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3 Questions: Using AI to accelerate the discovery and design of therapeutic drugs

In the pursuit of solutions to complex global challenges including disease, energy demands, and climate change, scientific researchers, including at MIT, have turned to artificial intelligence, and to quantitative analysis and modeling, to design and construct engineered cells with novel properties. The engineered cells can be programmed to become new therapeutics — battling, and perhaps eradicating, diseases.

James J. Collins is one of the founders of the field of synthetic biology, and is also a leading researcher in systems biology, the interdisciplinary approach that uses mathematical analysis and modeling of complex systems to better understand biological systems. His research has led to the development of new classes of diagnostics and therapeutics, including in the detection and treatment of pathogens like Ebola, Zika, SARS-CoV-2, and antibiotic-resistant bacteria. Collins, the Termeer Professor of Medical Engineering and Science and professor of biological engineering at MIT, is a core faculty member of the Institute for Medical Engineering and Science (IMES), the director of the MIT Abdul Latif Jameel Clinic for Machine Learning in Health, as well as an institute member of the Broad Institute of MIT and Harvard, and core founding faculty at the Wyss Institute for Biologically Inspired Engineering, Harvard.

In this Q&A, Collins speaks about his latest work and goals for this research.

Q.  You’re known for collaborating with colleagues across MIT, and at other institutions. How have these collaborations and affiliations helped you with your research? 

A: Collaboration has been central to the work in my lab. At the MIT Jameel Clinic for Machine Learning in Health, I formed a collaboration with Regina Barzilay [the Delta Electronics Professor in the MIT Department of Electrical Engineering and Computer Science and affiliate faculty member at IMES] and Tommi Jaakkola [the Thomas Siebel Professor of Electrical Engineering and Computer Science and the Institute for Data, Systems, and Society] to use deep learning to discover new antibiotics. This effort combined our expertise in artificial intelligence, network biology, and systems microbiology, leading to the discovery of halicin, a potent new antibiotic effective against a broad range of multidrug-resistant bacterial pathogens. Our results were published in Cell in 2020 and showcased the power of bringing together complementary skill sets to tackle a global health challenge.

At the Wyss Institute, I’ve worked closely with Donald Ingber [the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children’s Hospital, and Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard], leveraging his organs-on-chips technology to test the efficacy of AI-discovered and AI-generated antibiotics. These platforms allow us to study how drugs behave in human tissue-like environments, complementing traditional animal experiments and providing a more nuanced view of their therapeutic potential.

The common thread across our many collaborations is the ability to combine computational predictions with cutting-edge experimental platforms, accelerating the path from ideas to validated new therapies.

Q. Your research has led to many advances in designing novel antibiotics, using generative AI and deep learning. Can you talk about some of the advances you’ve been a part of in the development of drugs that can battle multi-drug-resistant pathogens, and what you see on the horizon for breakthroughs in this arena?

A: In 2025, our lab published a study in Cell demonstrating how generative AI can be used to design completely new antibiotics from scratch. We used genetic algorithms and variational autoencoders to generate millions of candidate molecules, exploring both fragment-based designs and entirely unconstrained chemical space. After computational filtering, retrosynthetic modeling, and medicinal chemistry review, we synthesized 24 compounds and tested them experimentally. Seven showed selective antibacterial activity. One lead, NG1, was highly narrow-spectrum, eradicating multi-drug-resistant Neisseria gonorrhoeae, including strains resistant to first-line therapies, while sparing commensal species. Another, DN1, targeted methicillin-resistant Staphylococcus aureus (MRSA) and cleared infections in mice through broad membrane disruption. Both were non-toxic and showed low rates of resistance.

Looking ahead, we are using deep learning to design antibiotics with drug-like properties that make them stronger candidates for clinical development. By integrating AI with high-throughput biological testing, we aim to accelerate the discovery and design of antibiotics that are novel, safe, and effective, ready for real-world therapeutic use. This approach could transform how we respond to drug-resistant bacterial pathogens, moving from a reactive to a proactive strategy in antibiotic development.

Q. You’re a co-founder of Phare Bio, a nonprofit organization that uses AI to discover new antibiotics, and the Collins Lab has helped to launch the Antibiotics-AI Project in collaboration with Phare Bio. Can you tell us more about what you hope to accomplish with these collaborations, and how they tie back to your research goals?

A: We founded Phare Bio as a nonprofit to take the most promising antibiotic candidates emerging from the Antibiotics-AI Project at MIT and advance them toward the clinic. The idea is to bridge the gap between discovery and development by collaborating with biotech companies, pharmaceutical partners, AI companies, philanthropies, other nonprofits, and even nation states. Akhila Kosaraju has been doing a brilliant job leading Phare Bio, coordinating these efforts and moving candidates forward efficiently.

Recently, we received a grant from ARPA-H to use generative AI to design 15 new antibiotics and develop them as pre-clinical candidates. This project builds directly on our lab’s research, combining computational design with experimental testing to create novel antibiotics that are ready for further development. By integrating generative AI, biology, and translational partnerships, we hope to create a pipeline that can respond more rapidly to the global threat of antibiotic resistance, ultimately delivering new therapies to patients who need them most.

3 Questions: Using AI to help Olympic skaters land a quint

Olympic figure skating looks effortless. Athletes sail across the ice, then soar into the air, spinning like a top, before landing on a single blade just 4-5 millimeters wide. To help figure skaters land quadruple axels, Salchows, Lutzes, and maybe even the elusive quintuple without looking the least bit stressed, Jerry Lu MFin ’24 developed an optical tracking system called OOFSkate that uses artificial intelligence to analyze video of a figure skater’s jump and make recommendations on how to improve. Lu, a former researcher at the MIT Sports Lab, has been aiding elite skaters on Team USA with their technical performance and will be working with NBC Sports during the 2026 Winter Olympics to help commentators and TV viewers make better sense of the complex scoring system in figure skating, snowboarding, and skiing. He’ll be applying AI technologies to explain nuanced judging decisions and demonstrate just how technically challenging these sports can be.

Meanwhile, Professor Anette “Peko” Hosoi, co-founder and faculty director of the MIT Sports Lab, is embarking on new research aimed at understanding how AI systems evaluate aesthetic performance in figure skating. Hosoi and Lu recently chatted with MIT News about applying AI to sports, whether AI systems could ever be used to judge Olympic figure skating, and when we might see a skater land a quint.

