Thousands celebrate Tech Reunions ’24

Take a beautiful spring weekend, add brass rats and Tim the Beaver swag, mix in technology talks and outdoor activities, fuse it all together with a lot of socializing, and what do you get? MIT Tech Reunions, which this year drew more than 3,300 alumni, family, and friends to campus.

Events got under way when the 50th-reunion Class of 1974 led the traditional procession into Killian Court for the OneMIT Commencement Ceremony. Sporting their signature red jackets, class members embraced the rain to help welcome 3,666 graduates into the community of nearly 149,000 alumni worldwide.

Ray Larson ’49, from the 75th-reunion class, waved to fellow alums who filled Boston Symphony Hall for the 126th Tech Night at Pops.

The celebration continued throughout the weekend at events such as an ice cream social, the Recent Grad Bash, class dinners, and the Baker House 75th reunion.

At Saturday’s Toast to Tech, alums enjoyed temporary tattoos, a live band, a brass rat photo booth, cotton candy, and more.

The long weekend, May 30–June 2, featured nearly 120 events, ranging from lab tours to ice cream socials to the ever-popular Tech Night at Pops, Technology Day, and Toast to Tech. 

A tool that lets users fight misinformation online

Social media platforms are often urged to fight the spread of misinformation through content moderation, but two MIT-affiliated researchers are proposing an alternative: empowering users themselves to identify which information sources are trustworthy.

The Trustnet browser extension, built by EECS professor David Karger and Farnaz Jahanbakhsh, SM ’21, PhD ’23, an assistant professor at the University of Michigan, works for content on any website, including news aggregators and video-­streaming platforms as well as social media sites.

Users click a button to open a side panel where they label content as accurate or inaccurate or question its accuracy, and they can identify other sources whose assessments are trustworthy. Then, when the user visits a website that contains assessments from these sources, the side panel automatically pops up to show them. The extension also checks all links on the page a user is reading. If trusted sources have assessed content on any linked pages, the extension indicates as much and fades the links to content deemed inaccurate.

In a two-week study, the researchers found that untrained individuals could use the tool effectively. Participants said having the ability to assess content and see assessments from others helped them think critically about it. The researchers are considering ways to keep users from being trapped in their own information bubbles by identifying trust relationships in a more structured way, perhaps by suggesting reliable sources like the FDA as assessors to follow.

“In today’s world, it’s trivial for bad actors to create unlimited amounts of misinformation that looks accurate, well-sourced, and carefully argued. The only way to protect ourselves from this flood will be to rely on information that has been verified by trustworthy sources,” Karger says. “Trustnet presents a vision of how that future could look.” 

Screening new materials with computer vision

Boosting the performance of solar cells and other devices will require novel electronic materials that researchers are working to identify with the help of AI. Now a computer vision technique developed by MIT engineers offers a speedy way to confirm that such materials perform as expected—one of the biggest bottlenecks in the screening process. 

The technique automatically analyzes images of semiconductor samples created by a robotic printer and estimates two key properties for each one: band gap (a major factor in a semiconductor’s ability to convert light to electricity) and stability.

Graduate students Eunice Aissi and Alexander Siemenn, SM ’21, who reported on the work with colleagues including professor of mechanical engineering Tonio Buonassisi, used the technique to analyze perovskites, materials that have great promise for solar cells but tend to degrade quickly. About 70 samples—each with a slightly different composition—were deposited on a single slide that was then scanned with a hyperspectral camera, which captures much richer visual information than a human can process. With this data, one of the algorithms they developed was able to compute the band gap for three slides of samples in a total of six minutes—a process that would take a human expert several days.

To test for stability, the team placed the slide in a chamber in which they varied conditions such as humidity, temperature, and light exposure. They photographed the samples with a standard camera every 30 seconds for two hours and used a second algorithm to estimate how they changed color over time, indicating the degree to which they degraded in the different environments. It took 20 minutes to analyze 48,000 images.

The ultimate goal is an autonomous lab, says Aissi: “The whole system would allow us to give a computer a materials problem, have it predict potential compounds, and then run 24-7 making and characterizing those predicted materials until it arrives at the desired solution.” 

Lakes and seas on Titan may be shaped by waves

Saturn’s moon Titan is the only body in the solar system besides Earth that has active lakes and seas—in this case thought to have formed as liquid methane and ethane flooded a landscape crisscrossed with river valleys. Now MIT geologists have found evidence that those mysterious features may be shaped by waves.

Until now, scientists have found indirect and conflicting signs of wave activity by studying images of Titan’s surface taken by NASA’s Cassini spacecraft between 2004 and 2017. “Some people who tried to see evidence for waves didn’t see any and said, ‘These seas are mirror-smooth,’” says Rose Palermo, PhD ’22, a research geologist at the US Geological Survey, who is first author of a paper on the work. “Others said they did see some roughness on the liquid surface but weren’t sure if waves caused it.”

The MIT team took a different approach: investigating the shoreline shape. First they modeled the ways in which a lake’s shores can erode on Earth; then they used their model to determine what could have eroded the shorelines in Cassini’s images. Waves, they found, were the most likely explanation.

“If we could stand at the edge of one of Titan’s seas, we might see waves of liquid methane and ethane lapping on the shore and crashing on the coasts during storms,” says Taylor Perron, a professor of Earth, Atmospheric, and Planetary Sciences. “And they would be capable of eroding the material that the coast is made of.”

The researchers simulated how hundreds of different shoreline shapes would evolve under each of three scenarios: no coastal erosion; erosion driven by waves; and “uniform erosion,” which occurs when liquid passively dissolves a coast’s material or the coast gradually sloughs off under its own weight.

In the model, an initial shoreline (first) evolves differently under conditions of wave erosion (second) and uniform erosion (third).

“We had the same starting shorelines, and we saw that you get a really different final shape under uniform erosion versus wave erosion,” Perron says. “They all kind of look like the Flying Spaghetti Monster because of the flooded river valleys, but the two types of erosion produce very different endpoints.”

The team mapped the shorelines of the four large seas that were completely imaged by Cassini and applied their modeling to see which erosion mechanism best explained their shapes. They found that all four shorelines resembled those produced by the wave-driven model. “We found that if the coastlines have eroded, their shapes are more consistent with erosion by waves than by uniform erosion or no erosion at all,” Perron says.

The researchers, who note that their results must still be confirmed by direct observation, are now working to determine how strong Titan’s winds must be in order to stir up waves that could repeatedly chip away at the coasts. They also hope to decipher, from the shape of Titan’s shorelines, the directions from which the wind is predominantly blowing.

“Titan presents this case of a completely untouched system,” Palermo says. “It could help us learn more fundamental things about how coasts erode without the influence of people, and maybe that can help us better manage our coastlines on Earth in the future.” 

Stress test

Elizabeth Sajdel-Sulkowska was just three months old when Nazi soldiers set fire to her family’s home in the midst of the Warsaw Uprising of August 1944, as the Polish resistance attempted to seize control of the city from the Germans. When that revolt ultimately failed, the city was razed, and there was no time to grab diapers and milk as the family rushed from the burning building. Sajdel-Sulkowska’s parents were taken to Dulag 121, a transitional camp from which they were to be sent to a concentration camp. They escaped that fate only because her mother gave the camp’s milkman her jewelry to deliver a letter to Sajdel-Sulkowska’s godfather, who paid the Germans in charge to release them.

Although her parents’ lives were spared, her father, a biology professor, died of cancer three years later. When her mother, a chemist, got a job as head of a food quality laboratory in Łódź, she eventually had to place Elizabeth in the care of nuns in the countryside, 11 miles away. From ages six through nine, she lived with about 30 other half-orphans and orphans, without running water or electricity or personal attention, taking an hour-long train ride to see her mother on weekends.    

It was a childhood, she says, of “tremendous stress.” 

So perhaps it’s no accident that as an adult, Sajdel-Sulkowska was drawn to the study of stress—whether caused by burns, altered gravity, chemical pollutants, or bacterial infection—and its effect on brain development. In the course of her 57-year career, she has published more than 100 papers, chronicling her research in cells, in animal models, and with postmortem human brain tissue. She has studied the interactions between neurons and the glial cells that protect and support them, the changes in RNA transcription during brain development and in Alzheimer’s disease, and the role of the thyroid hormone in brain development, and published literature reviews on the role of the gut microbiome and gut-brain axis in autism and covid.

