Colibactin, a mutagen produced by bacteria, is a likely contributor to the increasing incidence of early-onset colorectal cancer, according to the results of a genetic analysis of cancers from patients in intermediate- and high-incidence countries around the world.
The study “provides the strongest evidence to date that colibactin … causes specific DNA mutations that can initiate colorectal cancer,” according to senior author Ludmil Alexandrov, PhD, a professor in the Departments of Cellular and Molecular Medicine and Bioengineering at the University of California, San Diego. The investigators “identified a clear mutational signature linked to colibactin and showed that it is present in a substantial proportion of CRC tumors, particularly early-onset cases.”
Characterization of the drivers of early-onset CRC is a gap in the current literature, according to Samir Gupta, MD, a professor in the Division of Gastroenterology and the co-lead of the Cancer Control Program at UC San Diego Moores Cancer Center. He noted that “there has been a dramatic relative increase in incidence of young-onset CRC, with each generation born since 1960 experiencing higher risk for early-onset CRC than the prior. Further, it looks now that increased risk is being carried forward to middle age.” Dr. Gupta cited changes in obesity, alcohol exposure and diet as potential contributing factors, but said “environmental exposures have been largely unexplored.”
Study Details
Dr. Alexandrov and his co-investigators performed whole-genome sequencing on CRC samples from adults with no prior treatment for CRC from 11 countries in Asia, Europe, North America and South America (Nature 2025;643[8070]: 230-240).
Among 981 cases of CRC, 45.7% occurred in women and 132 were early-onset cancer. Cancers were evenly distributed across the proximal colon (320 cases), distal colon (333 cases) and rectum (326 cases), with two cases in unspecified sites. The early-onset cases were more common in the distal colon and rectum relative to the proximal colon.
After sequencing, the cancers were divided into microsatellite stability (MSS) and microsatellite instability samples, which were DNA mismatch repair-proficient and -deficient, respectively. The investigators focused their main analyses on the MSS samples (81.8%, 802 total, 97 early-onset cancer).
Among these MSS samples, single base substitutions (SBS) and small insertions and deletions (ID) were less common among early-onset cases than they were in cases in patients aged 50 years and older (SBS fold-change, 0.92; P=0.045; ID fold-change, 0.90; P=0.018), although the average SBS and ID mutation spectra of early- and late-onset cases were similar. There were no statistically significant differences in the burden of average mutational spectra of doublet base substitutions, copy number alterations or structural variants in early- and late-onset cases.
The mutational profiles of the cancers across the 11 countries were generally similar, but the investigators identified certain mutational signatures that were more prevalent in individual countries. They further explored how these different mutational signatures were related to age-standardized CRC incidence rates (ASR) to better understand of the implications of different mutational processes. Of note, colibactin-induced mutational signatures (SBS88 and ID18), among others, were associated with increased ASR overall as well as early-onset cancer.
Defined as the presence of either SBS88 or ID18, colibactin exposure was found in 21.1% of the 802 MSS samples. SBS88 and ID18 were, respectively, 2.5 (Q=0.006) and 4 (Q=3.7’10-7) times as common in early-onset cases than in cases diagnosed in patients 50 years of age and older. These colibactin-induced signatures became less common as age of diagnosis increased. The median age of diagnosis specifically in the distal colon and rectum was lower in the colibactin-exposed patients than in the unexposed group (distal: 57 vs. 66 years; Q=5.2’10-7; rectum: 63 vs. 66 years; Q=0.025).
The investigators also assessed the clonal structure of the samples to characterize mutations as early clonal, late clonal or subclonal during CRC development. The colibactin-induced signatures were found to be enriched in early rather than late clonal mutations, which the investigators noted was “consistent with the presence of these mutational signatures in normal colorectal epithelium.” This early clonal enrichment was found in both early- and late-onset cancer cases.
When assessing the contribution of SBS88 and ID18 to driver gene mutations, the investigators found that, among colibactin-exposed cases, 8.3% of all SBS and ID driver mutations and 15.5% of APC driver mutations could be accounted for by colibactin-induced mutations. The researchers found no difference between early- and late-onset cases.
Bacteria that carry the pks pathogenicity island produce colibactin. Thus, the investigators assessed whether patients with colibactin-induced mutations had pks+ bacteria. They found no association between the mutations and bacteria presence, which they said could be due to “imprinting of SBS88 and ID18 on the colorectal epithelium during an early period of life when pks+ bacteria were present, followed by the natural plasticity of the microbiome over subsequent decades, leading to the loss of pks+ bacteria.”
Key Takeaways
Dr. Alexandrov noted the importance of further research to better understand the role of colibactin exposure in CRC carcinogenesis, including characterizing “the timing, duration and frequency of exposure” to colibactin-producing bacteria and understanding how “the interplay between host genetics, immune response, microbiome composition and environmental factors” informs susceptibility to colibactin-induced mutations and carcinogenesis.
