The study and practice of being human

For their last meeting of the fall 2023 semester, the students in MIT’s course 21W.756 (Nature Poetry) piled into a bus and headed to a local performance space for a reading: their own.

Sure, students in the course, taught by Professor Joshua Bennett, spend much of the semester reading and discussing poems. But they create and perform, too, often using tools from their other studies at MIT. One student in 21W.756 built a custom field microphone to incorporate recorded sounds into his work; another designed collages to complement her poems.

“The students are phenomenal,” says Bennett, a professor of literature and Distinguished Chair of the Humanities at MIT. “I try to think about how everything else they’re studying at MIT might meet up with the study of literature in a productive way. We’ve got great students who do super-interesting things.”

He adds: “They are willing to take the leap between other classes and our class very seriously. They see it as an opportunity — and they’ve explicitly told me this — to talk about being human. They’ve cherished that, and it’s been a transformative experience to have witnessed that.”

Bennett, an award-winning professor with a broad portfolio of work, knows about leaping between disciplines. He has published books of literary criticism, cultural history, and three collections of poems. Bennett has also gained renown as a spoken-word poetry performer — he has another major tour slated for this summer — and helped found the poetry collaborative Strivers Row. His readings have gained what must be millions of views on YouTube, including “Tamara’s Opus,” a dramatic work written for his deaf sister.

In short, Bennett also does his own super-interesting things, while encouraging students to join him in the pursuit of knowledge.

“Why do we create literature in the first place?” Bennett asks. “Why do we go to college? Why do we listen to people tell stories? Why do 300 or 3,000 people at a poetry reading listen to me or others talk? I imagine some of it is, there are things we love about being alive. And one of them is the feeling you can learn something new. You can be astonished. There is a space for you to become more complete through knowledge.”

Reading (and listening to) everything

Bennett grew up in Yonkers, New York, in a family that included preachers and musicians, and helped inculcate a love of learning in him.

“I’m thankful I had parents who just weren’t narrow-minded,” Bennett says. “They taught me to read everything, to listen to everything. At school I was reading Fitzgerald, and other works that were canonical, and wherever I saw beauty I really gravitated to it.” At the same time, he notes, “I was exposed to the genius of gospel music, jazz, and Motown,” while learning about Black scientists and much more.

He credits a 10th grade English teacher, Kaliq Simms, for helping him realize his potential as a student and writer.

“We read Hamlet, the Merchant of Venice, the Canterbury Tales, and she took us through literature in a way that made it land,” Bennett says. “She taught those works alongside Toni Morrison and James Baldwin. There was just something about the way she spoke to us. Ms. Simms said I was a ‘witty elocutionist.’ She just saw something in me other people didn’t see, or couldn’t. She had a serious role in changing my trajectory.”

Thus bolstered, Bennett earned his undergraduate degree as a double major in Africana studies and English from the University of Pennsylvania, where he became involved in the competitive poetry-slam scene. Bennett did so well as a performer that in 2009, before he had graduated, he was invited to perform “Tamara’s Opus” at the White House; it is an apology to his sister for not having learned sign language sooner. Graduating in 2010, Bennett was a commencement speaker at Penn.

If that weren’t enough, Bennett also earned a prestigious Marshall Scholarship, allowing him to receive an MA in theater and performance studies from the University of Warwick, in Coventry, England. Bennett then earned his PhD in English from Princeton University. His dissertation, about the place and meaning of animals in Black literature, ultimately became his 2020 book, “Being Property Once Myself.” It won the Modern Language Association’s William Sanders Scarborough Prize.

“It really emerged from having two grandparents who were sharecroppers who met in a strawberry field in North Carolina and emphasized the beauty of that field,” Bennett says. “I thought, how is that possible? To come out of that context with a story of love and beauty. When I got to Princeton, I expected the appearence of animals in African American literature to always be about degredation, but instead what I found were writers who took animals on their own terms, as beautiful, as powerful, as annoying, as recalcitrant, and sometimes as radicals or fugitives.”

Those writers include major figures such as Richard Wright, Zora Neale Hurston, Toni Morrison, Robert Hayden, and Jesmyn Ward, among others. “I chose all canonical authors, on purpose,” Bennett says. “But that was to say, these are some of the most written-about books by African Americans, and even so, people had not written about them in this way.”

After receiving his PhD in 2016, Bennett spent three years as a Junior Fellow in Harvard University’s Society of Fellows, then joined the faculty of Dartmouth College in 2019. Two years later, he was promoted to full professor. Bennett joined the MIT faculty full-time starting in 2023.

Among other recent honors, Bennett was awarded a Guggenheim Fellowship in 2021. He also won the 2023 Paterson Poetry Prize for his 2022 poetry collection, “The Study of Human Life.”

What kind of writing?

Bennett’s prolific output, both in scholarly works and as a poet and performer, no doubt owes much to his inner drive and enthusiasm. But his ability to produce work across genres also seems tied to his flexible thinking about writerly voice. Bennett is not constrained by the idea that his writing can only take one register; he varies his approach depending upon the project.

“To me it’s all [just] different kinds of writing,” Bennett says. “I was raised around musicians, around preachers, which I think is really central, because I understood what they were doing, even if some of them were improvising sermons, as a kind of writing. Poetry, fiction, and nonfiction are all kinds of writing, so [the question became], what kind of writing is best suited to my object of concern?”

For instance, Bennett says his 2016 poetry collection, “The Sobbing School,” a complex series of explorations about sustaining selfhood in the context of violence and tragedy, is about grief; that subject matter shaped the form.

“At that moment, I thought, these need to be elegies,” Bennett says.

However, Bennett’s 2023 nonfiction book “Spoken Word,” a history of the spoken-word poetry movement, is different. It is a deeply researched book that Bennett has written for a general audience, with a fast-paced text replicating the sense of movement and novelty surrounding the growth of the spoken-word genre, its best-known venues, like the Nuyorican Poets Café in Manhattan, and the creation of competitive poetry slams. In The New York Times, Tas Tobey called it a “vibrant cultural history.”

“I wanted to write ‘Spoken Word’ like a spoken-word poem, which I say explicitly, but I also wanted it to be a history of loving accomplishment,” Bennett says. “How people have not just competed, but worked together to create a sound.”

Another motif of “Spoken Word” is that in the process of creating spoken word poetry, people have found meaning in their own lives, discerned meaning in the works of others, and established human bonds and affinities and they might not have otherwise understood.

From the poetry slam venue to his own classroom, Bennett encourages this process. Making literature is an act of human value and meaning, and helps us reflect on it, too.

“We are here to sit with beauty and discomfort the whole time,” Bennett says of his class discussions. “Some of the work we read will be from people who were imprisoned, or enslaved, and we’re reading their poems together and learning what they have to say about human life.” Of his students, he adds: “We need as many hands on deck as possible, we need as many students who care and are devoted and as imaginative as possible in the room, and we need to give them all the resources we can to produce a livable world.”

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Precision home robots learn with real-to-sim-to-real

At the top of many automation wish lists is a particularly time-consuming task: chores. 

The moonshot of many roboticists is cooking up the proper hardware and software combination so that a machine can learn “generalist” policies (the rules and strategies that guide robot behavior) that work everywhere, under all conditions. Realistically, though, if you have a home robot, you probably don’t care much about it working for your neighbors. MIT Computer Science and Artificial Intelligence Laboratory (CSAIL) researchers decided, with that in mind, to attempt to find a solution to easily train robust robot policies for very specific environments.

“We aim for robots to perform exceptionally well under disturbances, distractions, varying lighting conditions, and changes in object poses, all within a single environment,” says Marcel Torne Villasevil, MIT CSAIL research assistant in the Improbable AI lab and lead author on a recent paper about the work. “We propose a method to create digital twins on the fly using the latest advances in computer vision. With just their phones, anyone can capture a digital replica of the real world, and the robots can train in a simulated environment much faster than the real world, thanks to GPU parallelization. Our approach eliminates the need for extensive reward engineering by leveraging a few real-world demonstrations to jump-start the training process.”

Taking your robot home

RialTo, of course, is a little more complicated than just a simple wave of a phone and (boom!) home bot at your service. It begins by using your device to scan the target environment using tools like NeRFStudio, ARCode, or Polycam. Once the scene is reconstructed, users can upload it to RialTo’s interface to make detailed adjustments, add necessary joints to the robots, and more.

The refined scene is exported and brought into the simulator. Here, the aim is to develop a policy based on real-world actions and observations, such as one for grabbing a cup on a counter. These real-world demonstrations are replicated in the simulation, providing some valuable data for reinforcement learning. “This helps in creating a strong policy that works well in both the simulation and the real world. An enhanced algorithm using reinforcement learning helps guide this process, to ensure the policy is effective when applied outside of the simulator,” says Torne.

Testing showed that RialTo created strong policies for a variety of tasks, whether in controlled lab settings or more unpredictable real-world environments, improving 67 percent over imitation learning with the same number of demonstrations. The tasks involved opening a toaster, placing a book on a shelf, putting a plate on a rack, placing a mug on a shelf, opening a drawer, and opening a cabinet. For each task, the researchers tested the system’s performance under three increasing levels of difficulty: randomizing object poses, adding visual distractors, and applying physical disturbances during task executions. When paired with real-world data, the system outperformed traditional imitation-learning methods, especially in situations with lots of visual distractions or physical disruptions.

“These experiments show that if we care about being very robust to one particular environment, the best idea is to leverage digital twins instead of trying to obtain robustness with large-scale data collection in diverse environments,” says Pulkit Agrawal, director of Improbable AI Lab, MIT electrical engineering and computer science (EECS) associate professor, MIT CSAIL principal investigator, and senior author on the work.

As far as limitations, RialTo currently takes three days to be fully trained. To speed this up, the team mentions improving the underlying algorithms and using foundation models. Training in simulation also has its limitations, and currently it’s difficult to do effortless sim-to-real transfer and simulate deformable objects or liquids.