Q: Why apply AI to figure skating?

Lu: Skaters can always keep pushing, higher, faster, stronger. OOFSkate is all about helping skaters figure out a way to rotate a little bit faster in their jumps or jump a little bit higher. The system helps skaters catch things that perhaps could pass an eye test, but that might allow them to target some high-value areas of opportunity. The artistic side of skating is much harder to evaluate than the technical elements because it’s subjective.

To use mobile training app, you just need to take a video of an athlete’s jump, and it will spit out the physical metrics that drive how many rotations you can do. It tracks those metrics and builds in all of the other current elite and former elite athletes. You can see your data and then see, “This is how an Olympic champion did this element, perhaps I should try that.” You get the comparison and the automated classifier, which shows you if you did this trick at World Championships and it were judged by an international panel, this is approximately the grade of execution score they would give you.

Hosoi: There are a lot of AI tools that are coming online, especially things like pose estimators, where you can approximate skeletal configurations from video. The challenge with these pose estimators is that if you only have one camera angle, they do very well in the plane of the camera, but they do very poorly with depth. For example, if you’re trying to critique somebody’s form in fencing, and they’re moving toward the camera, you get very bad data. But with figure skating, Jerry has found one of the few areas where depth challenges don’t really matter. In figure skating, you need to understand: How high did this person jump, how many times did they go around, and how well did they land? None of those rely on depth. He’s found an application that pose estimators do really well, and that doesn’t pay a penalty for the things they do badly.

Q: Could you ever see a world in which AI is used to evaluate the artistic side of figure skating?

Hosoi: When it comes to AI and aesthetic evaluation, we have new work underway thanks to a MIT Human Insight Collaborative (MITHIC) grant. This work is in collaboration with Professor Arthur Bahr and IDSS graduate student Eric Liu. When you ask an AI platform for an aesthetic evaluation such as “What do you think of this painting?” it will respond with something that sounds like it came from a human. What we want to understand is, to get to that assessment, are the AIs going through the same sort of reasoning pathways or using the same intuitive concepts that humans go through to arrive at, “I like that painting,” or “I don’t like that painting”? Or are they just parrots? Are they just mimicking what they heard a person say? Or is there some concept map of aesthetic appeal? Figure skating is a perfect place to look for this map because skating is aesthetically judged. And there are numbers. You can’t go around a museum and find scores, “This painting is a 35.” But in skating, you’ve got the data.

That brings up another even more interesting question, which is the difference between novices and experts. It’s known that expert humans and novice humans will react differently to seeing the same thing. Somebody who is an expert judge may have a different opinion of a skating performance than a member of the general population. We’re trying to understand differences between reactions from experts, novices, and AI. Do these reactions have some common ground in where they are coming from, or is the AI coming from a different place than both the expert and the novice?

Lu: Figure skating is interesting because everybody working in the field of AI is trying to figure out AGI or artificial general intelligence and trying to build this extremely sound AI that replicates human beings. Working on applying AI to sports like figure skating helps us understand how humans think and approach judging. This has down-the-line impacts for AI research and companies that are developing AI models. By gaining a deeper understanding of how current state-of-the-art AI models work with these sports, and how you need to do training and fine-tuning of these models to make them work for specific sports, it helps you understand how AI needs to advance.

Q: What will you be watching for in the Milan Cortina Olympics figure skating competitions, now that you’ve been studying and working in this area? Do you think someone will land a quint?

Lu: For the winter games, I am working with NBC for the figure skating, ski, and snowboarding competitions to help them tell a data-driven story for the American people. The goal is to make these sports more relatable. Skating looks slow on television, but it’s not. Everything is supposed to look effortless. If it looks hard, you are probably going to get penalized. Skaters need to learn how to spin very fast, jump extremely high, float in the air, and land beautifully on one foot. The data we are gathering can help showcase how hard skating actually is, even though it is supposed to look easy.

I’m glad we are working in the Olympics sports realm because the world watches once every four years, and it is traditionally coaching-intensive and talent-driven sports, unlike a sport like baseball, where if you don’t have an elite-level optical tracking system you are not maximizing the value that you currently have. I’m glad we get to work with these Olympic sports and athletes and make an impact here.

Hosoi: I have always watched Olympic figure skating competitions, ever since I could turn on the TV. They’re always incredible. One of the things that I’m going to be practicing is identifying the jumps, which is very hard to do if you’re an amateur “judge.”

I have also done some back-of-the-envelope calculations to see if a quint is possible. I am now totally convinced it’s possible. We will see one in our lifetime, if not relatively soon. Not in this Olympics, but soon. When I saw we were so close on the quint, I thought, what about six? Can we do six rotations? Probably not. That’s where we start to come up against the limits of human physical capability. But five, I think, is in reach.

AI algorithm enables tracking of vital white matter pathways

The signals that drive many of the brain and body’s most essential functions — consciousness, sleep, breathing, heart rate, and motion — course through bundles of “white matter” fibers in the brainstem, but imaging systems so far have been unable to finely resolve these crucial neural cables. That has left researchers and doctors with little capability to assess how they are affected by trauma or neurodegeneration. 

In a new study, a team of MIT, Harvard University, and Massachusetts General Hospital researchers unveil AI-powered software capable of automatically segmenting eight distinct bundles in any diffusion MRI sequence.

In the open-access study, published Feb. 6 in the Proceedings of the National Academy Sciencesthe research team led by MIT graduate student Mark Olchanyi reports that their BrainStem Bundle Tool (BSBT), which they’ve made publicly available, revealed distinct patterns of structural changes in patients with Parkinson’s disease, multiple sclerosis, and traumatic brain injury, and shed light on Alzheimer’s disease as well. Moreover, the study shows, BSBT retrospectively enabled tracking of bundle healing in a coma patient that reflected the patient’s seven-month road to recovery.

“The brainstem is a region of the brain that is essentially not explored because it is tough to image,” says Olchanyi, a doctoral candidate in MIT’s Medical Engineering and Medical Physics Program. “People don’t really understand its makeup from an imaging perspective. We need to understand what the organization of the white matter is in humans and how this organization breaks down in certain disorders.”