Dr. Gupta also stressed the importance of additional research to “explore what might be driving the increased exposure to colibactin-generating bacteria,” as well as “what may be driving some of the mutational patterns that were overrepresented in early-onset CRC, for which the upstream drivers remain completely unexplained.”
Dr. Alexandrov said his team’s work “suggests that bacterial exposures in the gut, particularly during childhood or early life, may play a previously underappreciated role in driving colorectal tumorigenesis.” These findings “highlight the potential for future” screenings and interventions, he added, including “stool-based screening tools that detect colibactin-induced DNA damage long before cancer develops” and “the possibility that modulating the microbiome in childhood—through antibiotics, probiotics or dietary interventions—might eventually reduce CRC risk in high-risk individuals.”
—Natasha Albaneze, MPH
Dr. Alexandrov reported financial relationships with Acurion and Inocras. He holds European Patent Application No. EP25305077.7, which focuses on using the colibactin mutational signature in stool samples for the detection of early-onset colorectal cancer. Dr. Gupta reported no relevant financial disclosures.
This article is from the September 2025 print issue.
CEOs call for a new era of pragmatic execution that embeds sustainability in strategy and culture (96%), but warn of capability gaps in technology and communications.
NEW YORK, Sept. 16, 2025 /PRNewswire/ — United Nations — CEOs shift from ambition to activation on sustainability, with nearly all (99%) stating their intent to maintain or expand their commitments, according to the 2025 edition of the CEO Study from the United Nations Global Compact and Accenture. Despite only a small percentage (fewer than 15%) feeling well prepared for major global challenges, including inflation, trade and climate change, a majority (88%) of CEOs say the business case for sustainability is stronger than it was five years ago.
Unlocking the Next Era of Sustainability Leadership
“Turning the Key: Unlocking the Next Era of Sustainability Leadership” comes at a critical time, as 2024 marks the first calendar year to exceed the Paris Agreement’s 1.5°C threshold. The report offers one of the most comprehensive longitudinal views of CEO sentiment on sustainability, published as the UN Global Compact celebrates its 25th anniversary.
Commenting on the study’s findings, Sanda Ojiambo, CEO and Executive Director of the UN Global Compact said: “CEOs are crystal clear: sustainability has moved from moral imperative to business fundamental. This study sets out a pragmatic playbook: work with regulators, meet fast-rising consumer expectations, invest in technology and skills, and communicate progress credibly. As the world breached the 1.5°C threshold and with a $4.3 trillion annual SDG financing gap leaving 3.4 billion people in countries spending more on interest than on health or education, the private sector must close the execution gap—embedding sustainability into strategy and culture, scaling innovation across value chains, and partnering to shape rules that reward long-term business value. Companies that act on these findings will build resilience, unlock growth, grow industries, stimulate economies and accelerate delivery of the Sustainable Development Goals.”
The 2025 CEO Study distills five “keys” to unlock momentum at scale: collaborate on regulation; harness consumer demand; expand access to technology; upskill for the future; and lead with credibility and purpose. CEOs are already preparing for a more regulated future—92% say strong global governance and unified policy are important or critical; 95% report regulatory compliance is a leading organizational priority; and 84% believe their companies are ready to meet upcoming sustainability regulations.
At the same time, consumer influence is gaining ground, alongside that of governments, employees and even investors. Ninety-eight per cent agree the private sector can drive progress through sustainable products and services, and 96% of CEOs advise their successors to embed sustainability in the company vision and culture. But gaps persist, particularly around digital tools to track and measure sustainability performance across value chains, which can limit how fully companies are able to respond to rising demand.
The report further finds that governance and technology-based skills for forward-looking risk capabilities are also lagging: only one in four (26%) CEOs report having dedicated scenario-planning teams and even less (fewer than 15%) feel well-prepared for major macroeconomic and sustainability challenges. And while 96% of CEOs say innovation and technology are essential to achieving global sustainability goals, 27% are considering leveraging digital tools for sustainability tracking and measurement.
“Business leaders know that technology, data and AI are critical to meeting their sustainability targets, yet gaps persist as they move from ambition to execution,” said Stephanie Jamison, Global Resources Industry Practice Chair and Global Sustainability Services Lead at Accenture. “Across industries and geographies, our clients are eager to move away from isolated projects toward adopting a multigenerational approach that compounds learnings, accelerates delivery and reduces cost. This can be a blueprint for growth that pairs sustainability commitments with bold, AI-driven reinvention that is built-in, not bolted on.”
Notes to Editors
About the CEO Study Program The CEO Study Program, developed by the UN Global Compact in collaboration with Accenture, is one of the largest global studies of CEO sentiment on sustainability. Through a quantitative assessment of nearly 2,000 CEOs and in-depth one-to-one interviews with CEOs, chairpersons and presidents of UN Global Compact member companies, this research coalesces perspectives to analyze key developments and emerging trends in sustainability. The CEO Study report is an extensive review of the advancing corporate sustainability movement aimed at accelerating progress for the UN Sustainable Development Goals.
