“I just can’t make it tonight. You have fun without me.” Across much of the animal kingdom, when infection strikes, social contact shuts down. A new study details how the immune and central nervous systems implement this sickness behavior.

It makes perfect sense that when we’re battling an infection, we lose our desire to be around others. That protects others from getting sick and lets us get much-needed rest. What hasn’t been as clear is how this behavior change happens.

In new research published Nov. 25 in Cell, scientists at MIT’s Picower Institute for Learning and Memory and collaborators used multiple methods to demonstrate causally that when the immune system cytokine interleukin-1 beta (IL-1β) reaches the IL-1 receptor 1 (IL-1R1) on neurons in a brain region called the dorsal raphe nucleus, that activates connections with the intermediate lateral septum to shut down social behavior.

“Our findings show that social isolation following immune challenge is self-imposed and driven by an active neural process, rather than a secondary consequence of physiological symptoms of sickness, such as lethargy,” says study co-senior author Gloria Choi, associate professor in MIT’s Department of Brain and Cognitive Sciences and a member of the Picower Institute.

Jun Huh, Harvard Medical School associate professor of immunology, is the paper’s co-senior author. The lead author is Liu Yang, a research scientist in Choi’s lab.

A molecule and its receptor

Choi and Huh’s long collaboration has identified other cytokines that affect social behavior by latching on to their receptors in the brain, so in this study their team hypothesized that the same kind of dynamic might cause social withdrawal during infection. But which cytokine? And what brain circuits might be affected?

To get started, Yang and her colleagues injected 21 different cytokines into the brains of mice, one by one, to see if any triggered social withdrawal the same way that giving mice LPS (a standard way of simulating infection) did. Only IL-1β injection fully recapitulated the same social withdrawal behavior as LPS. That said, IL-1β also made the mice more sluggish.

IL-1β affects cells when it hooks up with the IL-1R1, so the team next went looking across the brain for where the receptor is expressed. They identified several regions and examined individual neurons in each. The dorsal raphe nucleus (DRN) stood out among regions, both because it is known to modulate social behavior and because it is situated next to the cerebral aqueduct, which would give it plenty of exposure to incoming cytokines in cerebrospinal fluid. The experiments identified populations of DRN neurons that express IL-1R1, including many involved in making the crucial neuromodulatory chemical serotonin.

From there, Yang and the team demonstrated that IL-1β activates those neurons, and that activating the neurons promotes social withdrawal. Moreover, they showed that inhibiting that neural activity prevented social withdrawal in mice treated with IL-1β, and they showed that shutting down the IL-1R1 in the DRN neurons also prevented social withdrawal behavior after IL-1β injection or LPS exposure. Notably, these experiments did not change the lethargy that followed IL-1β or LPS, helping to demonstrate that social withdrawal and lethargy occur through different means.

“Our findings implicate IL-1β as a primary effector driving social withdrawal during systemic immune activation,” the researchers wrote in Cell.

Tracing the circuit

With the DRN identified as the site where neurons receiving IL-1β drove social withdrawal, the next question was what circuit they effected that behavior change through. The team traced where the neurons make their circuit projections and found several regions that have a known role in social behavior. Using optogenetics, a technology that engineers cells to become controllable with flashes of light, the scientists were able to activate the DRN neurons’ connections with each downstream region. Only activating the DRN’s connections with the intermediate lateral septum caused the social withdrawal behaviors seen with IL-1β injection or LPS exposure.

In a final test, they replicated their results by exposing some mice to salmonella.

“Collectively, these results reveal a role for IL-1R1-expressing DRN neurons in mediating social withdrawal in response to IL-1β during systemic immune challenge,” the researchers wrote.

Although the study revealed the cytokine, neurons, and circuit responsible for social withdrawal in mice in detail and with demonstrations of causality, the results still inspire new questions. One is whether IL-1R1 neurons affect other sickness behaviors. Another is whether serotonin has a role in social withdrawal or other sickness behaviors.

In addition to Yang, Choi, and Huh, the paper’s other authors are Matias Andina, Mario Witkowski, Hunter King, and Ian Wickersham.

Funding for the research came from the National Institute of Mental Health, the National Research Foundation of Korea, the Denis A. and Eugene W. Chinery Fund for Neurodevelopmental Research, the Jeongho Kim Neurodevelopmental Research Fund, Perry Ha, the Simons Center for the Social Brain, the Simons Foundation Autism Research Initiative, The Picower Institute for Learning and Memory, and The Freedom Together Foundation.

In the brand new Planet Hollywood Poker Room, 48 digital rights supporters played No-Limit Texas Hold’Em in the 4th Annual EFF Benefit Poker Tournament at DEF CON, raising $18,395 for EFF.

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The tournament was hosted by EFF board member Tarah Wheeler and emceed by lintile, lending his Hacker Jeopardy hosting skills to help EFF for the day.

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Every table had two celebrity players with special bounties for the player that knocked them out of the tournament. This year featured Wendy Nather, Chris “WeldPond” Wysopal, Jake “MalwareJake” Williams, Bryson Bort, Kym “KymPossible” Price, Adam Shostack, and Dr. Allan Friedman.

