Peter Dedon named a 2022 AAAS Fellow

Peter Dedon, an MIT professor of biological engineering, has been elected a fellow of the American Association for the Advancement of Science (AAAS).

The 2022 class of AAAS Fellows includes 506 scientists, engineers, and innovators spanning 24 scientific disciplines who are being recognized for their scientifically and socially distinguished achievements.  

Dedon is the Singapore Professor in the Department of Biological Engineering, a lead principal investigator of the Antimicrobial Resistance Interdisciplinary Research Group at the Singapore-MIT Alliance for Research and Technology (SMART), a member of the Center for Environmental Health Sciences, and a member of the HMS Initiative for RNA Medicine.  

His research program applies chemical approaches to understanding nucleic acid biology in human disease. His research groups at MIT and in Singapore are leveraging discoveries in the areas of epigenetics, epitranscriptomics, and genetic toxicology to develop new enzymatic tools for biotechnology, new methods for industrial microbiology and protein production, and novel therapeutics in screening- and structure-based drug discovery programs. Dedon and his former students and postdocs have translated their science and technologies in several startup companies.

Dedon earned a BA in chemistry from St. Olaf College in 1979 and an MD and PhD in pharmacology from the University of Rochester in 1987. He pursued postdoctoral research at the University of Rochester and Harvard Medical School, and joined the MIT faculty in 1991. Dedon helped create the Department of Biological Engineering in 1998.

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How to make hydrogels more injectable

Gel-like materials that can be injected into the body hold great potential to heal injured tissues or manufacture entirely new tissues. Many researchers are working to develop these hydrogels for biomedical uses, but so far very few have made it into the clinic.

To help guide in the development of such materials, which are made from microscale building blocks akin to squishy LEGOs, MIT and Harvard University researchers have created a set of computational models to predict the material’s structure, mechanical properties, and functional performance outcomes. The researchers hope that their new framework could make it easier to design materials that can be injected for different types of applications, which until now has been mainly a trial-and-error process.

“It’s really exciting from a material standpoint and from a clinical application standpoint,” says Ellen Roche, an associate professor of mechanical engineering and a member of the Institute for Medical Engineering and Science at MIT. “More broadly, it’s a nice example of taking lab-based data and synthesizing it into something usable that can give you predictive guidelines that could be applied to things beyond these hydrogels.”

Roche and Jennifer Lewis, the Hansjörg Wyss Professor of Biologically Inspired Engineering at Harvard, are the senior authors of the study, which appears today in the journal Matter. Connor Verheyen, a graduate student in the Harvard-MIT Program in Health Sciences and Technology, is the lead author of the paper.

Material modeling

When individual hydrogel blocks are densely compacted together, they form a gel-like material known as a granular matrix. These materials can act as a solid or a liquid, depending on the conditions, which makes them good candidates for applications such as 3D-bioprinting engineered tissues. Once injected or implanted into the body, they could release drugs or help to regenerate injured tissue.

“These materials have a lot of flexibility and customizability, so there’s a lot of excitement about using them for biomedical applications,” Verheyen says.

While working in Lewis’ lab, Verheyen, who is co-advised by Lewis and Roche, began trying to figure out how to get these materials to be reliably injectable. This turned out to be a difficult task that required a lot of trial-and-error experimentation, by changing different features of the gels in hopes of optimizing their structure and mechanical behavior for injectability.

“That spurred the effort to take the empirical data, turn it into something that a machine could read and work with, and then ask it to build a predictive map that we could interrogate to help us understand what was going on and how to go to the next step,” he says.

To create their design framework, the researchers broke the assembly process down into several stages. They modeled each of these stages separately, using data from their own experiments, which were done under a variety of different conditions.

In the first stage, the model analyzed how bioblock properties are affected by the starting material of the blocks and how they are assembled. In the second stage, the bioblocks are packed together to form structures called “granular hydrogels.” Through their modeling, the researchers identified several factors that influence the injectability of the final gel, including the size and stiffness of the bioblocks, the viscosity of the interstitial fluid between the blocks, and the dimensions of the needle and syringe used to inject the gel.

Better injectability

Now that they have modeled the process from start to finish, the researchers can use their model to predict the best way to create a material with the traits they need for a particular application, instead of going through an extensive trial-and-error process for each new material.

“Our long-term goal was to get to the point where we had reliable and predictable injection properties, because that was something that we really struggled with in the lab — getting these materials to flow properly,” Verheyen says.

He and others in Roche’s lab now plan to use this modeling approach to try to develop materials that could be used for medical applications such as repairing heart defects or delivering drugs to the gastrointestinal tract.

The researchers have also made their models and the data they used to generate them available online for other labs to use.

“It’s all open source, and hopefully it will reduce the amount of frustration with issues that you might have reproducing something that happened in another lab, or even within one lab when you’re transferring knowledge from one person to another,” Roche says.

The research was funded by the Vannevar Bush Faculty Fellowship Program, the National Science Foundation, and a MathWorks Seed Fund grant.

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Paying it forward

Since arriving at MIT in fall 2019, senior Sherry Nyeo has conducted groundbreaking work in multiple labs on campus, acted as a mentor to countless other students, and made a lasting mark on the Institute community. But despite her well-earned bragging rights, Nyeo isn’t one to boast. Instead, she takes every opportunity to express just how grateful she is to the professors, alumni, and fellow students who have helped and inspired her during her time at MIT. “I like helping people if I can,” says Nyeo, who is majoring in computer science and molecular biology, “because I got helped so much.”

Nyeo’s passion for science began when she applied for the Selective Science Program at Tainan First Senior High School, widely considered one of the most prestigious high schools in Taiwan. “Preparing for that process made me realize that biology was pretty cool,” she recalls.

When Nyeo was 16, her family moved from Taiwan to Colorado, where she continued to cultivate her interest in STEM. Although she excelled at biology, she initially struggled to master computer science. “[Programming] was really hard for me,” she says. “It was a completely different way of thinking.” When she arrived at MIT, she decided to pursue a degree in computer science precisely because she knew she would find it challenging and because she appreciates how vital data analysis is to the field of biology. After all, she says, when you’re working at the scale of cells and molecules, “you need a lot of data to describe what’s going on.”

In the winter of her first year at MIT, Nyeo began doing hands-on research in laboratories on campus through the Undergraduate Research Opportunities Program (UROP). Her work in the lab of Whitehead Fellow Silvi Rouskin sparked an enduring interest in RNA, which she has come to regard as her “favorite biomolecule.”

Nyeo’s work in the Rouskin lab focused on alternative RNA structures and the roles they play in human and viral biology. While DNA mostly exists as a double helix, RNA can fold itself into a huge variety of structures in order to fulfill different functions. During her time as a student researcher, Nyeo has demonstrated a similar ability to adapt to different circumstances. When MIT campus members evacuated due to the Covid-19 pandemic in March 2020, and her UROP became entirely remote, she treated her time away from the lab as an opportunity to explore the computational side of research. Her work was subsequently included in a Nature Communications paper on the SARS-CoV-2 genome, on which she is listed as a co-author.

Since returning to campus, Nyeo has often worked in multiple labs simultaneously, conducting innovative research while also juggling classes, internships, and several demanding extracurriculars. Through it all, she has continued to pursue her fascination with RNA, a tiny, somewhat unassuming molecule that nonetheless has a massive impact on practically every aspect of our biology. Nyeo, who has shown herself to be equally multifaceted, seems especially well-suited to the study of this remarkable biomolecule.

Although Nyeo’s work in the life sciences keeps her busy, she finds time to nurture a diverse set of other passions. She took a class on experimental ethics, is working on an original screenplay, and has even picked up a minor in German. Since her sophomore year, she has also been a part of the New Engineering Education Transformation (NEET) program, which provides students with multidisciplinary interests the opportunity to collaborate across departments. Through NEET, currently directed by professor of biological engineering Mark Bathe, Nyeo has been able to pursue her interest in bioengineering research and connect to a vast community of students and professors. Most recently, she has been working within the Bathe BioNano Lab to use DNA to engineer new materials at the nanometer scale.

Nyeo hopes to put her skills to use by pursuing a career in biotechnology. She is currently minoring in management and dreams of one day starting her own company. But she doesn’t want to leave academia behind just yet and has begun working on applications for PhD programs in biology. “I originally came in thinking that I would just go straight into the biotech industry,” Nyeo explains. “And then I realized that I don’t dislike research and that I actually enjoy it.”

As part of her current work in the lab of professor of biology David Bartel, Nyeo investigates how viral infection affects RNA metabolism, and she often finds herself using her computational skills to help postdocs with their data analysis. In fact, one of the things Nyeo has most enjoyed about working as a student researcher is the opportunity to join a network of people who provide one another with support and guidance.

Nyeo’s willingness to help others is perhaps the aspect of her personality that best suits her to the study of RNA. Over the past few decades, researchers have discovered an increasingly large number of therapeutic uses for RNA, including cancer immunotherapy and vaccine development. In the summer of 2022, Nyeo worked as an intern at Eli Lilly and Company, where she helped identify potential targets for RNA therapeutics. She may continue to explore this area of research when she eventually enters the biotech industry. In the meantime, however, she’s finding ways to help people closer to home.

Since her first year, Nyeo has been a part of the MIT Biotech Group. When she first joined, the group had a fairly small undergraduate presence, and most events were geared toward graduate students and postdocs. Nyeo immediately dedicated herself to making the group more welcoming for undergraduates. As the director of the Undergraduate Initiative and later the undergraduate student president, she was a leading architect of a new seminar series in which MIT alumni came to campus to teach undergraduates about biotechnology. “There are a lot of technical terms associated with [biotech],” Nyeo explains. “If you just come in as an undergrad, not knowing what’s happening, that can be a bit daunting.”