As a child, Sajdel-Sulkowska would tell anyone who asked that when she grew up, she wanted to be a professor like her father. At 10, she returned from the orphanage to live with her mother, who had remarried, and she eventually attended an all-girls high school in Łódź. When her metallurgist cousin Witold Vatha Kosicki, SM ’29, learned of her interest in science, he invited her to visit the US so she could interview at MIT, a school she’d never heard of. Getting accepted to Warsaw University’s highly competitive department of mathematics and physics helped her qualify for a visa to the US—and convinced MIT that she was qualified to attend the Institute. After arriving in the US in 1962 and completing a six-week English course (“I barely passed it,” she confesses), she started at the Institute in the spring semester of 1963.

At MIT, Sajdel-Sulkowska planned to study nuclear physics until she took a course on DNA and RNA with Gene Brown, a professor of biochemistry and a pioneer in the field of metabolism. The material was so new there wasn’t even a textbook. But Brown’s lecture on the discovery of the double helix inspired her to switch to biology. “It was fascinating,” she says. “The lectures were so incredible—I knew I wasn’t going back to physics.”

COURTESY OF ELIZABETH SAJDEL-SULKOWSKA

Sajdel-Sulkowska’s cousin had provided money for her to attend MIT for one semester. “The rest of it had to be kind of patched,” she says. So she washed dishes in the chemistry department, plotted soil stress on graph paper in the mechanical engineering department, collected animal urine samples, and for one year worked as an au pair.

During most of her time at MIT, Sajdel-Sulkowska lived with her mother, who had come with her to the US and worked as a technician in a medical lab on Ames Street. They initially lived on Beacon Street in Boston, in a basement room with exposed pipes and wires, sharing a bathroom with other families. But her advisor, Margaret Freeman of the Russian studies department, visited one day and was so appalled at the conditions that she invited Sajdel-Sulkowska and her mother to stay at her home in Belmont. Then, midway through her undergraduate career, she spent a year in McCormick Hall, which had opened in 1963.

Sajdel-Sulkowska’s time in McCormick was a “turning point,” she says. When she lived off campus, she studied and worked on her problem sets alone and assumed everyone else was doing the same. Her isolation was exacerbated by the language barrier, and she felt even more alone in the face of male peers brimming with confidence, relatives suggesting she switch to secretarial school, and an instructor who told her, after a bad experience with a rat in an animal laboratory class, that MIT was not the place for her. At McCormick, she says, she learned that “not everybody knows everything” and that “there are people helping you—that you don’t have to do it all yourself.”

Her first paper on stress was published in 1969, 16 years after the double-helix structure of DNA was discovered. At the time, the finding that stress could alter the body at a cellular level was a revelation.

Sajdel-Sulkowska started her career at a time when there were very few women in science. Though MIT began formally accepting women in 1882, she was one of only two or three women earning a bachelor’s degree in biology in 1967; her entire class of more than 900 had only 20 to 30 women.

Being one of those few women was not easy. In the 1960s and ’70s, when she continued at MIT for graduate school, the field of biology had a culture of what she calls “unchecked harassment.” There was no way to complain without retribution. “That kind of culture created intimidation,” she says. “If you go through incidents of harassment, you become more vigilant.” Male colleagues had to be treated as male colleagues, not as colleagues. Still, she says, there were “a lot of helpful people.”

Many of those helpful people were those she encountered in the Margaret Cheney Room, a Building 3 sanctuary for female students complete with a bedroom, shower, and telephone booths. “That was a haven,” she says—a place where she made lifelong friends. It was also there that she wrote her doctoral thesis—longhand, with her husky, Amis, at her side, over the course of three months. She would write for three hours, sleep for 20 minutes, and repeat.

Sajdel-Sulkowska earned an SM in nutrition and food science (or, as she calls it, “eukaryotic biology in disguise”) and an ScD in the same subject with a minor in neuroendocrinology. Her graduate work would be her first foray into the study of stress as she examined DNA-dependent RNA polymerase II, an enzyme that copies DNA into RNA, and its regulation by cortisol, the stress hormone. Through studies in rat liver cells and then, after a nudge from her committee, in live rats, she found that there is a physiological response to stress through regulation of RNA transcription. Her research showed that artificial cortisol injected into rats altered the RNA polymerase enzymes that synthesize the RNA component of ribosomes. Those ribosomes in turn synthesize the proteins that carry out functions in the cell. 

Her first paper on this work was published in 1969, 16 years after the double­helix structure of DNA was discovered; a second paper followed in 1971. At the time, the finding that stress could alter the body at a cellular level was a revelation.

It was an exhilarating time to be studying biology, says Sajdel-Sulkowska; while she was working on her doctorate, researchers at MIT, Caltech, and the University of Wisconsin, Madison, discovered reverse transcriptase, the enzyme that copies RNA into DNA (the counterpart to the RNA polymerases she studied), for which they would later earn a Nobel Prize. “I was working in the laboratory, I was in a great group, things were happening—it was exciting!” she says.

Reflecting on her time at MIT, Sajdel-Sulkowska says she loved the atmosphere (“I liked the fact that you could work late in the evening”) and the energy. The challenges she had to overcome to succeed at the Institute were worth it, she says: “I wanted to do it, and I did it.”

After earning her ScD in 1972, she interviewed for a faculty position at Northwestern University and was offered the job. But she had recently met Adam Sulkowski, a psychiatrist and postdoctoral fellow, who had just arrived from Poland via France on a visa sponsored by Boston University and could not relocate. She returned to Boston, they married that October, and she became a postdoctoral fellow at Brandeis, where she continued to study RNA polymerase in yeast. Two years later, the first of their four sons was born.

Sajdel-Sulkowska carved out a career that was both broad and deep at a time when combining scientific work and motherhood was extremely rare and accommodations for US working mothers practically nonexistent. When her oldest son was born, in 1974, her three-month maternity leave was unpaid. After her second son arrived while she was completing another postdoc, at Shriners Burn Institute at Harvard Medical School (HMS), the cost of day care for two children exceeded her salary. So with no day care, her husband watched the two boys in the morning, and she found herself under a “tremendous amount of stress.”  

And at Shriners, stress was again the subject of her work. In guinea pigs that have suffered severe burns, she discovered, an increase in cortisol inhibits DNA synthesis in the thymus, which plays a key role in immune function. Her research revealed that removing burned tissue as soon as possible leads to a faster return to normal thymus function and a faster recovery from burns.

In 1980 she became a lecturer in the HMS department of psychiatry with an appointment at McLean Hospital, and she was named an assistant professor six years later. Over the next two decades, she would work on a wide range of topics, including the relationship between mercury and autism, the mechanisms of Alzheimer’s disease, and the role of the thyroid hormone in brain development. She balanced work and motherhood with the help of her mother and her husband, who was supportive and proud of her. “Where there is a will, there is a way,” she says.

In 1989, Sajdel-Sulkowska spent a sabbatical in the lab of Nobel laureate Walter Gilbert at Harvard, gaining experience in cloning, sequencing, and polymerase chain reaction (PCR)—a time she sees as another turning point in her career. In the Gilbert lab, which she describes as a large, vibrant group of young and older scientists, everyone’s work and opinion mattered. “We frequently met as a group and could freely discuss our experiments,” she says. The experience gave her confidence. “At that point I felt that I may be able to start something by myself,” she says.

Once back at HMS, she strove to create the same sort of atmosphere in her lab and began pursuing grants to fund more independent work. When inspiration struck for an especially ambitious research project a few years later, in 1998, Sajdel-Sulkowska embraced the challenge. She’d been watching Star Trek with her sons when she came up with the idea for an experiment examining the effect of yet another kind of stress: altered gravity. In recent NASA brain research on pregnant rats on the space shuttle Columbia, more than half of the rat pups had died. She wrote a grant proposal to work with NASA’s Ames Research Center to study altered gravity’s impact on rats’ brain development. For her study, she positioned pregnant rats in cages at different points on a 24-foot centrifuge, exposing them and their developing pups to varying levels of greater-than-Earth gravity for 42 days, through pregnancy and lactation. Then she measured the length of time the rat pups were able to stay on top of a motorized rotating cylinder (what’s known as a rotarod test) and discovered that hypergravity decreased motor function. Rat pups that developed at 1.65 times Earth gravity could only stay on the spinning wheel for as little as 10 seconds before falling off, while the pups that developed at Earth gravity were able to stay on for almost a minute. 

