow the operator to handle the cell culture. Only small areas of the lab need to be adapted for this purpose. For all other operations, including biomanufacturing, local interventions to shield cells from room light are typically sufficient.

    5. How many cellular functions can be controlled with light in a single cell line?

    Current systems can independently regulate cellular functions using two or three different wavelengths. For example, one color may control production while another modulates a critical quality‑related pathway. Functions that require coordinated timing can be linked to the same wavelength. As genetic circuit design advances, the number of independently controllable functions is expected to increase.

    6. When might optogenetically manufactured biologics reach clinical and commercial stages?

    Optogenetic cell line development is already being explored for multiple programs. Regulatory agencies have established pathways for evaluating emerging bioprocess technologies, and optogenetic systems are beginning to move through these mechanisms. If early development proceeds as expected, optogenetically controlled processes could support clinical filings in the next two years, with commercial adoption following thereafter.

    7. Can optogenetics be integrated into existing facilities?

    Yes. Optogenetic manufacturing does not require new bioreactor designs; illumination hardware can be added to standard single‑use or stainless‑steel systems. For single‑use bags, light is delivered externally through the bag without breaching the sterility barrier; for stainless‑steel tanks, cultures can be circulated through illuminated loops. No cleanroom redesign is required.

    8. How does optogenetic manufacturing scale to larger bioreactors?

    Scaling optogenetic systems depends on three factors: the sensitivity of the photoreceptors, the lifetime of their activated state in the dark, and the mixing and light-scattering characteristics of the bioreactor. Modern optogenetic systems for biomanufacturing are designed to respond to very low light intensities, and once activated, they gradually return to the off state in the dark at a characteristic rate, typically over tens of minutes.

    Since stirred-tank bioreactors mix continuously and scatter light throughout the vessel, cells receive sufficient illumination over the photoreceptor’s characteristic activation lifetime even at large volumes. Simulation studies and early pilot-scale experiments up to the 200 L scale suggest that optogenetic activation can be achieved at commercially relevant scales, including stainless steel and single-use systems.

    9. What has convinced established players to evaluate this technology?

    Biologics development and manufacturing are intentionally conservative, with new technologies adopted only when they demonstrate clear, reproducible benefits and maintain patient safety. For any emerging bioprocess platform, the threshold for evaluation is data showing that it can deliver meaningful improvements without introducing new risks or operational complexity.

    In comparative studies, optogenetic induction has produced more than two‑fold increases in titer for standard monoclonal antibodies as well as for more difficult‑to‑express therapeutic proteins. These gains have been achieved while maintaining or improving critical quality attributes, including those influenced by folding, assembly, and post‑translational modification.

    As the next generation of therapeutics become increasingly complex, leading biopharma and CDMO players see the need for novel biomanufacturing platforms capable of meeting that complexity without compromising titers, and for that reason several key players are actively evaluating optogenetic technology for potential integration.

    10. Where is optogenetic biomanufacturing headed in the next decade?

    If current trends continue, optogenetic control may become a standard tool for managing expression, quality, and other cellular functions in biologics manufacturing. The ability to modulate gene expression dynamically opens possibilities for more efficient production of complex therapeutics, more predictable quality profiles, and more flexible facility design. As the technology matures, it is likely to be adopted across CDMOs, biotech, and biopharma companies seeking greater control over their manufacturing processes.

    Maximilian Hoerner, PhD, is the head of optogenetics at Prolific Machines

  • UCB Dedicates Future U.S. Biologics Manufacturing Campus in Georgia

    UCB Dedicates Future U.S. Biologics Manufacturing Campus in Georgia

    UCB has dedicated the Rowen, GA, site where it plans to build a $2 billion biologics manufacturing campus that is set to open as the Belgian-based drug developer’s first U.S. manufacturing site.

    When completed in 2032 or 2033, the campus is expected to support commercial production of recently approved and future biologic medicines, applying artificial intelligence, automation, and advanced manufacturing technologies. The campus is intended to further integrate UCB’s U.S. patient value chain from research and development through manufacturing and delivery.

    Some 330 permanent jobs are expected to be based at the approximately 460,000-square-foot campus, which will occupy 79 acres within the Rowen innovation district in Georgia’s Gwinnett County. UCB bought the 79 acres from the Rowen Foundation, which is developing a 1,900-acre campus on Highway 316, launched in 2020 as a “knowledge” community for biopharma and other innovation-based fields.

    In its announcement of the campus site dedication, UCB said it chose to build its first U.S. manufacturing campus in Georgia because of what it called the Peach State’s strong life sciences ecosystem, highly skilled workforce, robust infrastructure, and access to leading academic and research institutions.

    Another factor in the decision: Gwinnett County has committed $174 million in incentives and infrastructure investments to support UCB’s project.

    UCB’s project is the brightest recent success of Georgia life sciences leaders, who worked through industry group Georgia Life Sciences to lay out a 10-year “Roadmap” last year with the aim of “positioning Georgia as the scale-up manufacturing hub of the Southeast.” The UCB project, announced in March, helped place Georgia among the “Next 5 States” within GEN’s Next 10 U.S. Biopharma Clusters A-List.

    “Long-term commitment”

    “Our manufacturing investment in the United States reflects our long-term commitment to patients, strengthening our ability to serve them while contributing to scientific innovation, highly skilled jobs, and economic growth in Georgia,” UCB CEO Jean-Christophe Tellier said in a statement.

    UCB executives and dignitaries cut a ceremonial ribbon to mark the dedication of UCB’s future biologics manufacturing campus in Rowen, GA. Jeffrey Kessler, U.S. Department of Commerce Under Secretary for Industry and Security, stands at left. At the center are Georgia Gov. Brian Kemp (R); UCB CEO Jean-Christophe Tellier; Katherine Raeymaekers, Consul General of Belgium in Atlanta; and Nicole Love Hendrickson (D), Chairwoman of the Gwinnett County Board of Commissioners. [UCB]

    Tellier and other UCB leaders were joined at a dedication ceremony by dignitaries that included Georgia Gov. Brian Kemp (R); Jeffrey Kessler, U.S. Department of Commerce Under Secretary for Industry and Security; Nicole Love Hendrickson (D), Chairwoman of the Gwinnett County Board of Commissioners; and Katherine Raeymaekers, Consul General of Belgium in Atlanta.