Between her research in the Bartel lab and her work with NEET and the MIT Biotech Group, Nyeo doesn’t have a lot of free time, but she dedicates most of it to making MIT a friendlier environment for new students. She promotes research opportunities as a UROP panelist and has worked as an associate advisor since her junior year. She helps first-year students choose and register for classes, works with faculty advisors, and provides moral support to students who are feeling overwhelmed with options. “When I came [to MIT], I also didn’t know what I wanted to do,” Nyeo explains. “Upperclassmen helped me a lot with that process, and I want to pay it forward.”

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“Spleen-on-a-chip” yields insight into sickle cell disease

Every day, billions of red blood cells pass through the spleen, an organ that is responsible for filtering out old or damaged blood cells. This task is made more difficult when the blood cells are misshapen, as they are in patients with sickle cell disease, which affects millions of people throughout the world. Sickled blood cells can clog the spleen’s filters, leading to a potentially life-threatening situation.

Researchers at MIT, Nanyang Technological University in Singapore, the Pasteur Institute in Paris, and other institutions have now designed a microfluidic device, or “spleen-on-a-chip,” that can model how this phenomenon, known as acute splenic sequestration, arises.

The researchers found that low oxygen levels make it more likely that the spleen’s filters will become clogged. They also showed that boosting oxygen levels can unclog the filters, which may help to explain how blood transfusions help patients suffering from this condition.

“If we increase the oxygen levels, it will reverse the blockage,” says Ming Dao, a principal research scientist in MIT’s Department of Materials Science and Engineering and one of the senior authors of the study. “This mimics what’s done when there’s a splenic sequestration crisis. The first thing doctors do is transfusion, and in most cases, that gives some relief to the patient.”

Subra Suresh, former dean of engineering at MIT, the Vannevar Bush Professor Emeritus of Engineering, and former president of Singapore’s Nanyang Technological University; Pierre Buffet, medical director of the Pasteur Institute and a professor at the University of Paris; and George Karniadakis, the Robinson and Barstow Professor of Applied Mathematics at Brown University, are also senior authors of the study. MIT postdoc Yuhao Qiang is the lead author of the paper, which appears in Proceedings of the National Academy of Sciences this week.

Clogged filters

Most red blood cells have a lifespan of about 120 days, so nearly 1 percent of the supply has to be removed every day. Within the spleen, blood flows through tissue known as red pulp, which contains narrow passages called interendothelial slits.

These slits, formed by the spaces between the endothelial cells lining the spleen’s blood vessels, have maximum opening dimensions significantly smaller than those of a red blood cell. Any red blood cells that can’t pass through these tiny openings, because they’re damaged, stiffened or misshapen, become trapped and are destroyed by immune cells called macrophages.

To model the spleen’s filtration function, the researchers created a microfluidic device with two modules — the S chip, which mimics the interendothelial slits, and the M chip, which mimics the macrophages. The device also includes a gas channel that can be used to control the oxygen concentration of each chip to simulate conditions in the body.

Using this device, the researchers sought to better understand acute splenic sequestration, which occurs in about 5 percent of patients with sickle cell disease, usually in children. When this happens, the spleen becomes enlarged, and the patient becomes severely anemic. Doctors usually treat it with blood transfusions, but if that doesn’t help, the spleen may need to be surgically removed.

Working with healthy red blood cells and sickled red cells from sickle cell disease patients, the researchers allowed the cells to flow through their device under controlled oxygen levels.

Under normal oxygen conditions (20 percent oxygen) sickled cells created some blockage at the slits, but there was still space for other blood cells to pass through. However, when the oxygen level decreased to 2 percent, the slits quickly became fully blocked.

When the researchers increased the oxygen level again, the blockage cleared up. This may partly explain why blood transfusions, which bring oxygenated blood cells into the spleen, can help patients who are experiencing acute splenic sequestration, Dao says.

“Our findings provide a general scientific framework to guide and rationalize what doctors observe. They also help to elucidate how the spleen provides a critical function to help filter blood cells,” Suresh says.

The researchers found that mildly deoxygenated conditions (5 percent oxygen) cause some clogging but not enough to produce a splenic sequestration crisis, which may explain why such crises occur rarely, Dao says.

Slow digestion

The researchers then used the other device module, the M chip, to model what happens as red blood cells encounter macrophages under different conditions. They found that when oxygen levels were low, sickled red blood cells were much more likely to be trapped by macrophages and ingested by them. In fact, so many blood cells were caught that macrophages became overwhelmed and couldn’t destroy them fast enough, contributing to the clogging of the slits.

The researchers also found that stiff sickled cells retained their sickled shape even after being ingested, which made it harder for macrophages to break them down. “About half of these cells stay sickled for a very long time and slow down the whole digestion process,” Dao says.

When oxygen levels were increased, the blood cells regained their normal shape, even the cells that had been ingested. This allowed macrophages to more easily digest them and clear up the clogged filters.

The researchers are now using the spleen-on-a-chip to study how drugs used to treat sickle cell disease, such as voxelotor and hydroxyurea, affect the cell behavior that they observed in this study. They also hope that the device could one day be used to help doctors analyze individual patients’ blood cells and monitor how their disease is progressing.

“This approach should help design assays to give patient-specific diagnosis and prognosis,” says Buffet, who is also a practicing clinician. “That may give doctors some idea of how well the patient is doing and in what situation they need to do a splenectomy or take other measures.”

The team also included MIT postdocs Ting Dong and Fuyin Zheng, Abdoulaye Sissoko from University of Paris, Zixiang Liu from Brown University, Fang Kong from Nanyang Technological University, and John Higgins from Massachusetts General Hospital. The research was funded by the National Institutes of Health and Nanyang Technological University.

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Study: Superconductivity switches on and off in “magic-angle” graphene

With some careful twisting and stacking, MIT physicists have revealed a new and exotic property in “magic-angle” graphene: superconductivity that can be turned on and off with an electric pulse, much like a light switch.

The discovery could lead to ultrafast, energy-efficient superconducting transistors for neuromorphic devices — electronics designed to operate in a way similar to the rapid on/off firing of neurons in the human brain.

Magic-angle graphene refers to a very particular stacking of graphene — an atom-thin material made from carbon atoms that are linked in a hexagonal pattern resembling chicken wire. When one sheet of graphene is stacked atop a second sheet at a precise “magic” angle, the twisted structure creates a slightly offset “moiré” pattern, or superlattice, that is able to support a host of surprising electronic behaviors.

In 2018, Pablo Jarillo-Herrero and his group at MIT were the first to demonstrate magic-angle twisted bilayer graphene. They showed that the new bilayer structure could behave as an insulator, much like wood, when they applied a certain continuous electric field. When they upped the field, the insulator suddenly morphed into a superconductor, allowing electrons to flow, friction-free.

That discovery was a watershed in the field of “twistronics,” which explores how certain electronic properties emerge from the twisting and layering of two-dimensional materials. Researchers including Jarillo-Herrero have continued to reveal surprising properties in magic-angle graphene, including various ways to switch the material between different electronic states. So far, such “switches” have acted more like dimmers, in that researchers must continuously apply an electric or magnetic field to turn on superconductivity, and keep it on.

Now Jarillo-Herrero and his team have shown that superconductivity in magic-angle graphene can be switched on, and kept on, with just a short pulse rather than a continuous electric field. The key, they found, was a combination of twisting and stacking.

In a paper appearing today in Nature Nanotechnology, the team reports that, by stacking magic-angle graphene between two offset layers of boron nitride — a two-dimensional insulating material — the unique alignment of the sandwich structure enabled the researchers to turn graphene’s superconductivity on and off with a short electric pulse.

“For the vast majority of materials, if you remove the electric field, zzzzip, the electric state is gone,” says Jarillo-Herrero, who is the Cecil and Ida Green Professor of Physics at MIT. “This is the first time that a superconducting material has been made that can be electrically switched on and off, abruptly. This could pave the way for a new generation of twisted, graphene-based superconducting electronics.”

His MIT co-authors are lead author Dahlia Klein PhD ’21, graduate student Li-Qiao Xia, and former postdoc David MacNeill, along with Kenji Watanabe and Takashi Taniguchi of the National Institute for Materials Science in Japan.

Flipping the switch

In 2019, a team at Stanford University discovered that magic-angle graphene could be coerced into a ferromagnetic state. Ferromagnets are materials that retain their magnetic properties, even in the absence of an externally applied magnetic field.

The researchers found that magic-angle graphene could exhibit ferromagnetic properties in a way that could be tuned on and off. This happened when the graphene sheets were layered between two sheets of boron nitride such that the crystal structure of the graphene was aligned to one of the boron nitride layers. The arrangement resembled a cheese sandwich in which the top slice of bread and the cheese orientations are aligned, but the bottom slice of bread is rotated at a random angle with respect to the top slice. The result intrigued the MIT group.

“We were trying to get a stronger magnet by aligning both slices,” Jarillo-Herrero says. “Instead, we found something completely different.”

In their current study, the team fabricated a sandwich of carefully angled and stacked materials. The “cheese” of the sandwich consisted of magic-angle graphene — two graphene sheets, the top rotated slightly at the “magic” angle of 1.1 degrees with respect to the bottom sheet. Above this structure, they placed a layer of boron nitride, exactly aligned with the top graphene sheet. Finally, they placed a second layer of boron nitride below the entire structure and offset it by 30 degrees with respect to the top layer of boron nitride.