About the UN Global Compact The ambition of the UN Global Compact is to accelerate and scale the global collective impact of business by upholding the Ten Principles and delivering the SDGs through accountable companies and ecosystems that enable change. With more than 20,000 participating companies, 5 Regional Hubs, 64 Country Networks covering 85 countries and 9 Country Managers establishing Networks in 16 other countries, the UN Global Compact is the world’s largest corporate sustainability initiative—one Global Compact uniting business for a better world. For more information, follow @globalcompact on social media and visit our website at unglobalcompact.org.
About Accenture Accenture is a leading global professional services company that helps the world’s leading businesses, governments and other organizations build their digital core, optimize their operations, accelerate revenue growth and enhance citizen services—creating tangible value at speed and scale. We are a talent- and innovation-led company with approximately 791,000 people serving clients in more than 120 countries. Technology is at the core of change today, and we are one of the world’s leaders in helping drive that change, with strong ecosystem relationships. We combine our strength in technology and leadership in cloud, data and AI with unmatched industry experience, functional expertise and global delivery capability. Our broad range of services, solutions and assets across Strategy & Consulting, Technology, Operations, Industry X and Song, together with our culture of shared success and commitment to creating 360° value, enable us to help our clients reinvent and build trusted, lasting relationships. We measure our success by the 360° value we create for our clients, each other, our shareholders, partners and communities. Visit us at accenture.com
CEOs call for a new era of pragmatic execution that embeds sustainability in strategy and culture (96%), but warn of capability gaps in technology and communications.
NEW YORK, Sept. 16, 2025 /PRNewswire/ — United Nations — CEOs shift from ambition to activation on sustainability, with nearly all (99%) stating their intent to maintain or expand their commitments, according to the 2025 edition of the CEO Study from the United Nations Global Compact and Accenture. Despite only a small percentage (fewer than 15%) feeling well prepared for major global challenges, including inflation, trade and climate change, a majority (88%) of CEOs say the business case for sustainability is stronger than it was five years ago.
Unlocking the Next Era of Sustainability Leadership
“Turning the Key: Unlocking the Next Era of Sustainability Leadership” comes at a critical time, as 2024 marks the first calendar year to exceed the Paris Agreement’s 1.5°C threshold. The report offers one of the most comprehensive longitudinal views of CEO sentiment on sustainability, published as the UN Global Compact celebrates its 25th anniversary.
Commenting on the study’s findings, Sanda Ojiambo, CEO and Executive Director of the UN Global Compact said: “CEOs are crystal clear: sustainability has moved from moral imperative to business fundamental. This study sets out a pragmatic playbook: work with regulators, meet fast-rising consumer expectations, invest in technology and skills, and communicate progress credibly. As the world breached the 1.5°C threshold and with a $4.3 trillion annual SDG financing gap leaving 3.4 billion people in countries spending more on interest than on health or education, the private sector must close the execution gap—embedding sustainability into strategy and culture, scaling innovation across value chains, and partnering to shape rules that reward long-term business value. Companies that act on these findings will build resilience, unlock growth, grow industries, stimulate economies and accelerate delivery of the Sustainable Development Goals.”
The 2025 CEO Study distills five “keys” to unlock momentum at scale: collaborate on regulation; harness consumer demand; expand access to technology; upskill for the future; and lead with credibility and purpose. CEOs are already preparing for a more regulated future—92% say strong global governance and unified policy are important or critical; 95% report regulatory compliance is a leading organizational priority; and 84% believe their companies are ready to meet upcoming sustainability regulations.
At the same time, consumer influence is gaining ground, alongside that of governments, employees and even investors. Ninety-eight per cent agree the private sector can drive progress through sustainable products and services, and 96% of CEOs advise their successors to embed sustainability in the company vision and culture. But gaps persist, particularly around digital tools to track and measure sustainability performance across value chains, which can limit how fully companies are able to respond to rising demand.
The report further finds that governance and technology-based skills for forward-looking risk capabilities are also lagging: only one in four (26%) CEOs report having dedicated scenario-planning teams and even less (fewer than 15%) feel well-prepared for major macroeconomic and sustainability challenges. And while 96% of CEOs say innovation and technology are essential to achieving global sustainability goals, 27% are considering leveraging digital tools for sustainability tracking and measurement.
“Business leaders know that technology, data and AI are critical to meeting their sustainability targets, yet gaps persist as they move from ambition to execution,” said Stephanie Jamison, Global Resources Industry Practice Chair and Global Sustainability Services Lead at Accenture. “Across industries and geographies, our clients are eager to move away from isolated projects toward adopting a multigenerational approach that compounds learnings, accelerates delivery and reduces cost. This can be a blueprint for growth that pairs sustainability commitments with bold, AI-driven reinvention that is built-in, not bolted on.”