    During the ceremony, the dignitaries joined top UCB executives in unveiling the Emmanuel Janssen Circle, a commemorative stonework installation just completed within the roundabout to the entrance of the future campus. Janssen (1879-1955) was a Belgian businessman who founded Union Chimique Belge (UCB) on January 18, 1928. The company initially focused on industrial chemicals before evolving into a developer of biologics for indications in neurology and immunology.

    “UCB’s new biomanufacturing campus builds on the entrepreneurial legacy of Baron Emmanuel Janssen, founder of UCB, while strengthening the transatlantic collaboration that drives economic growth, scientific innovation, and improving people’s lives,” Raeymaekers stated. “Today’s site dedication reflects the strength of the partnership between Belgium, the United States, and the State of Georgia—and our shared commitment to enduring progress, innovation, and opportunity.”

    UCB worked with numerous public and private partners to locate its biologics manufacturing campus in Rowen—including the Metro Atlanta Chamber; Georgia Quick Start, which provides customized workforce training through the Technical College System of Georgia; Gwinnett County Government; Georgia Power Company; the public-private economic development initiative Partnership Gwinnett; and the Georgia Department of Economic Development.

    Headquartered in Brussels, UCB employs more than 10,000 people in nearly 40 countries—including the United States, where the company employs more than 2,000 people in research, development, manufacturing, commercial operations, and corporate functions.

    UCB has maintained a U.S. presence for nearly a century. The company now employs more than 400 people in Georgia, where it established its Stateside headquarters in Atlanta in 1993.

    More than 1,000 construction jobs are expected to be created in connection with the campus during the six- to seven-year projected timeframe for design and construction.

    “At UCB, our purpose is to create value for people living with severe diseases, and that purpose guides the science we pursue, where we invest, and the choices we make for the long term,” Tellier added.

  • Scientists recreate a bizarre quantum effect that stops a particle cold

    Scientists recreate a bizarre quantum effect that stops a particle cold

    A particle does not have to pass through a magnetic field to be influenced by it. That surprising feature of quantum physics has now been recreated by researchers at the University of Oxford, who used a hybrid quantum computer to demonstrate how an invisible magnetic influence can bring a simulated particle’s movement to a complete stop.

    The experiment reproduced a phenomenon known as the Aharonov-Bohm effect, in which a charged particle traveling around a region containing magnetic flux experiences a measurable change in its quantum state, even though its path never takes it through the magnetic field itself.

    The Oxford team achieved this using a quantum system that combines qubits, the basic units of quantum information, with quantum oscillators, which represent vibrating motion. Their findings, published in Nature Physics, demonstrate how this combination could help scientists investigate fundamental interactions between matter and fields that are increasingly difficult to simulate using conventional computers.

    A Strange Quantum Effect Predicted in 1959

    In everyday physics, a charged particle responds to the electric and magnetic fields it encounters. Quantum mechanics, however, reveals that particles can behave in ways that have no straightforward counterpart in our ordinary experience.

    In 1959, physicists Yakir Aharonov and David Bohm predicted that a charged particle could be affected by magnetic flux even if it traveled entirely outside the region containing the magnetic field. Rather than experiencing a conventional magnetic force along its path, the particle would undergo a change in its quantum phase.

    Quantum phase describes an aspect of a particle’s wave behavior that influences how different possible paths interfere with one another. Although the phase itself is not directly visible, differences in phase can produce measurable effects.

    The prediction became known as the Aharonov-Bohm effect and was eventually verified in experiments involving real electrons. It remains one of the clearest demonstrations that the quantum world operates according to rules that go beyond the familiar laws of classical physics.

    Researchers are now exploring how this phenomenon behaves in more complex theoretical systems known as lattice gauge theories.

    These theories describe how matter interacts with fields associated with fundamental forces. They represent space as a grid, with matter located at individual points and fields associated with the connections between them. Such models are particularly important in particle physics and high-energy physics, where scientists study the basic particles and interactions that make up the universe.

    The challenge is that the mathematics becomes extraordinarily demanding as these systems grow more complicated. Even powerful conventional computers can struggle to calculate how all the interacting components evolve.

    Quantum computers offer a different approach. Instead of attempting to calculate every aspect of a quantum system using classical computing methods, scientists can construct another quantum system that follows the same underlying rules. They can then observe its behavior directly, an approach known as quantum simulation.

    How Scientists Built the Quantum Experiment

    The Oxford project began in 2022, when lead author Dr. Sebastian Saner, Dr. Oana Bazavan, and their colleagues started developing a way to simulate lattice gauge theories using a hybrid quantum system. They collaborated with Dr. Alejandro Bermudez of the Instituto de Física Teórica in Madrid.

    Their experimental design relied on two different quantum components that performed separate functions.

    The first consisted of qubits encoded in the internal states of trapped ions, which are electrically charged atoms held in place using electromagnetic fields. These qubits represented the gauge fields in the theoretical model.

    The second component used quantum oscillators, created by the vibrations of those same trapped ions. These oscillators represented matter.

    By combining the two, the researchers constructed a simple loop that served as a basic building block of a lattice gauge theory. Two oscillators represented matter at two different locations, while two qubits represented the fields connecting those locations.

    Although the arrangement was small, it was sufficient to reproduce an important interaction between matter and magnetic flux.

    Quantum Entanglement Creates a Surprising Solution

    The researchers next placed the two qubits into an entangled quantum state. Entanglement is a phenomenon in which quantum systems become linked in ways that cannot be fully explained by classical physics.

    Within the team’s simulated lattice gauge theory, this entangled state represented magnetic flux passing through the center of the loop.

    Initially, the researchers had planned to introduce the magnetic flux as a fixed background condition. However, creating the necessary interaction would have required capabilities that their quantum hardware did not possess.