The team then measured the electrical resistance of the graphene layers as they applied a gate voltage. They found, as others have, that the twisted bilayer graphene switched electronic states, changing between insulating, conducting, and  superconducting states at certain known voltages.

What the group did not expect was that each electronic state persisted rather than immediately disappearing once the voltage was removed — a property known as bistability. They found that, at a particular voltage, the graphene layers turned into a superconductor, and remained superconducting, even as the researchers removed this voltage.  

This bistable effect suggests that superconductivity can be turned on and off with short electric pulses rather than a continuous electric field, similar to flicking a light switch. It isn’t clear what enables this switchable superconductivity, though the researchers suspect it has something to do with the special alignment of the twisted graphene to both boron nitride layers, which enables a ferroelectric-like response of the system. (Ferroelectric materials display bistability in their electric properties.)

“By paying attention to the stacking, you could add another tuning knob to the growing complexity of magic-angle, superconducting devices,” Klein says. 

For now, the team sees the new superconducting switch as another tool researchers can consider as they develop materials for faster, smaller, more energy-efficient electronics.

“People are trying to build electronic devices that do calculations in a way that’s inspired by the brain,” Jarillo-Herrero says. “In the brain, we have neurons that, beyond a certain threshold, they fire. Similarly, we now have found a way for magic-angle graphene to switch superconductivity abruptly, beyond a certain threshold. This is a key property in realizing neuromorphic computing.”  

This research was supported in part by the U.S. Air Force Office of Scientific Research, the U.S. Army Research Office, and the Gordon and Betty Moore Foundation.

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Making computer science research more accessible in India

Imagine that you are teaching a technical subject to children in a small village. They are eager to learn, but you face a problem: There are few resources to educate them in their mother tongue.

This is a common experience in India, where the quality of textbooks written in many local languages pales in comparison to those written in English. To address educational inequality, the Indian government launched an initiative in 2020 that would improve the quality of these resources for hundreds of millions of people, but its implementation remains a massive undertaking.

Siddhartha Jayanti, an MIT PhD student in electrical engineering and computer science (EECS) who is an affiliate of MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL) and Google Research, encountered this problem first-hand when teaching students in India about math, science, and English. During the summer after his first year as an undergraduate at Princeton University, Jayanti visited the town of Bhimavaram, volunteering as an organizer, teacher, and mentor at a five-week education camp. He worked with economically disadvantaged children from villages across the region. They spoke Telugu, Jayanti’s mother tongue, but faced linguistic barriers because of the complex English used in academic work.

According to the World Economic Forum and U.S. Census data, Telugu is the United States’ fastest-growing language, while Ethnologue estimates over 95 million speakers worldwide, further emphasizing the need for more academic materials in the vernacular.

As a distributed computing and AI researcher with a shared cultural background, Jayanti was in a unique position to help. With millions of Telugu speakers in mind, Jayanti wrote the first original computer science paper to be composed entirely in Telugu in 2018. This research then became publicly accessible on arXiv in 2022, focusing on designing simple, fast, scalable, and reliable multiprocessor algorithms and analyzing fundamental communication and coordination tasks between processors.

Processors are electronic circuitry that execute computer programs, making them notorious for their many moving parts. “Think about processors as people completing a task,” says Jayanti. “If you have one processor, that is like one person doing a task. If you have 200 people instead, then ideally your team will solve problems faster, but this is not always the case. Coordinating multiple processors to achieve speedups requires clever algorithmic design, and there are sometimes fundamental communication barriers that limit how fast we can solve problems.”

To solve computing problems, each process in a multicore system follows a strict procedure, which is also known as a multiprocessor algorithm. Still, there are certain limits on how quickly processors can interact with each other to compute solutions. Jayanti’s paper highlighted a key communication bottleneck for these algorithms, known as generalized wake-up (GWU), where a processor “wakes up” when it has executed its first line of code. 

But the question remains: Can each processor figure out that the others have woken up? Jayanti indicates that the answer is yes, but due to the work each solution requires, there are certain mathematical limits to how quickly GWU can be resolved.

The issue is part of a larger trend: The multicore revolution, where many chip manufacturers are no longer prioritizing faster processing speed. Instead, chips are now commonly designed with multiple cores, or smaller processors within larger CPUs. Multicore chips are now commonplace in many phones and laptops.

“Modern technology requires simple, fast, and reliable multiprocessor algorithms,” says Jayanti. “Huge speedups and better coordination is the goal, but even using multiprocessor algorithms, we can prove that communication problems can only be solved so quickly.”

Overcoming significant linguistic barriers to communicating state-of-the-art research in Telugu, Jayanti invented new technical vocabulary for the paper using Sanskrit, the classical language of India, which heavily influences Telugu. For example, there was no word for technical terms like “shared-memory multiprocessor” in Telugu. Jayanti changed that, coining the word saṁvibhakta-smr̥ti bahusaṁsādhakamu (సంవిభక్తస్మృతి బహుసంసాధకము).

While the term may seem daunting and complex at first, Jayanti’s process was simple: Use Sanskrit root words to coin new words in Telugu. For instance, the Sanskrit root “vibhaj” means “to partition” while “smr̥” means “to remember, recollect, or memorize.” After modifying these words with prefixes and suffixes, the results are “saṁvibhakta” (“shared”) and “smr̥ti” (“memory”), or “saṁvibhakta-smr̥ti” (“shared-memory”) in Telugu.

Passionate about creating educational opportunities in India, Jayanti has visited schools in several states, including Telangana, Andhra Pradesh, and Karnataka. He travels to India yearly, occasionally making stops at universities like the International Centre for Theoretical Sciences and those within the Indian Institutes of Technology.

By creating new technical vocabulary, Jayanti sees his work as an opportunity to empower more people to pursue their dreams in science. His Telugu paper opens the doors for millions of native speakers to access STEM research.

“Knowledge is universal, brings joy, opens doors to new opportunities, and has the power to enlighten and bring people of diverse backgrounds closer together in pursuit of a better world,” says Jayanti. “My scientific learnings and discoveries have brought me in contact with great minds around the world, and I hope that some of my work can open up a gateway for more people worldwide.”

As part of his PhD thesis, Jayanti proposed the Samskrtam Technical Lexicon Project, which would bridge further education gaps by developing a dictionary of modern technical terms in STEM for speakers of local Indian languages and academics. “The project aims to forge a close collaboration between scholars of STEM, Sanskrit, and other vernaculars to expand science-availability in language communities that span over a billion people,” according to Jayanti.

Jayanti’s research also fueled further studies of multicore processing speeds. In 2019, he teamed up with Robert Tarjan, a professor of computer science at Princeton and Turing Award winner, as well as Enric Boix-Adserà, an MIT PhD student in EECS to demonstrate lower bound speed limits for data structures like union-find, where algorithms can create a “union” between disjointed datasets while “finding” whether two items are currently in the same set. 

The team leveraged Jayanti’s research on GWU to prove certain limits on how fast algorithms can be, even harnessing the power of multiple cores. Jayanti and Tarjan have designed some of the fastest algorithms for the concurrent union-find problem yet, making analysis of large graphs like the internet and road networks much more efficient. In fact, these algorithms are close to the mathematical speed barrier for solving union-find.

Jayanti’s 2018 research paper in Telugu was presented along with an abstract in Sanskrit as one of the 14 chapters of his thesis last year, and his team’s 2019 paper was presented at the Symposium on Principles of Distributed Computing. His graduate studies were supported by the U.S. Department of Defense through the National Defense Science and Engineering Graduate Fellowship.

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Startups led by MIT mechanical engineers offer health care solutions

Health care has always been ripe for innovation. Whether it’s increasing safety in operating rooms, developing systems to reduce patient wait times, or improving drug delivery, there are endless opportunities to improve the efficacy and efficiency of health care. The Covid-19 pandemic made the need for these solutions all the more pressing.

“There were a number of startups from MIT that addressed problems related to the pandemic,” says George Whitfield, entrepreneur in residence at the Martin Trust Center for MIT Entrepreneurship. “One company, Biobot Analytics, developed a technology to monitor disease spread by looking at wastewater in sewers. In a case of unbelievable serendipity, they developed this right as Covid was starting to spread.”

Another startup inspired by the Covid-19 pandemic, Teal Bio, developed a comfortable, reusable, and transparent respirator that can be worn by health care professionals on long shifts. The company has identified a number of benefits to their design, including lower costs, decreased waste, and an improved ability to identify emotions. Teal Bio was co-founded by Department of Mechanical Engineering (MechE) Leaders for Global Operations alumnus Jason Troutner MBA ’19, SM ’19 and Giovanni Traverso, assistant professor of mechanical engineering at MIT.

Traverso is no stranger to startups. He has co-founded seven of them. An MD-PhD, Traverso is both an assistant professor at MIT and a physician at Brigham and Women’s Hospital. His companies range in size from one employee to 140 employees. With the exception of Teal Bio, the thread that connects his companies is gastroenterology.

“These companies are launching systems that make it easier for patients to receive medication one way or another, particularly through the GI tract,” says Traverso.

One of the companies that Traverso co-founded, Lyndra Therapeutics, hopes to revolutionize how patients take medications. They have developed an oral drug-delivery platform called LYNX, which consistently delivers one, two, or four weeks of medication in one capsule that releases the medication over a specific time period. The capsule dissolves in the stomach and a star-shaped drug delivery system emerges.