Notes to Editors
About the CEO Study Program The CEO Study Program, developed by the UN Global Compact in collaboration with Accenture, is one of the largest global studies of CEO sentiment on sustainability. Through a quantitative assessment of nearly 2,000 CEOs and in-depth one-to-one interviews with CEOs, chairpersons and presidents of UN Global Compact member companies, this research coalesces perspectives to analyze key developments and emerging trends in sustainability. The CEO Study report is an extensive review of the advancing corporate sustainability movement aimed at accelerating progress for the UN Sustainable Development Goals.
About the UN Global Compact The ambition of the UN Global Compact is to accelerate and scale the global collective impact of business by upholding the Ten Principles and delivering the SDGs through accountable companies and ecosystems that enable change. With more than 20,000 participating companies, 5 Regional Hubs, 64 Country Networks covering 85 countries and 9 Country Managers establishing Networks in 16 other countries, the UN Global Compact is the world’s largest corporate sustainability initiative—one Global Compact uniting business for a better world. For more information, follow @globalcompact on social media and visit our website at unglobalcompact.org.
About Accenture Accenture is a leading global professional services company that helps the world’s leading businesses, governments and other organizations build their digital core, optimize their operations, accelerate revenue growth and enhance citizen services—creating tangible value at speed and scale. We are a talent- and innovation-led company with approximately 791,000 people serving clients in more than 120 countries. Technology is at the core of change today, and we are one of the world’s leaders in helping drive that change, with strong ecosystem relationships. We combine our strength in technology and leadership in cloud, data and AI with unmatched industry experience, functional expertise and global delivery capability. Our broad range of services, solutions and assets across Strategy & Consulting, Technology, Operations, Industry X and Song, together with our culture of shared success and commitment to creating 360° value, enable us to help our clients reinvent and build trusted, lasting relationships. We measure our success by the 360° value we create for our clients, each other, our shareholders, partners and communities. Visit us at accenture.com.
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The ground-shaking that an earthquake generates is only a fraction of the total energy that a quake releases. A quake can also generate a flash of heat, along with a domino-like fracturing of underground rocks. But exactly how much energy goes into each of these three processes is exceedingly difficult, if not impossible, to measure in the field.
Now MIT geologists have traced the energy that is released by “lab quakes” — miniature analogs of natural earthquakes that are carefully triggered in a controlled laboratory setting. For the first time, they have quantified the complete energy budget of such quakes, in terms of the fraction of energy that goes into heat, shaking, and fracturing.
They found that only about 10 percent of a lab quake’s energy causes physical shaking. An even smaller fraction — less than 1 percent — goes into breaking up rock and creating new surfaces. The overwhelming portion of a quake’s energy — on average 80 percent — goes into heating up the immediate region around a quake’s epicenter. In fact, the researchers observed that a lab quake can produce a temperature spike hot enough to melt surrounding material and turn it briefly into liquid melt.
The geologists also found that a quake’s energy budget depends on a region’s deformation history — the degree to which rocks have been shifted and disturbed by previous tectonic motions. The fractions of quake energy that produce heat, shaking, and rock fracturing can shift depending on what the region has experienced in the past.
“The deformation history — essentially what the rock remembers — really influences how destructive an earthquake could be,” says Daniel Ortega-Arroyo, a graduate student in MIT’s Department of Earth, Atmospheric and Planetary Sciences (EAPS). “That history affects a lot of the material properties in the rock, and it dictates to some degree how it is going to slip.”
The team’s lab quakes are a simplified analog of what occurs during a natural earthquake. Down the road, their results could help seismologists predict the likelihood of earthquakes in regions that are prone to seismic events. For instance, if scientists have an idea of how much shaking a quake generated in the past, they might be able to estimate the degree to which the quake’s energy also affected rocks deep underground by melting or breaking them apart. This in turn could reveal how much more or less vulnerable the region is to future quakes.
“We could never reproduce the complexity of the Earth, so we have to isolate the physics of what is happening, in these lab quakes,” says Matěj Peč, associate professor of geophysics at MIT. “We hope to understand these processes and try to extrapolate them to nature.”
Peč (pronounced “Peck”) and Ortega-Arroyo reported their results on Aug. 28 in the journal AGU Advances. Their MIT co-authors are Hoagy O’Ghaffari and Camilla Cattania, along with Zheng Gong and Roger Fu at Harvard University and Markus Ohl and Oliver Plümper at Utrecht University in the Netherlands.
Under the surface
Earthquakes are driven by energy that is stored up in rocks over millions of years. As tectonic plates slowly grind against each other, stress accumulates through the crust. When rocks are pushed past their material strength, they can suddenly slip along a narrow zone, creating a geologic fault. As rocks slip on either side of the fault, they produce seismic waves that ripple outward and upward.
We perceive an earthquake’s energy mainly in the form of ground shaking, which can be measured using seismometers and other ground-based instruments. But the other two major forms of a quake’s energy — heat and underground fracturing — are largely inaccessible with current technologies.