Her research suggested that this may be because the higher gravity increases oxidative stress (an excess accumulation of free radicals that can damage the body’s cells) or suppresses thyroid activity, a problem that she had previously found to decrease the mass of the developing cerebellum.She also showed that hypergravity decreases the number of a crucial type of neurons in that region of the brain, which is responsible for movement, among other functions.Curiously, she found that male developing brains were more sensitive to hypergravity than their female counterparts. At the end of the experiment, the cerebellums of the male pups were visibly smaller than normal. 

As her hypergravity research was underway, Sajdel-Sulkowska also examined the effect on brain development of another environmental stressor that had become pervasive: polychlorinated biphenyls, or PCBs, a group of toxic synthetic chemicals used so widely from the 1930s through the 1970s that they contaminated the air, water, and soil. She subjected rat pups that had been exposed to PCBs from before birth to rotarod tests and found that their performance decreased as well. So did the mass of their cerebellums, and as with hypergravity, the effect was greater in males than in females.

In 2010 Sajdel-Sulkowska, who had lost her husband to cancer in 2002, was devastated when her youngest son died at the age of 23 as he was recovering from an accident. Work would prove to be a lifeline. She moved back to Poland, where diving into new research “helped me survive,” she says. First as a visiting professor in veterinary medicine at the Warsaw University of Life Sciences and then teaching and doing research at the Medical University of Warsaw, she had an opportunity to work with many young scientists. Her research collaboration with Katarzyna Czarzasta, who is now an assistant professor at the Medical University of Warsaw, was particularly fruitful—and continues today. “She is a very good mentor,” says Czarzasta, who adds that she treated her students as equals.

While teaching in Poland, Sajdel-Sulkowska encountered many students who suffered from depression. “I also observed great stigma associated with psychiatric disorders in Poland, specifically with depression during pregnancy,” she says. That got her thinking about recent research on the use of probiotics—which are readily available in the grocery store—as an alternative treatment for depression. And that led to several projects on perinatal depression that she hoped would lay the groundwork for a study on probiotics as a treatment for it.

The differences in stress response between males and females are at least partly due to the sex hormones. Testosterone increases cortisol levels, so the stress response is greater in males.

In one, she applied chronic mild stress to rats just before pregnancy to model perinatal depression, which she verified by measuring cortisol levels and time spent grooming. Then she studied their pups and documented negative effects on their neurodevelopment and cardiac development. The effects differed in male and female offspring, and the sex-­dependent cardiovascular effects in females persisted as they aged, potentially affecting the following generation as well. The study added to the growing body of research showing that the impact of environment and behavior—also known as epigenetic effects—can be passed along to offspring. 

In the past, Sajdel-Sulkowska says, experimental work, including research on depression, was performed only on males, so that researchers wouldn’t have to control for women’s monthly hormone fluctuations. But thanks in part to pioneering studies like hers, scientists are beginning to recognize the importance of studying the sexes separately. 

The differences in stress response between males and females are at least partly due to the sex hormones, says Sajdel-Sulkowska. Testosterone increases cortisol levels, so the stress response is greater in males; the effects of stressors on the thyroid hormone, too, are different. But beyond that, she points out that each sex has different issues when it comes to health in general: different microbiota, different disease risks, and different disease progressions and mortality rates. As a result, treatments for many diseases may need to be tailored specifically for males or females to be effective. (See “Depression is different for women. One-size-fits-all drugs aren’t helping.”) And even once both environmental factors and sex differences are considered, individual differences, such as a person’s unique microbiome, are likely to matter too. Sajdel-Sulkowska foresees a day when artificial intelligence will make it possible to correlate the differences in individuals’ microbiomes with disease, ultimately leading to individualized probiotic treatments for a variety of conditions—perhaps including depression. 

Sajdel-Sulkowska would remain in Poland for a full decade, returning to the US in September of 2020. A year later, after 35 years as an assistant professor, she was forced to retire from HMS when Harvard didn’t renew her faculty appointment. Having focused on research without giving much thought to advancement, she was suddenly without an academic home. In 2022, she joined the National Coalition of Independent Scholars (NCIS) so she could continue her work without being affiliated with a particular university.

Sajdel-Sulkowska never had the security of a tenured position and estimates that over the course of her career, her average salary was $35,000 a year. (“I never realized that I could name my compensation,” she says.) But she was never in it for the money; she was driven by the work itself. And in her home country, she received some of the recognition that eluded her at Harvard. During her decade of research and teaching in Poland, she was awarded the country’s highest academic honor when she was named a Presidential Professor by Polish president Andrzej Duda.

CIARA CROCKER

Upon returning to the US during the pandemic, Sajdel-Sulkowska tackled a literature review to look for connections between covid, the microbiome, and the gut-brain axis, the physical and biochemical signals that go back and forth between the digestive system and the central nervous system (see sidebar). But the theme of stress continued to intrigue her; she published a paper on maternal stress in rats in 2021 and has another in progress. This recent research closes the circle opened with her doctoral thesis at MIT, she says: “I did my PhD thesis on stress—and I’m ending my career with [studying] stress.”

Sajdel-Sulkowska sees how her current work might apply to her own life. Her mother endured extreme stress during World War II, and she experienced extreme stress herself as a child born just before the Warsaw Uprising. Now, she wonders how that might affect her own children—in humans, the epigenet­ic effect of stress is known to stretch for multiple generations.

Depression is different for women. One-size-fits-all drugs aren’t helping.

The trauma of an accident, an assault, abuse, or even simply losing someone we love can have long-term effects. For some, it can trigger mental illnesses. But what if, in the hours after the experience, you could take a pill that made you less likely to fall ill? And what if there were such a pill tailored specifically for women? That’s the goal Briana K. Chen ’16, a postdoctoral neuroscientist at Columbia University, spends her days nudging us closer to.

To grasp the problem she’s working toward solving, it’s useful to understand the perverse situation we face now: women are roughly twice as likely as men to experience depression, yet antidepressants were predominantly tested on male subjects. Moreover, while certain antidepressants seem to work better in men and others in women, that usually isn’t reflected in how they’re prescribed. Women are also more likely to experience adverse side effects with antidepressant use. Likewise, women face a higher risk of developing PTSD and anxiety, and again, the drugs used to treat these conditions were tested mainly on men. This means millions of women around the world suffer unnecessarily.

Chen’s research suggests it doesn’t have to be that way. She investigates the interaction between sex differences, stress, and mental illnesses, and her work could lead to some of the first female-specific treatments for depression, PTSD, and anxiety. 

Chen finds it baffling that women and men receive the same medical treatments for psychiatric disorders when the differences between them are so significant—not only biologically, but also in terms of howthey experience the same illnesses. Women, for example, are more likely to have anxiety alongside depression. In men, on the other hand, depression is likelier to coincide with substance abuse disorders. 

Part of Chen’s frustration with the status quo can be traced back to her upbringing. She went to all-girls schools from second grade through high school. The process of emerging from an insulated, all-­female environment into the wider world was eye-opening for her. “One thing that was really striking, in the transition from high school to college, was the realization that the default is not female. The default is male. That was a bit of a shock to me,” she says. 

Chen credits her abrupt exit from that nurturing environment with giving her a more clear-eyed view of current societal issues. “Injustices and inequalities exist, and you’re better poised to be able to see them and therefore address them,” she says. 

Early results suggest that one dose of the drug is enough to prevent a whole range of fearful, depressive, and anxiety-like behaviors in female mice—and it appears to have very long-lasting effects.