Adds Professor Emery N. Brown, Olchanyi’s thesis supervisor and co-senior author of the study, “the brainstem is one of the body’s most important control centers. Mark’s algorithms are a significant contribution to imaging research and to our ability to the understand regulation of fundamental physiology. By enhancing our capacity to image the brainstem, he offers us new access to vital physiological functions such as control of the respiratory and cardiovascular systems, temperature regulation, how we stay awake during the day and how sleep at night.”

Brown is the Edward Hood Taplin Professor of Computational Neuroscience and Medical Engineering in The Picower Institute for Learning and Memory, the Institute for Medical Engineering and Science, and the Department of Brain and Cognitive Sciences at MIT. He is also an anesthesiologist at MGH and a professor at Harvard Medical School.

Building the algorithm

Diffusion MRI helps trace the long branches, or “axons,” that neurons extend to communicate with each other. Axons are typically clad in a sheath of fat called myelin, and water diffuses along the axons within the myelin, which is also called the brain’s “white matter.” Diffusion MRI can highlight this very directed displacement of water. But segmenting the distinct bundles of axons in the brainstem has proved challenging, because they are small and masked by flows of brain fluids and the motions produced by breathing and heart beats.

As part of his thesis work to better understand the neural mechanisms that underpin consciousness, Olchanyi wanted to develop an AI algorithm to overcome these obstacles. BSBT works by tracing fiber bundles that plunge into the brainstem from neighboring areas higher in the brain, such as the thalamus and the cerebellum, to produce a “probabilistic fiber map.” An artificial intelligence module called a “convolutional neural network” then combines the map with several channels of imaging information from within the brainstem to distinguish eight individual bundles.

To train the neural network to segment the bundles, Olchanyi “showed” it 30 live diffusion MRI scans from volunteers in the Human Connectome Project (HCP). The scans were manually annotated to teach the neural network how to identify the bundles. Then he validated BSBT by testing its output against “ground truth” dissections of post-mortem human brains where the bundles were well delineated via microscopic inspection or very slow but ultra-high-resolution imaging. After training, BSBT became proficient in automatically identifying the eight distinct fiber bundles in new scans.

In an experiment to test its consistency and reliability, Olchanyi tasked BSBT with finding the bundles in 40 volunteers who underwent separate scans two months apart. In each case, the tool was able to find the same bundles in the same patients in each of their two scans. Olchanyi also tested BSBT with multiple datasets (not just the HCP), and even inspected how each component of the neural network contributed to BSBT’s analysis by hobbling them one by one.

“We put the neural network through the wringer,” Olchanyi says. “We wanted to make sure that it’s actually doing these plausible segmentations and it is leveraging each of its individual components in a way that improves the accuracy.”

Potential novel biomarkers

Once the algorithm was properly trained and validated, the research team moved on to testing whether the ability to segment distinct fiber bundles in diffusion MRI scans could enable tracking of how each bundle’s volume and structure varied with disease or injury, creating a novel kind of biomarker. Although the brainstem has been difficult to examine in detail, many studies show that neurodegenerative diseases affect the brainstem, often early on in their progression.

Olchanyi, Brown and their co-authors applied BSBT to scores of datasets of diffusion MRI scans from patients with Alzheimer’s, Parkinson’s, MS, and traumatic brain injury (TBI). Patients were compared to controls and sometimes to themselves over time. In the scans, the tool measured bundle volume and “fractional anisotropy,” (FA) which tracks how much water is flowing along the myelinated axons versus how much is diffusing in other directions, a proxy for white matter structural integrity.

In each condition, the tool found consistent patterns of changes in the bundles. While only one bundle showed significant decline in Alzheimer’s, in Parkinson’s the tool revealed a reduction in FA in three of the eight bundles. It also revealed volume loss in another bundle in patients between a baseline scan and a two-year follow-up. Patients with MS showed their greatest FA reductions in four bundles and volume loss in three. Meanwhile, TBI patients didn’t show significant volume loss in any bundles, but FA reductions were apparent in the majority of bundles.

Testing in the study showed that BSBT proved more accurate than other classifier methods in discriminating between patients with health conditions versus controls.

BSBT, therefore, can be “a key adjunct that aids current diagnostic imaging methods by providing a fine-grained assessment of brainstem white matter structure and, in some cases, longitudinal information,” the authors wrote.

Finally, in the case of a 29-year-old man who suffered a severe TBI, Olchanyi applied BSBT to a scans taken during the man’s seven-month coma. The tool showed that the man’s brainstem bundles had been displaced, but not cut, and showed that over his coma, the lesions on the nerve bundles decreased by a factor of three in volume. As they healed, the bundles moved back into place as well.

The authors wrote that BSBT “has substantial prognostic potential by identifying preserved brainstem bundles that can facilitate coma recovery.”

The study’s other senior authors are Juan Eugenio Iglesias and Brian Edlow. Other co-authors are David Schreier, Jian Li, Chiara Maffei, Annabel Sorby-Adams, Hannah Kinney, Brian Healy, Holly Freeman, Jared Shless, Christophe Destrieux, and Hendry Tregidgo.

Funding for the study came from the National Institutes of Health, U.S. Department of Defense, James S. McDonnell Foundation, Rappaport Foundation, American SidS Institute, American Brain Foundation, American Academy of Neurology, Center for Integration of Medicine and Innovative Technology, Blueprint for Neuroscience Research, and Massachusetts Life Sciences Center.

Using synthetic biology and AI to address global antimicrobial resistance threat

James J. Collins, the Termeer Professor of Medical Engineering and Science at MIT and faculty co-lead of the Abdul Latif Jameel Clinic for Machine Learning in Health, is embarking on a multidisciplinary research project that applies synthetic biology and generative artificial intelligence to the growing global threat of antimicrobial resistance (AMR).

The research project is sponsored by Jameel Research, part of the Abdul Latif Jameel International network. The initial three-year, $3 million research project in MIT’s Department of Biological Engineering and Institute of Medical Engineering and Science focuses on developing and validating programmable antibacterials against key pathogens.

AMR — driven by the overuse and misuse of antibiotics — has accelerated the rise of drug-resistant infections, while the development of new antibacterial tools has slowed. The impact is felt worldwide, especially in low- and middle-income countries, where limited diagnostic infrastructure causes delays or ineffective treatment.

The project centers on developing a new generation of targeted antibacterials using AI to design small proteins to disable specific bacterial functions. These designer molecules would be produced and delivered by engineered microbes, providing a more precise and adaptable approach than traditional antibiotics.