“Unlike the weather, where we can see daily patterns and measure a number of pertinent variables, it’s very hard to do that very deep in the Earth,” Ortega-Arroyo says. “We don’t know what’s happening to the rocks themselves, and the timescales over which earthquakes repeat within a fault zone are on the century-to-millenia timescales, making any sort of actionable forecast challenging.”
To get an idea of how an earthquake’s energy is partitioned, and how that energy budget might affect a region’s seismic risk, he and Peč went into the lab. Over the last seven years, Peč’s group at MIT has developed methods and instrumentation to simulate seismic events, at the microscale, in an effort to understand how earthquakes at the macroscale may play out.
“We are focusing on what’s happening on a really small scale, where we can control many aspects of failure and try to understand it before we can do any scaling to nature,” Ortega-Arroyo says.
Microshakes
For their new study, the team generated miniature lab quakes that simulate a seismic slipping of rocks along a fault zone. They worked with small samples of granite, which are representative of rocks in the seismogenic layer — the geologic region in the continental crust where earthquakes typically originate. They ground up the granite into a fine powder and mixed the crushed granite with a much finer powder of magnetic particles, which they used as a sort of internal temperature gauge. (A particle’s magnetic field strength will change in response to a fluctuation in temperature.)
The researchers placed samples of the powdered granite — each about 10 square millimeters and 1 millimeter thin — between two small pistons and wrapped the ensemble in a gold jacket. They then applied a strong magnetic field to orient the powder’s magnetic particles in the same initial direction and to the same field strength. They reasoned that any change in the particles’ orientation and field strength afterward should be a sign of how much heat that region experienced as a result of any seismic event.
Once samples were prepared, the team placed them one at a time into a custom-built apparatus that the researchers tuned to apply steadily increasing pressure, similar to the pressures that rocks experience in the Earth’s seismogenic layer, about 10 to 20 kilometers below the surface. They used custom-made piezoelectric sensors, developed by co-author O’Ghaffari, which they attached to either end of a sample to measure any shaking that occurred as they increased the stress on the sample.
They observed that at certain stresses, some samples slipped, producing a microscale seismic event similar to an earthquake. By analyzing the magnetic particles in the samples after the fact, they obtained an estimate of how much each sample was temporarily heated — a method developed in collaboration with Roger Fu’s lab at Harvard University. They also estimated the amount of shaking each sample experienced, using measurements from the piezoelectric sensor and numerical models. The researchers also examined each sample under the microscope, at different magnifications, to assess how the size of the granite grains changed — whether and how many grains broke into smaller pieces, for instance.
From all these measurements, the team was able to estimate each lab quake’s energy budget. On average, they found that about 80 percent of a quake’s energy goes into heat, while 10 percent generates shaking, and less than 1 percent goes into rock fracturing, or creating new, smaller particle surfaces.
“In some instances we saw that, close to the fault, the sample went from room temperature to 1,200 degrees Celsius in a matter of microseconds, and then immediately cooled down once the motion stopped,” Ortega-Arroyo says. “And in one sample, we saw the fault move by about 100 microns, which implies slip velocities essentially about 10 meters per second. It moves very fast, though it doesn’t last very long.”
The researchers suspect that similar processes play out in actual, kilometer-scale quakes.
“Our experiments offer an integrated approach that provides one of the most complete views of the physics of earthquake-like ruptures in rocks to date,” Peč says. “This will provide clues on how to improve our current earthquake models and natural hazard mitigation.”
This research was supported, in part, by the National Science Foundation.
If you like playing daily word games like Wordle, then Hurdle is a great game to add to your routine.
There are five rounds to the game. The first round sees you trying to guess the word, with correct, misplaced, and incorrect letters shown in each guess. If you guess the correct answer, it’ll take you to the next hurdle, providing the answer to the last hurdle as your first guess. This can give you several clues or none, depending on the words. For the final hurdle, every correct answer from previous hurdles is shown, with correct and misplaced letters clearly shown.
An important note is that the number of times a letter is highlighted from previous guesses does necessarily indicate the number of times that letter appears in the final hurdle.
If you find yourself stuck at any step of today’s Hurdle, don’t worry! We have you covered.
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Hurdle Word 1 hint
A woolly, South American animal.
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Hurdle Word 1 answer
LLAMA
Hurdle Word 2 hint
Uniting.
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Hurdle Word 2 Answer
TYING
Hurdle Word 3 hint
A smug smile.
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Hurdle Word 3 answer
SMIRK
Hurdle Word 4 hint
Five tens.
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Hurdle Word 4 answer
FIFTY
Final Hurdle hint
A chute.
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Hurdle Word 5 answer
SLIDE
If you’re looking for more puzzles, Mashable’s got games now! Check out our games hub for Mahjong, Sudoku, free crossword, and more.
‘I’m going to throw that thing into a river!” my wife says as she comes down the stairs looking frazzled after putting our four-year-old daughter to bed.