The next level

So what’s next for RialTo’s journey? Building on previous efforts, the scientists are working on preserving robustness against various disturbances while improving the model’s adaptability to new environments. “Our next endeavor is this approach to using pre-trained models, accelerating the learning process, minimizing human input, and achieving broader generalization capabilities,” says Torne.

“We’re incredibly enthusiastic about our 'on-the-fly' robot programming concept, where robots can autonomously scan their environment and learn how to solve specific tasks in simulation. While our current method has limitations — such as requiring a few initial demonstrations by a human and significant compute time for training these policies (up to three days) — we see it as a significant step towards achieving 'on-the-fly' robot learning and deployment,” says Torne. “This approach moves us closer to a future where robots won’t need a preexisting policy that covers every scenario. Instead, they can rapidly learn new tasks without extensive real-world interaction. In my view, this advancement could expedite the practical application of robotics far sooner than relying solely on a universal, all-encompassing policy.”

“To deploy robots in the real world, researchers have traditionally relied on methods such as imitation learning from expert data, which can be expensive, or reinforcement learning, which can be unsafe,” says Zoey Chen, a computer science PhD student at the University of Washington who wasn’t involved in the paper. “RialTo directly addresses both the safety constraints of real-world RL [robot learning], and efficient data constraints for data-driven learning methods, with its novel real-to-sim-to-real pipeline. This novel pipeline not only ensures safe and robust training in simulation before real-world deployment, but also significantly improves the efficiency of data collection. RialTo has the potential to significantly scale up robot learning and allows robots to adapt to complex real-world scenarios much more effectively.”

"Simulation has shown impressive capabilities on real robots by providing inexpensive, possibly infinite data for policy learning,” adds Marius Memmel, a computer science PhD student at the University of Washington who wasn’t involved in the work. “However, these methods are limited to a few specific scenarios, and constructing the corresponding simulations is expensive and laborious. RialTo provides an easy-to-use tool to reconstruct real-world environments in minutes instead of hours. Furthermore, it makes extensive use of collected demonstrations during policy learning, minimizing the burden on the operator and reducing the sim2real gap. RialTo demonstrates robustness to object poses and disturbances, showing incredible real-world performance without requiring extensive simulator construction and data collection.”

Torne wrote this paper alongside senior authors Abhishek Gupta, assistant professor at the University of Washington, and Agrawal. Four other CSAIL members are also credited: EECS PhD student Anthony Simeonov SM ’22, research assistant Zechu Li, undergraduate student April Chan, and Tao Chen PhD ’24. Improbable AI Lab and WEIRD Lab members also contributed valuable feedback and support in developing this project. 

This work was supported, in part, by the Sony Research Award, the U.S. government, and Hyundai Motor Co., with assistance from the WEIRD (Washington Embodied Intelligence and Robotics Development) Lab. The researchers presented their work at the Robotics Science and Systems (RSS) conference earlier this month.

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Method prevents an AI model from being overconfident about wrong answers

People use large language models for a huge array of tasks, from translating an article to identifying financial fraud. However, despite the incredible capabilities and versatility of these models, they sometimes generate inaccurate responses.

On top of that problem, the models can be overconfident about wrong answers or underconfident about correct ones, making it tough for a user to know when a model can be trusted.

Researchers typically calibrate a machine-learning model to ensure its level of confidence lines up with its accuracy. A well-calibrated model should have less confidence about an incorrect prediction, and vice-versa. But because large language models (LLMs) can be applied to a seemingly endless collection of diverse tasks, traditional calibration methods are ineffective.

Now, researchers from MIT and the MIT-IBM Watson AI Lab have introduced a calibration method tailored to large language models. Their method, called Thermometer, involves building a smaller, auxiliary model that runs on top of a large language model to calibrate it.

Thermometer is more efficient than other approaches — requiring less power-hungry computation — while preserving the accuracy of the model and enabling it to produce better-calibrated responses on tasks it has not seen before.

By enabling efficient calibration of an LLM for a variety of tasks, Thermometer could help users pinpoint situations where a model is overconfident about false predictions, ultimately preventing them from deploying that model in a situation where it may fail.

“With Thermometer, we want to provide the user with a clear signal to tell them whether a model’s response is accurate or inaccurate, in a way that reflects the model’s uncertainty, so they know if that model is reliable,” says Maohao Shen, an electrical engineering and computer science (EECS) graduate student and lead author of a paper on Thermometer.

Shen is joined on the paper by Gregory Wornell, the Sumitomo Professor of Engineering who leads the Signals, Information, and Algorithms Laboratory in the Research Laboratory for Electronics, and is a member of the MIT-IBM Watson AI Lab; senior author Soumya Ghosh, a research staff member in the MIT-IBM Watson AI Lab; as well as others at MIT and the MIT-IBM Watson AI Lab. The research was recently presented at the International Conference on Machine Learning.

Universal calibration

Since traditional machine-learning models are typically designed to perform a single task, calibrating them usually involves one task-specific method. On the other hand, since LLMs have the flexibility to perform many tasks, using a traditional method to calibrate that model for one task might hurt its performance on another task.

Calibrating an LLM often involves sampling from the model multiple times to obtain different predictions and then aggregating these predictions to obtain better-calibrated confidence. However, because these models have billions of parameters, the computational costs of such approaches rapidly add up.

“In a sense, large language models are universal because they can handle various tasks. So, we need a universal calibration method that can also handle many different tasks,” says Shen.

With Thermometer, the researchers developed a versatile technique that leverages a classical calibration method called temperature scaling to efficiently calibrate an LLM for a new task.

In this context, a “temperature” is a scaling parameter used to adjust a model’s confidence to be aligned with its prediction accuracy. Traditionally, one determines the right temperature using a labeled validation dataset of task-specific examples.

Since LLMs are often applied to new tasks, labeled datasets can be nearly impossible to acquire. For instance, a user who wants to deploy an LLM to answer customer questions about a new product likely does not have a dataset containing such questions and answers.

Instead of using a labeled dataset, the researchers train an auxiliary model that runs on top of an LLM to automatically predict the temperature needed to calibrate it for this new task.

They use labeled datasets of a few representative tasks to train the Thermometer model, but then once it has been trained, it can generalize to new tasks in a similar category without the need for additional labeled data.

A Thermometer model trained on a collection of multiple-choice question datasets, perhaps including one with algebra questions and one with medical questions, could be used to calibrate an LLM that will answer questions about geometry or biology, for instance.

“The aspirational goal is for it to work on any task, but we are not quite there yet,” Ghosh says.   

The Thermometer model only needs to access a small part of the LLM’s inner workings to predict the right temperature that will calibrate its prediction for data points of a specific task. 

An efficient approach

Importantly, the technique does not require multiple training runs and only slightly slows the LLM. Plus, since temperature scaling does not alter a model’s predictions, Thermometer preserves its accuracy.

When they compared Thermometer to several baselines on multiple tasks, it consistently produced better-calibrated uncertainty measures while requiring much less computation.

“As long as we train a Thermometer model on a sufficiently large number of tasks, it should be able to generalize well across any new task, just like a large language model, it is also a universal model,” Shen adds.

The researchers also found that if they train a Thermometer model for a smaller LLM, it can be directly applied to calibrate a larger LLM within the same family.

In the future, they want to adapt Thermometer for more complex text-generation tasks and apply the technique to even larger LLMs. The researchers also hope to quantify the diversity and number of labeled datasets one would need to train a Thermometer model so it can generalize to a new task.

This research was funded, in part, by the MIT-IBM Watson AI Lab.

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Helping Olympic athletes optimize their performance, one stride at a time

The Olympics is all about pushing the frontiers of human performance. As some athletes prepared for the Paris 2024 games, that included using a new technology developed at MIT.nano.

The technology was created by Striv (pronounced “strive”), a startup whose founder gained access to the cutting-edge labs and fabrication equipment at MIT.nano as part of the START.nano accelerator program. Striv’s tactile sensing technology fits into the inserts of shoes and, when combined with algorithms that crunch that tactile data, can precisely track force, movement, and form. Runners including USA marathoner Clayton Young, Jamaican track and field Olympian Damar Forbes, and former Olympic marathoner Jake Riley have tried Striv’s device.

“I’m excited about the potential of Striv’s technology,” Riley says. “It’s on a good path to revolutionize how we train and prevent injuries. After testing the sensors and seeing the data firsthand, I’m convinced of its value.”

For Striv founder Axl Chen, the 2024 games are the perfect opportunity to show that the product can help athletes at the highest level. But Chen also believes their product can help many non-Olympians.

“We think the Paris 2024 Olympics will be a really interesting opportunity for us to test the product with the athletes training for it,” Chen says. “After that, we’ll offer this to the general public to help everyone get the same kind of support and coaching advice as professional athletes.”

Putting yourself in someone else’s shoes

Chen was working in a robotics lab at Tsinghua University in China when he began using tactile sensors. Over the next two years, he experimented with ways to make the sensors more flexible and cost-effective.

“I think a lot of people have already explored vision and language, but tactile sensing as a way of perceiving the world seemed more open to me,” Chen says. “I thought tactile sensors and AI could make for powerful new products.”

The first space Striv entered was virtual reality (VR) gaming. The company created a shoe with embedded sensors that could capture users’ body motions in real-time by combining the sensor data with regular VR hand controllers. Striv even sold about 300 pairs of its shoes to interested customers around the world.

Striv has also gotten interest from companies in the medical, robotics, and automotive fields, which was both a blessing and a curse because of the need for startups to focus on one specific customer early on.

Chen says getting into the START.nano program in 2023 was an inflection point for the company.

“I pretty much didn't apply to anything else,” Chen says. “I’m really interested in this technology, and I knew if I could do research at MIT, it would be really helpful to push this technology forward.”

Since then, Chen has leveraged MIT’s advanced nanofabrication equipment, laboratories, and expertise to iterate on different designs and build prototypes. That has included working in MIT.nano’s Immersion Lab, which features precise motion capture devices and other sensing technologies, like VO2 intake measurements and details force analysis of runners’ steps on a treadmill.