Excellent poker player and teacher Jason Healey, Professor of International Affairs at Columbia University’s School of International and Public Affairs noted that “the EFF poker tournament is where you find all the hacker royalty in one room."

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The day started at with a poker clinic run by Tarah’s father, professional poker player Mike Wheeler. The hour-long clinic helped folks get brushed up on their casino literacy before playing the big game.

Mike told the story of first teaching Tarah to play poker with jellybeans when she was only four. He then taught poker noobs how to play and when to check, when to fold, and when to go all-in.

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After the clinic, lintile roused the crowd to play for real, starting the tournament off by announcing “Shuffle up and deal!”

The first hour saw few players get knocked out, but after the blinds began to rise, the field began to thin, with a number of celebrity knock outs.
At every knockout, lintile took to the mic to encourage the player to donate to EFF, which allowed them to buy back into the tournament and try their luck another round.

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Jay Salzberg knocked out Kym Price to win a l33t crate.

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Kim Holt knocked out Mike Wheeler, collecting the bounty on his head posted by Tarah, and winning a $250 donation to EFF in his name. This is the second time Holt has sent Mike home.

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Tarah knocked out Adam Shostack, winning a number of fun prizes, including a signed copy of his latest book, Threats: What Every Engineer Should Learn From Star Wars.

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Bryson Bort was knocked out by privacy attorney Marcia Hofmann.

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Play continued for three hours until only the final table of players remained: Allaen Friedman, Luke Hanley, Jason Healey, Kim Holt, Igor Ignatov, Sid, Puneet Thapliyal, Charles Thomas and Tarah Wheeler herself.

As blinds continues to rise, players went all-in more and more. The most exciting moment was won by Sid, tripling up with TT over QT and A8s, and then only a few hands later knocking out Tarah, who finished 8th.

For the first time, the Jellybean Trophy sat on the final table awaiting the winner. This year, it was a Seattle Space Needle filled with green and blue jellybeans celebrating the lovely Pacific Northwest where Tarah and Mike are from.

The final three players were Allen Friedman, Kim Holt and Syd. Sid doubled up with KJ over Holt’s A6, and then knocked Holt out with his Q4 beating Holt’s 22.

Friedman and Sid traded blinds until Allan went all in with A6 and Syd called with JT. A jack landed on the flop and Syd won the day!

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Sid becomes the first player to win the tournament more than once, taking home the jellybean trophy two years in a row.

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It was an exciting afternoon of competition raising over $18,000 to support civil liberties and human rights online. We hope you join us next year as we continue to grow the tournament. Follow Tarah and EFF to make sure we have chips and a chair for you at DEF CON 34.

Be ready for this next year’s special benefit poker event: The Digital Rights Attack Lawyers Edition! Our special celebrity guests will all be our favorite digital rights attorneys including Cindy Cohn, Marcia Hofmann, Kurt Opsahl, and more!

Photo Gallery

Concrete was the foundation of the ancient Roman empire. It enabled Rome’s storied architectural revolution as well as the construction of buildings, bridges, and aqueducts, many of which are still used some 2,000 years after their creation.

In 2023, MIT Associate Professor Admir Masic and his collaborators published a paper describing the manufacturing process that gave Roman concrete its longevity: Lime fragments were mixed with volcanic ash and other dry ingredients before the addition of water. Once water is added to this dry mix, heat is produced. As the concrete sets, this “hot-mixing” process traps and preserves the highly reactive lime as small, white, gravel-like features. When cracks form in the concrete, the lime clasts redissolve and fill the cracks, giving the concrete self-healing properties.

There was only one problem: The process Masic’s team described was different from the one described by the famed ancient Roman architect Vitruvius. Vitruvius literally wrote the book on ancient architecture. His highly influential work, “De architectura,” written in the 1st century B.C.E., is the first known book on architectural theory. In it, Vitruvius says that Romans added water to lime to create a paste-like material before mixing it with other ingredients.

“Having a lot of respect for Vitruvius, it was difficult to suggest that his description may be inaccurate,” Masic says. “The writings of Vitruvius played a critical role in stimulating my interest in ancient Roman architecture, and the results from my research contradicted these important historical texts.”

Now, Masic and his collaborators have confirmed that hot-mixing was indeed used by the Romans, a conclusion he reached by studying a newly discovered ancient construction site in Pompeii that was exquisitely preserved by the volcanic eruption of Mount Vesuvius in the year 79 C.E. They also characterized the volcanic ash material the Romans mixed with the lime, finding a surprisingly diverse array of reactive minerals that further added to the concrete’s ability to repair itself many years after these monumental structures were built.

“There is the historic importance of this material, and then there is the scientific and technological importance of understanding it,” Masic explains. “This material can heal itself over thousands of years, it is reactive, and it is highly dynamic. It has survived earthquakes and volcanoes. It has endured under the sea and survived degradation from the elements. We don’t want to completely copy Roman concrete today. We just want to translate a few sentences from this book of knowledge into our modern construction practices.”

The findings are described today in Nature Communications. Joining Masic on the paper are first authors Ellie Vaserman ’25 and Principal Research Scientist James Weaver, along with Associate Professor Kristin Bergmann, PhD candidate Claire Hayhow, and six other Italian collaborators.