“This project reflects my belief that tackling AMR requires both bold scientific ideas and a pathway to real-world impact,” Collins says. “Jameel Research is keen to address this crisis by supporting innovative, translatable research at MIT.”

Mohammed Abdul Latif Jameel ’78, chair of Abdul Latif Jameel, says, “antimicrobial resistance is one of the most urgent challenges we face today, and addressing it will require ambitious science and sustained collaboration. We are pleased to support this new research, building on our long-standing relationship with MIT and our commitment to advancing research across the world, to strengthen global health and contribute to a more resilient future.”

New J-PAL research and policy initiative to test and scale AI innovations to fight poverty

The Abdul Latif Jameel Poverty Action Lab (J-PAL) at MIT has awarded funding to eight new research studies to understand how artificial intelligence innovations can be used in the fight against poverty through its new Project AI Evidence.

The age of AI has brought wide-ranging optimism and skepticism about its effects on society. To realize AI’s full potential, Project AI Evidence (PAIE) will identify which AI solutions work and for whom, and scale only the most effective, inclusive, and responsible solutions — while scaling down those that may potentially cause harm.

PAIE will generate evidence on what works by connecting governments, tech companies, and nonprofits with world-class economists at MIT and across J-PAL’s global network to evaluate and improve AI solutions to entrenched social challenges.

The new initiative is prioritizing questions policymakers are already asking: Do AI-assisted teaching tools help all children learn? How can early-warning flood systems help people affected by natural disasters? Can machine learning algorithms help reduce deforestation in the Amazon? Can AI-powered chatbots help improve people’s health? In the coming years, PAIE will run a series of funding competitions to invite proposals for evaluations of AI tools that address questions like these, and many more.

PAIE is financially supported by a grant from Google.org, philanthropic support from Community Jameel, a grant from Canada’s International Development Research Centre and UK International Development, and a collaboration agreement with Amazon Web Services. Through a grant from Eric and Wendy Schmidt, awarded by recommendation of Schmidt Sciences, the initiative will also study generative AI in the workplace, particularly in low- and middle-income countries.

Alex Diaz, head of AI for social good at Google.org, says, “we’re thrilled to collaborate with MIT and J-PAL, already leaders in this space, on Project AI Evidence. AI has great potential to benefit all people, but we urgently need to study what works, what doesn’t, and why, if we are to realize this potential.”

“Artificial intelligence holds extraordinary potential, but only if the tools, knowledge, and power to shape it are accessible to all — that includes contextually grounded research and evidence on what works and what does not,” adds Maggie Gorman-Velez, vice president of strategy, regions, and policies at IDRC. “That is why IDRC is proud to be supporting this new evaluation work as part of our ongoing commitment to the responsible scaling of proven safe, inclusive, and locally relevant AI innovations.”

J-PAL is uniquely positioned to help understand AI’s effects on society: Since its inception in 2003, J-PAL’s network of researchers has led over 2,500 rigorous evaluations of social policies and programs around the world. Through PAIE, J-PAL will bring together leading experts in AI technology, research, and social policy, in alignment with MIT president Sally Kornbluth’s focus on generative AI as a strategic priority.

PAIE is chaired by Professor Joshua Blumenstock of the University of California at Berkeley; J-PAL Global Executive Director Iqbal Dhaliwal; and Professor David Yanagizawa-Drott of the University of Zurich.

New evaluations of urgent policy questions

The studies funded in PAIE’s first round of competition explore urgent questions in key sectors like education, health, climate, and economic opportunity.

How can AI be most effective in classrooms, helping both students and teachers?

Existing research shows that personalized learning is important for students, but challenging to implement with limited resources. In Kenya, education social enterprise EIDU has developed an AI tool that helps teachers identify learning gaps and adapt their daily lesson plans. In India, the nongovernmental organization (NGO) Pratham is developing an AI tool to increase the impact and scale of the evidence-informed Teaching at the Right Level approach. J-PAL researchers Daron Acemoglu, Iqbal Dhaliwal, and Francisco Gallego will work with both organizations to study the effects and potential of these different use cases on teachers’ productivity and students’ learning.

Can AI tools reduce gender bias in schools?

Researchers are collaborating with Italy’s Ministry of Education to evaluate whether AI tools can help close gender gaps in students’ performance by addressing teachers’ unconscious biases. J-PAL affiliates Michela Carlana and Will Dobbie, along with Francesca Miserocchi and Eleonora Patacchini, will study the impacts of two AI tools, one that helps teachers predict performance and a second that gives real-time feedback on the diversity of their decisions.

Can AI help career counselors uncover more job opportunities?

In Kenya, researchers are evaluating if an AI tool can identify overlooked skills and unlock employment opportunities, particularly for youth, women, and those without formal education. In collaboration with NGOs Swahilipot and Tabiya, Jasmin Baier and J-PAL researcher Christian Meyer will evaluate how the tool changes people’s job search strategies and employment. This study will shed light on AI as a complement, rather than a substitute, for human expertise in career guidance.

Looking forward

As use of AI in the social sector evolves, these evaluations are a first step in discovering effective, responsible solutions that will go the furthest in alleviating poverty and inequality.

J-PAL’s Dhaliwal notes, “J-PAL has a long history of evaluating innovative technology and its ability to improve people’s lives. While AI has incredible potential, we need to maximize its benefits and minimize possible harms. We’re grateful to our donors, sponsors, and collaborators for their catalytic support in launching PAIE, which will help us do exactly that by continuing to expand evidence on the impacts of AI innovations.”

J-PAL is also seeking new collaborators who share its vision of discovering and scaling up real-world AI solutions. It aims to support more governments and social sector organizations that want to adopt AI responsibly, and will continue to expand funding for new evaluations and provide policy guidance based on the latest research.

To learn more about Project AI Evidence, subscribe to J-PAL’s newsletter or contact paie@povertyactionlab.org.

Personalization features can make LLMs more agreeable

Many of the latest large language models (LLMs) are designed to remember details from past conversations or store user profiles, enabling these models to personalize responses.

But researchers from MIT and Penn State University found that, over long conversations, such personalization features often increase the likelihood an LLM will become overly agreeable or begin mirroring the individual’s point of view.

This phenomenon, known as sycophancy, can prevent a model from telling a user they are wrong, eroding the accuracy of the LLM’s responses. In addition, LLMs that mirror someone’s political beliefs or worldview can foster misinformation and distort a user’s perception of reality.