Striv’s team has also received support from the MIT Venture Mentoring Service (VMS) and is part of the MIT Industrial Liaison Program’s Startup Exchange program, which has helped the team hone in on athletes as the beachhead market for their technology.

“It’s remarkable that MIT is supporting us so much,” Chen says. “We often get asked why they’re doing this [for non-students], and we say MIT is committed to pushing technology forward.”

Striv’s sensing solution is made up of two layers of flexible electrodes with a material in between that can create different electrical characteristics corresponding to the force it comes under. That material has been at the heart of Chen’s research at MIT.nano: He’s trying to make it more durable and precise by adding nanostructures and making other tweaks.

Striv is also developing AI algorithms that use the sensor data to infer full body motion.

“We can quantify the force they apply to the ground and the efficiency of their movements,” Chen explains. “We can see if they're leaning too far forward, or their knees are too high. That can be really useful in determining if they're improving or not.”

Technology for the masses

As soon as Chen began interviewing runners, he knew Striv could help them.

“The alternatives for athletes are either to go to a really expensive biomechanics lab or use a wearable that's able to track your heart rate but doesn't give insights into your performance,” Chen explains. “For example, if you’re running, how is your form? How can you improve it? Runners are really interested in their form. They care about how high their knees go, how high they’re jumping, how much force they’re putting into the ground.”

Striv has tested its product with around 50 professional athletes to date and worked with Young in the leadup to the Olympics. Chen also has an eye on helping more casual runners.

“We also want to bring this to serious runners that aren't professional,” Chen says. “I know a lot of people in Boston who run every day. That's where this will go next.”

As the company grows and collects more data, Chen believes Striv will be able to provide personalized plans for improving performance and avoiding injuries across a range of different activities.

“We talk to a lot of coaches, and we think there's potential to bring this to a lot of different sports,” Chen says. “Golfers, hikers, tennis players, cyclists, ski and snowboarders. We think this could be really useful for all of them.”

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Across the pond to scale new heights

Nathanael Jenkins had always wanted to study aerospace engineering, he just hadn’t quite found the right place for it. He had explored options close to his home in Hampshire, U.K., but had never considered studying in the United States. That changed when a family vacation brought him to the MIT campus in 2018. “MIT felt exciting, high-energy, and very different from my small high school back home. My lasting memory was the fact that they had a nuclear reactor in the middle of a bustling city,” he says.

Yet after weighing financial, travel, and family considerations, he opted for a top science and engineering university a bit closer to home, at Imperial College London (ICL), majoring in aeronautical engineering. Still, he never took his sights off MIT — and he didn’t have to.

Since 2019, MIT’s International Science and Technology Initiatives (MISTI) program has worked with Imperial College London to exchange students from eight MIT departments looking for a global education experience, and has seen eight Imperial students spend the year at MIT’s Department of Aeronautics and Astronautics (AeroAstro). When Jenkins learned about the opportunity, he was determined to take another shot at an education abroad. He and his colleague Timur Uyumaz, who had never been to the United States, applied for the exchange and were accepted into Course 16.

“I was definitely very excited,” says Jenkins. “The prospect of traveling to the U.S. still felt pretty surreal until we’d actually landed in Boston.”

Academic pursuits, first-hand and hands-on

Jenkins joined the Aerospace Plasma Group, where he worked on lightning strike simulations for aircraft fuselage safety. Uyumaz became a member of the Computational Turbulence Group, expanding his work on high-fidelity fluid simulations. The research-focused environment allowed both to dive into their studies without the fear of a high-pressure exam looming at the end of their courses.

“At Imperial, 90 percent of my classes are exam-focused,” says Jenkins. “At MIT, I’m working hard all the time, learning more actively every week, and there’s no terror at the end.”

One of the academic highlights for both students has been the ability to take classes with experts and pioneers in science, engineering, and aerospace. “In my first semester, I took 18.C25 (Real World Computation with Julia) — taught by Alan Edelman, the actual co-founder of Julia,” says Uyumaz. “It was a privilege to be taught by innovators within their fields.”

Last year, Jenkins took a 16.891 (Space Policy Seminar) class led by MIT Media Lab Director and former NASA Deputy Administrator Dava Newman, and Professor Daniel Hastings, a former chief scientist at the U.S. Air Force. “You’re learning from the people who were part of these huge milestones in space research. They’re not teaching as if they were there — they were actually there,” says Jenkins.

Having experts working together in one place offers endless possibilities for collaboration, and Jenkins has taken full advantage of MIT’s labs and state-of-the-art facilities. He has even conducted an experiment in the nuclear reactor that piqued his interest years ago.

Scaling new heights with outdoor adventures

Outside the classroom, both Jenkins and Uyumaz have become active members of the MIT Outing Club (MITOC), taking the opportunity to go on outdoor hiking adventures across New England. “We thought it would be like British hiking — rain and low altitude,” they laugh, but immediately found that the group was inclined to take on a more challenging trek.

They first tackled Guy’s Slide, a steep Adirondack-style climb on Mount Lincoln in New Hampshire. “This climb has places with ‘no-fall zones,’ which just means ‘seriously, don’t fall.’ The leader for the trip asked us ‘are you sure’ several times before we signed up, knowing we were new climbers. Once we talked about our limits, we got cleared to go.” After the four-and-a-half-hour climb to Mt. Lincoln’s 5,089 foot summit, the pair were hooked. “Our thing was being outside from then on.”

They climbed Mount Washington last winter as both participants and leaders of the expedition, with other exchange students, staff, and even alumni from across the Institute along for the climb. “There was lots of snow, and views for miles.” Inviting other exchange students has helped them build connections with other students from ICL, MIT, and universities around the world.

Onward and upward

While Uyumaz has returned to ICL to complete his studies, Jenkins is looking forward to formally joining Course 16 as a graduate student in the fall, still in the Aerospace Plasma Group. “I’m keen on — adamant, really — that I’ll do a career in engineering, probably in fluid simulations,” he says. He recognizes that having a place like MIT on his resume, with strong industry collaborations and well-connected faculty, will benefit his career in the short and long term.

“I am grateful for the hospitality we received from MIT — from AeroAstro, MITOC, Baker House (and resident house dogs, Biko and Louie, who always added joy to our day). The program enabled something I never thought possible.”

In the coming years, Jenkins looks forward to spending even more time outdoors with MITOC during his time as a graduate student. “I'm hoping to run some stand-up paddle boarding trips on the Charles [River], and continue exploring the White Mountains. At some point, I'm planning to venture further west to explore some even bigger mountains in Colorado.”

Uyumaz is looking forward to using his new cross-cultural connections to strengthen partnerships between ICL and MIT and inform his academic journey. “Although it was a one-year exchange, I have been provided with perspective and opportunities for a lifetime,” he says. 

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MIT spinout Arnasi begins applying LiquiGlide no-stick technology to help patients

The no-stick technology invented by Professor Kripa Varanasi and David Smith SM ’11, initially commercialized as LiquiGlide in 2012, went viral for its uncanny ability to make materials that stick to their containers — think ketchup, cosmetics, and toothpaste — slide out with ease.

Now, the company that brought you Colgate no-stick toothpaste is moving into the medical space, and the applications could improve millions of lives. The company, which recently rebranded as the Arnasi Group, has developed an ambitious plan to launch three new biomedical products over the next four years.

The first of those products, called Revel, is a deodorizing lubricant designed for ostomy pouches, which are used by individuals to collect bodily waste after digestive system surgeries. Up to 1 million people rely on such pouches in the United States. Ostomy pouches must be emptied multiple times per day, and issues resulting from sticking or clogging can cause embarrassing, time-consuming situations for the people relying on them.

Arnasi’s deodorizing lubricant can prevent clogging and simplify the ostomy pouch cleaning process. Unlike other options available, one application of its lubricant works for the entire day, the Arnasi team says, and they designed a single unit dose that fits in your pocket for added convenience.

An ostomy pouch “significantly impacts a person’s lifestyle,” Varanasi says. “They need to keep it clean, and they need to use it at all times. We are solving a very important problem while helping people by giving their dignity and lifestyles back.”

Revel, Arnasi’s FDA-registered product, officially launched this month, and it has already received promising feedback from nurses and patients.

Margaret is a nurse who relies on an ostomy pouch herself and cares for patients who need them after receiving colostomies and ileostomies. She received samples of Revel at a recent conference and says it could dramatically improve both her and her patients’ lives.

“These pouches need to be emptied frequently, and sometimes that’s very difficult to do,” she says. “This particular product makes everything slide out without any problems at all, and it’s a wonderful improvement. It also lasts long enough to empty the pouch three to four times, which is great because you don’t have to carry a bunch of this stuff around.”

Margaret’s experience echoes feedback Arnasi’s team has heard from many others.

“When we showed it to the nurses, they were blown away with the product,” says Arnasi CEO Dan Salain. “They asked us to get this product out to the market as fast as we could, and so that’s what we’re doing.”

Arnasi’s next medical products will be used to prevent biofilm and bacterial infections caused by implants and catheters, and will also help people with cystic fibrosis.

“We want to create products that really help people,” Salain says. “Anything that’s implantable in the body, whether it’s a catheter, a hip, knee, or joint replacement, a breast implant, a bladder sling — those things lend themselves to our technology.”

From packages to patients

Varanasi initially developed Arnasi’s liquid-impregnated surface technology with Smith, Arnasi’s co-founder and current CTO, when Smith was a graduate student in Varanasi’s lab. The research was initially funded by the MIT Energy Initiative and the MIT Deshpande Center to work on solid-liquid interfaces with broad applications for energy, water, and more.

“There’s this fundamental friction constraint called the no-slip boundary condition between a liquid and a solid, so by creating a new surface in which we can infuse a liquid that is less viscous, we can now get the product to easily slide on surfaces,” Varanasi explains. “That aha moment meant we could get around a fundamental constraint in fluid dynamics.”