The arms of the “star” are made of a polymer that holds the medication and are connected to a central core through degradable linkers. Once the dosing period is complete, the linkers disintegrate, the arms separate, and the entire system safely moves from the stomach into the small intestines, where it passes through the gastrointestinal tract. The platform is being studied with a variety of drugs, including an oral memantine for Alzheimer’s disease.

“Many patients need a loved one or caretaker to help them take oral medication daily, so giving them the ability to take a pill once a week or once a month would positively affect adherence and be hugely impactful on their quality of life,” says Traverso.

Lyndra has raised $240 million to date. One of the therapies they developed to deliver drugs used to treat schizophrenia has advanced to phase-two clinical trials.

Clinical trials are one example of the unique hurdles that medtech startups like Lyndra face on the path to commercialization. Bodies like the U.S. Food and Drug Administration (FDA) and the National Institute for Occupational Safety and Health require strict regulations that need to be met before any medical device, drug, or health care platform can be sold to end users.

“Having an understanding of the regulatory, manufacturing, and business challenges that need to be met to launch a successful product is really crucial. It speaks to the resources that are required to actually be able to execute on these regulations,” adds Traverso. In his first year on MIT’s faculty, Traverso introduced a new class, 2.S988 (Translational Engineering), which aims to introduce these critical elements to students.

Ellen Roche, associate professor of mechanical engineering, is currently trying to determine the regulatory needs for her own startup. In May, she won the grand prize at the inaugural MIT Future Founders Initiative Prize Competition for her pitch.

Roche has developed a minimally invasive technology that occludes the left atrial appendage in patients with atrial fibrillation. The technology, which she developed alongside Professor Jennifer Lewis at Harvard University, decreases the likelihood that blood clots will dislodge, thereby preventing stroke.

“The Future Founders program was invaluable for refining the vision for our company and identifying the correct regulatory and commercialization path to move forward,” says Roche. “Creating a pitch deck forced us to really think through aspects such as our beachhead market, our clinical target population, our funding, and IP [intellectual property] strategy, all the while having access to a network of experts.”

In September, Roche and her team also won the Lab Central Ignite Golden Ticket to support startup founders from traditionally underrepresented groups in the biotech industry.

Both Traverso and Roche have served as instructors for mechanical engineering class 2.75 (Medical Device Design), alongside Professor Alexander Slocum and Nevan Hanumara. The class culminates in a project in which students work with clinicians from Boston-area hospitals and representatives from industry on designing medical devices that address a particular problem. Throughout the class, regulatory experts introduce students to the unique challenges of starting a company or launching a product in the health-care space.

One former student of 2.75, Adam Sachs ’13, co-founded the startup Vicarious Surgical. The company has developed a robotic system that enables minimally invasive surgery. A camera and two robotic instruments enter the abdomen via an incision smaller than the size of a dime. The surgeon can then operate with 360-degree visibility inside a patient’s body.

“Course 2.75 gave me a deep understanding of the entire medical device design process, which was incredibly valuable when we founded Vicarious Surgical. It helped me understand the needs of a user, showed me how to deliver on a product, and allowed me to dip my toes into the process of developing a device from start to finish — much of which I still reference as the company grows and we continue to develop our system,” says Sachs.

Vicarious Surgical, which is based in Waltham, Massachusetts, and currently has just over 200 full-time employees, is in the development process. They have received positive feedback from surgeons regarding their Beta 2 prototypes. After securing the appropriate approvals from the FDA, Sachs and his team plan to bring their product to market for use in hernia and other general surgery procedures.

Traverso sees mechanical engineers, like himself, Roche, and Sachs, as being particularly well-suited to launch medtech startups.

“A huge part of our program is hands-on experience, which we introduce and nurture through many of our course offerings. I think that’s so valuable when you’re developing a device that will be engaging with another human being,” he says.

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Exploring the rich traditions of Brazilian music

Student presentations tackled themes of identity, nation-building, racism, multiculturalism, and more, as reflected in the rich traditions of Brazilian music at “The Beat of Brazil” last month at the Lewis Music Library. The presentations were by students of Portuguese enrolled in class 21G.821 (The Beat of Brazil: Portuguese Language Through Brazilian Society), taught by Nilma Dominique.

Three professional musicians were invited to perform as part of the event: Anna Borges and Bill Ward (from the duo Receita de Samba), along with Grammy Award-winning drummer Rafael Barata. After each student spoke about the historical and cultural context for a particular Brazilian style of music, the musicians performed selections in the discussed styles.

Theo St. Francis (an MIT senior in aeronautics and astronautics) explained Brazil’s history of enslaving Africans to work in the sugar fields. He said, “With the workers came their traditions in food, crafts, religion, and mythology, and especially music and dance. … This forced mixing of cultures rendered a brilliant mix of rhythms and sounds among the three primary influences — African, European, and Native Brazilian.” He explained that the music genre choro is imbued with “influences from lundu dances from Angola, the maxixe or Brazilian tango (itself a mix of African rhythms with European polka dance of that time), as well as flute rhythms from European musicians.”

Samba is not really just one genre, but “is better thought of as the backbone of most genres in Brazil,” explained Alessandre Santos, an MIT senior in mathematics. Samba has strong roots in African music, and contains within it many sub-genres. But throughout Brazil’s history, music has been a site for conflicting forces. Modern samba has been reclaimed by Afro-Brazilians as a kind of resistance to racist oppression. Santos explained that samba-canção is a very poetic variant of samba, characterized by soft melodies and slow rhythms, and two examples of this style were performed.

Laura Leal de Souza, a junior at Wellesley College majoring in Latin American Studies, made a remote presentation over a large monitor. She explained that the samba-exaltação nomenclature first appeared in 1939. She explained, “Composers began to write lyrics that worshiped Brazil and the government.” This was used “to create a sense of ‘Brazilianness’ in Brazilian citizens in order to facilitate the dictatorship later implemented by [then-president] Vargas.” She also described the emergence of samba-enredo in the same period, which became strongly identified with government-backed “samba schools,” becoming “the main rhythm of the Brazilian carnival, characterized by its strong percussion and themes that portray specific elements of Brazilian culture.” Leal de Souza also presented on the protest music of the 1960s later in the program.

The role of television and radio was discussed by Ygor Moura, an MIT junior majoring in chemistry, who explained how that media helped to propagate and essentialize aspects of Brazilian culture. The U.S. government’s “Good Neighbor Policy” of the 1930s sought to advance U.S. interests in Central and South America through trade and other means. He pointed to the promotion of Broadway actress and film star Carmen Miranda as the “origin of most of the visual stereotypes Americans have about Brazilians.” Moura also discussed the role of Brazilian music festivals, which became sites for protest during the Brazilian dictatorship of 1964-85.

One of the best-known Brazilian songs, “The Girl from Ipanema,” is an example of bossa nova (Portuguese for “new wave”), explained Dasha Castillo, an MIT senior in computation and cognition. Castillo explained that this music moved away from samba’s larger group ensembles, toward arrangements typically focus on a “lone singer with a guitar, or a singer with another accompanist on another instrument like a piano.” The best-known artists associated with bossa nova are Antonio Carlos Jobim, Vinícius de Moraes, and João Gilberto.

The upbeat music interludes inspired some audience members to get up and dance during the event. One highlight of the evening was a performance by three MIT students (Allessandre Santos, Ygor Moura, and Dasha Castillo) of the well-known Brazilian song “Águas de Março,” known in English as “Waters of March,” accompanied by drummer Rafael Barata.

Nilma Dominique has offered several classes over the years that teach Portuguese language skills through the vehicle of either film or music. “Language and culture go hand-in-hand,” she said. In her class 21G.821, Dominique guides students in examining Brazilian music genres with within a historical context, and “analyzing cultural production from a transnational perspective ... Throughout the course, there was a strong emphasis on developing critical thinking, often centering discussions on how Brazilian musical production reflects questions of identity, social class, race, inequality, and politics.”

Nilma Dominique explained that the Lewis Music library was not just the venue for the event. The staff and student workers at Lewis played a key role in publicizing the event, and event setup and staffing. She added, “This was actually the second time I had the pleasure of working in partnership with the Lewis Library to put on a program of Brazilian music."

After the event, Avery Boddie, the Rosalind Denny Lewis Music Library department head, explained that the library was involved as a continuation of the tradition of “offering engaging programming and outreach to the MIT community through workshops, lectures, and in this case, concerts.” He also pointed out that the library has a “vast collection on music from most regions of the world, including Brazilian music, so any opportunity to support research and education in diverse genres of music across different cultures is something that we value strongly in our department. And who doesn’t enjoy a little samba?”

Funding for the program was from the Council for the Arts at MIT, the Kelly Douglas Fund through the MIT School of Humanities, Arts, and Social Sciences, and the MIT Brazilian Student Association.

Some attendees provided post-event comments. Abby Mrvos said, “The Beat of Brazil show was an absolute treat. The performances were a joy to watch, and the introductions by the students really gave color and context to the experience. I would love to see more events like this in the future!”

Sam Heath agreed, saying: “Listening to a captivating live performance of a selection of Brazilian music along with its historical context, my mind took a journey through time in Brazil, a much-needed escape after a long semester.”