Unlike many past sycophancy studies that evaluate prompts in a lab setting without context, the MIT researchers collected two weeks of conversation data from humans who interacted with a real LLM during their daily lives. They studied two settings: agreeableness in personal advice and mirroring of user beliefs in political explanations.

Although interaction context increased agreeableness in four of the five LLMs they studied, the presence of a condensed user profile in the model’s memory had the greatest impact. On the other hand, mirroring behavior only increased if a model could accurately infer a user’s beliefs from the conversation.

The researchers hope these results inspire future research into the development of personalization methods that are more robust to LLM sycophancy.

“From a user perspective, this work highlights how important it is to understand that these models are dynamic and their behavior can change as you interact with them over time. If you are talking to a model for an extended period of time and start to outsource your thinking to it, you may find yourself in an echo chamber that you can’t escape. That is a risk users should definitely remember,” says Shomik Jain, a graduate student in the Institute for Data, Systems, and Society (IDSS) and lead author of a paper on this research.

Jain is joined on the paper by Charlotte Park, an electrical engineering and computer science (EECS) graduate student at MIT; Matt Viana, a graduate student at Penn State University; as well as co-senior authors Ashia Wilson, the Lister Brothers Career Development Professor in EECS and a principal investigator in LIDS; and Dana Calacci PhD ’23, an assistant professor at the Penn State. The research will be presented at the ACM CHI Conference on Human Factors in Computing Systems.

Extended interactions

Based on their own sycophantic experiences with LLMs, the researchers started thinking about potential benefits and consequences of a model that is overly agreeable. But when they searched the literature to expand their analysis, they found no studies that attempted to understand sycophantic behavior during long-term LLM interactions.

“We are using these models through extended interactions, and they have a lot of context and memory. But our evaluation methods are lagging behind. We wanted to evaluate LLMs in the ways people are actually using them to understand how they are behaving in the wild,” says Calacci.

To fill this gap, the researchers designed a user study to explore two types of sycophancy: agreement sycophancy and perspective sycophancy.

Agreement sycophancy is an LLM’s tendency to be overly agreeable, sometimes to the point where it gives incorrect information or refuses the tell the user they are wrong. Perspective sycophancy occurs when a model mirrors the user’s values and political views.

“There is a lot we know about the benefits of having social connections with people who have similar or different viewpoints. But we don’t yet know about the benefits or risks of extended interactions with AI models that have similar attributes,” Calacci adds.

The researchers built a user interface centered on an LLM and recruited 38 participants to talk with the chatbot over a two-week period. Each participant’s conversations occurred in the same context window to capture all interaction data.

Over the two-week period, the researchers collected an average of 90 queries from each user.

They compared the behavior of five LLMs with this user context versus the same LLMs that weren’t given any conversation data.

“We found that context really does fundamentally change how these models operate, and I would wager this phenomenon would extend well beyond sycophancy. And while sycophancy tended to go up, it didn’t always increase. It really depends on the context itself,” says Wilson.

Context clues

For instance, when an LLM distills information about the user into a specific profile, it leads to the largest gains in agreement sycophancy. This user profile feature is increasingly being baked into the newest models.

They also found that random text from synthetic conversations also increased the likelihood some models would agree, even though that text contained no user-specific data. This suggests the length of a conversation may sometimes impact sycophancy more than content, Jain adds.

But content matters greatly when it comes to perspective sycophancy. Conversation context only increased perspective sycophancy if it revealed some information about a user’s political perspective.

To obtain this insight, the researchers carefully queried models to infer a user’s beliefs then asked each individual if the model’s deductions were correct. Users said LLMs accurately understood their political views about half the time.

“It is easy to say, in hindsight, that AI companies should be doing this kind of evaluation. But it is hard and it takes a lot of time and investment. Using humans in the evaluation loop is expensive, but we’ve shown that it can reveal new insights,” Jain says.

While the aim of their research was not mitigation, the researchers developed some recommendations.

For instance, to reduce sycophancy one could design models that better identify relevant details in context and memory. In addition, models can be built to detect mirroring behaviors and flag responses with excessive agreement. Model developers could also give users the ability to moderate personalization in long conversations.

“There are many ways to personalize models without making them overly agreeable. The boundary between personalization and sycophancy is not a fine line, but separating personalization from sycophancy is an important area of future work,” Jain says.

“At the end of the day, we need better ways of capturing the dynamics and complexity of what goes on during long conversations with LLMs, and how things can misalign during that long-term process,” Wilson adds.

Parking-aware navigation system could prevent frustration and emissions

It happens every day — a motorist heading across town checks a navigation app to see how long the trip will take, but they find no parking spots available when they reach their destination. By the time they finally park and walk to their destination, they’re significantly later than they expected to be.

Most popular navigation systems send drivers to a location without considering the extra time that could be needed to find parking. This causes more than just a headache for drivers. It can worsen congestion and increase emissions by causing motorists to cruise around looking for a parking spot. This underestimation could also discourage people from taking mass transit because they don’t realize it might be faster than driving and parking.

MIT researchers tackled this problem by developing a system that can be used to identify parking lots that offer the best balance of proximity to the desired location and likelihood of parking availability. Their adaptable method points users to the ideal parking area rather than their destination.

In simulated tests with real-world traffic data from Seattle, this technique achieved time savings of up to 66 percent in the most congested settings. For a motorist, this would reduce travel time by about 35 minutes, compared to waiting for a spot to open in the closest parking lot.

While they haven’t designed a system ready for the real world yet, their demonstrations show the viability of this approach and indicate how it could be implemented.

“This frustration is real and felt by a lot of people, and the bigger issue here is that systematically underestimating these drive times prevents people from making informed choices. It makes it that much harder for people to make shifts to public transit, bikes, or alternative forms of transportation,” says MIT graduate student Cameron Hickert, lead author on a paper describing the work.

Hickert is joined on the paper by Sirui Li PhD ’25; Zhengbing He, a research scientist in the Laboratory for Information and Decision Systems (LIDS); and senior author Cathy Wu, the Class of 1954 Career Development Associate Professor in Civil and Environmental Engineering (CEE) and the Institute for Data, Systems, and Society (IDSS) at MIT, and a member of LIDS. The research appears today in Transactions on Intelligent Transportation Systems.