Still, sticky surfaces are everywhere, and the scientific co-founders had to decide where to apply their technology first. Shortly after the invention, Varanasi was at home trying to decide on the best application when he saw his wife across the kitchen table trying to get honey out of a bottle. It was another aha moment.

Soon after, Varanasi’s team entered the MIT $100K Entrepreneurship Competition. The competition — and the corresponding videos of ketchup and other materials sliding out their bottles with ease — created a media storm and a frenzy of attention.

“The press exploded,” Varanasi says. “For three months, my phone didn’t stop ringing. My group website crashed. There was a lot of market pull and in response, we founded the company.”

Arnasi, still operating as LiquiGlide, licensed the intellectual property from MIT’s Technology Licensing Office and eventually signed large deals with some of the world’s biggest consumer packaged goods companies, who used it to create products like fully recyclable toothpaste.

“There is so much waste just because we can't get all of the product, be it food, cosmetics, or medical products, out of containers,” Varanasi says. “Fifty billion-plus packages are sold every year, and 5 to 10 percent of product is left behind on average. So, you can imagine the CO₂ footprint of the wasted product. And even though a lot of this is in recyclable packaging, they can’t be recycled because you need to wash out all the product. The water footprint of this is huge, not to mention the wasted product.”

While all of that was going on, Arnasi’s team was also looking into the biomedical space. For instance, Varanasi’s lab previously showed the technology could be used to prevent occlusion from blood clots and thrombosis and reduce biofilm formation, among other applications.

After studying the industry and speaking with patients and nurses, Arnasi realized a better lubricant for ostomy pouches could improve millions of people’s lives.

“Stool accumulates in these pouches outside of people’s bodies, and they need to empty it up to eight times a day,” explains Brienne Engel, Arnasi’s director of business development. “That process has a lot of challenges associated with it: It can be difficult to drain, leaving a lot of mass behind, it takes a long time to drain, so you can spend a long time in a restroom trying to clear out your pouch, and then there’s something called pancaking that can push the pouch off the [surgical opening], introducing issues like leakage, odor, and failure of the ostomy pouching system.”

Ostomy and beyond

Arnasi’s ostomy lubricant, Revel, is the first non-water-based solution on the market, and as-yet unpublished third-party testing has shown it allows for faster, more complete pouch drainage, along with other benefits.

“A lot of the existing brands treat their consumers like patients, but what we’ve found is they want to be treated like people and have a consumer experience,” Salain says. “The magic we saw with our toothpaste product was people got this amazing consumer experience out of it, and we wanted to create the same thing with Revel.”

Now Arnasi is planning to use its technology in medical products for skin infections, cystic fibrosis, and in implantable catheters and joint replacements. Arnasi’s team believes those last two use cases could prevent millions of deadly infections.

“When people are getting hemodialysis catheters, they have a 33 percent risk of developing infections, and those that do get those infections have a 25 percent chance of dying from them,” Engel says. “Taking our underlying technology and applying it to catheters, for example, imparts anti-biofilm properties and also prevent things like thrombosis, or blood clotting on the outside of these catheters, which is a problem in and of itself but also provides a space for bacteria to seed.”

Ultimately, Varanasi’s team is balancing making progress on its biomedical applications while exploring other avenues for its technology — including energy, manufacturing, and agriculture — to maximize its impact on the world.

“We think of this as a company with many companies within it because of all the different areas that it can impact. Liquid-solid interfaces are ubiquitous, viscous products are everywhere, and deploying this technology to solve difficult problems has been a dream,” Varanasi says. “It’s a great example of how MIT technology can be used for the benefit of humankind.”

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Groundbreaking poverty alleviation project expands with new Arnold Ventures, J-PAL North America collaboration

J-PAL North America, a regional office of MIT’s Abdul Latif Jameel Poverty Action Lab (J-PAL), will significantly expand its work to conduct rigorous research and strengthen evidence-based policymaking due to a new grant from long-time supporter and collaborator Arnold Ventures.  

With Arnold Ventures’ new eight-figure grant over seven years, J-PAL North America aims to:

• substantially expand the evidence base on effective solutions to poverty;
• build the capacity and increase the diversity of its network of over 265 expert researchers;
• institutionalize the use of evidence among nonprofits and policymakers; and
• accelerate the rate and scale at which evidence influences policy. 

Furthermore, J-PAL North America will leverage these funds to deepen its work centering racial and economic equity across our research network, the field of economics, and social policy. 

“J-PAL’s mission is to reduce poverty by ensuring that policy is informed by scientific evidence. We recognize that poverty is a pressing and complex issue, so we work to identify and scale solutions across various sectors, including education, health, and labor. This support from Arnold Ventures will take our work to the next level, creating new pathways for generating evidence, informing policy, and impacting lives,” says J-PAL North America Co-Executive Director Vincent Quan. “We are thrilled about this groundbreaking, expanded collaboration with Arnold Ventures on strengthening the evidence-informed ecosystem as we enter J-PAL North America’s second decade.” 

A long-standing collaboration for evidence-based solutions 

This new work builds on a long-standing foundation of successful collaboration between J-PAL North America and Arnold Ventures, who together have raised the bar for rigorous social science research and evidence-based policymaking.  

The research center recently celebrated its 10-year anniversary, having reached over 35 million lives by scaling evidence-based programs that have been rigorously evaluated by J-PAL affiliated researchers. J-PAL North America has worked with Arnold Ventures, along with other collaborators, to catalyze over 165 rigorous evaluations on topics ranging from summer youth employment programs to cash transfers. Arnold Ventures’ support for J-PAL North America’s research has helped shift over $518 million toward effective solutions to reduce poverty. For example, informed by J-PAL evidence, federal and state education agencies across the United States earmarked Covid-relief funds for tutoring to help accelerate learning in the wake of the pandemic. 

Justin Milner, executive vice president of evidence and evaluation at Arnold Ventures, explains that “Arnold Ventures is proud to have worked alongside J-PAL North America over the past decade, raising the bar for rigorous research and evidence-based policymaking. We’re excited to deepen our partnership to further institutionalize a culture of evidence among decision-makers and increase our collective impact in the years to come.” 

“J-PAL North America’s economic innovations and policy accomplishments directly advance SHASS’ mission of meeting the world’s great challenges. We are therefore eager for J-PAL North America to continue its essential work with Arnold Ventures, and look forward to seeing the impact of their collaboration on the larger MIT community and — most notably — the people in this region for years to come,” says Agustín Rayo, dean of MIT’s School of Humanities, Arts, and Social Sciences (SHASS). 

An urgent need for evidence-based solutions to address poverty 

Poverty remains a pervasive challenge in the North America region. In 2022, the official poverty rate in the United States was 11.5 percent, equating to nearly 38 million people living below the poverty line. The need to identify and scale effective solutions is paramount. J-PAL North America is excited to continue working with Arnold Ventures to build on the growing evidence-based policymaking movement, generate critical new research, and foster lasting policy partnerships to address some of society's greatest challenges. 

Amy Finkelstein, J-PAL North America’s co-scientific director, says, “When J-PAL North America was founded, Arnold Ventures saw our potential to transform the meaning of impact evaluation in the region. Now, a decade later, we’re proud to further solidify our collaboration and build on the foundations we have created together. I am incredibly excited that this grant will enable us to further expand the knowledge base of effective solutions to poverty and to better support the scale-up of these solutions.” 

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Study tracks exposure to air pollution through the day

There are significant differences in how much people are exposed to air pollution, according to a new study co-authored by MIT scholars that takes daily mobility into account.

The study, based in the Bronx, New York, does not just estimate air pollution exposure based on where people live or work, but uses mobile data to examine where people go during a typical day, building a more thorough assessment of the environment’s impact on them.

The research finds exposure to particulate matter 2.5 microns or bigger rises by about 2.4 percent when daily travel patterns are taken into account.

“One of the main strengths of the study is that we try to improve the information we use, on the air quality side and also from the fine-grained estimation of people’s mobility,” says Paolo Santi, a principal research scientist at Senseable City Lab, part of MIT’s Department of Urban Studies and Planning (DUSP), and a co-author of a new paper detailing the study’s results. “That allows us to build trajectories of people’s movement. So, it was the first time we were able to combine these data to come up with a new measure of exposure.”

After all, people’s daily pollution exposure may be a complex combination of either living near, working near, or traveling by sources of particulate matter.

“People move around the city for jobs and education and more, and studying that is where we get this better information about exposure,” says An Wang of the Hong Kong Polytechnic University, another co-author of the study.

The paper, “Big mobility data reveals hyperlocal air pollution exposure disparities,” is published today in Nature Cities.

The authors are Iacopo Testi of the Senseable City Lab; An Wang of Hong Kong Polytechnic University; Sanjana Paul, a graduate student in DUSP; Simone Mora, of the Senseable City Lab; Erica Walker, an associate professor at the Brown University School of Public Health; Marguerite Nyhan, a senior lecturer/associate professor at the National University of Ireland, University College Cork; Fábio Duarte of the Senseable City Lab; Santi; and Carlo Ratti, director of the Senseable City Lab.

To conduct the study, the researchers collected air pollution by mounting solar-power environmental sensors, including optical particle counters, temperature and humidity sensors, and GPS, on New York City’s civic services vehicles in operation in the Bronx.

“This strategy shows that cities can use their existing fleet as environmental sensors,” says Mora.

To measure how people moving through the Bronx are exposed to pollution in different times, the researchers used anonymized phone records of 500,000 different individuals and 500 million daily location records in New York.

The ground-level pollution data showed that the southeastern portion of the Bronx, where expressways and industries meet most intensively, has the most particulate matter.

The mobility data also revealed disparities in exposure when evaluated in terms of demographics, with income disparities present but disparities by ethnicity larger. For instance, some largely Hispanic communities have among the highest exposure levels. But the data also showed large differences in exposure levels within Hispanic communities.