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Two Lincoln Laboratory software products honored with national Excellence in Technology Transfer Awards

The Federal Laboratory Consortium (FLC) has awarded 2023 Excellence in Technology Transfer Awards at the national level to two MIT Lincoln Laboratory software products developed to improve security: Keylime and the Forensic Video Exploitation and Analysis (FOVEA) tool suite. Keylime increases the security and privacy of data and services in the cloud, while FOVEA expedites the process of reviewing and extracting useful information from existing surveillance videos. These technologies both previously won FLC Northeast regional awards for Excellence in Technology Transfer, as well as R&D 100 Awards.

"Lincoln Laboratory is honored to receive these two national FLC awards, which demonstrate the capacity of government-nonprofit-industry partnerships to enhance our national security while simultaneously driving new economic growth," says Louis Bellaire, acting chief technology ventures officer at the laboratory. "These awards are particularly meaningful because they show Lincoln Laboratory teams at their best, developing transformative R&D [research and development] and transferring these results to achieve the strongest benefits for the nation."

A nationwide network of more than 300 government laboratories, agencies, and research centers, FLC helps facilitate the transfer of technologies out of research labs and into the marketplace. Ultimately, the goal of FLC — organized in 1974 and formally chartered by the Federal Technology Transfer Act of 1986 — is to “increase the impact of federal laboratories’ technology transfer for the benefit of the U.S. economy, society, and national security.” Each year, FLC confers awards to commend outstanding technology transfer efforts of employees of FLC member labs and their partners from industry, academia, nonprofit, or state and local government. The Excellence in Technology Transfer Award recognizes exemplary work in transferring federally developed technology.

Keylime: Enabling trust in the cloud 

Cloud computing services are an increasingly convenient way for organizations to store, process, and disseminate data and information. These services allow organizations to rent computing resources from a cloud provider, who handles the management and security of those rented machines. Although cloud providers claim that the machines are secure, customers have no way to verify this security. As a result, organizations with sensitive data, such as U.S. government agencies and financial institutions, are reluctant to reap the benefits of flexibility and low cost that commercial cloud providers offer.

Keylime is an open-source software that enables customers with sensitive data to continuously verify the security of cloud machines, and edge and internet-of-things (IoT) devices. To enact its constant security checks, Keylime leverages a piece of hardware called a trusted platform module (TPM). The TPM generates a hash (a string of characters representing data) that will change significantly if data are tampered with. Keylime was designed to make TPMs compatible with cloud technology and reacts to a TPM hash change within seconds to shut down a compromised machine. Keylime also enables users to securely bootstrap secrets (in other words, upload cryptographic keys, passwords, and certificates into the rented machines) without divulging these secrets to the cloud provider.

Lincoln Laboratory transitioned Keylime to the public via an open-source license and distribution strategy that involved a series of partnerships. In 2015, after completing a prototype of Keylime, laboratory researchers Charles Munson and Nabil Schear collaborated with Boston University and Northeastern University to implement it as a core security component in the Mass Open Cloud (MOC) alliance, a public cloud service supporting thousands of researchers in the state. That experience led the team to work with Red Hat (under a pilot program funded by the U.S. Department of Homeland Security) to mature the technology in the open-source community.

Through the efforts of the Red Hat partnership, Keylime was accepted into the Linux Foundation’s highly selective Cloud Native Computing Foundation as a Sandbox project technology in 2019, a significant step in establishing the technology's prestige. More than 50 open-source developers are now contributing to Keylime from around the world, and large organizations, including IBM, are deploying the technology to their cloud machines. Most recently, Red Hat released Keylime into its Enterprise Linux 9.1 operating system.

"We are proud that the Keylime team, our partners, and open-source developers have been recognized for their hard work and dedication with this national FLC award. We look forward to maintaining and building impactful collaborations, and helping the Keylime open-source community continue to grow," says Munson.

The team members recognized with the FLC award are Munson and Schear (creators of Keylime at Lincoln Laboratory); Orran Krieger (MOC and Boston University); Luke Hinds and Michael Peters (Red Hat); Gheorghe Almasi (IBM); and Dan Dardani (formerly of the MIT Technology Licensing Office).

FOVEA: Accelerating video surveillance review 

While significant investments have improved camera coverage and video quality, the burden on video operators to analyze and obtain meaningful insights from surveillance footage — still a largely manual process — has greatly increased. The large-scale closed-circuit television systems patrolling public and commercial spaces can comprise hundreds or thousands of cameras, making daily investigation tasks burdensome. Examples of these tasks include searching for events of interest, investigating abandoned objects, and piecing together people's activity from multiple cameras. As with any investigation, time is of the essence in apprehending persons of interest before they have inflicted widespread harm.

FOVEA dramatically reduces the time required for such forensic video analysis. With FOVEA, security personnel can review hours of video in minutes and perform complex investigations in hours rather than days, translating to faster reaction times to in-progress events and a stronger overall security posture. No pre-analysis video curation or proprietary server equipment are required; the add-on suite of video analytic capabilities can be applied to any video stream in an on-demand fashion and support both routine investigations and unforeseen or catastrophic circumstances such as terrorist threats. This suite includes capabilities for jump back, which automatically rewinds video to critical times and detects general scene changes; video summarization, which condenses all motion activity from long raw video into a short visual summary; multicamera navigation and path reconstruction, which tracks activity over place and time and camera to camera in chronological order; and on-demand person search, which scans neighboring cameras for persons of similar appearance.

Lincoln Laboratory began developing FOVEA under sponsorship from the U.S. Department of Homeland Security to address the critical needs of security operators in mass transit security centers. Through an entrepreneurial training program based on the National Science Foundation's Innovation Corps, Lincoln Laboratory conducted a broad set of customer interviews, which ultimately led to Doradus Labs licensing FOVEA. The Colorado-based software development and technical support small business offered FOVEA to two of their casino customers and is now introducing the technology to their customers in the educational and transportation industries.

The laboratory team members recognized with the FLC award are Marianne DeAngelus and Jason Thornton (technology invention and primary contact with Doradus); Natalya Luciw, Diane Staheli, Sanjeev Mohindra, and (formerly) Tyler Shube (customer discovery); Ronald Duarte, Zach Elko, Brett Levasseur (software design and technology demonstrations); Jesslyn Alekseyev, Heather Griffin, and Kimberlee Chang and (formerly) Christine Russ, Aaron Yahr, and Marc Valliant (algorithm and software development); Dan Dardani (formerly of the MIT Technology Licensing Office) and Louis Bellaire (licensing); and Drinalda Kume, Jayme Selinger, and Zach Sweet (contracting services).

“It is wonderful to see the software team’s efforts recognized with this award,” says DeAngelus. “I am grateful for the many friendly people across Lincoln Laboratory and MIT who made this transition happen — especially the licensing, contracts, and communications offices.”

The FLC 2023 award winners will be recognized on March 29 at an awards reception and ceremony during the FLC National Meeting. 

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Targeting cancer with a multidrug nanoparticle

Treating cancer with combinations of drugs can be more effective than using a single drug. However, figuring out the optimal combination of drugs, and making sure that all of the drugs reach the right place, can be challenging.

To help address those challenges, MIT chemists have designed a bottlebrush-shaped nanoparticle that can be loaded with multiple drugs, in ratios that can be easily controlled. Using these particles, the researchers were able to calculate and then deliver the optimal ratio of three cancer drugs used to treat multiple myeloma.

“There’s a lot of interest in finding synergistic combination therapies for cancer, meaning that they leverage some underlying mechanism of the cancer cell that allows them to kill more effectively, but oftentimes we don’t know what that right ratio will be,” says Jeremiah Johnson, an MIT professor of chemistry and one of the senior authors of the study.

In a study of mice, the researchers showed that nanoparticles carrying three drugs in the synergistic ratio they identified shrank tumors much more than when the three drugs were given at the same ratio but untethered to a particle. This nanoparticle platform could potentially be deployed to deliver drug combinations against a variety of cancers, the researchers say.

Irene Ghobrial, a professor of medicine at Harvard Medical School and Dana-Farber Cancer Institute, and P. Peter Ghoroghchian, president of Ceptur Therapeutics and a former MIT Koch Institute Clinical Investigator, are also senior authors of the paper, which appears today in Nature Nanotechnology. Alexandre Detappe, an assistant professor at the Strasbourg Europe Cancer Institute, and Hung Nguyen PhD ’19 are the paper’s lead authors.

Controlled ratio

Using nanoparticles to deliver cancer drugs allows the drugs to accumulate at the tumor site and reduces toxic side effects because the particles protect the drugs from being released prematurely. However, only a handful of nanoparticle drug formulations have received FDA approval to treat cancer, and only one of these particles carries more than one drug.

For several years, Johnson’s lab has been working on polymer nanoparticles designed to carry multiple drugs. In the new study, the research team focused on a bottlebrush-shaped particle. To make the particles, drug molecules are inactivated by binding to polymer building blocks and then mixed together in a specific ratio for polymerization. This forms chains that extend from a central backbone, giving the molecule a bottlebrush-like structure with inactivated drugs — prodrugs — along the bottlebrush backbone. Cleavage of the linker that holds the drug to the backbone release the active agent.  

“If we want to make a bottlebrush that has two drugs or three drugs or any number of drugs in it, we simply need to synthesize those different drug conjugated monomers, mix them together, and polymerize them. The resulting bottlebrushes have exactly the same size and shape as the bottlebrush that only has one drug, but now they have a distribution of two, three, or however many drugs you want within them,” Johnson says.

In this study, the researchers first tested particles carrying just one drug: bortezomib, which is used to treat multiple myeloma, a cancer that affects a type of B cells known as plasma cells. Bortezomib is a proteasome inhibitor, a type of drug that prevents cancer cells from breaking down the excess proteins they produce. Accumulation of these proteins eventually causes the tumor cells to die.