    Encoding the flux directly into the qubits provided a practical alternative. More importantly, it allowed the magnetic flux to become part of the evolving quantum system rather than remaining an unchanging external influence.

    “For us, the exciting step was to encode the magnetic flux in a gauge field that was itself dynamical,” says Dr. Saner. “Rather than having matter evolve in a fixed background, the matter and gauge field become part of the same quantum dynamics.”

    What began as a technical workaround ultimately enabled the researchers to explore a more interesting version of the phenomenon, one in which matter and the field could participate together in the quantum dynamics.

    A Quantum Effect That Stops Particle Motion

    With their simulated loop in place, the scientists examined how a matter particle moved between locations through a process known as quantum tunneling.

    Quantum tunneling allows particles to move between states in ways that would not be possible under ordinary classical rules.

    When the researchers ran their simulation without magnetic flux, the particle could tunnel freely around the loop.

    Introducing the simulated flux produced a strikingly different result.

    The particle had two possible paths around the loop, but the magnetic flux changed their relative quantum phases. As a result, the two paths interfered destructively, meaning their quantum contributions canceled each other out.

    This interference completely suppressed the tunneling, leaving the simulated particle frozen in its original state.

    The outcome demonstrated the Aharonov-Bohm effect within a lattice gauge theory containing a dynamical field. Rather than simply reproducing the familiar behavior of a particle moving around a fixed magnetic influence, the experiment showed how the phenomenon can emerge when matter and the field are both represented by interacting quantum components.

    A New Tool for Exploring Fundamental Physics

    The Oxford findings were published alongside a related study by researchers at the University of Maryland, led by Professor Norbert Linke.

    The Maryland team also used a hybrid quantum system, but their experiment focused on simulating the Yukawa potential, a mathematical description of an interaction relevant to nuclear and particle physics.

    Although the two research groups developed their methods independently, they later coordinated the submission of their studies to Nature Physics.

    Together, the experiments demonstrate how hybrid quantum computers could become valuable tools for investigating fundamental interactions that are difficult to reproduce using classical simulations.

    By combining different types of quantum components, researchers can build systems in which matter and fields are represented in ways that more closely reflect the physics they want to study.

    The Oxford experiment provides an example of that potential. A phenomenon first predicted in 1959 and later observed with electrons has now been recreated in a quantum simulator where the field itself participates in the dynamics, offering scientists another way to explore the unusual rules governing the quantum world.

  • Physicists discover “astonishing” property of light that defies expectations

    Physicists discover “astonishing” property of light that defies expectations

    Scientists have discovered a surprising ability of light that allows it to develop spinning patterns as it moves through empty space, without relying on special lenses, mirrors, or materials. The finding reveals that light possesses a hidden geometric structure that can influence its behavior in ways researchers previously thought were difficult to achieve.

    The discovery comes from an international team led by researchers at the University of East Anglia (UEA) in the United Kingdom, working with scientists in South Africa. Their experiments demonstrate that carefully prepared light can be controlled through its own internal geometry, offering a new approach to manipulating how light spins and twists.

    The findings challenge long-standing assumptions about how different properties of light interact. They could eventually lead to more sensitive medical tests, faster and more secure communications, and advanced quantum technologies that use light to transmit and protect information.

    Why the Direction of Light’s Spin Matters

    One of the most intriguing aspects of the discovery involves chirality, a scientific term describing the difference between left-handed and right-handed structures.

    Human hands provide a familiar example. Although they are mirror images of each other, a left hand cannot be perfectly superimposed on a right hand. Many molecules have a similar property, including compounds used in medicines. Two versions of the same molecule can have nearly identical chemical structures yet produce very different effects in the body.

    Scientists can distinguish these molecular forms by studying how they interact with light that has a particular rotational behavior. Traditionally, producing and controlling such light has often involved specialized materials, carefully designed surfaces, or powerful lenses that focus beams extremely tightly.

    The research demonstrates that appropriately prepared light can develop this behavior naturally as it travels, without requiring those additional optical components.

    “Our work shows that light can naturally develop this handed behavior all on its own,” said Dr. Kayn Forbes from UEA’s School of Chemistry, Pharmacy and Pharmacology.

    “You just have to prepare it in the right way.

    “Most people think of light as traveling in straight lines. But scientists can also create structured light — light whose brightness, shape, and direction are carefully arranged.

    “One extreme example is light that twists as it travels, forming a corkscrew shape known as an optical vortex. Each twist can carry information, making this kind of light valuable for high-speed internet, secure communications, and advanced sensors.

    “Light can also spin as it travels, depending on how it is polarized. This spin can be left-handed or right-handed — another form of chirality.”

    Scientists Discover How Light Develops a Hidden Spin

    Light can exhibit different kinds of rotational behavior. An optical vortex, for example, has a wave pattern that twists around its direction of travel, much like a corkscrew. Light also has a property known as polarization, which describes how its electric field oscillates. Certain polarization patterns produce a form of rotation called spin.

    Physicists have long studied the relationship between these two properties. However, the interactions responsible for the newly observed effect were generally considered extremely weak and difficult to detect without specialized experimental conditions.

    The researchers found that the situation changes when a beam of light is prepared in a particular balanced configuration.

    Under those conditions, the beam can initially have no spin, yet distinct regions with spinning behavior emerge as it travels through free space. The effect does not require the light to pass through engineered materials or additional optical devices.

    “It starts off with no spin at all,” explained MSc student Light Mkhumbuza, who carried out key experiments. “But as the beam travels forward, spinning regions appear and separate out — almost as if the spin was hiding and then revealed itself.”

    Rather than creating spin through an external optical component, the researchers demonstrated how the beam’s existing internal structure can determine where spinning regions develop during propagation.

    The Hidden Geometry That Controls Light

    To explain this unexpected behavior, the researchers turned to topology, a mathematical field concerned with properties that remain unchanged when objects are continuously stretched, bent, or reshaped.