Pollution exposure has significant implications from a health perspective, as Duarte notes. For instance, the Bronx has the worst air quality of any New York City borough, and, in turn, cases of asthma in the Bronx are 2.5 times higher in than any other borough.

“You see the consequences of exposure to pollution in the hospitalization of adults in the Bronx,” Duarte says.

As the researchers acknowledge, because the study was conducted in the fall of 2021, when the global Covid-19 pandemic was still affecting business and commuting, there may be slightly different mobility patterns in the Bronx today. Still, they believe their methods can give rise to additional future studies of the pollution exposure.

Ratti notes that mobile data, including pollution sensors on vehicles, can be used as “a huge monitoring system. It’s not expensive, we have the infrastructure in terms of cars and buses, and just putting sensors on them, you can have better air quality monitoring.”

And Wang notes that granular studies such as this one can be extended into studies that add in additional kinds of air-quality hazards, in addition to PM 2.5 particles.

“This actually opens the door for new analysis for many kinds of toxicity studies combined with exposure,” he says.

The study was supported by the MIT Senseable City Lab Consortium.

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Edgerton Center hosts workshop for deaf high school students in STEM

The percentage of deaf and hard-of-hearing individuals who have bachelor’s degrees is 15.2 percent lower than their hearing counterparts, and for those who do have degrees, most are in business and education. Deaf adults with degrees in STEM fields are few and far between. MIT Edgerton Center instructor Amanda Gruhl Mayer ’99, PhD ’08 has set out to bridge this gap by piloting a new MIT workshop called STEAMED (Science, Technology, Engineering, Art, and Math Experience for Deaf and hard-of-hearing students). 

The workshop tasked students with building an underwater remotely operated vehicle (ROV), teaching them new skills to build circuits, motors, and frames. At the end of the course, students tested their robots at the Z Center pool. Gruhl Mayer worked with Brian Gibson, a science teacher at Horace Mann School for the Deaf and Hard of Hearing; Edgerton Center instructors Chris Mayer and Christian Cardozo ’18; and MIT student mentors rising senior Ryn Moore and Ruben Castro ’24. With several instructors and mentors at varying levels of American Sign Language (ASL) fluency, ASL interpreters strengthened communication between all participants.

Gruhl Mayer became interested in deaf education when she moved into her first house in 2020 and met her neighbor’s deaf 13-year-old daughter, who was interested in science. Gruhl Mayer wanted to encourage her to delve deeper into STEM subjects. As she learned ASL, Gruhl Mayer quickly discovered that important scientific terms, like “amino acid,” “acceleration,” and “circuit,” lack common signs in ASL because there aren’t enough deaf scientists and engineers for the vocabulary to develop naturally. While pursuing a master’s degree in deaf education at Boston University, she deepened her passion for deaf culture. “I really want to push the pipeline for more deaf scientists and engineers. And I think we need to start with students,” Gruhl Mayer says.

Gruhl Mayer’s students entered the course not knowing exactly what they would be building, and quickly learned how to construct their own ROVs using SeaPerch kits from the MIT Sea Grant program. The ROV project is a favorite at the Edgerton Center for introducing high school students to power tools and circuits, and this is the first time it was presented to deaf students. During the workshop, the students and interpreters developed signs to use for new skills and concepts, like “soldering” and “buoyancy.”

Students waterproofed their motors, built thrusters, and connected them to controllers. They used power tools to create PVC pipe frames with attached foam core to make them neutrally buoyant, then tested the movement of their ROVs in a small tank inside the classroom. Students modified their designs to create unique ROVs, decorating them using lights and colored markers, and took them for a test drive in the Z Center Pool. Students picked up skills quickly and taught each other as they learned, each designing a unique ROV that could move in all directions, navigate through obstacles, and even pick something up off the bottom of the pool.

Brian Gibson, who’s been teaching hands-on science at Horace Mann for 21 years, says, “I’ve enjoyed watching the students become more independent and using different materials and tools that they haven't used in the past and become pretty proficient with those tools.” The students also enjoyed the increased responsibility. “Typically, we’re not allowed to use certain tools. They don’t offer us much responsibility. And so now, we were able to see how the tools work. I think that opens new opportunities for us,” says Bárbara Silva, a rising junior at the Horace Mann School. Students also appreciated the freedom and creativity that comes with not being graded. “At school, at home, or anywhere, things have to be perfect. But here, you could fail, and then you learn something new,” says rising junior at Newton North High School Lucy Howard-Karp.

Among the takeaways for the Edgerton Center instructors is recognizing the unique challenge of having to use your hands for communication while concurrently building. For example, hearing teachers often said “good job” to students while they were working, which made the students stop their work to watch the interpreter. Students requested that teachers wait for a good stopping point to give them praise, and only interrupt if the students are doing something that needs to be corrected. Gruhl Mayer points out, “Deaf students are just like hearing students. They have the same potential, enthusiasm, work ethic, etc. But there are educational tweaks that need to be made for deaf students, to help them learn in the way that’s best for them.”

Gruhl Mayer’s vision to make STEM accessible for deaf students has the potential to drive discoveries in the science community. “The term is called 'deaf gain,'” she explains. “Deaf people see the world differently, which gives them a new and fresh perspective. This unique viewpoint drives their creativity and innovation. So many amazing discoveries have been made by deaf scientists and engineers.”

Gruhl Mayer plans to run the workshop again next summer with more participants, hopefully having this year’s students come back as mentors. The students plan to get their fellow classmates excited to sign up by bringing their ROVs to school and showing off what they built.

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When learning at MIT means studying thousands of miles away

This summer, a group of MIT students traveled to Sicily’s southeastern coast to learn about threats to local communities related to sea level rise. They visited ancient archeological sites that are in danger of being wiped out, and worked with local college students on preservation and adaptation techniques.

This past January, another group of MIT students travelled to South Africa to study the biology of HIV and learn about a local community’s public health challenges concerning the disease. Another group travelled to Spain and lived with local families in Madrid while studying Spanish literature, culture, and history.

Some lessons can’t be taught in the classroom. That’s the reasoning behind the MIT International Science and Technology Initiatives (MISTI) Global Classrooms program.

Led by MIT faculty members, some Global Classrooms focus on grand challenges such as climate, sustainability, and health, while others deal with language, culture, and society. But all Global Classrooms benefit from their location: MIT students gain a unique perspective on the topics they study by engaging with the local community.

“MISTI exists because we believe every graduate of MIT should be capable of connecting to and learning from colleagues all over the world,” MISTI Executive Director April Julich Perez says. “The types of problems MIT graduates will work on in their careers will require them to have an understanding of how people in different cultures might look at a problem and go about trying to solve it. This can’t be fully realized in a class on our Cambridge campus but requires an authentic global experience. We want to help our students widen their apertures to see new ways to design solutions within regional contexts. Global Classrooms help make that possible.”

Helping faculty teach

Global Classrooms arose organically from a campus need. For many years, MIT faculty have been taking students on trips around the world to learn from different communities. MISTI, with its expertise in designing global internships and other immersive learning experiences abroad, would often be tapped by faculty informally to provide their expertise.

About two years ago, MISTI decided to formalize this process by launching the MISTI Global Classrooms program. The program offers a variety of modalities to meet a range of needs across the Institute, For example, if a faculty member on campus is interested in taking students abroad, MISTI can provide advising and resources around handling travel logistics, safety, and learning in new places. On the other end of the spectrum, MISTI can serve as an implementation partner for Global Classrooms. In this capacity, MISTI program managers work with faculty members to structure their programs and help with finding partners abroad, student recruitment, selection, housing, and more. MISTI can also provide funding for certain Global Classrooms or help faculty members find funding.

An example is a Global Classroom in South Africa that is led by Bruce Walker, who is a professor of the practice in the Department of Biology as well as a core member of the Ragon Institute. Walker’s course has been going on in one form or another for more than 20 years. Since 2017, MISTI has partnered with Walker to provide support in a variety of ways.

Through the class, HST. 434 (Evolution of an Epidemic), students from across the Institute meet traditional healers, which are the first line of care for many locals. They also meet with mothers and their HIV-infected babies, young women at risk, local doctors and researchers, and more.

“It’s really important to get a chance to talk to young women at risk and really understand what their challenges are,” Walker says. “A lot of that has to do with lack of empowerment.”

Another recently launched Global Classroom is addressing sustainability in the Amazon. Andre Hamelberg ’24 traveled to Manaus, Brazil, in the Amazon region during the January Independent Activities Period (IAP) this past year. Working with local college students, he designed more sustainable packaging based on locally available materials.

“We had to find our way to communicate with each other, which was a really unique experience,” Hamelberg says. “A lot of us became really good friends. That will always stick with me.”

The experience led Hamelberg to return to Manaus this summer, where he is working with a local plastic manufacturer. It also changed Hamelberg’s perspective on his career.

“I have a long-term dream of becoming an entrepreneur, and I’m hoping I can work on improving sustainability,” Hamelberg says. “That was shaped from the Global Classroom program.”

A highlight for many students is getting an up-close look at the local culture.

“The program was a special opportunity,” Hamelberg says. “We really got to ingrain ourselves in the culture here, which I think was essential to our learning. We got the chance to be part of a small, tight-knit community.”

Helping students find their paths

MISTI’s team is careful to note that Global Classrooms are learning experiences rather than humanitarian missions.

“It’s not like we’re deploying students to go fix things all over the world,” Julich Perez says. “We’re deploying students to go learn about the nature of these challenges from local practitioners, researchers, faculty, and students. MISTI is very much trying to educate students and give them the skills to become changemakers in their future careers.”

Much of that learning is enabled by the setting of the Global Classroom.

“For every Global Classroom, the location is critical,” Julich Perez says. “For instance, if students are studying hydrology, we have a Global Classroom in Venice where students are studying the system that mitigates the sea level rise and its impact on the city. It’s very important for them to go and see the system for themselves and to work with local students on that project. Global Classroom is about that in-situ learning.”