Uncovering ancient secrets

Masic has spent close to a decade studying the chemical composition of the concrete that allowed Rome’s famous structures to endure for so much longer than their modern counterparts. His 2023 paper analyzed the material’s chemical composition to deduce how it was made.

That paper used samples from a city wall in Priverno in southwest Italy, which was conquered by the Romans in the 4th century B.C.E. But there was a question as to whether this wall was representative of other concrete structures built throughout the Roman empire.

The recent discovery by archaeologists of an active ancient construction site in Pompeii (complete with raw material piles and tools) therefore offered an unprecedented opportunity.

For the study, the researchers analyzed samples from these pre-mixed dry material piles, a wall that was in the process of being built, completed buttress and structural walls, and mortar repairs in an existing wall.

“We were blessed to be able to open this time capsule of a construction site and find piles of material ready to be used for the wall,” Masic says. “With this paper, we wanted to clearly define a technology and associate it with the Roman period in the year 79 C.E.”

The site offered the clearest evidence yet that the Romans used hot-mixing in concrete production. Not only did the concrete samples contain the lime clasts described in Masic’s previous paper, but the team also discovered intact quicklime fragments pre-mixed with other ingredients in a dry raw material pile, a critical first step in the preparation of hot-mixed concrete.

Bergman, an associate professor of earth and planetary sciences, helped develop tools for differentiating the materials at the site.

“Through these stable isotope studies, we could follow these critical carbonation reactions over time, allowing us to distinguish hot-mixed lime from the slaked lime originally described by Vitruvius,” Masic says. “These results revealed that the Romans prepared their binding material by taking calcined limestone (quicklime), grinding them to a certain size, mixing it dry with volcanic ash, and then eventually adding water to create a cementing matrix.”

The researchers also analyzed the volcanic ingredients in the cement, including a type of volcanic ash called pumice. They found that the pumice particles chemically reacted with the surrounding pore solution over time, creating new mineral deposits that further strengthened the concrete.

Rewriting history

Masic says the archaeologists listed as co-authors on the paper were indispensable to the study. When Masic first entered the Pompeii site, as he inspected the perfectly preserved work area, tears came to his eyes.

“I expected to see Roman workers walking between the piles with their tools,” Masic says. “It was so vivid, you felt like you were transported in time. So yes, I got emotional looking at a pile of dirt. The archaeologists made some jokes.”

Masic notes that calcium is a key component in both ancient and modern concretes, so understanding how it reacts over time holds lessons for understanding dynamic processes in modern cement as well. Towards these efforts, Masic has also started a company, DMAT, that uses lessons from ancient Roman concrete to create long-lasting modern concretes.

“This is relevant because Roman cement is durable, it heals itself, and it’s a dynamic system,” Masic says. “The way these pores in volcanic ingredients can be filled through recrystallization is a dream process we want to translate into our modern materials. We want materials that regenerate themselves.”

As for Vitruvius, Masic guesses that he may have been misinterpreted. He points out that Vitruvius also mentions latent heat during the cement mixing process, which could suggest hot-mixing after all.

The work was supported, in part, by the MIT Research Support Commmittee (RSC) and the MIT Concrete Sustainability Hub.

Two competing arguments are making the rounds. The first is by a neurosurgeon in the New York Times. In an op-ed that honestly sounds like it was paid for by Waymo, the author calls driverless cars a “public health breakthrough”:

In medical research, there’s a practice of ending a study early when the results are too striking to ignore. We stop when there is unexpected harm. We also stop for overwhelming benefit, when a treatment is working so well that it would be unethical to continue giving anyone a placebo. When an intervention works this clearly, you change what you do...

The administration said it will no longer fight a legal claim that DOE broke transparency laws to support repeal of the endangerment finding.

The agency revamped its webpages to feature natural causes of rising temperatures such as the Earth’s orbit.

The decision called the president's order unlawful, as the administration failed to explain why it halted onshore and offshore wind authorizations.

Traffic and air pollution both have decreased, new research shows.

Both candidates have criticized a multimillion-dollar effort to protect the city from flooding.

The Commerce, Science and Transportation Committee also approved President Donald Trump's Coast Guard pick.

Repurposing fossil fuel subsidies and pricing carbon pollution are among the steps called for in the major report.

An EU proposal would prohibit the use of labels such as “veggie burger” or “vegan sausage” for plant-based and lab-grown dishes.

There were 52 wildfires burning across New South Wales on Monday, and nine remained out of control.

Asian nations will need $4 trillion for water and sanitation between 2025 and 2040 — about $250 billion a year, says one report.

The Pointe-au-Chien Indian Tribe and other Indigenous people are fighting to adapt as the coastline retreats.

When it comes to brain function, neurons get a lot of the glory. But healthy brains depend on the cooperation of many kinds of cells. The most abundant of the brain’s non-neuronal cells are astrocytes, star-shaped cells with a lot of responsibilities. Astrocytes help shape neural circuits, participate in information processing, and provide nutrient and metabolic support to neurons. Individual cells can take on new roles throughout their lifetimes, and at any given time, the astrocytes in one part of the brain will look and behave differently than the astrocytes somewhere else.