When she arrived at MIT in the fall of 2012, Chen knew she wanted to major in brain and cognitive sciences. Through the Undergraduate Research Opportunities Program (UROP), she got a chance to delve into neuroscience research in several MIT labs, including that of Nobel Prize winner Susumu Tonegawa, whose team had just identified brain cells involved in encoding memories. Soon her interest in mental health more broadly was piqued.

“This whole journey began at MIT,” she says—referring both to her studies and to her deepening personal interest in the topic. The school “has a really big focus on mental health, especially for undergrads,” she adds. “Maybe it has something to do with the stressful, high-achieving environment.” 

Chen says her parents inadvertently played a role in getting her interested in stress and resilience. They are first-­generation immigrants—her mother from China and her father from Malaysia—who met in the UK while studying chemistry. Both went to the US for graduate school and then, in her mother’s case, postdoctoral training. “They are immigrants who did really well, but there are lots of other immigrants who struggle. And it’s very interesting to see what the combination of factors is behind that, how changes and different environments interact with intrinsic biological properties to do with resilience and adaptation,” she says.  

In 2014, the summer before her junior year, Chen got a summer UROP working for Steve Ramirez, PhD ’15, who was then a doctoral student in Tonegawa’s lab, studying how we form memories and how optogenetics—a technique that uses light to control the activity of specific neurons—can be used to reactivate positive memories in the brain as a treatment for PTSD and depression. (Ramirez is now a professor of neuroscience at Boston University.) 

COURTESY OF BRIANA CHEN

The work was a revelation for Chen, who realized while working with Ramirez that she wanted to focus on studying stress-related disorders. In 2016 she applied to the doctoral program at Columbia University and got in. She landed in the lab of neuroscientist Christine Ann Denny, where she focused on developing sex-specific drugs that can enhance stress resilience and prevent stress-induced mental illnesses. Today Chen is a postdoc in Denny’s lab, and Denny describes Chen as her “right hand.” 

“Most students leave my lab with no patents, or perhaps one. Honestly, with Bri I lose track,” she adds, with a laugh. (Chen says she’s filed six nonprovisional patents—formal patents that will be reviewed by the patent office—but even she has lost track of the informal provisional ones.) 

Among the many patents she’s filed, one stands out. It’s for a mental-health application of a peptide drug called Bay 55-9837 that she’s currently investigating in animal models. Originally developed by Bayer in 2002 as a potential treatment for diabetes, the drug binds to and activates a receptor in the brain called VPAC2, which is known to regulate stress responses in female mice. Chen’s idea is that it could also serve as a “vaccine” for mental illness, which women could take in the wake of a trauma. 

Chen and her colleagues discovered the compound’s potential for warding off negative mental effects of trauma in a roundabout way. They knew ketamine, an anesthetic sometimes used to treat depression, reduces the likelihood that people at risk for psychiatric disorders will develop them, but they wanted to investigate exactly how it does that. Chen decided to test whether ketamine was acting through the VPAC2 receptor or some other mechanism, so she used Bay 55-9837 while administering it, as a means to dial activity of the receptor up and down during testing. In the process, she discovered that the drug was effective in female mice—but not males—as a prophylactic on its own, without any ketamine involved.

Early results suggest that one dose of the drug is enough to prevent a whole range of fearful, depressive, and anxiety-­like behaviors in female mice. Not only that, but it appears to have very long-­lasting effects after a single dose is administered. It’s a finding that’s hugely promising, although Chen warns there’s still a lot to investigate—including safety, possible side effects, and dosing levels—before it can be tested in humans.

Chen is optimistic about the drug’s potential but acknowledges it could fail at a future clinical hurdle. It’s crucial to “proceed with caution and make sure we have all the data so that we can ensure the safety of any potential future patients,” she adds. “Women’s mental health is definitely an urgent matter, but that just means it is even more important for us to make sure that we are as informed and careful as possible when developing treatments.” 

Her main goal as a researcher, she explains, is to contribute to how we understand the specific neurobiological mechanisms behind the ways women respond to stress. In the longer term, she hopes a more sex-specific approach will be adopted by other fields within medicine. It’s a way of treating people that could lead to far better outcomes, she argues.

“If we can make female-specific antidepressants, why stop there?” she says. “Couldn’t we start developing female-­specific drugs to treat cardiac disease or autoimmune disorders? Could we start developing male-specific drugs to treat diseases as well? Overall, I think we could use this approach to move toward a more widespread model of personalized medicine where we use sex to inform treatment plans to improve the health of all patients.” 

Fighting fatphobia

“I felt too fat to be a feminist in public.”

The startling admission appears in the opening paragraph of Kate Manne’s new book, Unshrinking: How to Face Fatphobia. With that single frank and sobering sentence, Manne, an associate professor of philosophy at Cornell, captures the pervasiveness of anti-fat bias—and its stifling impact.  

Manne had tapped into the zeitgeist of #MeToo with her 2017 book, Down Girl: The Logic of Misogyny, and was frequently called upon by the press to comment on current events like Supreme Court Justice Brett Kavanaugh’s confirmation hearings. But in early 2019 she turned down the opportunity to go on an all-
expenses-paid publicity tour of London to promote the paperback release because she felt too self-conscious about her weight. The experience made her uncomfortably aware that even she, an Ivy League academic with a PhD from MIT, had internalized our society’s anti-fat bias. 

“The combination of being publicly feminist and fat is a way of violating patriarchal norms and expectations in this very fundamental way,” she says, making it difficult to speak out “in a body that is ripe to be belittled and mocked.”

Manne grew up in Melbourne, Australia, where she recalls being called fat for the first time by a classmate in fifth grade PE class. She’d been fascinated by philosophy, which she describes as “thinking about thinking,” since the age of five, when a family friend who was a philosopher asked her why she was catching butterflies in a net and taking away their freedom. So she studied the subject in college and then wound up at MIT for grad school because she wanted to study with Sally Haslanger, a professor of philosophy and women’s and gender studies. “Sally proved to me, and continues to do so today, that philosophy can be rigorous, nuanced, socially aware, and politically savvy,” Manne says. After earning her PhD in 2011 and spending two years as a junior fellow at the Harvard Society of Fellows, she joined the faculty at Cornell, where her research focuses on moral, feminist, and social philosophy.

In Down Girl, Manne outlined the distinction between sexism (a patriarchal belief system) and misogyny (the enforcement of patriarchal norms by punishing women who violate them). The book was widely hailed: Rebecca Traister, author of Good and Mad: The Revolutionary Power of Women’s Anger, said Manne did “a jaw-droppingly brilliant job of explaining gender and power dynamics,” and in 2019 Manne was voted one of the world’s top 10 thinkers by the UK magazine Prospect. Her second book, Entitled: How Male Privilege Hurts Women, made it onto the Atlantic’s list of the best 15 books of 2020 and Esquire’s list of 15 exceptional feminist books.

Haslanger isn’t at all surprised by her former graduate student’s success: “It was clear to those who knew her well that with her philosophical training, her beautiful writing, and her keen insight into the social domain, she would become a major public intellectual. And she has surpassed even our expectations.”

Nonetheless, says Manne, “it took 25 years for the personal piece of [feminism] to fall into place along with the political piece.” That personal aspect is chronicled in painful detail in Unshrinking, as Manne connects the dots between misogyny and the fatphobic bullying she suffered as a teen. “The form misogyny took was weaponized fatphobia against me as a slightly larger-than-average teen girl,” she explains.

“Since my early 20s, I have been on every fad diet. I have tried every weight-loss pill. And I have, to be candid, starved myself, even not so long ago,” Manne writes in the introduction to Unshrinking. “I can tell you precisely what I weighed on my wedding day, the day I defended my PhD dissertation, the day I became a professor, and the day I gave birth to my daughter. (Too much, too much, too much, and much too much, to my own mind then.) I even know what I weighed on the day I arrived in Boston—fresh off the plane from my hometown of Melbourne, Australia—to begin graduate school in philosophy, nearly twenty years ago.”

Although she had been aware of the work of fat activists, it was motherhood that finally pushed Manne to stop engaging in disordered eating and extreme dieting, and ultimately to write Unshrinking. She didn’t want her daughter “to bear witness to a mother trying to shrink herself in a futile and pointless and frankly sad way,” she says. In conducting research for the book, she came across some alarming statistics: by age six, more than half the girls in one study had worried about being fat, and another study found that by age 10, an astounding 80% of girls had been on a diet. Even many feminists “still want to shrink our bodies in ways that conform to patriarchal norms and expectations that are extremely hard to resist,” Manne says.