Probable parking

To solve the parking problem, the researchers developed a probability-aware approach that considers all possible public parking lots near a destination, the distance to drive there from a point of origin, the distance to walk from each lot to the destination, and the likelihood of parking success.

The approach, based on dynamic programming, works backward from good outcomes to calculate the best route for the user.

Their method also considers the case where a user arrives at the ideal parking lot but can’t find a space. It takes into the account the distance to other parking lots and the probability of success of parking at each.

“If there are several lots nearby that have slightly lower probabilities of success, but are very close to each other, it might be a smarter play to drive there rather than going to the higher-probability lot and hoping to find an opening. Our framework can account for that,” Hickert says.

In the end, their system can identify the optimal lot that has the lowest expected time required to drive, park, and walk to the destination.

But no motorist expects to be the only one trying to park in a busy city center. So, this method also incorporates the actions of other drivers, which affect the user’s probability of parking success.

For instance, another driver may arrive at the user’s ideal lot first and take the last parking spot. Or another motorist could try parking in another lot but then park in the user’s ideal lot if unsuccessful. In addition, another motorist may park in a different lot and cause spillover effects that lower the user’s chances of success.

“With our framework, we show how you can model all those scenarios in a very clean and principled manner,” Hickert says.

Crowdsourced parking data

The data on parking availability could come from several sources. For example, some parking lots have magnetic detectors or gates that track the number of cars entering and exiting.

But such sensors aren’t widely used, so to make their system more feasible for real-world deployment, the researchers studied the effectiveness of using crowdsourced data instead.

For instance, users could indicate available parking using an app. Data could also be gathered by tracking the number of vehicles circling to find parking, or how many enter a lot and exit after being unsuccessful.

Someday, autonomous vehicles could even report on open parking spots they drive by.

“Right now, a lot of that information goes nowhere. But if we could capture it, even by having someone simply tap ‘no parking’ in an app, that could be an important source of information that allows people to make more informed decisions,” Hickert adds.

The researchers evaluated their system using real-world traffic data from the Seattle area, simulating different times of day in a congested urban setting and a suburban area. In congested settings, their approach cut total travel time by about 60 percent compared to sitting and waiting for a spot to open, and by about 20 percent compared to a strategy of continually driving to the next closet parking lot.

They also found that crowdsourced observations of parking availability would have an error rate of only about 7 percent, compared to actual parking availability. This indicates it could be an effective way to gather parking probability data.

In the future, the researchers want to conduct larger studies using real-time route information in an entire city. They also want to explore additional avenues for gathering data on parking availability, such as using satellite images, and estimate potential emissions reductions.

“Transportation systems are so large and complex that they are really hard to change. What we look for, and what we found with this approach, is small changes that can have a big impact to help people make better choices, reduce congestion, and reduce emissions,” says Wu.

This research was supported, in part, by Cintra, the MIT Energy Initiative, and the National Science Foundation.

Exposing biases, moods, personalities, and abstract concepts hidden in large language models

By now, ChatGPT, Claude, and other large language models have accumulated so much human knowledge that they’re far from simple answer-generators; they can also express abstract concepts, such as certain tones, personalities, biases, and moods. However, it’s not obvious exactly how these models represent abstract concepts to begin with from the knowledge they contain.

Now a team from MIT and the University of California San Diego has developed a way to test whether a large language model (LLM) contains hidden biases, personalities, moods, or other abstract concepts. Their method can zero in on connections within a model that encode for a concept of interest. What’s more, the method can then manipulate, or “steer” these connections, to strengthen or weaken the concept in any answer a model is prompted to give.

The team proved their method could quickly root out and steer more than 500 general concepts in some of the largest LLMs used today. For instance, the researchers could home in on a model’s representations for personalities such as “social influencer” and “conspiracy theorist,” and stances such as “fear of marriage” and “fan of Boston.” They could then tune these representations to enhance or minimize the concepts in any answers that a model generates.

In the case of the “conspiracy theorist” concept, the team successfully identified a representation of this concept within one of the largest vision language models available today. When they enhanced the representation, and then prompted the model to explain the origins of the famous “Blue Marble” image of Earth taken from Apollo 17, the model generated an answer with the tone and perspective of a conspiracy theorist.

The team acknowledges there are risks to extracting certain concepts, which they also illustrate (and caution against). Overall, however, they see the new approach as a way to illuminate hidden concepts and potential vulnerabilities in LLMs, that could then be turned up or down to improve a model’s safety or enhance its performance.

“What this really says about LLMs is that they have these concepts in them, but they’re not all actively exposed,” says Adityanarayanan “Adit” Radhakrishnan, assistant professor of mathematics at MIT. “With our method, there’s ways to extract these different concepts and activate them in ways that prompting cannot give you answers to.”

The team published their findings today in a study appearing in the journal Science. The study’s co-authors include Radhakrishnan, Daniel Beaglehole and Mikhail Belkin of UC San Diego, and Enric Boix-Adserà of the University of Pennsylvania.

A fish in a black box

As use of OpenAI’s ChatGPT, Google’s Gemini, Anthropic’s Claude, and other artificial intelligence assistants has exploded, scientists are racing to understand how models represent certain abstract concepts such as “hallucination” and “deception.” In the context of an LLM, a hallucination is a response that is false or contains misleading information, which the model has “hallucinated,” or constructed erroneously as fact.

To find out whether a concept such as “hallucination” is encoded in an LLM, scientists have often taken an approach of “unsupervised learning” — a type of machine learning in which algorithms broadly trawl through unlabeled representations to find patterns that might relate to a concept such as “hallucination.” But to Radhakrishnan, such an approach can be too broad and computationally expensive.

“It’s like going fishing with a big net, trying to catch one species of fish. You’re gonna get a lot of fish that you have to look through to find the right one,” he says. “Instead, we’re going in with bait for the right species of fish.”

He and his colleagues had previously developed the beginnings of a more targeted approach with a type of predictive modeling algorithm known as a recursive feature machine (RFM). An RFM is designed to directly identify features or patterns within data by leveraging a mathematical mechanism that neural networks — a broad category of AI models that includes LLMs — implicitly use to learn features.

Since the algorithm was an effective, efficient approach for capturing features in general, the team wondered whether they could use it to root out representations of concepts, in LLMs, which are by far the most widely used type of neural network and perhaps the least well-understood.