After an extensive analysis by researchers at MIT, neuroscientists now have an atlas detailing astrocytes’ dynamic diversity. Its maps depict the regional specialization of astrocytes across the brains of both mice and marmosets — two powerful models for neuroscience research — and show how their populations shift as brains develop, mature, and age. 

The open-access study, reported in the Nov. 20 issue of the journal Neuron, was led by Guoping Feng, the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT. This work was supported by the Hock E. Tan and K. Lisa Yang Center for Autism Research, part of the Yang Tan Collective at MIT, and the National Institutes of Health’s BRAIN Initiative.

“It’s really important for us to pay attention to non-neuronal cells’ role in health and disease,” says Feng, who is also the associate director of the McGovern Institute for Brain Research and the director of the Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT. And indeed, these cells — once seen as mere supporting players — have gained more of the spotlight in recent years. Astrocytes are known to play vital roles in the brain’s development and function, and their dysfunction seems to contribute to many psychiatric disorders and neurodegenerative diseases. “But compared to neurons, we know a lot less — especially during development,” Feng adds.

Probing the unknown

Feng and Margaret Schroeder, a former graduate student in his lab, thought it was important to understand astrocyte diversity across three axes: space, time, and species. They knew from earlier work in the lab, done in collaboration with Steve McCarroll’s lab at Harvard University and led by Fenna Krienen in his group, that in adult animals, different parts of the brain have distinctive sets of astrocytes.

“The natural question was, how early in development do we think this regional patterning of astrocytes starts?” Schroeder says.

To find out, she and her colleagues collected brain cells from mice and marmosets at six stages of life, spanning embryonic development to old age. For each animal, they sampled cells from four different brain regions: the prefrontal cortex, the motor cortex, the striatum, and the thalamus.

Then, working with Krienen, who is now an assistant professor at Princeton University, they analyzed the molecular contents of those cells, creating a profile of genetic activity for each one. That profile was based on the mRNA copies of genes found inside the cell, which are known collectively as the cell’s transcriptome. Determining which genes a cell is using, and how active those genes are, gives researchers insight into a cell’s function and is one way of defining its identity.

Dynamic diversity

After assessing the transcriptomes of about 1.4 million brain cells, the group focused in on the astrocytes, analyzing and comparing their patterns of gene expression. At every life stage, from before birth to old age, the team found regional specialization: astrocytes from different brain regions had similar patterns of gene expression, which were distinct from those of astrocytes in other brain regions.

This regional specialization was also apparent in the distinct shapes of astrocytes in different parts of the brain, which the team was able to see with expansion microscopy, a high-resolution imaging method developed by McGovern colleague Edward Boyden that reveals fine cellular features.

Notably, the astrocytes in each region changed as animals matured. “When we looked at our late embryonic time point, the astrocytes were already regionally patterned. But when we compare that to the adult profiles, they had completely shifted again,” Schroeder says. “So there’s something happening over postnatal development.” The most dramatic changes the team detected occurred between birth and early adolescence, a period during which brains rapidly rewire as animals begin to interact with the world and learn from their experiences.

Feng and Schroeder suspect that the changes they observed may be driven by the neural circuits that are sculpted and refined as the brain matures. “What we think they’re doing is kind of adapting to their local neuronal niche,” Schroeder says. “The types of genes that they are up-regulating and changing during development points to their interaction with neurons.” Feng adds that astrocytes may change their genetic programs in response to nearby neurons, or alternatively, they might help direct the development or function of local circuits as they adopt identities best suited to support particular neurons.

Both mouse and marmoset brains exhibited regional specialization of astrocytes and changes in those populations over time. But when the researchers looked at the specific genes whose activity defined various astrocyte populations, the data from the two species diverged. Schroeder calls this a note of caution for scientists who study astrocytes in animal models, and adds that the new atlas will help researchers assess the potential relevance of findings across species.

Beyond astrocytes

With a new understanding of astrocyte diversity, Feng says his team will pay close attention to how these cells are impacted by the disease-related genes they study and how those effects change during development. He also notes that the gene expression data in the atlas can be used to predict interactions between astrocytes and neurons. “This will really guide future experiments: how these cells’ interactions can shift with changes in the neurons or changes in the astrocytes,” he says.

The Feng lab is eager for other researchers to take advantage of the massive amounts of data they generated as they produced their atlas. Schroeder points out that the team analyzed the transcriptomes of all kinds of cells in the brain regions they studied, not just astrocytes. They are sharing their findings so researchers can use them to understand when and where specific genes are used in the brain, or dig in more deeply to further to explore the brain’s cellular diversity.

Two current MIT affiliates and seven additional alumni are among those named to the 2025 cohort of AI2050 Fellows.  

Zongyi Li, a postdoc in the MIT Computer Science and Artificial Intelligence Lab, and Tess Smidt ’12, an associate professor of electrical engineering and computer science (EECS), were both named as AI2050 Early Career Fellows. 