Unshrinking joins the growing literature on anti-fat bias, including the work of sociologist Sabrina Strings, whose book Fearing the Black Body details its racist origins, tracing the shift from the admiration of plumpness as a sign of wealth to the vilification of fat that she argues developed alongside the transatlantic slave trade. Like recent books by Aubrey Gordon and journalist Virginia Sole-Smith, Manne’s uses scientific research to debunk pervasive misconceptions—for example, about the extent to which people can control the size of their bodies—and even to counter the idea that obesity is a disease that requires a cure or large-scale policy response. 

“I can tell you precisely what I weighed on my wedding day, the day I defended my PhD dissertation, the day I became a professor, and the day I gave birth to my daughter.” 

And although the medical establishment has been saying for decades that obesity leads to diseases like diabetes and hypertension, Manne points out that the dynamics are complex and there is much that is still unknown. While being very heavy is correlated with increased mortality, she maintains that we cannot assume it is a direct cause. For example, researchers have found that diabetes is associated not only with obesity but with poverty, food insecurity, and even past trauma as well.

Manne’s argument is not that being fat is unassociated with health risks, but rather that the connection is oversimplified. Given that there’s no proven route to long-term weight loss for most people, she says, we should focus on treating people’s diagnosable problems (such as diabetes and heart disease) rather than stigmatizing them because of their size. But anti-fat bias is all too common among medical professionals, who often misdiagnose fat people’s actual health problems because they ignore their reported symptoms. The prospect of dealing with this prejudice can also discourage fat people from going to the doctor at all. In 2020, a review of scientific publications led an international multidisciplinary expert panel to conclude that weight bias can lead to discrimination, undermining people’s human and social rights as well as their health. The 36 experts pledged in Nature Medicine to work to end the stigma attached to obesity in their fields.

What is needed, Manne argues, is to dismantle diet culture, which not only does not make people thinner in the long term but appears to make them fatter: “The studies that I draw on in the book make a very clear empirical case that a really excellent way to gain weight is to diet.” For example, a 2020 review in the International Journal of Obesity suggests that dieting can lead to eventually regaining more weight than was lost, given how one’s metabolism reacts to food restriction. A better way to improve public health, Manne argues, is to reduce the bias against larger bodies and make public spaces more accessible for people of all sizes. While data on the potential effects is limited, one 2018 study suggests that a weight-­neutral approach known as Health at Every Size (HAES) is beneficial for body image and quality of life.

As a philosopher, Manne offers novel insights by looking at the way fatness is framed as a moral issue. Western societies see fat people as moral failures because, it is assumed, they lack the willpower to eat healthy foods and exercise. Manne argues that we have been conditioned to feel disgust toward fat people, and that this disgust is both “socially contagious” and deeply ingrained. Furthermore, we don’t trust feelings of pleasure derived by eating, or we don’t believe we inherently deserve food that tastes good; instead, we think we have to “earn” it, usually by depriving ourselves. Indeed, most of us are subject to frequent moralizing about “good” and “bad” food—whether from friends, family members, or our own internal voices.

All of this is part of what Manne calls the “fallacy of the moral obligation to be thin.” Secular moral philosophy is “clear that happiness and pleasure are good things, which we should be increasing in the world and promoting,” she says. “There’s nothing shameful about something that feels good, that some people want intensely, as long as it doesn’t hurt others or deprive others.” 

So if diet culture causes pain, deprivation, and eating disorders, Manne maintains, we have a moral obligation to avoid it and instead to derive pleasure from eating. She reasons, “If you do think of there being a kind of moral value in self-care, then we really ought to be satisfying our appetites by eating satisfying food, as well as nourishing our bodies for instrumental reasons.” In her book, she calls diet culture a “morally bankrupt practice.”

But Manne’s experience as a fat academic has shown that most highly educated people still cling tightly to the “pseudo-obligation to try to shrink ourselves,” she says. Stereotypes of fat people as lazy and dumb are particularly harmful in spaces where intellect is highly prized. Anti-fat bias is pronounced in her field, Manne believes, “because as much as we pretend in philosophy not to all be dualists, we value the mind much more than the body, and we’re deeply suspicious of the body.” Tracing this “philosophical disapproval of indulgence” back to Plato and Aristotle, she says: “We think of the body as something feminine, wild, out of control, irrational—not a source of wisdom, but a source of really antiphilosophical distraction that will prevent us from … using our minds to think deep thoughts.”

The default image of an academic is thin, white, male, and able-bodied, which “distorts both our sense of who can think important thoughts and … what intellectual authority really is,” Manne says. This makes being a fat woman in academia particularly fraught. Favorable student evaluations are critical for gaining tenure, and numerous studies have shown that students already tend to judge female professors more harshly. 

UCLA sociology professor Abigail Saguy finds Manne’s work compelling because she writes in an accessible way, “really reaching beyond the ivory tower and communicating important and complex topics.” A decade ago, Saguy wrote What’s Wrong with Fat, and she has seen a rise in awareness about anti-fat discrimination. However, she also notes the co-optation of “body positivity” rhetoric by weight-loss companies and influencers in order to sell their products.

Of course, the biggest news in the weight-loss industry has been the explosion in popularity of injectable drugs like Ozempic, which was originally developed to treat type 2 diabetes. Although Ozempic can be life-changing for diabetics, as well as potentially for those with cardiovascular risks, Manne says, “the majority of people who are pursuing intentional weight loss via these drugs are not even in higher risk categories” based on their body mass index, or BMI. A measure of body fat based on height and weight, BMI classifies people as underweight, normal, overweight, or obese and has been deemed deeply flawed by the American Medical Association (AMA) since it relies on data collected from non-Hispanic white people and has been used in racist ways. Even so, Manne notes that an analysis of data from the US National Health Interview Survey showed that people in the “overweight” category actually have the lowest all-cause mortality (lower than those in the “normal” category) even after controlling for smoking and preexisting diseases. So there’s often no medical need for people in this group—about a third of the US population—to use weight-loss drugs, she says.

With enormous profits at stake—the valuation of Novo Nordisk, which makes Ozempic, exceeds Denmark’s annual GDP—companies are eager to promote the idea of an obesity “epidemic” that got a boost in 2013, when the AMA declared obesity a disease even though a council it had convened on the matter advised against doing so. “Obviously these companies have a massive incentive to overinflate the extent and the seriousness of the problem,” she says, adding that if people discontinue these drugs because their side effects are intolerable or they’re too expensive, “the weight is gonna come roaring back.” 

Manne believes that while people are entitled to pursue intentional weight loss, no one should feel obligated to do so. And when fat influencers or activists lose weight in a very public way, she says, they further stigmatize fat people who choose the path of fat acceptance. A recent New York Times article buttresses her argument. Manne is worried about “a real reversal of the progress we’ve made in fat-activist communities,” fearing that it may be easier for doctors to prescribe drugs to fat patients than to reexamine their own long-held negative beliefs about them. 

However, the positive feedback for Manne’s work suggests that it can make an impact. Roxane Gay, author of Hunger, proclaimed Unshrinking “an elegant, fierce, and profound argument for fighting fat oppression in ourselves, our communities, and our culture.” Booklist called it “a brilliant takedown of fatphobia” in its starred review. Manne is particularly heartened by readers who have told her that the book convinced them to stop dieting or helped them advocate for themselves—for example, by asking for an airplane seatbelt extender without shame. Progress may be slow, but it’s progress.

“I wanted to work on something that didn’t exist”

In 2017 Polina Anikeeva, PhD ’09, was invited to a conference in the Netherlands to give a talk about magnetic technologies that she and her team had developed at MIT and how they might be used for deep brain stimulation to treat Parkinson’s disease. After sitting through a long day of lectures, she was struck by one talk in particular, in which a researcher brought up the idea that Parkinson’s might be linked to pathogens in the digestive system. And suddenly Anikeeva, who had pioneered the development of flexible, multifunction brain probes, found herself thinking about how she might use these probes to study the gut.