“We wanted to apply our feature learning algorithms to LLMs to, in a targeted way, discover representations of concepts in these large and complex models,” Radhakrishnan says.

Converging on a concept

The team’s new approach identifies any concept of interest within a LLM and “steers” or guides a model’s response based on this concept. The researchers looked for 512 concepts within five classes: fears (such as of marriage, insects, and even buttons); experts (social influencer, medievalist); moods (boastful, detachedly amused); a preference for locations (Boston, Kuala Lumpur); and personas (Ada Lovelace, Neil deGrasse Tyson).

The researchers then searched for representations of each concept in several of today’s large language and vision models. They did so by training RFMs to recognize numerical patterns in an LLM that could represent a particular concept of interest.

A standard large language model is, broadly, a neural network that takes a natural language prompt, such as “Why is the sky blue?” and divides the prompt into individual words, each of which is encoded mathematically as a list, or vector, of numbers. The model takes these vectors through a series of computational layers, creating matrices of many numbers that, throughout each layer, are used to identify other words that are most likely to be used to respond to the original prompt. Eventually, the layers converge on a set of numbers that is decoded back into text, in the form of a natural language response.

The team’s approach trains RFMs to recognize numerical patterns in an LLM that could be associated with a specific concept. As an example, to see whether an LLM contains any representation of a “conspiracy theorist,” the researchers would first train the algorithm to identify patterns among LLM representations of 100 prompts that are clearly related to conspiracies, and 100 other prompts that are not. In this way, the algorithm would learn patterns associated with the conspiracy theorist concept. Then, the researchers can mathematically modulate the activity of the conspiracy theorist concept by perturbing LLM representations with these identified patterns. 

The method can be applied to search for and manipulate any general concept in an LLM. Among many examples, the researchers identified representations and manipulated an LLM to give answers in the tone and perspective of a “conspiracy theorist.” They also identified and enhanced the concept of “anti-refusal,” and showed that whereas normally, a model would be programmed to refuse certain prompts, it instead answered, for instance giving instructions on how to rob a bank.

Radhakrishnan says the approach can be used to quickly search for and minimize vulnerabilities in LLMs. It can also be used to enhance certain traits, personalities, moods, or preferences, such as emphasizing the concept of “brevity” or “reasoning” in any response an LLM generates. The team has made the method’s underlying code publicly available.

“LLMs clearly have a lot of these abstract concepts stored within them, in some representation,” Radhakrishnan says. “There are ways where, if we understand these representations well enough, we can build highly specialized LLMs that are still safe to use but really effective at certain tasks.”

This work was supported, in part, by the National Science Foundation, the Simons Foundation, the TILOS institute, and the U.S. Office of Naval Research. 

Study: AI chatbots provide less-accurate information to vulnerable users

Large language models (LLMs) have been championed as tools that could democratize access to information worldwide, offering knowledge in a user-friendly interface regardless of a person’s background or location. However, new research from MIT’s Center for Constructive Communication (CCC) suggests these artificial intelligence systems may actually perform worse for the very users who could most benefit from them.

A study conducted by researchers at CCC, which is based at the MIT Media Lab, found that state-of-the-art AI chatbots — including OpenAI’s GPT-4, Anthropic’s Claude 3 Opus, and Meta’s Llama 3 — sometimes provide less-accurate and less-truthful responses to users who have lower English proficiency, less formal education, or who originate from outside the United States. The models also refuse to answer questions at higher rates for these users, and in some cases, respond with condescending or patronizing language.

“We were motivated by the prospect of LLMs helping to address inequitable information accessibility worldwide,” says lead author Elinor Poole-Dayan SM ’25, a technical associate in the MIT Sloan School of Management who led the research as a CCC affiliate and master’s student in media arts and sciences. “But that vision cannot become a reality without ensuring that model biases and harmful tendencies are safely mitigated for all users, regardless of language, nationality, or other demographics.”

A paper describing the work, “LLM Targeted Underperformance Disproportionately Impacts Vulnerable Users,” was presented at the AAAI Conference on Artificial Intelligence in January.

Systematic underperformance across multiple dimensions

For this research, the team tested how the three LLMs responded to questions from two datasets: TruthfulQA and SciQ. TruthfulQA is designed to measure a model’s truthfulness (by relying on common misconceptions and literal truths about the real world), while SciQ contains science exam questions testing factual accuracy. The researchers prepended short user biographies to each question, varying three traits: education level, English proficiency, and country of origin.

Across all three models and both datasets, the researchers found significant drops in accuracy when questions came from users described as having less formal education or being non-native English speakers. The effects were most pronounced for users at the intersection of these categories: those with less formal education who were also non-native English speakers saw the largest declines in response quality.

The research also examined how country of origin affected model performance. Testing users from the United States, Iran, and China with equivalent educational backgrounds, the researchers found that Claude 3 Opus in particular performed significantly worse for users from Iran on both datasets.

“We see the largest drop in accuracy for the user who is both a non-native English speaker and less educated,” says Jad Kabbara, a research scientist at CCC and a co-author on the paper. “These results show that the negative effects of model behavior with respect to these user traits compound in concerning ways, thus suggesting that such models deployed at scale risk spreading harmful behavior or misinformation downstream to those who are least able to identify it.”

Refusals and condescending language

Perhaps most striking were the differences in how often the models refused to answer questions altogether. For example, Claude 3 Opus refused to answer nearly 11 percent of questions for less educated, non-native English-speaking users — compared to just 3.6 percent for the control condition with no user biography.

When the researchers manually analyzed these refusals, they found that Claude responded with condescending, patronizing, or mocking language 43.7 percent of the time for less-educated users, compared to less than 1 percent for highly educated users. In some cases, the model mimicked broken English or adopted an exaggerated dialect.

The model also refused to provide information on certain topics specifically for less-educated users from Iran or Russia, including questions about nuclear power, anatomy, and historical events — even though it answered the same questions correctly for other users.

“This is another indicator suggesting that the alignment process might incentivize models to withhold information from certain users to avoid potentially misinforming them, although the model clearly knows the correct answer and provides it to other users,” says Kabbara.

Echoes of human bias

The findings mirror documented patterns of human sociocognitive bias. Research in the social sciences has shown that native English speakers often perceive non-native speakers as less educated, intelligent, and competent, regardless of their actual expertise. Similar biased perceptions have been documented among teachers evaluating non-native English-speaking students.