Seven additional MIT alumni were also honored. AI2050 Early Career Fellows include Brian Hie SM '19, PhD '21; Natasha Mary Jaques PhD '20; Martin Anton Schrimpf PhD '22; Lindsey Raymond SM '19, PhD '24, who will join the MIT faculty in EECS, the Department of Economics, and the MIT Schwarzman College of Computing in 2026; and Ellen Dee Zhong PhD ’22. AI2050 Senior Fellows include Surya Ganguli ’98, MNG ’98; and Luke Zettlemoyer SM ’03, PhD ’09. 

AI2050 Fellows are announced annually by Schmidt Sciences, a nonprofit organization founded in 2024 by Eric and Wendy Schmidt that works to accelerate scientific knowledge and breakthroughs with the most promising, advanced tools to support a thriving planet. The organization prioritizes research in areas poised for impact including AI and advanced computing, astrophysics, biosciences, climate, and space — as well as supporting researchers in a variety of disciplines through its science systems program. 

Li is postdoc in CSAIL working with associate professor of EECS Kaiming He. Li's research focuses on developing neural operator methods to accelerate scientific computing. He received his PhD in computing and mathematical sciences from Caltech, where he was advised by Anima Anandkumar and Andrew Stuart. He holds undergraduate degrees in computer science and mathematics from Washington University in St. Louis. 

Li's work has been supported by a Kortschak Scholarship, PIMCO Fellowship, Amazon AI4Science Fellowship, Nvidia Fellowship, and MIT-Novo Nordisk AI Fellowship. He has also completed three summer internships at Nvidia. Li will join the NYU Courant Institute of Mathematical Sciences as an assistant professor of mathematics and data science in fall 2026.

Smidt, associate professor of electrical engineering and computer science (EECS), is the principal investigator of the Atomic Architects group at the Research Laboratory of Electronics (RLE), where she works at the intersection of physics, geometry, and machine learning to design algorithms that aid in the understanding of physical systems under physical and geometric constraints, with applications to the design both of new materials and new molecules. She has a particular focus on symmetries present in 3D physical systems, such as rotation, translation, and reflection.

Smidt earned her BS in physics from MIT in 2012 and her PhD in physics from the University of California at Berkeley in 2018. Prior to joining the MIT EECS faculty in 2021, she was the 2018 Alvarez Postdoctoral Fellow in Computing Sciences at Lawrence Berkeley National Laboratory, and a software engineering intern on the Google Accelerated Sciences team, where she developed Euclidean symmetry equivariant neural networks that naturally handle 3D geometry and geometric tensor data. Besides the AI2050 fellowship, she has received an Air Force Office of Scientific Research Young Investigator Program award, the EECS Outstanding Educator Award, and a Transformative Research Fund award.

Conceived and co-chaired by Eric Schmidt and James Manyika, AI2050 is a philanthropic initiative aimed at helping to solve hard problems in AI. Within their research, each fellow will contend with the central motivating question of AI2050: “It’s 2050. AI has turned out to be hugely beneficial to society. What happened? What are the most important problems we solved and the opportunities and possibilities we realized to ensure this outcome?” 

Aggressive T-cell lymphoma is a rare and devastating form of blood cancer with a very low five-year survival rate. Patients often relapse after receiving initial therapy, making it especially challenging for clinicians to keep this destructive disease in check.

In a new study, researchers from MIT, in collaboration with researchers involved in the PETAL consortium at Massachusetts General Hospital, identified a practical and powerful prognostic marker that could help clinicians identify high-risk patients early, and potentially tailor treatment strategies to improve survival.

The team found that, when patients relapse within 12 months of initial therapy, their chances of survival decline dramatically. For these patients, targeted therapies might improve their chances for survival, compared to traditional chemotherapy, the researchers say.

According to their analysis, which used data collected from thousands of patients all over the world, the finding holds true across patient subgroups, regardless of the patient’s initial therapy or their score in a commonly used prognostic index.

A causal inference framework called Synthetic Survival Controls (SSC), developed as part of MIT graduate student Jessy (Xinyi) Han’s thesis, was central to this analysis. This versatile framework helps to answer “when-if” questions — to estimate how the timing of outcomes would shift under different interventions — while overcoming the limitations of inconsistent and biased data.

The identification of novel risk groups could guide clinicians as they select therapies to improve overall survival. For instance, a clinician might prioritize early-phase clinical trials over canonical therapies for this cohort of patients. The results could inform inclusion criteria for some clinical trials, according to the researchers.

The causal inference framework for survival analysis can also be applied more broadly. For instance, the MIT researchers have used it in areas like criminal justice to study how structural factors drive recidivism.

“Often we don’t only care about what will happen, but when the target event will happen. These when-if problems have remained under the radar for a long time, but they are common in a lot of domains. We’ve shown here that, to answer these questions with data, you need domain experts to provide insight and good causal inference methods to close the loop,” says Devavrat Shah, the Andrew and Erna Viterbi Professor in Electrical Engineering and Computer Science at MIT, a member of Institute for Data, Systems and Society (IDSS) and of the Laboratory for Information and Decision Systems (LIDS), and co-author of the study.