While the idea of switching gears might give some researchers pause, Anikeeva thrives on venturing beyond her academic comfort zones. In fact, the path that led to her becoming the Matoula S. Salapatas Professor in Materials Science and Engineering—as well as a professor of brain and cognitive sciences, associate director of MIT’s Research Laboratory of Electronics, and an associate investigator at MIT’s McGovern Institute for Brain Research—was rarely a clear or obvious one. There is, however, one constant in everything she does: an indefatigable curiosity that pushes her toward the edge of risk—or, as she likes to call it, “the intellectual abyss.”

After the conference in the Netherlands, she soon dove into studying the human gut, a system that doesn’t simply move nutrients through the body but also has the capacity to interpret or send information. In fact, she has come to think of it as a largely uncharted “distributed nervous system.” In 2022, she became the director of the newly launched K. Lisa Yang Brain-Body Center at MIT, where she’s directing research into the neural pathways beyond the brain—work that could shed light on the processes implicated in aging and pain, the mechanisms behind acupuncture, and the ways digestive issues might be linked not just to Parkinson’s but to autism and other conditions.

Although she hadn’t heard of it before that conference in the Netherlands, the hypothesis that piqued Anikeeva’s interest in studying the brain-body connection was first posed by the German anatomist Heiko Braak in 2003. He and colleagues posited that a type of Parkinson’s disease has environmental origins: a pathogen that enters the body through the mouth or the nasal cavity and ends up in the digestive tract,where it triggers the formation of abnormal, possibly toxic clumps of protein within neurons. That condition, known as Lewy pathology, is the hallmark of the disease.

“The reason the environmental hypothesis came about is because those Lewy bodies actually have been found in the GI tract of patients with Parkinson’s,” Anikeeva explains. “But what’s more striking is that if you go back in the medical history, Parkinson’s patients—many of them, like 80% or so—have been diagnosed with GI dysfunction, most commonly constipation, years before they get a Parkinson’s diagnosis.”

Functions, behaviors, and diseases long thought to originate in the brain might be influenced by signals from other parts of the body.

Researchers have debated the hypothesis and have yet to make definite causal connections between the ingestion of pathogens and the progression of Parkinson’s disease. But Anikeeva was intrigued. 

“It’s quite controversial and it has seen some attempts at testing, but nothing conclusive,” she says. “I thought that my lab had a unique tool kit to start testing this hypothesis.”  

GRETCHEN ERTL

At the time, Anikeeva’s lab was focused on flexible polymer-fiber probes that can interface with the brain and spinal cord. Having developed these fibers, she and her team were testing them in mice, both to stimulate neurons and to record their signals so they could study the ways in which those signals underlie behavior. The lab had also been working on using magnetic nanomaterials to stimulate neurons so their activity could be regulated remotely—without needing to run fibers to a mouse’s brain at all.  

Braak’s hypothesis made Anikeeva wonder: Could similar multifunctional probes be used to explore the digestive system? Could she and her team engineer gut-­specific tools to study the neurons that make up what’s known as the enteric nervous system, which regulates sensing, moving, absorbing, and secreting—the tasks that the gastrointestinal tract must perform to digest food? And for that matter, could they study any of the body’s peripheral systems?

“I started thinking about interfacing not only with the central nervous system, but also with other organ systems in the body, and about how those organ systems contribute to brain function,” she explains.

Ultimately, this interface could help researchers understand the way the body communicates with the brain and vice versa, and to pinpoint where diseases, including Parkinson’s, originate.

“For many years neuroscience has essentially considered the brain in a vacuum. It was this beautiful thing floating, disconnected,” Anikeeva says. “Now we know that it’s not in a vacuum … The body talks back to the brain. It’s not a strictly downward information flow. Whatever we think—our personality, our emotions—may not only come from what we perceive as the conscious brain.” In other words, functions, behaviors, and neurodegenerative diseases long thought to originate in the brain—perhaps even the act of thinking itself—might be influenced by signals from other parts of the body. “Those are the signals that I’m very excited about studying,” she says. “And now we have the tools to do that.”

“It’s opened technological floodgates into these neuroscience questions,” she adds. “This is a new frontier.”

Anikeeva grew up in Saint Petersburg, Russia, the child of engineers, and showed brilliance from an early age. She was admitted to a selective science magnet school, but she briefly considered pursuing a career in art.

“I was about 15 years old when I was choosing between professional art and professional physics, and I didn’t want to be poor,” she says with a laugh. “Being good at watercolor doesn’t help with leaving Russia, which was my objective. I grew up in a very unstable political environment, a very unstable economic environment. Nobody becomes an artist if they can do something else that’s more practical.” She chose science and earned her undergraduate degree in biophysics at Saint Petersburg State Polytechnic. 

But Anikeeva says her artistic brain, along with the mind-clearing avocations of climbing and long-distance running, helps her with her work today: “I use that way of thinking, the imagination, to think conceptually about how a device might come together. The idea comes first as an image.”

After graduating, Anikeeva got an internship in physical chemistry with the Los Alamos National Laboratory in New Mexico and worked on solar cells using quantum dots. In 2004, she arrived at MIT to begin her PhD in materials science and engineering.

PHOTO COURTESY OF THE RESEARCHERS

As a graduate student, Anikeeva helped develop quantum-dot ­LED display technology that’s now used by television manufacturers and sold in stores around the world. She has coauthored two papers on that research with her primary advisor, Vladimir Bulović, the Fariborz Maseeh (1990) Professor of Emerging Technology, associate dean for innovation at the School of Engineering, and director of MIT.nano, and seven with Bulović and Nobel Prize winner Moungi Bawendi, MIT’s Lester Wolfe Professor of Chemistry.

But after earning her PhD in 2009, Anikeeva says, she got bored—as she frequently does. “I wanted to work on something that didn’t exist,” she says.

That led her to seek out a postdoctoral fellowship in neuroscience at Stanford University in the lab of Karl Deisseroth, one of the inventors of optogenetics, which uses laser light to activate proteins in genetically modified brain cells. Optogenetic tools make it possible to trigger or inhibit neurons in test rodents, creating an on/off switch that lets researchers study how the neurons work. 

“I was really fortunate to be hired into that lab, despite the fact that my PhD, ultimately, was not in neuroscience but in optical electronics,” she says. “I saw all these animals running around with optical cables coming out of their heads, and it was amazing. I wanted to learn how to do that. That’s how I came to neuroscience.”

Realizing that the tools neuroscientists used to study complex biological phenomena in the brain were inadequate, she started to develop new ones. In Deisseroth’s lab, she found a way to improve upon the fiber-optic probes they were using. Her version incorporated multiple electrodes, allowing them to better capture neuronal signals. 

Probing the brain is challenging because it’s very soft—“like pudding,” as she puts it—and the tools researchers used then were rigid and potentially damaging. So when Anikeeva returned to MIT as an assistant professor, her lab collaborated with Yoel Fink, PhD ’00, a professor of materials science and engineering as well as electrical engineering and computer science and director of MIT’s Research Laboratory of Electronics, to create very thin, highly flexible fibers that can enter the brain and the spinal cord without doing any harm (see “A Better Way to Probe the Brain,” MIT News, May/June 2015). Unlike the bulky hardware that Deisseroth was using to deliver light for optogenetics, Anikeeva’sfibers are multifunctional. They’re made of an optical core surrounded by polycarbonate and lined with electrodes and microfluidic channels, all of which are heated and then stretched in production. “You pull, pull, pull and you get kilometers of fiber that are pretty tiny,” Anikeeva explains. “Ultimately it gets drawn down to about a hair-thin structure.”

Using these ultrathin fibers, researchers can record neuronal signals and send their own signals to neurons in the brain and spinal cord of genetically engineered mice to turn them on and off. The fibers offered a new way to investigate neural responses—and earned Anikeeva a spot on our 2015 list of 35 Innovators Under 35. They also proved to be a useful therapeutic tool for drug delivery using the fibers’ microfluidic channels.

As this work hummed along, Anikeeva heard about Braak’s hypothesis in 2017 and set out to find resources to investigate the gut-brain connection. “I promptly wrote an NIH grant, and I promptly got rejected,” she says. 