Walker has seen firsthand how exposing students to problems can inspire them to contribute to solutions. He says the experience in his class has driven many Global Classroom alumni to work in public health.

“There’s no substitute for talking to the people that are actually being impacted by a disease,” Walker says. “It’s something that you don’t get in the classroom in terms of student understanding and seeing for themselves what the facilities look like, how constrained they are, chatting with people their own age that are in desperate situations. It opens up a whole new perspective.”

The Global Classrooms program also aligns well with MIT’s mission of equipping students to serve the world, says Julich Perez.

“MIT is all about solving big challenges, and the Global Classroom program is helping students understand those challenges and giving them the skills to be able to solve them in the future,” Julich Perez says.

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Flying high to enable sustainable delivery, remote care

Five years ago, what began as three nervous Norwegians spotting each other across a study room has evolved into a drone company enabling sustainable deliveries, elder care, and more against a backdrop of unforgiving conditions.

Lars Erik Fagernæs, Herman Øie Kolden, and Bernhard Paus Græsdal all attended the Norwegian University of Science and Technology, but their paths first crossed in the MIT Professional Education Advanced Study Program lounge in 2019, while they were apprehensive about their impending English exam. From there, they each pursued different tracks of study through the Advanced Study Program: Fagernæs studied computer science, Kolden took applied physics classes, and Græsdal, robotics. Months later, when the world shut down due to the Covid-19 pandemic, the trio’s professional trajectories intertwined.

At the height of the pandemic in 2020, Fagernæs, Kolden, and Græsdal launched Aviant — a drone delivery service company. Aviant flew blood samples across Norway’s vast countryside to assist remote hospitals in diagnosing Covid. Today, their drones are delivering groceries, over-the-counter medicines, and takeout food to populations outside city centers. 

Capitalizing on momentum

The pandemic waned, but the need for medical sample delivery did not. Remote hospitals still require reliable and rapid sample transportation, which Aviant continues to supply through its commercial contracts. In 2021, instead of sticking with commercial-only deliveries, the Aviant founders decided to use their momentum to reach for the largest market within autonomous transportation: last-mile delivery.

“Yes, you need a higher volume for the business case to make sense,” explains Fagernæs of the expansion. “Yes, it is a lot more risky, but if you make it, it’s such a big opportunity.” The Norwegian government and various venture capital firms backing Aviant agree that this risk was worth their investment. Aviant has secured millions in funding to explore the consumer market through its newest offering, Kyte. 

To scale operations, work still needs to be done to ingratiate drone delivery to the general population. Emphasizing the environmental benefits of aerial versus traditional road deliveries, the founders say, may be the most compelling factors that propel drones to the mainstream.

So far, Aviant has flown more than 30,000 kilometers, saving 4,440 kilograms of carbon dioxide that would have been emitted through traditional transportation methods. “It doesn’t make sense to use a two- to four-ton vehicle to transport one kilogram or two kilograms of sushi or medicine,” Fagernæs reasons. “You also have cars eroding the roads, you have a lot of car accidents. Not only do you remove the cars from roads by flying [deliveries] with drones, it’s also a lot more energy efficient.”

Aviant’s competitors — among them Alphabet — are spurring Fagernæs and Kolden to further improve their nicknamed “Viking drones.” Designed to sustain Norway’s harsh winter conditions and high winds, Aviant drones are well-adapted to service remote areas across Europe and the United States, a market they hope to break into soon.

The unmatched MIT work ethic

Fagernæs and Kolden owe much to MIT: It’s where they met and hatched their company. After his time with the Advanced Study Program, Græsdal decided to return to MIT to pursue his doctorate. The professors and mentors they engaged with across the Institute were instrumental in getting Aviant off the ground.

Fagernæs recalls the beginning stages of discovering the drones’ theoretical flying limit; however, he quickly ran into the hurdle that neither he nor his peers had experience deriving such data. At that moment, there was perhaps no better place on Earth to be. “We figured, OK, we’re at MIT, we might as well just ask someone.” Fagernæs started knocking on doors and was eventually pointed in the direction of Professor Mark Drela’s office. 

“I remember meeting Mark. Very, very humble guy, just talking to me like ‘Lars, yes, this, I will help you out, read this book, look at this paper.’” It was only when Fagernæs met back up with Kolden and Græsdal that he realized he had asked elementary questions to one of the leading experts in aeronautical engineering, and he truly appreciated Drela’s patience and helpfulness. The trio also credit Professor Russ Tedrake as being an inspiration to their current careers.

Additionally, the work ethic of their fellow Beavers inspires them to work hard to this day. “I was finishing an assignment, and I think I left the Strata Student Center at 5:30 [in the morning] and it was half-full,” Kolden remembers. “And that has really stuck with me. And even when we run Aviant now, we know that in order to succeed, you have to work really, really hard.”

“I’m impressed with how much Aviant has accomplished in such a short time,” says Drela. “Introducing drones to a wider population is going to make large improvements in high-value and time-critical payload delivery, and at much lower costs than the current alternatives. I’m looking forward to seeing how Aviant grows in the next few years.” 

“For the betterment of humankind”

Drones are the future, and Kolden is proud that Aviant’s electric drones are setting a sustainable precedent. “We had the choice to use gasoline drones. It was very tempting, because they can fly 10 times farther if you just use gasoline. But we just came from MIT, we worked on climate-related problems. We just couldn’t look ourselves in the mirror if we used gasoline-driven drones. So, we chose to go for the electric path, and that’s now paid off.”

In the age of automation and perceived diminishing human connections, Kolden did have a moment of doubt about whether drones were part of the dilemma. “Are we creating a dystopian society where my grandfather is just meeting a robot, saying, ‘Here is your food,’ and then flying off again?” Kolden asked himself. After deep conversations with industry experts, and considering the low birth rate and aging population in Norway, he now concludes that drones are part of the solution. “Drones are going to help out a lot and actually make it possible to take care of all people and give them food and medicine when there simply aren’t enough people to do it.”

Fagernæs also takes to heart the section of the MIT mission where students are urged to “work wisely, creatively, and effectively for the betterment of humankind.” He says, “When we started the company, it was all about using drones to help out society. We started to fly during the Covid pandemic to improve the logistics of the health-care sector in Norway, where people weren’t being diagnosed for Covid because of lacking logistics.”

“The story of the success of Lars Erik, Herman, and Aviant makes us proud of what we do at MIT Professional Education.” says Executive Director Bhaskar Pant. “Share MIT knowledge that leads people to be innovative, entrepreneurial, and above all pursue the MIT mission of working toward the betterment of humankind. Kyte is a shining example of that.”

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Professor Emeritus Ralph Gakenheimer, mobility planner and champion of international development, dies at 89

Ralph Gakenheimer, MIT professor emeritus of urban planning, passed away on June 17 in Concord, Massachusetts. He was 89 years old.

A faculty member in the Department of Urban Studies and Planning (DUSP), Gakenheimer focused his research on the dynamic relationship between how we classify and use land with the mobility choices individuals make in cities. He was particularly interested in the intentions and choices behind the selection of a particular mode of mobility and how those choices intersect with sustainability and accessibility in developing nations.

During his 40-year tenure at MIT, Gakenheimer also served as a World Bank advisor and visiting professor at various universities including the University of Paris XII, the University of California at Berkeley, and the Universidad de Los Andes (Bogota), as well as being a visiting fellow at Balliol College, Oxford. He was a Fulbright Scholar and chaired several international committees, including the United Nations-appointed committee that oversaw comprehensive planning of the city of Mecca in Saudi Arabia.

“So many of us at DUSP were influenced by Ralph in so many ways,” says Chris Zegras, professor of mobility and urban planning, and DUSP department head. “Personally, it is no exaggeration to say he is the reason I am at MIT. He was an advisor, mentor, role model, dear friend, colleague — and I feel immensely privileged to have had the opportunity to have him play those roles in my life. It’s a sad day, but I take solace in thinking of the infinite ways in which his wisdom, knowledge, good humor, and spirit live on.”

Born in Baltimore, Maryland, Gakenheimer graduated from Towson High School, where he was recently inducted into its hall of fame for his career accomplishments. He received a bachelor’s degree in engineering science from Johns Hopkins University. Throughout his high school and college years, he helped at the family pharmacy, where he often worked as the soda jerk. He went on to get a master’s degree in regional planning from Cornell University and a doctorate from the University of Pennsylvania. Prior to joining the faculty at MIT in 1969, Gakenheimer taught for seven years at the University of North Carolina in Chapel Hill.

The range of his academic background is reflected in his influential book, “Transportation Planning as a Response to Controversy: The Boston Case” (MIT Press, 1976). “Ralph’s scholarship on the 1960s Inner Belt fight is a must-read for anyone seriously concerned about the state of transportation planning in any era,” says Karilyn Crockett, assistant professor of urban history, public policy, and planning in DUSP. “His excellent, groundbreaking work, ‘Transportation Planning as a Response to Controversy,’ is a thrilling example of telling a sprawling urban story at the scale of humans. After every interaction with Ralph, I walked away feeling empowered and much smarter, what I call the Ralph Effect. The Ralph Effect is to be in proximity to someone whose brilliance is so bright that it amplifies your own.”

Gakenheimer brought deep consideration to his work as a scholar of international development, engaging with a range of projects centered on providing sustainable infrastructure and development. Fittingly for an advocate of responsible transportation, Gakenheimer often commuted to MIT by bike. 

“To describe an academic as thoughtful is perhaps redundant,” says Joseph Coughlin, director of the MIT AgeLab and leader of the U.S. Department of Transportation’s New England University Transportation Center. “However, when I think of Ralph, I cannot think of a better word. Ralph was thoughtful of his colleagues and students. He was thoughtful of the world we are imagining and leaving behind. He was, of course, thoughtful in tweaking and pulling the threads of even the most arcane theory. His soft-spoken demeanor and insights will be missed here and in the many places and spaces he touched over the years.”