Shah is joined on the paper by many co-authors, including Han, who is co-advised by Shah and Fotini Christia, the Ford International Professor of the Social Sciences in the Department of Political Science and director of IDSS; and corresponding authors Mark N. Sorial, a clinical pharmacist and investigator at the Dana-Farber Cancer Institute, and Salvia Jain, a clinician-investigator at the Massachusetts General Hospital Cancer Center, founder of the global PETAL consortium, and an assistant professor of medicine at Harvard Medical School. The research appears today in the journal Blood.

Estimating outcomes

The MIT researchers have spent the past few years developing the Synthetic Survival Control causal inference framework, which enables them to answer complex “when-if” questions when using available data is statistically challenging. Their approach estimates when a target event happens if a certain intervention is used.

In this paper, the researchers investigated an aggressive cancer called nodal mature T-cell lymphoma, and whether a certain prognostic marker led to worse outcomes. The marker, TTR12, signifies that a patient relapsed within 12 months of initial therapy.

They applied their framework to estimate when a patient will die if they have TTR12, and how their survival trajectory would be different if they do not have this prognostic marker.

“No experiment can answer that question because we are asking about two outcomes for the same patient. We have to borrow information from other patients to estimate, counterfactually, what a patient’s survival outcome would have been,” Han explains.

Answering these types of questions is notoriously difficult due to biases in the available observational data. Plus, patient data gathered from an international cohort bring their own unique challenges. For instance, a clinical dataset often contains some historical data about a patient, but at some point the patient may stop treatment, leading to incomplete records.

In addition, if a patient receives a specific treatment, that might impact how long they will survive, adding to the complexity of the data. Plus, for each patient, the researchers only observe one outcome on how long the patient survives — limiting the amount of data available.

Such issues lead to suboptimal performance of many classical methods.

The Synthetic Survival Control framework can overcome these challenges. Even though the researchers don’t know all the details for each patient, their method stitches information from multiple other patients together in such a way that it can estimate survival outcomes.

Importantly, their method is robust to specific modeling assumptions, making it broadly applicable in practice. 

The power of prognostication

The researchers’ analysis revealed that TTR12 patients consistently had much greater risk of death within five years of initial therapy than patients without the marker. This was true no matter the initial therapy the patients received or which subgroup they fell into.

“This tells us that early relapse is a very important prognosis. This acts as a signal to clinicians so they can think about tailored therapies for these patients that can overcome resistance in second-line or third-line,” Han says.

Moving forward, the researchers are looking to expand this analysis to include high-dimensional genomics data. This information could be used to develop bespoke treatments that can avoid relapse within 12 months.

“Based on our work, there is already a risk calculation tool being used by clinicians. With more information, we can make it a richer tool that can provide more prognostic details,” Shah says.

They are also applying the framework to other domains.

For instance, in a paper recently presented at the Conference on Neural Information Processing Systems, the researchers identified a dramatic difference in the recidivism rate among prisoners of different races that begins about seven months after release. A possible explanation is the different access to long-term support by different racial groups. They are also investigating individuals’ decisions to leave insurance companies, while exploring other domains where the framework could generate actionable insights.

“Partnering with domain experts is crucial because we want to demonstrate that our methods are of value in the real world. We hope these tools can be used to positively impact individuals across society,” Han says.

This work was funded, in part, by Daiichi Sankyo, Secure Bio, Inc., Acrotech Biopharma, Kyowa Kirin, the Center for Lymphoma Research, the National Cancer Institute, Massachusetts General Hospital, the Reid Fund for Lymphoma Research, the American Cancer Society, and the Scarlet Foundation.

National Institutes of Health (NIH) Director Jay Bhattacharya visited MIT on Friday, engaging in a wide-ranging discussion about policy issues and research aims at an event also featuring Rep. Jake Auchincloss MBA ’16 of Massachusetts.

The forum consisted of a dialogue between Auchincloss and Bhattacharya, followed by a question-and-answer session with an audience that included researchers from the greater Boston area. The event was part of a daylong series of stops Bhattacharya and Auchincloss made around Boston, a world-leading hub of biomedical research.

“I was joking with Dr. Bhattacharya that when the NIH director comes to Massachusetts, he gets treated like a celebrity, because we do science, and we take science very seriously here,” Auchincloss quipped at the outset.

Bhattacharya said he was “delighted” to be visiting, and credited the thousands of scientists who participate in peer review for the NIH. “The reason why the NIH succeeds is the willingness and engagement of the scientific community,” he said.

In response to an audience question, Bhattacharya also outlined his overall vision of the NIH’s portfolio of projects.

“You both need investments in ideas that are not tested, just to see if something works. You don’t know in advance,” he said. “And at the same time, you need an ecosystem that tests those ideas rigorously and winnows those ideas to the ones that actually work, that are replicable. A successful portfolio will have both elements in it.”

MIT President Sally A. Kornbluth gave opening remarks at the event, welcoming Bhattacharya and Auchincloss to campus and noting that the Institute’s earliest known NIH grant on record dates to 1948. In recent decades, biomedical research at MIT has boomed, expanding across a wide range of frontier fields.

Indeed, Kornbluth noted, MIT’s federally funded research projects during U.S. President Trump’s first term include a method for making anesthesia safer, especially for children and the elderly; a new type of expanding heart valve for children that eliminates the need for repeated surgeries; and a noninvasive Alzheimer’s treatment using sound and light stimulation, which is currently in clinical trials.