But the idea persisted.

Later that year, neural engineers studying brain interfaces at Duke invited Anikeeva to give a talk. As she had gotten in the habit of doing during her travels to other universities, she looked up researchers working on GI systems there. She found the gut-brain neuroscientist Diego Bohórquez.

While the brain is extraordinarily complex, from an engineering and research standpoint it’s much more convenient to study than the digestive tract.

“I told him that I’m really interested in the gut, and he told me that they were … studying nutrient absorption in the gut and how it affects brain function,” Anikeeva recalls. “They wanted to use optogenetics for that.”

But the glass fibers he’d been trying to use for optogenetics in the gut could do serious damage to the fragile GI system. So Anikeeva proposed a trade of sorts.

“I thought that we can easily solve Diego’s problems,” she says. “We can make devices that are highly flexible, basically in exchange for Diego teaching us everything about the gut and how to work in that really fascinating system.”

Bohórquez remembers their first meeting, the beginning of a fruitful collaboration, in some detail. “She said, ‘I see that you are doing some really interesting work in sensations and the gut. I’m sure that you’re probably trying to do something with behavior,’” he says. “And then she pulls out these fibers and said, ‘I have this flexible fiber. Do you think that you can do something with it?’”

She returned to MIT and, she says, began to “take this lab that is a rapidly moving aircraft carrier and start reorienting it from working on the brain to working on the gut.”

The move may have surprised colleagues, but Anikeeva refuses to do anything if it loses her interest—and while the brain is extraordinarily complex, from an engineering and research standpoint it’s much more convenient to study than the digestive tract. “The gut wall is about 300 microns or so,” Anikeeva says. “It’s like three to four hairs stuck together. And it’s in continuous motion and it’s full of stuff: bile, poop, all the things.” The challenges of studying it, in other words, are nothing short of daunting.

The nervous system in the gut, Anikeeva explains, can be thought of as two socks, one inside the other. The one on the outside is the myenteric plexus, which regulates peristalsis—the rhythmic contraction of muscles that enables food to move along the gastrointestinal tract, a process known as motility. The one on the inside is the submucosal plexus, which is closer to the mucosa (the mucus-coated inner lining) and facilitates sensing within the gut. But the roles of the plexuses are not fully understood. “That’s because we can’t just implant the gut full of hardware the same way we do in the brain,” Anikeeva says. “All the methods, like optogenetics and any kind of electrical physiology—all of that was pretty much impossible in the gut. These were almost intractable problems.”

Anikeeva’s work developing tools for the brain had been so successful and groundbreaking that it was difficult for her to find financial support for her pivot to other parts of the body. But then, she says, came “another fateful meeting.”

In 2018, she gave a presentation at a McGovern Institute board meeting, conveying her latest ideas about studying Parkinson’s disease and engineering tools to explore the GI system. Lisa Yang, a board member, mentioned that many people with autism also suffer from GI dysfunction—from motility disorders to food sensitivities. Yang was already deeply interested in autism, and she and her husband had just launched the McGovern Institute’s Hock E. Tan (’75, SM ’75) and K. Lisa Yang Center for Autism Research the year before. 

“She was interested in this gut-brain connection,” Anikeeva remembers. “I was brought into the Center for Autism Research for a small project, and that small project kind of nucleated my ability to do this research—to begin developing tools to study the gut-brain connection.”

As that effort got underway, a number of colleagues at MIT and elsewhere who were also interested in brain-body pathways were drawn to the new research.

STEPH STEVENS

“As our tools started to mature, I started meeting more people and it became clear to me that I’m not the only person interested in this area of inquiry at MIT,” she says. “The tools opened this frontier, and the Brain-Body Center bubbled up from that.” 

To launch into their work on the gut-brain connection, Anikeeva and her team had to completely rethink the fibers they had designed previously to study the brain. 

In brain probes, all the functional features sit at the tip of the fiber, and when that fiber is threaded into the skull, the light-emitting tip faces downward, allowing researchers a view of everything under it. That doesn’t work with the GI system. “It’s not how you want to interface with the gut,” Anikeeva says. “The gut is a lumenal organ—it’s a sock—and the nervous system is distributed in the wall.”

In other words, if the probe is looking downward, all it will see is matter passing through the gut. To research the GI tract, Anikeeva and her colleagues needed these features to sit laterally, along the length of the fiber. So with this fabrication challenge in mind, Anikeeva again approached Fink, a longtime mentor and collaborator—and a fellow TR35 veteran. 

Mice “would normally eat ferociously” when given access to food after fasting. “But if you stimulate those cells in the gut, they would feel full.”

Together they developed a way to distribute microelectronic components—LEDs for optogenetic stimulation, temperature sensors, and microfluidic channels that can deliver drugs, nutrients, and genetic material—along the fiber by essentially creating a series of pockets to contain them. Grad student Atharva Sahasrabudhe put in countless hours to make it happen and optimized the process with the help of technician Lee Maresco, Anikeeva says. Then, with Anantha P. Chandrakasan, dean of MIT’s School of Engineering, the Vannevar Bush Professor of EECS, and head of MIT’s Energy-Efficient Circuits and Systems Group, the team designed a wireless, battery-powered unit that could communicate with all those components.

The result was a fiber, about half a millimeter by one-third of a millimeter wide, made out of a rubbery material that can bend and conform to a mouse’s gut yet withstand its harsh environment. And all the electronic components housed within it can be controlled wirelessly via Bluetooth. 

“We had all the materials engineers, and then we collaborated with our wireless colleagues, and we made this device that could be implanted in the gut. And then, of course, similar principles can also be used in the brain,” Anikeeva explains. “We could do experiments both in the brain and the gut.”

GRETCHEN ERTL

In one of the first experiments with the new fibers, Anikeeva worked with Bohórquez and his team, who had determined that sensory cells in the GI tract, called neuropods, send signals to the brain that control sensations of satiety. Using mice whose cells are genetically engineered to respond to light, the MIT and Duke researchers used the specialized fibers to optically stimulate these cells in the gut.

“We could take mice that are hungry, that have been fasting for about 18 hours, and we could put them in a cage with access to food, which they would normally eat ferociously,” Anikeeva says. “But if you stimulate those cells in the gut, they would feel full even though they were hungry, and they would not eat, or not as much.”

This was a breakthrough. “We knew that the technology works,” she says, “and that we can control gut functions from the gut.”

Next Anikeeva’s team wanted to explore how these neural connections between the gut and the brain can influence a mouse’s perception of reward or pleasure. They put the new fiber into the area of the brain where reward perception is processed. It’s packed with neurons that release dopamine—the “happy hormone”—when activated.

Then they ran tests in which mice had a choice between two compartments in a cage; each time a mouse entered a particular one, the researchers stimulated its dopamine neurons, causing the mouse to prefer it. 

To see if they could replicate that reward-seeking behavior through the gut, the researchers used the gut-specific fibers’ microfluidic channels to infuse sucrose into the guts of the mice whenever they entered a particular compartment—and watched as dopamine neurons in the brain began firing rapidly in response. Those mice soon tended to prefer the sucrose-associated compartment. 

But Anikeeva’s group wondered if they could control the gut without any sucrose at all. In collaboration with Bohórquez and his team at Duke, the researchers omitted the sucrose infusion and simply stimulated the gut neurons when the mice entered a designated compartment. Once again, the mice learned to seek out that compartment.

“We didn’t touch the brain and we stimulated nerve endings in the gut, and the mice developed the exact same type of preference—they felt happy just when we stimulated the nerve endings in their small intestines using our technology,” Anikeeva says. “This, of course, was a technical demonstration that it is now possible to control the nervous system of the gut.”

The new tools will make it possible to study how different cells in the gut send information to the brain, and ultimately the researchers hope to understand the origins not only of digestive diseases, like obesity, but of autism and neurodegenerative diseases such as Parkinson’s.

Researchers at the Brain-Body Center are already exploring those connections.  “We’re particularly interested in the gut-brain connection in autism,” Anikeeva says. “And we’re also interested in more affective disorders, because there is a big genetic link, for instance, between anxiety and IBS [or irritable bowel syndrome].”