    Dr. Isaac Nape, from the University of the Witwatersrand in Johannesburg, South Africa, offered a simple way to understand the concept.

    “To explain it, imagine a mug and a doughnut,” he said. “You can morph one into the other without tearing it, because they both have one hole. That hole is a topological feature.”

    The researchers found that structured light possesses its own topological characteristics, encoded in the arrangement of its polarization.

    This underlying pattern acts like a mathematical fingerprint. Even as the light beam changes shape while traveling, its topological structure remains, influencing how different regions of the beam evolve.

    As a result, the arrangement of the light itself can determine where its left-handed and right-handed spinning patterns become visible.

    The discovery gives scientists a way to guide this behavior by designing the beam’s initial structure, rather than depending on specialized materials to produce the desired effect.

    “This gives us a completely new tuning knob for light. By adjusting its topology, we can decide how and where chirality appears,” said Dr. Nape.

    Potential Breakthroughs in Medicine and Communications

    The ability to control light through its geometry could eventually make several important optical technologies simpler, more affordable, and more versatile.

    One particularly promising application involves medical diagnostics and pharmaceutical research. Because many biologically important molecules have left-handed and right-handed forms, carefully structured light could help scientists identify these differences with greater sensitivity. Such tools could be valuable for evaluating drug safety and detecting biological markers associated with disease.

    The same principles could support smaller optical sensors capable of identifying chemicals or biological substances without requiring large, sophisticated laboratory instruments.

    Communications technology could also benefit. By encoding information into different twisting and spinning patterns, researchers may be able to increase the amount of data carried by individual light beams. This could contribute to faster optical communications, improved information security, and future quantum networks.

    Other potential uses include manipulating microscopic particles, cells, and molecules with light, as well as developing more resilient quantum systems. Topological properties may help protect delicate quantum information against certain forms of noise and interference.

    “The implications are wide-ranging,” said Dr. Forbes. “This work could lead to simpler and more sensitive medical tests, especially in drug development.

    “It could also be used to pack more information into laser beams — boosting data capacity for communications, including future quantum networks.

    “And because the effect doesn’t rely on fragile materials or precision-engineered surfaces, it could be easier and cheaper to use in real-world technologies.

    “This research could lay the foundations for a new generation of light-based technologies, by showing that light’s behavior can be controlled using its own internal geometry,” he added.

    These applications remain possibilities for future development, but the underlying discovery provides researchers with another way to design and control the behavior of light.

    A Hidden Property of Light Finally Revealed

    For decades, scientists have relied on increasingly sophisticated optical equipment to produce and manipulate unusual forms of light. The findings suggest that some of these behaviors can instead arise from carefully designed structures already encoded within a light beam.

    By showing how topology governs the emergence of spinning regions during propagation, the team has revealed a previously underappreciated connection between light’s geometry and its physical behavior.

    The discovery also illustrates how much remains to be learned about something as familiar and extensively studied as light.

    “For something so familiar, light is proving to be far richer, stranger and more powerful than anyone imagined,” said Dr. Forbes.

    “And astonishingly, this new behavior has been there all along — just waiting to be seen.”

    The research, ‘Topological Control of Chirality and Spin with Structured Light’, was published in the journal Light: Science & Applications.

  • After 30 years, scientists finally have a drug for a deadly brain disease

    After 30 years, scientists finally have a drug for a deadly brain disease

    The FDA has approved the first drug designed to directly treat Alexander disease, an extremely rare neurological disorder that progressively damages the nervous system and can be fatal. The treatment, called Zanvastro, represents a major advance for patients who previously had no options beyond managing their symptoms.

    Alexander disease can interfere with movement, thinking, and automatic bodily functions such as breathing and heart rate. Zanvastro is the first and only approved disease-modifying treatment for the condition, meaning it targets an underlying biological process responsible for the disease rather than simply relieving its effects.

    The drug emerged from more than three decades of scientific research at the University of Wisconsin-Madison’s School of Veterinary Medicine and Waisman Center. Much of that work took place in the laboratory of Albee Messing, professor emeritus of comparative biosciences and former director of the Waisman Center, whose discoveries helped make the treatment possible. Ionis Pharmaceuticals collaborated in developing the drug.

    Clinical trials offered encouraging results. Patients receiving Zanvastro generally experienced stabilization of their motor function, and some showed improvements in their ability to move.

    “This is a wonderful and long-awaited day for the Alexander disease community,” Messing says.

    Alexander Disease: A Rare and Devastating Brain Disorder

    Alexander disease affects fewer than one in every million people worldwide. Although exceptionally uncommon, its consequences can be severe, with symptoms that gradually interfere with everyday activities and essential bodily functions.

    People with the disorder may develop seizures, lose previously acquired developmental abilities, experience increasing difficulty walking or moving, and struggle with speaking or swallowing. Some also develop dangerously elevated pressure inside the brain.

    The disease does not follow a single predictable course. Symptoms may first emerge during infancy, childhood, or adulthood, and their severity and progression can differ depending on when the condition begins.

    For decades, doctors could offer supportive care and treatments to ease individual symptoms, but they had no approved medication capable of targeting the disease itself.

    An Unexpected Discovery Revealed the Genetic Cause

    The breakthrough can be traced to research Messing conducted with Michael Brenner, professor emeritus of neurobiology at the University of Alabama at Birmingham. In the late 1990s, their work identified the genetic changes responsible for Alexander disease, providing scientists with a specific biological target for developing treatments.

    The discovery began with an unexpected result in laboratory mice.

    Messing and Brenner had genetically engineered mice to produce unusually high amounts of a protein known as glial fibrillary acidic protein (GFAP). This protein is normally found in astrocytes, specialized cells that help support and maintain healthy function in the brain and spinal cord.

    To the researchers’ surprise, the modified mice developed abnormal protein deposits throughout their brains. These deposits appeared inside astrocytes and closely resembled the distinctive abnormalities seen in people with Alexander disease.

    “We had, really without intending to, created a mouse that produced these classic lesions of Alexander disease,” Messing says.