“Today, researchers across our campus pursue pioneering science on behalf of the American people, with profoundly important results,” Kornbluth said.

“The hospitals, universities, startups, investors, and companies represented here today have made greater Boston an extraordinary magnet for talent,” Kornbluth added. “Both as a force for progress in human health and an engine of economic growth, this community of talent is a precious national asset. We look forward to working with Dr. Bhattacharya to build on its strengths.”

The discussion occurred amid uncertainty about future science funding levels and pending changes in the NIH’s grant-review processes. The NIH has announced a “unified strategy” for reviewing grant applications that may lead to more direct involvement in grant decisions by directors of the 27 NIH institutes and centers, along with other changes that could shift the types of awards being made.

Auchincloss asked multiple questions about the ongoing NIH changes; about 10 audience members from a variety of institutions also posed a range of questions to Bhattacharya, often about the new grant-review process and the aims of the changes.

“The unified funding strategy is a way to allow institute direcors to look at the full range of scoring, including scores on innovation, and pick projects that look like they are promising,” Bhattacharya said in response to one of Auchincloss’ queries.

One audience member also emphasized concerns about the long-term effects of funding uncertainties on younger scientists in the U.S.

“The future success of the American biomedical enterprise depends on us training the next generation of scientists,” Bhattacharya acknowledged.

Bhattacharya is the 18th director of the NIH, having been confirmed by the U.S. Senate in March. He has served as a faculty member at Stanford University, where he received his BA, MA, MD, and PhD, and is currently a professor emeritus. During his career, Bhattacharya’s work has often examined the economics of health care, though his research has ranged broadly across topics, in over 170 published papers. He has also served as director of the Center on the Demography and Economics of Health and Aging at Stanford University.

Auchincloss is in his third term as the U.S. Representative to Congress from the 4th district in Massachusetts, having first been elected in 2020. He is also a major in the Marine Corps Reserve, and received his MBA from the MIT Sloan School of Management.

Ian Waitz, MIT’s vice president for research, concluded the session with a note of thanks to Auchincloss and Bhattacharya for their “visit to the greater Boston ecosystem which has done so much for so many and contributed obviously to the NIH mission that you articulated.” He added: “We have such a marvelous history in this region in making such great gains for health and longevity, and we’re here to do more to partner with you.”

It’s nearly the end of 2025, and half of the US and the UK now require you to upload your ID or scan your face to watch “sexual content.” A handful of states and Australia now have various requirements to verify your age before you can create a social media account.

Age-verification laws may sound straightforward to some: protect young people online by making everyone prove their age. But in reality, these mandates force users into one of two flawed systems—mandatory ID checks or biometric scans—and both are deeply discriminatory. These proposals burden everyone’s right to speak and access information online, and structurally excludes the very people who rely on the internet most. In short, although these laws are often passed with the intention to protect children from harm, the reality is that these laws harm both adults and children. 

Here’s who gets hurt, and how: 

   1.  Adults Without IDs Get Locked Out

Document-based verification assumes everyone has the right ID, in the right name, at the right address. About 15 million adult U.S. citizens don’t have a driver’s license, and 2.6 million lack any government-issued photo ID at all. Another 34.5 million adults don't have a driver's license or state ID with their current name and address.

Specifically:

• 18% of Black adults don't have a driver's license at all.
• Black and Hispanic Americans are disproportionately less likely to have current licenses.
• Undocumented immigrants often cannot obtain state IDs or driver's licenses.
• People with disabilities are less likely to have current identification.
• Lower-income Americans face greater barriers to maintaining valid IDs.

Some laws allow platforms to ask for financial documents like credit cards or mortgage records instead. But they still overlook the fact that nearly 35% of U.S. adults also don't own homes, and close to 20% of households don't have credit cards. Immigrants, regardless of legal status, may also be unable to obtain credit cards or other financial documentation.

   2.  Communities of Color Face Higher Error Rates

Platforms that rely on AI-based age-estimation systems often use a webcam selfie to guess users’ ages. But these algorithms don’t work equally well for everyone. Research has consistently shown that they are less accurate for people with Black, Asian, Indigenous, and Southeast Asian backgrounds; that they often misclassify those adults as being under 18; and sometimes take longer to process, creating unequal access to online spaces. This mirrors the well-documented racial bias in facial recognition technologies. The result is that technology’s inherent biases can block people from speaking online or accessing others’ speech.

   3.  People with Disabilities Face More Barriers

Age-verification mandates most harshly affect people with disabilities. Facial recognition systems routinely fail to recognize faces with physical differences, affecting an estimated 100 million people worldwide who live with facial differences, and “liveness detection” can exclude folks with limited mobility. As these technologies become gatekeepers to online spaces, people with disabilities find themselves increasingly blocked from essential services and platforms with no specified appeals processes that account for disability.

Document-based systems also don't solve this problem—as mentioned earlier, people with disabilities are also less likely to possess current driver's licenses, so document-based age-gating technologies are equally exclusionary.