When bortezomib is given on its own, the drug tends accumulate in red blood cells, which have high proteasome concentrations. However, when the researchers gave their bottlebrush prodrug version of the drug to mice, they found that the particles accumulated primarily in plasma cells because the bottlebrush structure protects the drug from being released right away, allowing it to circulate long enough to reach its target.

Synergistic combinations

Using the bottlebrush particles, the researchers were also able to analyze many different drug combinations to evaluate which were the most effective.

Currently, researchers test potential drug combinations by exposing cancer cells in a lab dish to different concentrations of multiple drugs, but those results often don’t translate to patients because each drug is distributed and absorbed differently inside the human body.

“If you inject three drugs into the body, the likelihood that the correct ratio of those drugs will arrive at the cancer cell at the same time can be very low. The drugs have different properties that cause them to go to different places, and that hinders the translation of these identified synergistic drug ratios quite immensely,” Johnson says.

However, delivering all three drugs together in one particle could potentially overcome that obstacle and make it easier to deliver synergistic ratios. Because of the ease of creating bottlebrush particles with varying concentrations of drugs, the researchers were able to compare particles carrying different ratios of bortezomib and two other drugs used to treat multiple myeloma: an immunostimulatory drug called pomalidomide, and dexamethasone, an anti-inflammatory drug.

Exposing these particles to cancer cells in a lab dish revealed combinations that were synergistic, but these combinations were different from the synergistic ratios that had been identified using drugs not bound to the bottlebrush.

“What that tells us is that whenever you are trying to develop a synergistic drug combination that you ultimately plan to administer in a nanoparticle, you should measure synergy in the context of the nanoparticle,” Johnson says. “If you measure it for the drugs alone, and then try to make a nanoparticle with that ratio, you can’t guarantee it will be as effective.”

New combinations

In tests in two mouse models of multiple myeloma, the researchers found that three-drug bottlebrushes with a synergistic ratio significantly inhibited tumor growth compared to the free drugs given at the same ratio and to mixtures of three different single-drug bottlebrushes. They also discovered that their bortezomib-only bottlebrushes were very effective at slowing tumor growth when given in higher doses. Although it is approved for blood cancers such as multiple myeloma, bortezomib has never been approved for solid tumors due to its limited therapeutic window and bioavailability.

“We were happy to see that the bortezomib bottlebrush prodrug on its own was an excellent drug, displaying improved efficacy and safety compared to bortezomib, and that has led us to pursue trying to bring this molecule to the clinic as a next-generation proteasome inhibitor,” Johnson says. “It has completely different properties than bortezomib and gives you the ability to have a wider therapeutic index to treat cancers that bortezomib has not been used in before.”

Johnson, Nguyen, and Yivan Jiang PhD ’19 have founded a company called Window Therapeutics, which is working on further developing these particles for testing in clinical trials. The company also hopes to explore other drug combinations that could be used against other types of cancer.

Johnson’s lab is also working on using these particles to deliver therapeutic antibodies along with drugs, as well as combining them with larger particles that could deliver messenger RNA along with drug molecules. “The versatility of this platform gives us endless opportunities to create new combinations,” he says.

The research was funded, in part, by the U.S. National Institutes of Health, the Leukemia and Lymphoma Society, the U.S. National Science Foundation, and the Koch Institute Support (core) Grant from the National Cancer Institute.

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Remembering Mary Morrissey, whose service to MIT spanned 45 years

Mary Louise Morrissey, whose career at MIT spanned 45 years, including her service as director of the Information and Special Events Center, passed away peacefully on Jan. 17 at the age of 95.

Morrissey joined the MIT community in 1950, working in the Registrar’s Office. At the time, all student transcripts were handwritten in India ink, and it was perhaps there — if not during her student days in Catholic schools — that she developed her precise and elegant script. Another responsibility of the registrar’s staff at the time was to notarize students’ draft-board and other documents and — during the Cold War era — faculty signatures on loyalty oaths. One student at the time, Paul Gray ’54, SM ’55, ScD ’60, recalled that he was not the only one who found multiple reasons to have things notarized by the charming but also somewhat intimidating Morrissey. A few decades later, she organized his inauguration as the 14th president of MIT.

Over the years, her responsibilities grew, as the Information Center became part of the greater President’s Office. The center coordinated the logistics for faculty-sponsored conferences and major Institute events. It oversaw the student-guided campus tours for prospective students and greeted visitors from throughout the country and overseas. In time, the center developed an array of services to facilitate the appointment and support of scholars and researchers from all over the world — what is today the International Scholars Office.  

Morrissey was perhaps best known at MIT as the impresario of countless Institute events, including new building dedications, milestone anniversaries, presidential inaugurations, memorial services, and the annual commencement exercises. David Ferriero, recently retired archivist of the United States, worked with Morrissey on events when he was a librarian at MIT: “Mary Morrissey brought style, grace, and magic to commencement and inauguration ceremonies, new building dedications, and the quality of Institute life for students, faculty, and staff.” 

Among the many innovations she orchestrated was moving the Commencement exercises in 1979 from Rockwell Cage (where they had been held since 1927) outdoors to Killian Court — despite skepticism and predictions of disaster from many quarters. Her main faculty partner in this endeavor was Professor Emeritus Gerald L. Wilson, former dean of the School of Engineering and chair of the Commencement Committee at the time, who became a good friend, as did so many who worked with her. “Mary had very high standards for everything she did on behalf of the Institute,” Wilson says. “She did so with a seriousness of purpose that never blurred her wonderful sense of humor. For many, her throaty laugh belied that stern look when 'Miss Mary' was not amused. She was a great friend to many. She certainly was one of the special ones that made being in the MIT community not just a vocation, but a wonderful experience.”

An exemplar of the iron fist in a velvet glove, she was able to persuade people from all corners of the Institute — faculty members, carpenters, students, administrators, custodians, and trustees — to share her vision of how best to mark significant occasions in the life of the Institute, and come together to make it reality. In recognition of her many contributions to MIT, she was made an honorary member of the Alumni Association in 1995, the same year in which she retired.

Through it all, she was a gifted mentor to individuals from many quarters of the Institute, but none more so than to her immediate staff.

Gayle Gallagher, recently retired as executive director of MIT Institute Events, says, "Mary was one of my dearest friends for more than 40 years. We shared an abundance of laughs, a few tears, and great affection and respect always. In the early years of my career, I most valued her role as mentor for nearly 15 years. Mary was politically astute, a tremendous judge of character, and a fearless and imaginative events creator. The lessons I learned were innumerable and she was my most stalwart champion. She gave me confidence I would never have known without her nurturing and guiding hand. I loved her dearly.”

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School of Engineering fourth quarter 2022 awards

Members of the MIT engineering faculty receive many awards in recognition of their scholarship, service, and overall excellence. The School of Engineering periodically recognizes their achievements by highlighting the honors, prizes, and medals won by faculty working in our academic departments, labs, and centers.

• Paul Blainey of the Department of Biological Engineering received the Chan Zuckerberg Initiative Collaborative Pairs Phase 2 on Oct. 19, 2022.
   
• Brett E. Bouma of the Institute for Medical Engineering and Science was named a 2022 National Academy of Inventors Fellow on Dec. 8.
   
• Markus Buehler of the departments of Civil and Environmental Engineering and Mechanical Engineering received the Society of Engineering Science's James R. Rice Medal on Oct. 21.
   
• Arup Chakraborty of the Department of Chemical Engineering received the APS Max Delbruck Prize in Biological Physics on Oct. 26.
   
• Gang Chen of the Department of Mechanical Engineering was named to the Physics World Top 10 Breakthroughs of 2022 for his work showing that cubic boron arsenide is the best semiconductor material ever found on Dec. 8.
   
• Connor Wilson Coley of the Department of Electrical Engineering and Computer Science was selected to the Schmidt Futures' AI2050 Early Career Fellows on Nov. 8.
   
• Brandon DeKosky of the Department of Chemical Engineering received the Antibody Society's James S. Huston Antibody Science Talent Award on Oct. 20.
   
• Lee Gehrke of the Institute for Medical Engineering and Science was named a 2022 National Academy of Inventors Fellow on Dec. 8.
   
• Asegun Henry of the Department of Mechanical Engineering was named to the Physics World Top 10 Breakthroughs of 2022 for his research on super-efficient electricity generation on Dec. 8.
   
• Klavs Jensen of the Department of Chemical Engineering was elected as a fellow of Academy of Inventors on Dec. 14.
   
• Gareth McKinley of the Department of Mechanical Engineering received the Society of Engineering Science's G.I. Taylor Medal on Oct. 21.
   
• Yuriy Roman of the Department of Chemical Engineering received the NACS 2023–24 Paul H. Emmett Award on Nov. 11.
   
• Giovanni Traverso of the Department of Mechanical Engineering was named a 2022 National Academy of Inventors Fellow on Dec. 8.
   
• Evelyn Wang of the Department of Mechanical Engineering was named a 2022 Highly Cited Researcher by Clarivate on Nov. 15.
   
• Bilge Yildiz of the departments of Materials Science and Engineering and Nuclear Science and Engineering received the Koç University Rahmi M. Koç Medal of Science on Dec. 27.
   
• Xuanhe Zhao of the Department of Mechanical Engineering was named to the Time magazine 200 Best Inventions of 2022 on Nov. 11.