    The abnormal deposits, called Rosenthal fibers, are a defining characteristic of the disorder. Additional genetic studies involving people diagnosed with Alexander disease confirmed that mutations in the gene responsible for producing GFAP were the underlying cause.

    “This provided an obvious and specific strategy for therapy — the GFAP protein,” Messing explains.

    Identifying the genetic cause also made diagnosing the condition much simpler. Instead of relying on invasive brain biopsies to look for characteristic tissue abnormalities, doctors could use genetic testing from a blood sample to identify the mutations associated with the disease.

    Scientists Develop a Drug That Targets Harmful Protein Buildup

    Once researchers understood the role of GFAP, their next challenge was finding a way to reduce its production and prevent damaging levels of the protein from accumulating in brain cells.

    Messing joined forces with Tracy Hagemann, an associate research professor at the Waisman Center, to create improved rodent models of Alexander disease. These models more closely reproduced important features of the disorder, giving scientists a way to investigate potential treatments before testing them in people.

    The team focused on a straightforward idea: If excessive GFAP contributes to the disease, lowering the amount produced might help protect the nervous system.

    In collaboration with Ionis Pharmaceuticals, the researchers pursued a technology known as antisense oligonucleotides (ASOs).

    These treatments use short, specially designed pieces of genetic material to interfere with instructions that cells use to manufacture particular proteins. Rather than targeting every protein in a cell, an ASO can be designed to reduce production of a specific one.

    For Alexander disease, that target was GFAP.

    The experimental treatment produced promising results in rodents, supporting the decision to move forward with human testing. A clinical trial began in the summer of 2021.

    Zanvastro uses this same targeted strategy. By limiting GFAP production, the drug aims to reduce the buildup of the protein before it can cause additional damage.

    Because the treatment needs to reach the central nervous system, it is administered through an injection into the spinal canal. A trained healthcare professional gives the injection once every three months.

    Clinical Trials Show Improvements in Walking and Movement

    The human trial provided evidence that lowering GFAP could offer meaningful benefits to people living with Alexander disease.

    Ionis Pharmaceuticals conducted the international study across 13 clinical sites, enrolling 54 patients to evaluate the treatment’s safety and effectiveness.

    After receiving Zanvastro for a little more than a year, treated patients demonstrated significantly better walking speeds than patients who had not received the drug.

    The results also indicated that treatment could stabilize motor function, an important outcome for a progressive disorder that can steadily undermine a person’s ability to move independently. Some participants experienced improvements in motor performance.

    These findings helped establish Zanvastro as the first treatment approved to modify the underlying disease process in Alexander disease, rather than focusing exclusively on symptom relief.

    The FDA approval covers people with Alexander disease across the full age spectrum, from infancy through adulthood.

    Zanvastro is expected to become available in the United States in the weeks following the approval. Outside the United States, access to the drug will be handled through a licensing agreement between Ionis Pharmaceuticals and Recordati, a major pharmaceutical company headquartered in Italy.

    A 30-Year Scientific Journey Offers New Hope

    For Messing and his colleagues, the approval represents the culmination of more than 30 years of research, beginning with basic investigations into brain cell biology and eventually leading to a treatment for patients.

    What started as an unexpected finding in genetically modified mice helped reveal the cause of an extremely rare disease, transformed how doctors diagnose it, and provided the foundation for developing a drug.

    The achievement is also an example of translational research, the process of turning discoveries made in laboratories into treatments that can directly benefit patients.

    Throughout that journey, individuals living with Alexander disease and their families played an essential role by supporting the research and participating in studies.

    “The whole program of research would not have been possible without the support and participation from the patient and family community, to whom we will always be grateful,” Messing says.

  • Your gut bacteria could be changing how many calories you absorb

    Your gut bacteria could be changing how many calories you absorb

    The calorie count printed on a food package might seem like a straightforward measure of how much energy you will get from eating it. But the number on the label does not necessarily match the calories your body actually absorbs. One reason is that digestion involves more than just breaking down food. It also depends on trillions of microorganisms living inside your digestive system.

    Researchers at Arizona State University have developed a mathematical model that explores this often overlooked part of digestion. Known as DAMM, short for digestion, absorption and microbial metabolism, the model tracks how food moves through the digestive tract, how much energy the body absorbs directly, and how gut microbes process whatever remains. It also estimates which products of digestion are absorbed and which leave the body as waste.

    By accounting for the relationship between diet, human digestion, and gut bacteria, the researchers hope to improve our understanding of obesity, diabetes, and other metabolic disorders. With further development, the approach could eventually help health care professionals create diets tailored to individual patients.

    “Digestion is not just a human process — it is a collaboration between our bodies and trillions of microbes living in the gut,” said Professor Rosa Krajmalnik-Brown. “DAMM gives us a powerful new way to quantify how those microbial partners contribute to human health and energy balance, and also point at the importance of properly feeding our gut microbes.”

    Krajmalnik-Brown is director of ASU’s Biodesign Center for Health Through Microbiomes and a professor in the university’s School of Sustainable Engineering and the Built Environment.

    The research team also included ASU Professor Bruce Rittmann, director of the Biodesign Swette Center for Environmental Biotechnology and a Regents Professor of environmental engineering, along with first author Taylor Davis, an ASU graduate research assistant. Scientists at the AdventHealth Translational Research Institute in Orlando, Florida, collaborated on the project.

    The findings were published in PLOS One.

    Why Traditional Calorie Counts Miss Part of the Picture

    For more than 100 years, scientists have used a system based on Atwater parameters to estimate how much energy people can obtain from food. This method assigns average calorie values to each gram of fat, carbohydrates, and protein, then uses those values to calculate the total available energy.

    Although this approach is practical and widely used, it cannot fully explain what happens during digestion. In particular, it does not account for how different foods nourish gut bacteria or how those bacteria transform undigested material into substances the body can use for energy.

    One important example involves short-chain fatty acids. These compounds are produced when microbes in the colon break down fiber and other food components that pass through the upper digestive tract without being absorbed. Some of these fatty acids can enter the bloodstream and provide additional calories.