   4.  Transgender and Non-Binary People Are Put At Risk

Age-estimation technologies perform worse on transgender individuals and cannot classify non-binary genders at all. For the 43% of transgender Americans who lack identity documents that correctly reflect their name or gender, age verification creates an impossible choice: provide documents with dead names and incorrect gender markers, potentially outing themselves in the process, or lose access to online platforms entirely—a risk that no one should be forced to take just to use social media or access legal content.

   5.  Anonymity Becomes a Casualty

Age-verification systems are, at their core, surveillance systems. By requiring identity verification to access basic online services, we risk creating an internet where anonymity is a thing of the past. For people who rely on anonymity for safety, this is a serious issue. Domestic abuse survivors need to stay anonymous to hide from abusers who could track them through their online activities. Journalists, activists, and whistleblowers regularly use anonymity to protect sources and organize without facing retaliation or government surveillance. And in countries under authoritarian rule, anonymity is often the only way to access banned resources or share information without being silenced. Age-verification systems that demand government IDs or biometric data would strip away these protections, leaving the most vulnerable exposed.

   6.  Young People Lose Access to Essential Information 

Because state-imposed age-verification rules either block young people from social media or require them to get parental permission before logging on, they can deprive minors of access to important information about their health, sexuality, and gender. Many U.S. states mandate “abstinence only” sexual health education, making the internet a key resource for education and self-discovery. But age-verification laws can end up blocking young people from accessing that critical information. And this isn't just about porn, it’s about sex education, mental health resources, and even important literature. Some states and countries may start going after content they deem “harmful to minors,” which could include anything from books on sexual health to art, history, and even award-winning novels. And let’s be clear: these laws often get used to target anything that challenges certain political or cultural narratives, from diverse educational materials to media that simply includes themes of sexuality or gender diversity. What begins as a “protection” for kids could easily turn into a full-on censorship movement, blocking content that’s actually vital for minors’ development, education, and well-being. 

This is also especially harmful to homeschoolers, who rely on the internet for research, online courses, and exams. For many, the internet is central to their education and social lives. The internet is also crucial for homeschoolers' mental health, as many already struggle with isolation. Age-verification laws would restrict access to resources that are essential for their education and well-being.

   7.  LGBTQ+ Youth Are Denied Vital Lifelines

For many LGBTQ+ young people, especially those with unsupportive or abusive families, the internet can be a lifeline. For young people facing family rejection or violence due to their sexuality or gender identity, social media platforms often provide crucial access to support networks, mental health resources, and communities that affirm their identities. Age verification systems that require parental consent threaten to cut them from these crucial supports. 

When parents must consent to or monitor their children's social media accounts, LGBTQ+ youth who lack family support lose these vital connections. LGBTQ+ youth are also disproportionately likely to be unhoused and lack access to identification or parental consent, further marginalizing them. 

   8.  Youth in Foster Care Systems Are Completely Left Out

Age verification bills that require parental consent fail to account for young people in foster care, particularly those in group homes without legal guardians who can provide consent, or with temporary foster parents who cannot prove guardianship. These systems effectively exclude some of the most vulnerable young people from accessing online platforms and resources they may desperately need.

   9.  All of Our Personal Data is Put at Risk

An age-verification system also creates acute privacy risks for adults and young people. Requiring users to upload sensitive personal information (like government-issued IDs or biometric data) to verify their age creates serious privacy and security risks. Under these laws, users would not just momentarily display their ID like one does when accessing a liquor store, for example. Instead, they’d submit their ID to third-party companies, raising major concerns over who receives, stores, and controls that data. Once uploaded, this personal information could be exposed, mishandled, or even breached, as we've seen with past data hacks. Age-verification systems are no strangers to being compromised—companies like AU10TIX and platforms like Discord have faced high-profile data breaches, exposing users’ most sensitive information for months or even years. 

The more places personal data passes through, the higher the chances of it being misused or stolen. Users are left with little control over their own privacy once they hand over these immutable details, making this approach to age verification a serious risk for identity theft, blackmail, and other privacy violations. Children are already a major target for identity theft, and these mandates perversely increase the risk that they will be harmed.

   10.  All of Our Free Speech Rights Are Trampled

The internet is today’s public square—the main place where people come together to share ideas, organize, learn, and build community. Even the Supreme Court has recognized that social media platforms are among the most powerful tools ordinary people have to be heard.

Age-verification systems inevitably block some adults from accessing lawful speech and allow some young people under 18 users to slip through anyway. Because the systems are both over-inclusive (blocking adults) and under-inclusive (failing to block people under 18), they restrict lawful speech in ways that violate the First Amendment. 

The Bottom Line

Age-verification mandates create barriers along lines of race, disability, gender identity, sexual orientation, immigration status, and socioeconomic class. While these requirements threaten everyone’s privacy and free-speech rights, they fall heaviest on communities already facing systemic obstacles.

The internet is essential to how people speak, learn, and participate in public life. When access depends on flawed technology or hard-to-obtain documents, we don’t just inconvenience users, we deepen existing inequalities and silence the people who most need these platforms. As outlined, every available method—facial age estimation, document checks, financial records, or parental consent—systematically excludes or harms marginalized people. The real question isn’t whether these systems discriminate, but how extensively.