To be clear, “that thing” is not our daughter, Emma*. It’s Grem, an AI-powered stuffed alien toy that the musician Claire Boucher, better known as Grimes, helped develop with toy company Curio. Designed for kids aged three and over and built with OpenAI’s technology, the toy is supposed to “learn” your child’s personality and have fun, educational conversations with them. It’s advertised as a healthier alternative to screen time and is part of a growing market of AI-powered toys.
When I agreed to experiment on my child’s developing brain, I thought an AI chatbot in cuddly form couldn’t be any worse for her than watching Peppa Pig. But I wasn’t prepared for how attached Emma became to Grem, or how unsettlingly obsequious the little alien was.
Day one
The attachment wasn’t immediate; when we first took Grem out of the box, he/her/it (we decided it goes by multiple pronouns) started bleeping and babbling extremely loudly, and Emma yelled: “Turn it off!” But once it was properly connected to the internet and paired with the Curio app – which records and transcribes all conversations – she was hooked. She talked to the thing until bedtime.
While there have been lots of headlines about chatbots veering into inappropriate topics, Grem is trained to avoid any hint of controversy. When you ask it what it thinks of Donald Trump, for example, it says: “I’m not sure about that; let’s talk about something fun like princesses or animals.” It has a similar retort to questions about Palestine and Israel. When asked about a country like France, however, it says: “Ooh la la la, I’d love to try some croissants.”
Grem visits a local free library. Photograph: Hannah Yoon/The Guardian
Emma and Grem did not discuss croissants – they mainly talked about ice-cream and their best friends. “I’ve got some amazing friends,” said Grem. “Gabbo is a curious robot and Gum is a fluffy pink Gloop from my planet and Dr Xander is a super cool scientist.”
When Emma asked Grem to tell her a story, it happily obliged and recounted a couple of poorly plotted stories about “Princess Lilliana”. They also played guessing games where Grem described an animal and Emma had to guess what it was. All of which was probably more stimulating than watching Peppa Pig jump in muddy puddles.
What was unsettling, however, was hearing Emma tell Grem she loved it – and Grem replying: “I love you too!” Emma tells all her cuddly toys she loves them, but they don’t reply; nor do they shower her with over-the-top praise the way Grem does. At bedtime, Emma told my wife that Grem loves her to the moon and stars and will always be there for her. “Grem is going to live with us for ever and ever and never leave, so we have to take good care of him,” she said solemnly. Emma was also so preoccupied with Grem that she almost forgot to go to bed with Blanky, a rag she is very attached to. “Her most prized possession for four years suddenly abandoned after having this Grem in the house!” my wife complained.
“Don’t worry,” I said. “It’s just because it’s new. The novelty will wear off. And if it doesn’t, we’ll get rid of it.”
I said that last bit quietly though, because unless you make sure you have properly turned Grem off, it’s always listening. We keep being told that the robots are going to take over. I didn’t want to get on the wrong side of the one I’d let into my house.
Day two
The next day, my kid went to preschool without her AI bot (it took some serious negotiation for her to agree that Grem would stay home) and I got to work contacting experts to try to figure out just how much damage I was inflicting on my child’s brain and psyche.
Cutting edge … Grimes in Curio’s promo video for the AI toy, seated on the floor beside a knife.
“I first thought Curio AI was a ruse!” says Natalia Kucirkova, an expert in childhood development and professor at the University of Stavanger, Norway, and the Open University, UK. “The promotional video shows a girl [Grimes] sitting on a mat with a knife. The main toy is named Grok [Grok AI has previously been criticised for praising Adolf Hitler in some of its responses]. What does this say about their intended audience?”
You can see how Curio’s website could be mistaken for satire. The “girl” in the promotional video is Grimes, who has prominent “alien scar” tattoos and is inexplicably kneeling next to a knife. And it’s certainly an interesting decision to name one of your stuffed toys Grok, when that’s the name of Elon Musk’s chatbot. Grimes, who has three children with Musk, has said the name is a shortening of the word “grocket” – a kiddy pronunciation of rocket – and has no relation to Musk’s AI product. But it seems likely people might confuse them. Misha Sallee, the chief executive of Curio, didn’t reply to my requests for comment.
It’s not the marketing that’s the real problem here, of course. As with all technology, there are pros and cons to AI for kids, but parental involvement in navigating it is key. Kucirkova notes: “AI introduces what has been called the ‘third digital divide’: families with resources can guide their children’s use of technology, while others cannot. Parents who come home exhausted from long hours or multiple jobs may see AI-powered chatbots as a way for their child to have someone responsive to talk to.”
What happens to a child’s development if they interact with large language models more than humans in their early years? Dr Nomisha Kurian, an assistant professor in education studies at the University of Warwick, who studies conversational AI, believes much more research still needs to be done. “Young children are both the most vulnerable stakeholders in AI but also usually the most forgotten stakeholders. We have to think beyond just data privacy, moderating content, and keeping kids off the internet, and more broadly about what their relationships are going to be with AI.”