    To better understand these interactions, the researchers built on an earlier controlled diet study investigating how the gut microbiome influences human energy balance. The gut microbiome consists of the enormous community of bacteria and other microorganisms that inhabit the digestive system.

    A High-Fiber Diet Led to 116 Fewer Calories Absorbed Per Day

    In the clinical study, healthy adults followed one of two carefully designed eating plans. The first was a microbiome-enhancer diet containing substantial amounts of fiber and resistant starch (less processed foods and foods with larger particle size). Resistant starch is a type of carbohydrate that escapes much of the usual digestion in the small intestine, allowing it to reach the colon, where microbes can break it down.

    The second eating plan resembled a typical Western diet, with lower amounts of fiber and resistant starch (more processed foods and smaller particle size).

    Despite both diets being designed for the study, participants absorbed noticeably different amounts of energy. Those consuming the Western diet absorbed approximately 116 more calories per day than those eating the fiber-rich diet.

    Perhaps just as interesting, the people following the higher-fiber eating plan did not report feeling hungrier.

    The findings suggest that the amount of energy people obtain from food depends partly on its composition and how it moves through the digestive system. Differences in food processing, fiber content, and microbial activity can all influence the final outcome.

    “What is truly unique about the DAMM model is that it quantitatively links human metabolism to the metabolism of the microorganisms in the colon in a way that matches the results from the clinical study and provides fundamental insight into how the microbial community works in partnership with the human host,” Rittmann said.

    Gut Bacteria Can Supply About 140 Calories a Day

    The DAMM model offers a more detailed way to follow the energy contained in food from the moment it enters the digestive system.

    First, it examines the protein, carbohydrate, and fat content of a person’s diet and estimates how much usable energy is absorbed in the upper gastrointestinal tract.

    It then tracks the remaining material as it moves into the colon. Here, gut microbes break down nutrients that escaped earlier digestion, producing compounds such as short-chain fatty acids. The body can absorb some of these compounds through the colon and use them as another source of energy.

    The model also includes methane production by certain microorganisms called methanogens, which generate methane as part of their metabolism.

    According to the researchers’ calculations, short-chain fatty acids absorbed from the colon supplied an average of approximately 140 calories per day. That represents about 7.4% of the total usable energy obtained from food.

    More broadly, the model estimated that roughly 85% of usable energy came from the upper gastrointestinal tract, while approximately 15% came from the lower gastrointestinal tract, where microbes are especially important.

    These findings highlight why traditional calorie calculations cannot fully describe human digestion. A meaningful share of the energy available to the body is influenced by microbial processes that conventional food-label calculations do not explicitly measure.

    When the team compared DAMM’s predictions with actual measurements from the controlled diet study, the model produced estimates that were closer to the observed calorie absorption than those generated using the conventional Atwater approach.

    The older method generally underestimated how many calories participants absorbed. By including microbial metabolism, DAMM provided a more accurate estimate of the energy obtained from the different diets.

    How Fiber Changes the Calorie Equation

    One of the model’s most revealing features is its ability to account for differences between diets.

    The microbiome-enhancer diet delivered more fiber and other fermentable material to the colon. This gave gut microbes additional substances to break down, increasing their production of short-chain fatty acids.

    DAMM predicted this increase, consistent with the pattern observed in the controlled clinical trial. Participants consuming the microbiome-enhancer diet had higher levels of short-chain fatty acids in measurements taken from their blood serum and feces.

    These compounds are important because they illustrate how closely microbial activity and human metabolism are connected. Gut bacteria can transform food components that would otherwise pass through the digestive system into molecules that the body can absorb and use for energy.

    However, producing more of these compounds does not necessarily mean absorbing more calories overall.

    In fact, participants following the microbiome-enhancer diet absorbed fewer net calories than those eating the Western diet, even though the higher-fiber diet supported greater microbial activity and increased short-chain fatty acid production.

    This apparent contradiction becomes easier to understand when the different stages of digestion are examined separately. Although gut microbes can generate additional usable energy, the amount absorbed directly from food in the upper digestive tract also matters.

    DAMM helps researchers distinguish between these contributions. It estimates how much energy the body extracts before food reaches the colon, how much energy microbes produce from the remaining material, and how much ultimately gets absorbed or eliminated.

    Toward More Personalized Diets and Better Nutrition

    By bringing human digestion and microbial metabolism into a single mathematical framework, the researchers have created a tool that could help explain why different diets produce different effects on the body’s energy balance.

    The approach may eventually improve scientists’ understanding of how diet influences obesity, diabetes, and other metabolic conditions. It also raises the possibility of designing nutrition plans that consider not only the nutrients in food but also how those nutrients interact with the microbes living inside each person’s gut.

    For now, the model provides a research framework rather than a ready-to-use method for prescribing personalized diets. Further studies will be needed to determine how well it performs across different populations, eating patterns, and microbiome compositions.

    The researchers also expect the model to become more sophisticated as scientists uncover additional details about how microorganisms and the human body exchange nutrients and energy.

    “The DAMM model is more than just a tool for characterizing diet,” Davis said. “It’s a framework designed to evolve. As we discover more on how diet, metabolism and the microbes interact, the new insights can be incorporated into the model, allowing it to grow with us as we learn.”

  • StockWatch: Caribou Plunges as It Pursues Strategic Alternatives

    StockWatch: Caribou Plunges as It Pursues Strategic Alternatives

    Caribou Biosciences (Nasdaq: CRBU), whose co-founders include Jennifer Doudna, PhD, capped a one-year 83% freefall of its stock after announcing plans to evaluate strategic alternatives, as investors responded with a selloff that sent shares of the CRISPR genome-editing cell therapy developer plunging 62% this past week.

    Caribou announced plans to carry out an unspecified “substantial” reduction of its workforce—which numbered 97 people as of February 27, according to its most recent Form 10-K Annual report, filed March 5—as well as a halt to trials of its two clinical-phase pipeline candidates, both allogeneic chimeric antigen receptor (CAR) T-cell therapy programs, and other cost reduction measures also yet to be specified.