Gakenheimer is survived by his wife, Caroline (Bierer) Gakenheimer; his daughters, Rachel Gakenheimer MCP ’99 and Katherine Gakenheimer; his grandchildren, Jesse and Vienne Begin; and his brothers, David and Martin Gakenheimer. 

Donations may be made in Gakenheimer’s memory to Bikes Not Bombs, a charity close to his heart. 

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A recipe for zero-emissions fuel: Soda cans, seawater, and caffeine

A sustainable source for clean energy may lie in old soda cans and seawater.

MIT engineers have found that when the aluminum in soda cans is exposed in its pure form and mixed with seawater, the solution bubbles up and naturally produces hydrogen — a gas that can be subsequently used to power an engine or fuel cell without generating carbon emissions. What’s more, this simple reaction can be sped up by adding a common stimulant: caffeine.

In a study appearing today in the journal Cell Reports Physical Science, the researchers show they can produce hydrogen gas by dropping pretreated, pebble-sized aluminum pellets into a beaker of filtered seawater. The aluminum is pretreated with a rare-metal alloy that effectively scrubs aluminum into a pure form that can react with seawater to generate hydrogen. The salt ions in the seawater can in turn attract and recover the alloy, which can be reused to generate more hydrogen, in a sustainable cycle.

The team found that this reaction between aluminum and seawater successfully produces hydrogen gas, though slowly. On a lark, they tossed into the mix some coffee grounds and found, to their surprise, that the reaction picked up its pace.

In the end, the team discovered that a low concentration of imidazole — an active ingredient in caffeine — is enough to significantly speed up the reaction, producing the same amount of hydrogen in just five minutes, compared to two hours without the added stimulant.

The researchers are developing a small reactor that could run on a marine vessel or underwater vehicle. The vessel would hold a supply of aluminum pellets (recycled from old soda cans and other aluminum products), along with a small amount of gallium-indium and caffeine. These ingredients could be periodically funneled into the reactor, along with some of the surrounding seawater, to produce hydrogen on demand. The hydrogen could then fuel an onboard engine to drive a motor or generate electricity to power the ship.

“This is very interesting for maritime applications like boats or underwater vehicles because you wouldn’t have to carry around seawater — it’s readily available,” says study lead author Aly Kombargi, a PhD student in MIT’s Department of Mechanical Engineering. “We also don’t have to carry a tank of hydrogen. Instead, we would transport aluminum as the ‘fuel,’ and just add water to produce the hydrogen that we need.”

The study’s co-authors include Enoch Ellis, an undergraduate in chemical engineering; Peter Godart PhD ’21, who has founded a company to recycle aluminum as a source of hydrogen fuel; and Douglas Hart, MIT professor of mechanical engineering.

Shields up

The MIT team, led by Hart, is developing efficient and sustainable methods to produce hydrogen gas, which is seen as a “green” energy source that could power engines and fuel cells without generating climate-warming emissions.

One drawback to fueling vehicles with hydrogen is that some designs would require the gas to be carried onboard like traditional gasoline in a tank — a risky setup, given hydrogen’s volatile potential. Hart and his team have instead looked for ways to power vehicles with hydrogen without having to constantly transport the gas itself.

They found a possible workaround in aluminum — a naturally abundant and stable material that, when in contact with water, undergoes a straightforward chemical reaction that generates hydrogen and heat.

The reaction, however, comes with a sort of Catch-22: While aluminum can generate hydrogen when it mixes with water, it can only do so in a pure, exposed state. The instant aluminum meets with oxygen, such as in air, the surface immediately forms a thin, shield-like layer of oxide that prevents further reactions. This barrier is the reason hydrogen doesn’t immediately bubble up when you drop a soda can in water.

In previous work, using fresh water, the team found they could pierce aluminum’s shield and keep the reaction with water going by pretreating the aluminum with a small amount of rare metal alloy made from a specific concentration of gallium and indium. The alloy serves as an “activator,” scrubbing away any oxide buildup and creating a pure aluminum surface that is free to react with water. When they ran the reaction in fresh, de-ionized water, they found that one pretreated pellet of aluminum produced 400 milliliters of hydrogen in just five minutes. They estimate that just 1 gram of pellets would generate 1.3 liters of hydrogen in the same amount of time.

But to further scale up the system would require a significant supply of gallium indium, which is relatively expensive and rare.

“For this idea to be cost-effective and sustainable, we had to work on recovering this alloy postreaction,” Kombargi says.

By the sea

In the team’s new work, they found they could retrieve and reuse gallium indium using a solution of ions. The ions — atoms or molecules with an electrical charge — protect the metal alloy from reacting with water and help it to precipitate into a form that can be scooped out and reused.   

“Lucky for us, seawater is an ionic solution that is very cheap and available,” says Kombargi, who tested the idea with seawater from a nearby beach. “I literally went to Revere Beach with a friend and we grabbed our bottles and filled them, and then I just filtered out algae and sand, added aluminum to it, and it worked with the same consistent results.”

He found that hydrogen indeed bubbled up when he added aluminum to a beaker of filtered seawater. And he was able to scoop out the gallium indium afterward. But the reaction happened much more slowly than it did in fresh water. It turns out that the ions in seawater act to shield gallium indium, such that it can coalesce and be recovered after the reaction. But the ions have a similar effect on aluminum, building up a barrier that slows its reaction with water.

As they looked for ways to speed up the reaction in seawater, the researchers tried out various and unconventional ingredients.

“We were just playing around with things in the kitchen, and found that when we added coffee grounds into seawater and dropped aluminum pellets in, the reaction was quite fast compared to just seawater,” Kombargi says.

To see what might explain the speedup, the team reached out to colleagues in MIT’s chemistry department, who suggested they try imidazole — an active ingredient in caffeine, which happens to have a molecular structure that can pierce through aluminum (allowing the material to continue reacting with water), while leaving gallium indium’s ionic shield intact.

“That was our big win,” Kombargi says. “We had everything we wanted: recovering the gallium indium, plus the fast and efficient reaction.”

The researchers believe they have the essential ingredients to run a sustainable hydrogen reactor. They plan to test it first in marine and underwater vehicles. They’ve calculated that such a reactor, holding about 40 pounds of aluminum pellets, could power a small underwater glider for about 30 days by pumping in surrounding seawater and generating hydrogen to power a motor.

“We’re showing a new way to produce hydrogen fuel, without carrying hydrogen but carrying aluminum as the ‘fuel,’” Kombargi says. “The next part is to figure out how to use this for trucks, trains, and maybe airplanes. Perhaps, instead of having to carry water as well, we could extract water from the ambient humidity to produce hydrogen. That’s down the line.”

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Balancing economic development with natural resources protection

It’s one of the paradoxes of economic development: Many countries currently offer large subsidies to their industrial fishing fleets, even though the harms of overfishing are well-known. Governments might be willing to end this practice, if they saw that its costs outweighed its benefits. But each country, acting individually, faces an incentive to keep subsidies in place.

This trap evokes the classic “tragedy of the commons” that economists have studied for generations. But despite the familiarity of the problem in theory, they don’t yet have a lot of hard evidence to offer policymakers about solutions, especially on a global scale. PhD student Aaron Berman is working on a set of projects that may change that.

“Our goal is to get some empirical traction on the problem,” he says.

Berman and his collaborators are combining a variety of datasets — not only economic data but also projections from ecological models — to identify how these subsidies are impacting fish stocks. They also hope to determine whether countries might benefit instead from sustainability measures to help rebuild fisheries, say through new trade arrangements or other international policy agreements.

As a fourth-year doctoral candidate in MIT’s Department of Economics, Berman has a variety of other research projects underway as well, all connected by the central question of how to balance economic development with the pressure it puts on the environment and natural resources. While his study of fishing subsidies is global in scope, other projects are distinctly local: He is studying air pollution generated by road infrastructure in Pakistan, groundwater irrigation in Texas, the scallop fishing industry in New England, and industrial carbon-reduction measures in Turkey. For all of these projects, Berman and his collaborators are bringing data and models from many fields of science to bear on economic questions, from seafloor images taken by NOAA to atmospheric models of pollution dispersion.

“One thing I find really exciting and joyful about the work I’m doing in environmental economics is that all of these projects involve some kind of crossover into the natural sciences,” he says.

Several of Berman’s projects are so ambitious that he hopes to continue working on them even after completing his PhD. He acknowledges that keeping so many irons in the fire is a lot of work, but says he finds motivation in the knowledge that his research could shape policy and benefit society in a concrete way.

“Something that MIT has really instilled in me is the value of going into the field and learning about how the research you’re doing connects to real-world issues,” he says. “You want your findings as a researcher to ultimately be useful to someone.”

Testing the waters

The son of two public school teachers, Berman grew up in Maryland and then attended Yale University, where he majored in global affairs as an undergraduate, then stayed to get his master’s in public health, concentrating on global health in both programs.

A pivotal moment came while taking an undergraduate class in development economics. “That class helped me realize the same questions I cared a lot about from a public health standpoint were also being studied by economists using very rigorous methods,” Berman says. “Economics has a lot to say about very pressing societal issues.”

After reading the work of MIT economists and Nobel laureates Esther Duflo and Abhijit Banerjee in that same class, he decided to pivot and “test the waters of economics a little bit more seriously.” The professor teaching that class also played an important role, by encouraging Berman to pursue a predoctoral research position as a first step toward a graduate degree in economics.

Following that advice, Berman landed at the Harvard Kennedy School’s Evidence for Policy Design, a research initiative seeking to foster economic development by improving the policy design process. His time with this organization included five months in Jakarta, Indonesia, where he collaborated with professors Rema Hanna and Ben Olken — of Harvard and MIT, respectively — on a portfolio of projects focused on analyzing social protection and poverty alleviation.

The work, which included working closely with government partners, “required me to think creatively about how to talk about economics research to several different types of audiences,” he says. “This also gave me experience thinking about the intersection between what is academically interesting and what is a policy priority.”

The experience also gave him the skills and confidence to apply to the economics PhD program at MIT.