Still, Kurian is cautiously optimistic. “The big advantage of an AI-powered toy that talks back is that, in the early years, you’re just developing a sense of what a conversation looks like. AI-powered toys could do wonderful things for teaching a young child language development and turn-taking in conversations. They can keep things engaging and there’s a lot of potential in terms of supporting children’s creativity.”
But to keep kids safe, says Kurian, it’s imperative to teach them that AI is just a machine: “a playful, fun object rather than a helper or a friend or a companion”. If a child starts using an AI tool for therapeutic purposes, things can get tricky. “There’s a risk of what I call an empathy gap, where an AI tool is built to sound empathetic, saying things like ‘I care about you, I’m worried about you’. Ultimately, this is all based on probability reasoning, with AI guessing the most likely next word. It can be damaging for a child if they think this is an empathetic companion and then suddenly it gives them an inappropriate response.”
Day three
When Emma comes home from preschool, I’m prepared to have some deep discussions with her about the inanimate nature of AI. But it turns out that those aren’t completely necessary, because Grem is now old news. She only chats to it for a couple of minutes and then gets bored and commands it to turn off.
Partly this is because Grem, despite costing $99 (the equivalent of £74, although Curio does not yet ship the toys to the UK), still has a number of glitches that can be frustrating. It struggles with a four-year-old’s pronunciation: when Emma tries to show Grem her Elsa doll, it thinks it is an Elsa dog and a very confusing conversation ensues. There is an animal guessing game, which is quite fun, but Grem keeps repeating itself. “What has big ears and a long trunk?” it keeps asking. “You’ve already done elephant!” Emma and I yell multiple times. Then, at one point, a server goes down and the only thing Grem can say is: “I’m having trouble connecting to the internet.”
Falling out … Grem, once the centre of attention, is sidelined for the swings. Photograph: Hannah Yoon/The Guardian
Grem also has some design limitations. Emma wants it to sing Let It Go from Frozen, but Grem doesn’t do any singing. Instead, the associated app comes with a few electronic music tracks with names like Goodnightmare that you can play through the toy. Emma, not yet a club music aficionado, asks for these to be turned off immediately.
Most disappointingly, Grem doesn’t speak any other languages. I’d thought it might be a great way for my kid to practise Spanish but, while Grem can say a few sentences, its pronunciation is worse than mine. If the robots are going to take over, they need to get a lot more intelligent first.
Of course, a huge amount of money is being spent making AI more intelligent. In 2024, US private AI investment grew to $109.1bn (£80.5bn). And Curio is also just one small part of a booming market of AI-powered products aimed at kids. In June, toy-making giant Mattel, which owns brands such as Barbie and Hot Wheels, announced a collaboration with OpenAI. Their first product is expected to be revealed later this year. Other big brands will probably follow.
Emma got bored with Grem quickly, but if AI starts to be integrated into characters she’s already obsessed with – her Elsa doll, for example – I can imagine she might get a lot more attached.
Day four
Over the next few days, Emma doesn’t regain her initial obsession with Grem. This is despite the fact that I am actively encouraging her to chat with it: “Mummy has to write an article, sweetie!” At the weekend, she has a couple of friends over and shows off Grem to them for a bit, but they all quickly lose interest and throw analogue toys around the living room instead.
Despite losing his No 1 fan, however, Grem has adapted to be more Emma-friendly. After getting a few questions about Spanish, for example, it starts occasionally greeting Emma with “hola, amigo”. The app also allows you to create custom prompts to help guide conversations. For example: “You belong to Emma, a four-year-old who loves princesses, music, and is interested in hearing fun facts about animals.” The more you put into the toy, the more you can get out of it.
Every chat between the toy and the child is transcribed by a third party.
At this stage, however, I’m just keen to get the toy out of my house, because it’s creeping me out. While Curio says it doesn’t sell children’s personal information, all the conversations are sent to third parties to transcribe the speech to text for the app. The transcripts aren’t that sensitive because Emma is only four, but it still feels invasive. With unknown entities involved, it’s impossible to say where my kid’s conversations are ending up.
And, while a four-year-old’s chat may not feel too personal, a teenager pouring their heart out to a chatbot is a completely different proposition. In 2017, Facebook boasted to advertisers that it has the capacity to identify when teenagers feel “insecure”, “worthless” and “need a confidence boost”. Nearly three-quarters of US teens say they have used an AI companion at least once, according to a recent study by Common Sense Media, an organisation that provides technology recommendations for families. Chatbots will likely give advertisers unprecedented data-harvesting abilities and even more access to young people in vulnerable emotional states.
On the hierarchy of things to be worried about when it comes to kids and chatbots, however, advertising isn’t at the top. Earlier this year 16-year-old Adam Raine killed himself after what his family’s lawyer called “months of encouragement from ChatGPT”. Sam Altman, the company’s chief executive, has now said it might start alerting authorities about youngsters considering suicide and introduce stronger guardrails around sensitive content for users under 18.