    Rachel Haurwitz, PhD, Caribou Biosciences co-founder, president, and CEO

    “Caribou’s story has taken a heartbreaking turn,” co-founder, president, and CEO Rachel Haurwitz, PhD, posted on LinkedIn, announcing the company’s strategic review. “This decision is not a loss of belief in our science, our clinical data, or what these programs could mean for patients. It reflects the difficult reality that the current financing environment for allogeneic CAR T-cell therapies has made it impossible to secure the capital required to responsibly advance them.”

    Haurwitz co-established Caribou in 2011 along with Doudna and two other co-founders: Martin Jínek, PhD, a former postdoctoral fellow in Doudna’s lab, now at the University of Zurich, who led the seminal 2012 study leading to the Nobel Prize; and James Berger, PhD, professor in the department of biophysics and biophysical chemistry at Johns Hopkins University School of Medicine.

    Caribou became operational in 2012, which would make it the oldest CRISPR therapeutics company as far as Haurwitz could recall in a 2021 interview. That year, Caribou went public through an upsized initial public offering (IPO) that raised $321 million in aggregate net proceeds after deducting underwriting discounts and commissions and other offering expenses. Caribou sold 21.85 million shares at an IPO price of $16 a share, up from earlier plans to sell 13.5 million shares.

    Two years later, Haurwitz shared with GEN her journey from graduate student in Doudna’s lab to launching a biotech start-up: “This is the only job I’ve ever had!”

    Trials halted

    As a result of the strategic review, Caribou has halted trials of vispacabtagene regedleucel (vispa-cel, formerly CB-010) a treatment for relapsed or refractory (r/r) B cell non-Hodgkin lymphoma. Caribou has said vispa-cel is the first allogeneic CAR T-cell therapy “to our knowledge” that has reached the clinic with a PD-1 knockout, a genome-editing strategy designed to improve antitumor activity by limiting premature CAR T-cell exhaustion.

    To manufacture vispa-cel, Caribou applies Cas9 hybrid RNA-DNA guide or “chardonnay” (chRDNA) to make three edits: A knockout of the TRAC gene to remove the T cell receptor; a site-specific insertion of an anti-CD19 CAR into the TRAC gene; and a knockout of PD-1.

    Also halted were clinical studies of CB-011, an allogeneic anti-BCMA CAR-T cell therapy for the treatment of patients with r/r multiple myeloma (RRMM). To manufacture CB-011, Caribou uses Cas12a chRDNAs designed to direct precise genome editing, in order to make four edits:

    • A knockout of the TRAC gene to remove the T-cell receptor
    • A site-specific insertion of a humanized anti-BCMA CAR into the TRAC gene
    • A site-specific insertion of a gene encoding a B2M–HLA-E-peptide fusion into the B2M gene
    • The resulting knockout of the endogenous B2M

    “This method simultaneously eliminates endogenous HLA class I presentation on the surface of the CAR T cells and expresses HLA-E, a minor HLA class I antigen, to blunt both T and NK cell-mediated rejection of the CAR T-cell therapy by the patient’s immune system,” Caribou explained on its website.

    Strategic pivot

    The development of CB-011 and vispa-cel followed a strategic pivot by Caribou from a platform company for biopharma partners applying genome editing in research or product development, to a developer of genome-edited therapies based on its own next-generation CRISPR technology.

    While that pivot has generated positive data readouts, it has not shielded Caribou from the financial challenges faced by numerous gene-edited therapy developers. In April 2025, Caribou chopped its workforce by 32% and pruned its pipeline by ending all preclinical research, the Phase I GALLOP trial (NCT06752876) of vispa-cel in lupus (before the first patient could be dosed), and development of CB-012, including the Phase I AMpLify trial (NCT06128044) assessing the candidate in relapsed or refractory acute myeloid leukemia (AML).

    “It was really about right sizing the organization relative to our focused priorities,” Haurwitz explained last year in an interview. Asked how hopeful she was about an improving economic environment over the next 12 months, she replied: “I remain a believer and I remain an optimist. I’d probably be in the wrong job in the wrong line of work if I weren’t.”

    “I certainly think for the work that we are doing, I continue to fully believe that doing right by patients is the North Star, because business success falls out from that in terms of nearer term clinical catalysts and opportunities that come from doing right by patients. And longer-term commercial opportunity also comes from doing right by patients,” Haurwitz added.

    Caribou has retained Wedbush Securities as its exclusive financial advisor to assist in evaluating strategic options.

    Caribou announced its pursuit of strategic alternatives after the closure of financial markets on October 6. The following day, Caribou shares began three days of stock declines, nosediving 46% from $1.14 to 62 cents. Those shares tumbled another 22% Thursday to 48 cents, but closed Friday with another 4% decline, finishing the week at 46 cents.

    Cash crunch

    Daina M. Graybosch, PhD, senior managing director, immuno-oncology and a senior research analyst with Leerink Partners, reported in a research note that Caribou was facing an increasingly pressing cash crunch at a time when the company needed significant capital to fund its planned Phase III ANTLER-3 trial, designed to assess vispa-cel in second-line auto-CAR T ineligible diffuse large B-cell lymphoma (DLBCL).

    Caribou never enrolled patients in the pivotal study, though it reached agreement with the FDA in May on a design for the trial, which was expected to be a randomized, controlled clinical study enrolling approximately 250 CD19-naïve second line (2L) large B cell lymphoma patients ineligible for transplant and not candidates or not eligible for autologous CAR T-cell therapy.

    “We are sympathetic to management’s stated rationale for exploring strategic alternatives,” Graybosch commented. “Evidently, investors were unwilling to fund the trial on what would have been highly dilutive terms, especially in the context of lingering clinical risk and uncertainty around the strength of vispa-cel’s Ph[ase I/II] outcomes and partial HLA-matching strategy, as well as substantial in- and out-of-class competition.”