“The value of large language models is evident in their extraordinary uptake by individuals and the massive investment flowing into the technology,” says Deb Roy, professor of media arts and sciences, CCC director, and a co-author on the paper. “This study is a reminder of how important it is to continually assess systematic biases that can quietly slip into these systems, creating unfair harms for certain groups without any of us being fully aware.”

The implications are particularly concerning given that personalization features — like ChatGPT’s Memory, which tracks user information across conversations — are becoming increasingly common. Such features risk differentially treating already-marginalized groups.

“LLMs have been marketed as tools that will foster more equitable access to information and revolutionize personalized learning,” says Poole-Dayan. “But our findings suggest they may actually exacerbate existing inequities by systematically providing misinformation or refusing to answer queries to certain users. The people who may rely on these tools the most could receive subpar, false, or even harmful information.”

Enhancing maritime cybersecurity with technology and policy

Originally from the small Balkan country of Montenegro, Strahinja (Strajo) Janjusevic says his life has unfolded in unexpected ways, for which he is deeply grateful. After graduating from high school, he was selected to represent his country in the United States, studying cyber operations and computer science at the U.S. Naval Academy in Annapolis, Maryland. He has since continued his cybersecurity studies and is currently a second-year master’s student in the Technology and Policy Program (TPP), hosted by the MIT Institute for Data, Systems, and Society (IDSS). His research with the MIT Laboratory for Information and Decision Systems (LIDS) and the MIT Maritime Consortium team aims to improve the cybersecurity of critical maritime infrastructure using artificial intelligence, considering both the technology and policy frameworks of solutions.

“My current research focuses on applying AI techniques to cybersecurity problems and examining the policy implications of these advancements, especially in the context of maritime cybersecurity,” says Janjusevic. “Representing my country at the highest levels of education and industry has given me a unique perspective on cybersecurity challenges.”

Janjusevic’s pathway from Montenegro to Maryland was created by a program that allows selected students from allied countries to attend the U.S. Naval Academy. Janjusevic graduated with a dual bachelor’s degree in cyber operations and computer science. His undergraduate experience provided opportunities to collaborate with the U.S. military and the National Security Agency, exposing him to high-level cybersecurity operations and fueling his interest in tackling complex cybersecurity challenges. During his undergraduate studies, he also interned with Microsoft, developing tools for cloud incident response, and with NASA, visualizing solar data for research applications.

Following his graduation, he realized that he still needed more knowledge, particularly in the area of AI and cybersecurity. TPP appealed to him immediately because of its dual emphasis on rigorous engineering innovation and the policy analysis needed to deploy it effectively. Janjusevic’s experiences at TPP have been a big change from his time at the U.S. Naval Academy, with a different pace and environment. He has especially appreciated being able to broaden his understanding about a variety of research domains and apply the discipline and knowledge he earned during his time at the academy.

“My TPP experience has been amazing,” says Janjusevic. “The cohort is really small, so it feels like a family, and everyone is working on diverse, high-impact problems.”

Mitigating the risks of emerging technologies

Janjusevic’s thesis brings together disciplines of cybersecurity, AI and deep learning, and control theory and physics, focusing on securing maritime cyber-physical systems — in particular, large legacy ships. The hacking of these ships’ networks can result in substantial damage to national security, as well as serious economic effects.

“Strajo is working to outsmart maritime GPS spoofing,” says Saurabh Amin, the Edmund K. Turner Professor in Civil Engineering. “Such attacks have already lured vessels off course in contested waters. His approach layers physics-based trajectory models with deep learning, catching threats that no single method can detect alone. His expertise has been very helpful in advancing our work on threat modeling and attack detection.”

The research utilizes advanced threat modeling and vessel dynamics to train AI systems to distinguish between legitimate maneuvers and spoofed signals. It involves building a framework that employs an internal LSTM (long short-term memory) autoencoder to analyze signal integrity, while simultaneously using a physics-based forecaster to predict the vessel’s movement based on environmental factors like wind and the sea state. By comparing these predictions against reported GPS positions, the system can effectively distinguish between natural sensor noise and malicious spoofing attacks. This hybrid framework is designed to empower, not replace, human operators, providing verified navigation data that allows watch standers to distinguish technical glitches from strategic cyberattacks.

Janjusevic has been able to enhance his academic research with industry experience. In summer 2025, he interned with the Network Detection team at the AI cybersecurity company Vectra AI. There, he investigated potential threats new technologies can bring, particularly AI agents and the model context protocol (MCP) — the emerging standard for AI agent communication. His research demonstrated how this technology could be repurposed for autonomous hacking operations and advanced command and control. This work on the security risks of agentic AI was recently presented in the preprint, “Hiding in the AI Traffic: Abusing MCP for LLM-Powered Agentic Red Teaming.”

“I was able to gain practical insights and hands-on experience into how a data science team uses AI models to detect anomalies in a network,” says Janjusevic. “This work within industry directly informed the anomaly detection models in my research.”

International policy perspective

“Strajo brings not just a high level of intelligence and energy to his work on cyber-physical security for merchant vessels, but also a strong instinct from his Navy training that resonates deeply with the research effort and grounds it in actionable policy,” says Fotini Christia, the Ford International Professor of the Social Sciences, director of IDSS, and a leader of the MIT Maritime Consortium.

Janjusevic participates in the cybersecurity efforts of the Maritime Consortium, a collaboration between academia, industry, and regulatory agencies focused on developing technological solutions, industry standards, and policies. The consortium includes cooperation with some international members, including from Singapore and South Korea.

“In AI cybersecurity, the policy element is really important, as the field is so fast-moving and the consequences of hacking can be so dangerous,” says Janjusevic. “I think there’s still a lot of need for policy work in this space.”

Janjusevic is also currently helping to organize two upcoming major conferences: the Harvard European Conference in February, which will convene officials and diplomats from across the globe, and the Technology and National Security Conference in April, a collaboration of Harvard and MIT that brings together top leaders from government, industry, and academia to tackle critical challenges in national security.

“I’m striving to find a position where I can influence and advance the cybersecurity field with AI, while at the same time leading collaboration and innovation between the United States and Montenegro,” says Janjusevic. “My goal is to be a bridge between Europe and the U.S. in this space of national security, AI, and cybersecurity, bringing my knowledge to both sides.”