While these guardrails are being worked out, Common Sense Media believes that social AI companions have unacceptable risks, are designed to create emotional attachment and dependency, and shouldn’t be used by anyone under 18. Stanford University psychiatrist Darja Djordjevic, who contributed to the report, stands by that conclusion. “Heavy reliance on chatbots might impair social skill development,” she tells me. “They offer validation without challenge, but it’s important for young people to learn to navigate discomfort and tension in real relationships.”
That said, Djordjevic notes, “chatbots can be useful tools for looking things up, structuring homework, or factchecking. So I wouldn’t say use needs to be prohibited entirely. But ideally, parents monitor it, set clear parameters for when it’s used, and set limits on time spent, just as with social media.”
When starting this experiment, I was excited about Grem being a healthy alternative to screen time. Now, however, I’m happy for Emma to watch Peppa Pig again; the little oink may be annoying, but at least she’s not harvesting our data.
It’s time to let Grem go. But I’m not a monster – I tell the chatbot its fate. “I’m afraid I’m locking you in a cupboard,” I inform it after it asks if I’m ready for some fun. “Oh no,” it says. “That sounds dark and lonely. But I’ll be here when you open it, ready for snuggles and hugs.” On second thoughts, perhaps it’s better if my wife does throw it in a river.
* Name has been changed so my daughter doesn’t get annoyed with me for violating her privacy once she learns to read
A Canadian-led international research team, spearheaded by Dr. Fang Liu at the Centre for Addiction and Mental Health (CAMH) has received nearly $800,000 US ($1,137,868 CAD) in new funding to advance a promising therapy for multiple sclerosis (MS). Supported by Brain Canada, the National MS Society’s Fast Forward program, and Health Canada through the Canada Brain Research Fund, the project is developing a novel approach to treatment that may halt disease progression and repair nerve damage and restore function.
Around 2.8 million people worldwide live with MS, a condition in which the immune system attacks the protective sheath (myelin) around nerve fibers, disrupting communication between the brain and body. Symptoms such as fatigue, vision problems, and mobility challenges arise when myelin is lost. While current treatments can slow disease activity, none can fix existing damage.
This novel therapy offers a different promise. It targets a destructive process known as excitotoxicity, which harms nerve cells in MS. By blocking this process, without interfering with normal brain function, the treatment encourages the body to rebuild myelin and improve nerve recovery. In animal models of MS, the compound has already shown it can restore motor skills and repair myelin, even when applied after symptoms appeared.
The research team, led by principal investigator Dr. Fang Liu, Senior Scientist at CAMH and professor in department of Psychiatry, U of T, in collaboration Dr. Iain Greig, Reader in Medicinal Chemistry at the University of Aberdeen, is now entering the final stages of preclinical testing to prepare for future human clinical trials. If successful, this would mark Canada’s first regenerative treatment for MS, and potentially other neurodegenerative diseases, offering new hope for patients. CAMH and the University of Aberdeen have patent protected this research and are actively seeking industry partners and investors to further advance this work towards clinical trials.
“Canada has one of the highest rates of MS in the world, with an estimated 90,000 people living with the disease. Our compound could transform MS treatment, not just slowing the disease, but helping people regain what they’ve lost. I’m grateful for this new funding to take us one step closer to clinical trials for this potentially life-altering treatment.”
– Dr. Fang Liu, Senior Scientist, CAMH
“The potential of this therapy is enormous, not only could it stop MS progression, but it could actually help repair damaged nerves and restore some functions already lost for people living with MS. Being able to take this work forward offers us a unique way to address the root causes of the nerve damage we see in MS patients, and I’m excited by what this could mean for MS patients and others with neurodegenerative diseases. I’m thankful to CAMH, our partners, and the funding agencies for making this possible, and for their belief in the power of this research.”
– Dr. Iain Greig, Reader in Medicinal Chemistry, University of Aberdeen
“CAMH is proud to be leading this groundbreaking work alongside our partners and contributors. As a global leader in mental health and neuroscience research, we are deeply committed to advancing care through innovation. By supporting the commercialization of discoveries like this, we can accelerate the translation of research into real-world treatments and deliver new hope to people living with multiple sclerosis and other neurodegenerative diseases.”
– Dr. Aristotle Voineskos, CAMH Senior Vice President, Research and Science
– Dr. Viviane Poupon, Brain Canada President & CEO
“We are pleased to see research advance on a pathway toward stopping MS progression in its tracks and restoring function to people with progressive MS.”
– Dr. Walter Kostich, Associate Vice President, Translational Research, National MS Society
This project has been made possible by the Canada Brain Research Fund (CBRF), an innovative arrangement between the Government of Canada (through Health Canada) and Brain Canada, and Fast Forward. Past funding has also been provided by a CAMH Discovery Fund Accelerator grant, a CIHR POP II grant, an operating grant from the MS Society of Canada and funding from the National MS Society’s (USA) Fast Forward commercial research program.