    That competition, she wrote, included epcoritamab, a bispecific T-cell engager (BiTE) therapy already marketed as Epkinly® by Genmab (Nasdaq Copenhagen and Nasdaq: GMAB) and AbbVie (NYSE: ABBV).

    On October 5—the day before Caribou’s strategic alternatives announcement—Genmab and AbbVie reported positive topline data from the Phase III EPCORE DLBCL-2 trial (NCT05578976) showing that the combination of epcoritamab, rituximab, the corticosteroid prednisone, and three chemotherapy drugs showed statistically significant and clinically meaningful improvement in progression-free survival (PFS) in frontline diagnosed DLBCL patients.

    The combination therapy, nicknamed R-CHOP, consists of rituximab—the CD20-directed cytolytic antibody marketed by Genentech, a member of the Roche Group (SIX Swiss: RO and ROP) and Biogen (Nasdaq: BIIB) as Rituxan®—plus cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone. In DLBCL patients with an International Prognostic Index (IPI) score of 2 to 5, R-CHOP reduced the risk of disease progression or death by 51% (HR 0.49 [95% CI 0.36, 0.67]; p-value < 0.0001).

    “Interesting” timing

    “The timing of [Caribou’s] initiative is interesting,” Graybosch observed. “We believe there is enhanced strategic value and clinical rationale for allogeneic cell therapies in a world where TCEs [T-cell engagers] become entrenched in the 1L [first-line] setting.”

    As for CB-011, it began development much earlier than vispa-cel, “with an appreciably more challenging competitive setup in RRMM, where we saw elevated clinical risk for its post-BCMA therapy development path due to potential efficacy-compromising loss-of-antigen,” the Leerink Partners analyst added.

    Single target allogeneic BCMA CAR-T treatments have posed a potential risk of RRMM relapse through antigen loss as myeloma cells mutate or downregulate BCMA to evade the CAR T cells. To minimize that risk, Caribou designed its Phase I CaMMouflage trial (NCT05722418) to limit the therapy dosing to BCMA-naïve patients—an approach that proved successful when the company last year announced positive data from a 12-patient, BCMA-naïve cohort showing a 92% overall response rate (11/12 patients), a 75% or greater complete response rate (9/12), and 91% minimal residual disease (MRD) negativity (10/11 evaluable patients).

    To avoid the risk of antigen loss, several developers of allogeneic BCMA CAR-Ts have designed dual targeting CAR Ts. For example, Allogene Therapeutics (Nasdaq: ALLO) is developing ALLO-329, which targets CD19 on B cells and CD70 on activated T cells. ALLO-329 generated positive preclinical data in April, with a data update from the Phase I RESOLUTION trial (NCT07085104) expected later in Q4.

    Another challenge to CB-011 and other allogenic therapies for RRMM: The multiple myeloma space has been reshaped by autologous BCMA CAR-T therapies that have won approval by demonstrating safety and effectiveness—including Carvykti® (ciltacabtagene autoleucel), co-marketed by Legend Biotech (Nasdaq: LEGN) and Johnson & Johnson (NYSE: JNJ); and Abecma® (idecabtagene vicleucel), marketed by Bristol Myers Squibb (NYSE: BMY).

    Souring on the stock

    Graybosch downgraded Caribou’s rating from “Outperform” to “Market Perform” and chopped the firm’s 12-month price target 75%, from $4 to $1. Graybosch was among several Wall Street analysts who responded to Caribou’s news by souring on the company’s stock, downgrading their ratings:

    • Brookline Capital Markets (Leah Ruch Cann)—From “Buy” to “Hold,” no price target.
    • H.C. Wainwright (Robert Burns)—From “Buy” to “Neutral,” no price target.
    • RBC Capital Markets (Luca Issi, PhD)—From “Outperform” to “Sector Perform,” price target slashed 90% from $10 to $1.

    Caribou reported $113.8 million in cash, cash equivalents, and marketable securities as of the end of the second quarter on June 30—a 4% dip from the $118.6 million reported at the end of Q1, but a 20% drop from the $142.8 million Caribou had as of December 31, 2025, and a 38% slide from the $183.9 million reported June 30, 2025.

    “We expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operations for at least the next 12 months from the date this Form 10-Q is filed with the SEC [U.S. Securities and Exchange Commission],” Caribou stated in its most recent Form 10-Q quarterly report detailing second-quarter results, filed August 13.

    Leaders and laggards

    • Arrivent BioPharma (Nasdaq: AVBP) shares plummeted 47% October 6 from $28.46 to $15.09 after the cancer drug developer announced that its lead pipeline candidate firmonertinib failed the Phase III FURVENT trial (NCT05607550) designed to assess the oral, mutation-selective epidermal growth factor receptor (EGFR) inhibitor in previously untreated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. Firmonertinib did not meet its primary endpoint of meaningful progression free survival (PFS) compared to chemotherapy as evaluated by blinded independent central review (BICR). Arrivent said that clinical benefit was seen in secondary endpoints such as PFS by investigator’s assessment and confirmed objective response rate by BICR. A trend toward improved overall survival was also seen, the company added.
    • Pacira BioSciences (Nasdaq: PCRX) shares soared 44% Thursday from $25.20 to $36.39 after Viatris (Nasdaq: VTRS) agreed to acquire the non-opioid pain drug developer for $1.65 billion. The deal adds to Pacira’s portfolio with two marketed drugs—the postsurgical pain relief therapy Exparel® (bupivacaine liposome injectable suspension), and the osteoarthritis knee pain treatment Zilretta® (triamcinolone acetonide extended-release injectable suspension). Viatris said it plans to apply its intellectual property expertise and ability to extend product lifecycles and sustain meaningful sales post-competition “to maximize the long-term value of the Pacira portfolio” and expects to expand its reach across select markets. Pacira generated approximately $746 million in revenue and approximately $177 million in adjusted earnings before interest, taxes, depreciation, and amortization (EBITDA) during the 12 months ending June 30. Viatris plans to commence a tender offer for all outstanding Pacira common stock shares for $36.50 per share cash. The deal is set to close by year’s end.