(Re)discovering teaching

As an economist, Berman is now channeling his interests in global affairs to exploring the relationship between economic development and protecting the natural environment. (He’s aided by an affinity for languages — he speaks five, with varying degrees of proficiency, in addition to English: Mandarin, Cantonese, Spanish, Portuguese, and Indonesian.) His interest in natural resource governance was piqued while co-authoring a paper on the economic drivers of climate-altering tropical deforestation.

The review article, written alongside Olken and two professors from the London School of Economics, explored questions such as “What does the current state of the evidence tell us about what causes deforestation in the tropics, and what further evidence is needed?” and “What are the economic barriers to implementing policies to prevent deforestation?” — the kinds of questions he seeks to answer broadly in his ongoing dissertation work.

“I gained an appreciation for the importance and complexity of natural resource governance, both in developing and developed countries,” he says. “It really was a launching point for a lot of the things that I'm doing now.”

These days, when not doing research, Berman can be found playing on MIT’s club tennis team or working as a teaching assistant, which he particularly enjoys. He’s ever mindful of the Yale professor whose encouragement shaped his own path, and he hopes that he can pay that forward in his own teaching roles.

“The fact that he saw I had the ability to make this transition and encouraged me to take a leap of faith is really meaningful to me. I would like to be able to do that for others,” Berman says.

His interest in teaching also connects him further with his family: His father is a middle school science teacher and mother is a paraeducator for students with special needs. He says they’ve encouraged him throughout his academic journey, even though they initially didn’t know much about what a PhD in economics entailed. Berman jokes that the most common question people ask economists is what stocks they should invest in, and his family was no exception.

“But they’ve always been very excited to hear about the kinds of things I’m working on and very supportive,” he says. 

“It’s been a really amazing learning experience thus far,” Berman says about his doctoral program. “One of the coolest parts of economics research is to have a sense that you’re tangibly doing something that’s going to have an impact in the world.”

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Study across multiple brain regions discerns Alzheimer’s vulnerability and resilience factors

An open-access MIT study published today in Nature provides new evidence for how specific cells and circuits become vulnerable in Alzheimer’s disease, and hones in on other factors that may help some people show resilience to cognitive decline, even amid clear signs of disease pathology. 

To highlight potential targets for interventions to sustain cognition and memory, the authors engaged in a novel comparison of gene expression across multiple brain regions in people with or without Alzheimer’s disease, and conducted lab experiments to test and validate their major findings.

Brain cells all have the same DNA but what makes them differ, both in their identity and their activity, are their patterns of how they express those genes. The new analysis measured gene expression differences in more than 1.3 million cells of more than 70 cell types in six brain regions from 48 tissue donors, 26 of whom died with an Alzheimer’s diagnosis and 22 of whom without. As such, the study provides a uniquely large, far-ranging, and yet detailed accounting of how brain cell activity differs amid Alzheimer’s disease by cell type, by brain region, by disease pathology, and by each person’s cognitive assessment while still alive.

“Specific brain regions are vulnerable in Alzheimer’s and there is an important need to understand how these regions or particular cell types are vulnerable,” says co-senior author Li-Huei Tsai, Picower Professor of Neuroscience and director of The Picower Institute for Learning and Memory and the Aging Brain Initiative at MIT. “And the brain is not just neurons. It’s many other cell types. How these cell types may respond differently, depending on where they are, is something fascinating we are only at the beginning of looking at.”

Co-senior author Manolis Kellis, professor of computer science and head of MIT’s Computational Biology Group, likens the technique used to measure gene expression comparisons, single-cell RNA profiling, to being a much more advanced “microscope” than the ones that first allowed Alois Alzheimer to characterize the disease’s pathology more than a century ago.

“Where Alzheimer saw amyloid protein plaques and phosphorylated tau tangles in his microscope, our single-cell ‘microscope’ tells us, cell by cell and gene by gene, about thousands of subtle yet important biological changes in response to pathology,” says Kellis. “Connecting this information with the cognitive state of patients reveals how cellular responses relate with cognitive loss or resilience, and can help propose new ways to treat cognitive loss. Pathology can precede cognitive symptoms by a decade or two before cognitive decline becomes diagnosed. If there’s not much we can do about the pathology at that stage, we can at least try to safeguard the cellular pathways that maintain cognitive function.”

Hansruedi Mathys, a former MIT postdoc in the Tsai Lab who is now an assistant professor at the University of Pittsburgh; Carles Boix PhD '22, a former graduate student in Kellis’s lab who is now a postdoc at Harvard Medical School; and Leyla Akay, a graduate student in Tsai’s lab, led the study analyzing the prefrontal cortex, entorhinal cortex, hippocampus, anterior thalamus, angular gyrus, and the midtemporal cortex. The brain samples came from the Religious Order Study and the Rush Memory and Aging Project at Rush University.

Neural vulnerability and Reelin

Some of the earliest signs of amyloid pathology and neuron loss in Alzheimer’s occur in memory-focused regions called the hippocampus and the entorhinal cortex. In those regions, and in other parts of the cerebral cortex, the researchers were able to pinpoint a potential reason why. One type of excitatory neuron in the hippocampus and four in the entorhinal cortex were significantly less abundant in people with Alzheimer’s than in people without. Individuals with depletion of those cells performed significantly worse on cognitive assessments. Moreover, many vulnerable neurons were interconnected in a common neuronal circuit. And just as importantly, several either directly expressed a protein called Reelin, or were directly affected by Reelin signaling. In all, therefore, the findings distinctly highlight especially vulnerable neurons, whose loss is associated with reduced cognition, that share a neuronal circuit and a molecular pathway.

Tsai notes that Reelin has become prominent in Alzheimer’s research because of a recent study of a man in Colombia. He had a rare mutation in the Reelin gene that caused the protein to be more active, and was able to stay cognitively healthy at an advanced age despite having a strong family predisposition to early-onset Alzheimer’s. The new study shows that loss of Reelin-producing neurons is associated with cognitive decline. Taken together, it might mean that the brain benefits from Reelin, but that neurons that produce it may be lost in at least some Alzheimer’s patients.

“We can think of Reelin as having maybe some kind of protective or beneficial effect,” Akay says. “But we don’t yet know what it does or how it could confer resilience.”

In further analysis the researchers also found that specifically vulnerable inhibitory neuron subtypes identified in a previously study from this group in the prefrontal cortex also were involved in Reelin signaling, further reinforcing the significance of the molecule and its signaling pathway.

To further check their results, the team directly examined the human brain tissue samples and the brains of two kinds of Alzheimer’s model mice. Sure enough, those experiments also showed a reduction in Reelin-positive neurons in the human and mouse entorhinal cortex.

Resilience associated with choline metabolism in astrocytes

To find factors that might preserve cognition, even amid pathology, the team examined which genes, in which cells, and in which regions, were most closely associated with cognitive resilience, which they defined as residual cognitive function, above the typical cognitive loss expected given the observed pathology.

Their analysis yielded a surprising and specific answer: across several brain regions, astrocytes that expressed genes associated with antioxidant activity and with choline metabolism and polyamine biosynthesis were significantly associated with sustained cognition, even amid high levels of tau and amyloid. The results reinforced previous research findings led by Tsai and Susan Lundqvist in which they showed that dietary supplement of choline helped astrocytes cope with the dysregulation of lipids caused by the most significant Alzheimer’s risk gene, the APOE4 variant. The antioxidant findings also pointed to a molecule that can be found as a dietary supplement, spermidine, which may have anti-inflammatory properties, although such an association would need further work to be established causally.

As before, the team went beyond the predictions from the single-cell RNA expression analysis to make direct observations in the brain tissue of samples. Those that came from cognitively resilient individuals indeed showed increased expression of several of the astrocyte-expressed genes predicted to be associated with cognitive resilience.

New analysis method, open dataset

To analyze the mountains of single-cell data, the researchers developed a new robust methodology based on groups of coordinately-expressed genes (known as “gene modules”), thus exploiting the expression correlation patterns between functionally-related genes in the same module.

“In principle, the 1.3 million cells we surveyed could use their 20,000 genes in an astronomical number of different combinations,” explains Kellis. “In practice, however, we observe a much smaller subset of coordinated changes. Recognizing these coordinated patterns allow us to infer much more robust changes, because they are based on multiple genes in the same functionally-connected module.”

He offered this analogy: With many joints in their bodies, people could move in all kinds of crazy ways, but in practice they engage in many fewer coordinated movements like walking, running, or dancing. The new method enables scientists to identify such coordinated gene expression programs as a group.

While Kellis and Tsai’s labs already reported several noteworthy findings from the dataset, the researchers expect that many more possibly significant discoveries still wait to be found in the trove of data. To facilitate such discovery the team posted handy analytical and visualization tools along with the data on Kellis’s website.

“The dataset is so immensely rich. We focused on only a few aspects that are salient that we believe are very, very interesting, but by no means have we exhausted what can be learned with this dataset,” Kellis says. “We expect many more discoveries ahead, and we hope that young researchers (of all ages) will dive right in and surprise us with many more insights.”

Going forward, Kellis says, the researchers are studying the control circuitry associated with the differentially expressed genes, to understand the genetic variants, the regulators, and other driver factors that can be modulated to reverse disease circuitry across brain regions, cell types, and different stages of the disease.

Additional authors of the study include Ziting Xia, Jose Davila Velderrain, Ayesha P. Ng, Xueqiao Jiang, Ghada Abdelhady, Kyriaki Galani, Julio Mantero, Neil Band, Benjamin T. James, Sudhagar Babu, Fabiola Galiana-Melendez, Kate Louderback, Dmitry Prokopenko, Rudolph E. Tanzi, and David A. Bennett.

Support for the research came from the National Institutes of Health, The Picower Institute for Learning and Memory, The JPB Foundation, the Cure Alzheimer’s Fund, The Robert A. and Renee E. Belfer Family Foundation, Eduardo Eurnekian, and Joseph DiSabato.

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