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MIT Gas Turbine Laboratory prepares to jet into the future

In 1941, the National Academy of Sciences appointed a committee to assess the use of gas turbine engines — which use heat released during fuel combustion to produce thrust for propulsion — in aviation. The group of luminaries concluded that due to the temperature limitations of existing materials, gas turbines did not have much of a future in propelling airplanes.

However, “Unknown to the committee, the first jet engine was already successfully run in Germany in 1940: the Junkers Jumo,” says Professor Zoltán Spakovszky, director of the MIT Gas Turbine Laboratory (GTL) and the T.A. Wilson Professor in Aeronautics and Astronautics. Although the committee had correctly identified the temperature limitations, “the German engineers and designers redefined the problem and introduced turbine cooling,” he explains.

The Junkers Jumo, the world’s first turbojet engine in production, was put in operation during World War II, while separately, Sir Frank Whittle had been leading progress on the development of the turbojet engine in Great Britain. With the United States falling behind Germany and Britain in developing turbojet engines, Professor Jerome C. Hunsaker had the vision of establishing a laboratory dedicated to gas turbine propulsion at MIT. Hunsaker, an aviation pioneer in his own right and member of the National Advisory Committee of Aeronautics, gathered funds and support from six U.S. industries and the U.S. Navy to get started.

On Oct. 7, 1947, the GTL, led by Professor Edward Story Taylor as its founding director, officially launched with all major U.S. aviation and aircraft companies of that time in attendance at the opening ceremony. Over the course of 75 years, the GTL, now housed in the Department of Aeronautics and Astronautics, has been at the cutting edge of applied research. It continues to do so by delivering “new perspectives on integration of propulsion systems with new aircraft concepts and high-impact collaborative projects cutting across disciplines,” Spakovszky says.

To describe the work of laboratory, Professor Edward Greitzer, a former GTL director and the H.N. Slater Professor in Aeronautics and Astronautics, quotes former prime minister of Singapore Lee Kuan Yew, who spoke of not “perfecting the known,” but rather reaching for the unknown. “That’s what we have always tried to do at the GTL,” Greitzer says. “We do our best to think strategically about things we could do that would not only be intellectually interesting but would also have an impact.”

The GTL “is still going very strong, tackling new and different challenges,” Spakovszky says. “Today, we’re not only working on the propulsion system, jet engines, and power plants, we’re also working on integrating jet engines into aircraft and on forward-looking challenges like electrification of aviation.”

In the early years, projects focused on one discipline and addressed one specific problem, Greitzer points out, but today’s GTL works on “problems with larger scope and scale, cutting across disciplines and sometimes organizations.” For example, a project working on a conceptual design of a fuel-efficient aircraft led to a test in a large wind tunnel, at a NASA facility.

Equally important, Spakovszky adds, is the lab’s focus on industry. True to its roots, the GTL continues to work on “projects that don’t just go into theses and sit on the shelf; they actually move the needle and start with real applications in industry,” he says. Super-high-pressure ratio compressors for carbon sequestration and ultrashort aeroengine inlets to reduce fuel burn are examples of the many different industry-focused projects that the GTL has worked on.

Fostering excellence, passion, and collaboration

Over the past three-quarters of a century, close to 500 students have called the GTL their academic home. In addition to being steeped in academic rigor, students came away with technical communication skills, says Borislav “Bobby” Sirakov SM ’01, PhD ’04. The ability, “developed at the GTL, to summarize and explain a complex topic in simple words has served me well in my career,” he states.

Andras Kiss ’13, SM ’15, PhD ’21, worked at the GTL from his sophomore year in Course 16 until he completed his doctoral degree in aerospace engineering. “The first thing that Zolti or Ed would say when you wrote a report or made a presentation was 'answer the Heilmeier questions [a series of questions addressing risks, costs and more] in plain language,’ Kiss laughs, “It was all about distilling your work into very approachable, clear language so you know exactly what you’re trying to do. Otherwise it’s very easy to hide behind detail.”

Kiss has many fond memories of the GTL, including the time he spent designing the electrical and fuel systems for a turbofan engine and having it work smoothly after 18 months of effort. “It was a real thrill, seeing the engine start up for the first time,” he remembers.

Phil Mullan SM ’59, ME ’62, ScD ’64, who majored in mechanical engineering at MIT while working in the GTL, loved the academic rigor. “The lab environment was very invigorating for me because the other research assistants were really bright people,” Mullan says. “They came from different backgrounds and had lots of good ideas to share and were always willing to help.” He remembers looking forward to the midmorning and midafternoon coffee breaks in the library.

According to Spakovszky, ideas that pushed the boundaries of so-called conventional wisdom have been an important differentiator of the GTL. Two research initiatives in this regard have been Micro-Engines, shirt-button-sized gas turbine engines for portable power made using computer chip manufacturing, and the Silent Aircraft Initiative, focused on the conceptual design of an aircraft whose noise would be imperceptible outside airport boundaries.

This approach was also evident when approaching challenges earlier in the lab's history, like finding the original drive system for the De Laval wind tunnel and air system. Not to be confused with MIT AeroAstro’s Wright Brothers Wind Tunnel, the reconfigurable De Laval wind tunnel is located within Building 31 and provides air to various test facilities. “The logistical challenge was getting a motor to run the compressor,” Spakovszky says. “It turns out that the USS Halibut, a Gato-class submarine, had run ashore and was decommissioned in New Hampshire in 1945. Eddie Taylor bought the motor drive system out of that submarine and put it here in 1947. We operated that equipment until we renovated a few years ago (in 2017) and now have a new electric motor to drive the De Laval air system.”

According to Greitzer, there have been pleasant technological surprises along the way since he joined the GTL (from Pratt and Whitney) in 1977. One of these was the Silent Aircraft Initiative. “My expectation was that we’d have a trade-off of performance — fuel burn for noise,” Greitzer says. “But we found that if you think about opening up the design of the aircraft … you don’t have to make those compromises and you can get both less noise and improved fuel burn performance.”

Celebrating a roaring future

In his 1947 welcome speech inaugurating the lab, Taylor said: “It hardly seems necessary to stress the growing importance of the gas turbine as a prime mover.” In the speech he also referred to the GTL as a “a new laboratory specifically designed for research in problems encountered in gas turbines.”

On Oct. 7, 2022, 75 years later to the day, Spakovszky addressed a room full of more than 140 alumni, industry members, and academic luminaries who came together from all over the world to return to campus and celebrate the historic milestone for the GTL. Mullan — with his grandson, an engineer with Pratt and Whitney, in tow — Sirakov, and Kiss were among the laboratory alumni in attendance.

“The challenges are different now compared to 75 years ago, but the way we do research and the way we collaborate has not changed. Today, we’re looking at electrifying aviation and working with new fuels like hydrogen,” Spakovszky says. “The bottom line is that our name has not changed, we’re still the Gas Turbine Lab, but we’re doing more than gas turbines, and addressing different aspects of the field.”

The lab’s invigorating environment and a passion for gas turbine technology were on full display at the celebrations where attendees were delighted to catch up with old friends and mentors and go down memory lane while touring the GTL’s renovated facilities to learn more about the latest research and even view a Junkers Jumo 004 engine on display, an emblem of the field’s history embedded in the present.

While 2022 marked an important milestone in the history of the GTL, Sirakov believes that the lab will always be at the forefront of advancements.

“I was very happy to see so many new test rigs and experimental projects going on,” he says. “I am proud of the long history of the lab, the long list of contributions to the field, and the powerful beginning with all the aerospace leaders attending the [launch]. It’s remarkable that after so many years the MIT GTL lab is still very relevant to the fields of aeronautics, space, and automotive [research] and to all of the new and exciting horizons like electrification and clean energy.”

Greitzer agrees. “The feeling that came through at the 75th anniversary celebration is that the Gas Turbine Lab is a special place, it’s distinctive and it’s different,” Greitzer says. “We continue on our voyage of discovery to learn the unknown.”

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MIT mathematicians receive honors for 2023

Members of the Department of Mathematics community — including faculty, students, and alumni — were recognized for their achievements at the recent 2023 Joint Mathematics Meetings in Boston.

Professor Tom Mrowka and his Harvard University collaborator Peter Kronheimer received the 2023 Leroy P. Steele Prize for Seminal Contribution to Research, awarded by the American Mathematical Society (AMS), for their joint paper “Gauge Theory for Embedded Surfaces.”

The AMS’ 2023 Joseph L. Doob Prize was awarded to Professor Bjorn Poonen for his 2017 book “Rational Points on Varieties,” in the series “Graduate Studies in Mathematics.” The citation called his book “an essential reference for anybody who wishes to apply the tools and techniques of modern algebraic geometry to the venerable area of Diophantine equations.”

Professor Scott Sheffield and former MIT postdoc and instructor Jason P. Miller, now at the University of Cambridge, have been awarded the AMS’ 2023 Leonard Eisenbud Prize in Mathematics and Physics. They earned this award “for their monumental series of papers on Liouville Quantum Gravity.”

CLE Moore instructor Jia Shi received the Association for Women in Mathematics’ Dissertation Prize for her thesis that “proves major results on two separate topics in fluid mechanics, a hard classical field.”  

The association also honored two MIT seniors who were nominees for the Alice T. Schafer Prize for excellence in mathematics by an undergraduate woman: Anqi Li was the 2023 runner-up, and Ilani Axelrod-Freed earned an honorable mention.  

Letong Carina Hong ’22, currently at Oxford University as a Rhodes Scholar for China, received the 2023 AMS-MAA-SIAM Frank and Brennie Morgan Prize for Outstanding Research in Mathematics by an Undergraduate Student, for proving a number of results and solving conjectures in combinatorics, number theory, and probability.

The Ruth Lyttle Satter Prize in Mathematics went to Rutgers University Associate Professor Nataša Šešum PhD ’04 and Panagiota Daskalopoulos of Columbia University “for groundbreaking work in the study of ancient solutions to geometric evolution equations.”

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Matthew Notowidigdo appointed co-scientific director of J-PAL North America

J-PAL North America has announced that Matthew “Matt” Notowidigdo ’03, MEng ’04, PhD ’10, professor of economics at the University of Chicago Booth School of Business, is joining Amy Finkelstein as co-scientific director of the organization, replacing Lawrence “Larry” Katz. 

Katz is stepping down after nearly 10 years of supporting the growth and development of J-PAL North America, having worked closely with Finkelstein to launch the regional office of J-PAL in 2013. He will continue his role as a co-chair of J-PAL North America’s Worker Prosperity Initiative and as an active affiliated researcher. 

“Over the past decade, J-PAL North America has had a major impact in expanding the field’s capacity to conduct randomized evaluations on key policy issues in the region,” says Katz. “I am excited to pass the baton to new leadership at the scientific director level. Matt is an excellent choice to join Amy in guiding the organization in its mission over the next decade.”

“We truly would not be where we are today without Larry’s efforts, including helping to launch the office, advising the launch of multiple research initiatives, reviewing over a hundred proposals as a review board member, expanding our research network, supporting high-quality evidence synthesis and policy outreach, and contributing to major fundraising successes,” says Finkelstein. “I now look forward to collaborating with Matt in providing scientific direction to the next phase of J-PAL North America’s work and driving forward a new generation of evidence.” 

In the co-scientific director role, Notowidigdo, alongside Finkelstein, will support and guide J-PAL North America in developing rigorous research on economic mobility and advise as the organization builds a focus on diversity, equity, and inclusion and develops a research agenda for racial equity. 

“Matt holds a deep commitment to our mission, a history of public service at J-PAL, excitement about randomized evaluations, and many ideas around how to strengthen our diversity, equity, and inclusion work,” says Vincent Quan, co-executive director of J-PAL North America. “His thought leadership in these areas will be extremely valuable to the growth of our organization.” 

A J-PAL affiliated researcher since 2015, Notowidigdo’s work spans labor market issues, social protection policies, and health interventions. He has experience conducting a number of randomized evaluations and working effectively with both nonprofit and government partners. Highlights of his evaluations in partnership with J-PAL North America include an influential study on increasing SNAP take-up in Pennsylvania and an ongoing study on managed care organizations with the South Carolina Department of Health and Human Services. 

Notowidigdo also serves as a co-chair for the Worker Prosperity Initiative and has been an active reviewer of proposals, a participant at J-PAL North America events, and a reviewer for the Invited Researcher Search Committee. He has provided guidance on J-PAL North America’s strategies to build a diverse economics pipeline, informed by his direct experience in serving as a mentor for both the Russell Sage Foundation’s Pipeline Grants Competition and for junior economists with the Committee on the Status of Women in the Economics Profession.

“I've had the pleasure of working with Matt on numerous research projects during his time as a J-PAL affiliate,” says Laura Feeney, co-executive director of J-PAL North America. “In addition to the experience he brings to his new role, I am excited for the mentorship he will bring to our staff, his enthusiasm for the work, and his commitment to supporting economics scholars from all backgrounds."

Notowidigdo holds a BS in economics, a BS in computer engineering, an MEng in computer science, and a PhD in economics from MIT. In addition to his work with J-PAL, he has served as a co-editor of the American Economic Journal: Economic Policy, a research associate at the National Bureau of Economics Research, and an associate editor at the Quarterly Journal of Economics.

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Putting clear bounds on uncertainty

In science and technology, there has been a long and steady drive toward improving the accuracy of measurements of all kinds, along with parallel efforts to enhance the resolution of images. An accompanying goal is to reduce the uncertainty in the estimates that can be made, and the inferences drawn, from the data (visual or otherwise) that have been collected. Yet uncertainty can never be wholly eliminated. And since we have to live with it, at least to some extent, there is much to be gained by quantifying the uncertainty as precisely as possible.

Expressed in other terms, we’d like to know just how uncertain our uncertainty is.

That issue was taken up in a new study, led by Swami Sankaranarayanan, a postdoc at MIT’s Computer Science and Artificial Intelligence Laboratory (CSAIL), and his co-authors — Anastasios Angelopoulos and Stephen Bates of the University of California at Berkeley; Yaniv Romano of Technion, the Israel Institute of Technology; and Phillip Isola, an associate professor of electrical engineering and computer science at MIT. These researchers succeeded not only in obtaining accurate measures of uncertainty, they also found a way to display uncertainty in a manner the average person could grasp.

Their paper, which was presented in December at the Neural Information Processing Systems Conference in New Orleans, relates to computer vision — a field of artificial intelligence that involves training computers to glean information from digital images. The focus of this research is on images that are partially smudged or corrupted (due to missing pixels), as well as on methods — computer algorithms, in particular — that are designed to uncover the part of the signal that is marred or otherwise concealed. An algorithm of this sort, Sankaranarayanan explains, “takes the blurred image as the input and gives you a clean image as the output” — a process that typically occurs in a couple of steps.

First, there is an encoder, a kind of neural network specifically trained by the researchers for the task of de-blurring fuzzy images. The encoder takes a distorted image and, from that, creates an abstract (or “latent”) representation of a clean image in a form — consisting of a list of numbers — that is intelligible to a computer but would not make sense to most humans. The next step is a decoder, of which there are a couple of types, that are again usually neural networks. Sankaranarayanan and his colleagues worked with a kind of decoder called a “generative” model. In particular, they used an off-the-shelf version called StyleGAN, which takes the numbers from the encoded representation (of a cat, for instance) as its input and then constructs a complete, cleaned-up image (of that particular cat). So the entire process, including the encoding and decoding stages, yields a crisp picture from an originally muddied rendering.

But how much faith can someone place in the accuracy of the resultant image? And, as addressed in the December 2022 paper, what is the best way to represent the uncertainty in that image? The standard approach is to create a “saliency map,” which ascribes a probability value — somewhere between 0 and 1 — to indicate the confidence the model has in the correctness of every pixel, taken one at a time. This strategy has a drawback, according to Sankaranarayanan, “because the prediction is performed independently for each pixel. But meaningful objects occur within groups of pixels, not within an individual pixel,” he adds, which is why he and his colleagues are proposing an entirely different way of assessing uncertainty.

Their approach is centered around the “semantic attributes” of an image — groups of pixels that, when taken together, have meaning, making up a human face, for example, or a dog, or some other recognizable thing. The objective, Sankaranarayanan maintains, “is to estimate uncertainty in a way that relates to the groupings of pixels that humans can readily interpret.”

Whereas the standard method might yield a single image, constituting the “best guess” as to what the true picture should be, the uncertainty in that representation is normally hard to discern. The new paper argues that for use in the real world, uncertainty should be presented in a way that holds meaning for people who are not experts in machine learning. Rather than producing a single image, the authors have devised a procedure for generating a range of images — each of which might be correct. Moreover, they can set precise bounds on the range, or interval, and provide a probabilistic guarantee that the true depiction lies somewhere within that range. A narrower range can be provided if the user is comfortable with, say, 90 percent certitude, and a narrower range still if more risk is acceptable.

The authors believe their paper puts forth the first algorithm, designed for a generative model, which can establish uncertainty intervals that relate to meaningful (semantically-interpretable) features of an image and come with “a formal statistical guarantee.” While that is an important milestone, Sankaranarayanan considers it merely a step toward “the ultimate goal. So far, we have been able to do this for simple things, like restoring images of human faces or animals, but we want to extend this approach into more critical domains, such as medical imaging, where our ‘statistical guarantee’ could be especially important.”

Suppose that the film, or radiograph, of a chest X-ray is blurred, he adds, “and you want to reconstruct the image. If you are given a range of images, you want to know that the true image is contained within that range, so you are not missing anything critical” — information that might reveal whether or not a patient has lung cancer or pneumonia. In fact, Sankaranarayanan and his colleagues have already begun working with a radiologist to see if their algorithm for predicting pneumonia could be useful in a clinical setting.

Their work may also have relevance in the law enforcement field, he says. “The picture from a surveillance camera may be blurry, and you want to enhance that. Models for doing that already exist, but it is not easy to gauge the uncertainty. And you don’t want to make a mistake in a life-or-death situation.” The tools that he and his colleagues are developing could help identify a guilty person and help exonerate an innocent one as well.

Much of what we do and many of the things happening in the world around us are shrouded in uncertainty, Sankaranarayanan notes. Therefore, gaining a firmer grasp of that uncertainty could help us in countless ways. For one thing, it can tell us more about exactly what it is we do not know.

Angelopoulos was supported by the National Science Foundation. Bates was supported by the Foundations of Data Science Institute and the Simons Institute. Romano was supported by the Israel Science Foundation and by a Career Advancement Fellowship from Technion. Sankaranarayanan's and Isola’s research for this project was sponsored by the U.S. Air Force Research Laboratory and the U.S. Air Force Artificial Intelligence Accelerator and was accomplished under Cooperative Agreement Number FA8750-19-2- 1000. MIT SuperCloud and the Lincoln Laboratory Supercomputing Center also provided computing resources that contributed to the results reported in this work.

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