In the future, the technology also could lead to new therapies that can control gut function more precisely and effectively than drugs, including semaglutides like Ozempic, which have made headlines in the past year for weight control.

Now that Anikeeva has developed and tested the device in the GI system and solved a lot of technical challenges, other peripheral systems in the body could be next.

“The gut is innervated, but so is every organ in the body. Now we can start asking questions: What is the connection to the immune system? The connection to the respiratory system?” she says. “All of these problems are now becoming tractable. This is the beginning.”

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Probing the mind-body connection

Founded in 2022, the K. Lisa Yang Brain-Body Center at MIT is focusing on four major lines of research for its initial projects.

GUT-BRAIN:

Polina Anikeeva’s group is expanding a toolbox of new technologies and applying these tools to examine major neurobiological questions about gut-brain pathways and connections in the context of autism spectrum disorders, Parkinson’s disease, and affective disorders.

AGING:

CRISPR pioneer Feng Zhang, the James and Patricia Poitras Professor of Neuroscience at MIT and an investigator at the McGovern Institute, is leading a group in developing molecular tools for precision epigenomic editing and erasing accumulated “errors” of time, injury, or disease in various types of cells and tissues.

PAIN:

The lab of Fan Wang, an investigator at the McGovern Institute and professor of brain and cognitive sciences, is designing new tools and imaging methods to study autonomic responses, activity of the sympathetic and parasympathetic neurons, and interactions between the brain and the autonomic nervous system, including how pain influences these interactions.

ACUPUNCTURE:

Wang is also collaborating with Kelly Metcalf Pate’s group in MIT’s Division of Comparative Medicine, to advance techniques for documenting changes in brain and peripheral tissues induced by acupuncture in mouse models. If successful, these techniques could help make it possible to better understand the mechanisms involved in acupuncture—specifically, how the treatment stimulates the nervous system and restores function. 

Part of the goal of the Brain-Body Center, Wang says, is to dissect how the circuits of the central nervous system interact with the peripheral autonomic system to generate emotional responses to pain. She says her research has led her to a deeper understanding of the two responses to pain—sensory and emotional. The latter, a function requiring the autonomic nervous system, is what leads to a sense of suffering. If researchers can prevent the autonomic responses elicited by pain, she explains, then the same stimulus may produce “a sensation without pain.” The idea is to develop devices to manipulate autonomic responses in mice, and then ultimately develop devices that can help humans.  —Julie Pryor and Georgina Gustin

A walking antidote to political cynicism

Burhan Azeem ’19 had never been to a city council meeting before he showed up to give a public comment on an affordable-­housing bill his senior year. Walking around Cambridge, he saw a “young, dynamic, racially diverse city,” but when he stepped inside City Hall, most of the others who had arrived to present comments were retirees reflecting a much narrower—and older—demographic.

Less than a year later, Azeem set out to shift the balance in who gets to make decisions on behalf of the city by running for city council himself.

A materials science and engineering major, Azeem had long been civically engaged, volunteering for Ayanna Pressley’s campaign for the US Congress as a junior. But what really set him on the path to local politics was his curiosity about why living in Cambridge is so expensive. He’d experienced the problems that arise from a lack of access to affordable housing as a kid in New York, and he wanted to understand what was contributing to that problem in the city where he’d chosen to live as an adult.

He launched his campaign a month before graduation—encouraged by Marc McGovern, himself a council member and at the time the city’s mayor, whom he’d met while campaigning for Pressley. (In Cambridge, the council chooses the mayor from within its ranks.) Azeem lost by a hundred votes, but he outperformed a candidate who’d raised more than $40,000, while he himself had raised less than $7,000. That made him think it might be worth another try. So in 2021 he ran again, and he won by 200 votes. At age 24, he was the youngest Cambridge city councilor ever elected. 

He quickly set to work trying to make Cambridge a better city, passing bills focused on housing, transit, and climate initiatives. Those successes set him up not just to win reelection in November 2023, but to garner more votes than any other council member but the mayor. 

“We passed a lot of policy—way more than an average term,” he says. “What’s cool about city council is that even though we don’t have as big a scope as Congress or the state house, we have absolute power where we do have power. Over our roads and housing zoning policy, even the president cannot tell me what to do. I think that’s why I’ve had so much success: I’m very narrowly focused on the places where we can make a really big change.”

TOAN TRINH

If Azeem didn’t have an average first term, maybe it’s because there’s very little about him that’s average. In addition to serving on the city council, he’s also employed full-time at Tandem, a startup offering pop-up veterinary clinics, a pharmacy, and telehealth for pets that he helped get off the ground with former classmates from MIT, among others. As the company’s head of AI engineering, Azeem has led an effort to use AI to suggest medications and is working on developing tools that could potentially help vets with diagnoses. The founding team is the same one with which he helped build DayToDay Health, a startup that offers digital tools and live chat to support human patients before and after medical procedures. Having served as an EMT with MIT’s Emergency Medical Services as an undergrad, Azeem found working for DayToDay especially meaningful during the pandemic, since it gave him a way to serve his fellow citizens when everyone was in lockdown at home. DayToDay scaled from eight people to over 400 and was sold just before Azeem was elected to his first term.

“He’s like a Swiss Army knife. It doesn’t matter what the challenge is—he’s the person you want to keep with you.”

Prem Sharma ’18, CEO and cofounder, Tandem and DayToDay

As if that weren’t enough, Azeem is also one of the cofounders and a current board member and treasurer of Abundant Housing Massachusetts, a nonprofit seeking to address the state’s housing shortage and legacy of housing segregation. The organization, which started in 2020 as a group of volunteers meeting in an MIT classroom, now has six full-time employees and a million-dollar annual budget. In addition to pushing for laws aimed at increasing the housing supply, it also creates tools and resources to help grassroots groups take advantage of existing legislation like the MBTA Communities Act, a zoning reform bill meant to help Massachusetts add more than 280,000 homes near existing public transit.

“I tell him all the time, ‘I don’t know how you do it,’” says Prem Sharma ’18, CEO and cofounder of Tandem and DayToDay, who’s called Azeem a coworker and friend for years. Though Azeem has lots going on, Sharma insists that he “delivers results” at work and “his output is always quality … he’s one of our top people.” 

“He’s like a Swiss Army knife,” Sharma adds. “It doesn’t matter what the challenge is—he’s the person you want to keep with you.”

Policy priorities from personal experience

Azeem was born in Multan, Pakistan, and moved to Staten Island, New York, with his family in 2001, when he was four. His parents had immigrated after winning the visa lottery, in pursuit of financial options that might help them pay down medical debt that had arisen from his sister’s premature birth. Money was tight, so they moved in with family friends.

“There were 11 of us living in this three-bedroom. We were too many people to be legal, so we would hide out in closets whenever the landlord came over,” he recalls. “We were very nervous about being caught, which is a big reason I skipped pre-K and kindergarten.”

The family moved often from one place to another within Staten Island over the next decade. Though in some ways it was a tough place to grow up as a Pakistani immigrant kid, especially in the years after 9/11, Azeem considers himself “very lucky” in that he was naturally gifted enough at science and math to get into a science and technology high school. That paved the way for him to eventually attend MIT on a full scholarship.

His experience growing up “very poor,” as he describes it, has informed his policy priorities as an adult. When he considers what he wants to accomplish in office, he’s looking for things that can ease the burden of day-to-day life for citizens who face the kinds of challenges his family did. Those struggles aren’t all just distant memories, either—in the middle of his first term, as he was pushing to pass affordable-housing legislation, he ran into his own difficulties finding an apartment he could afford to rent. Even as someone with a decent salary who was willing to share with roommates, he often found himself competing with upwards of 50 applicants for a single unit in an apartment search process he describes as “horrific.”

“I will do whatever needs to be done. I just don’t want to waste my life.”

“The way that I think about politics is by asking: What are the most expensive things for people [that I can take on as a city councilor]?” he says. “Number one is housing. Number two is child care. And number three is transit. So how can we make those better?”

Azeem has prioritized bills that address all of the above, plus climate policy, another issue he cares deeply about. In his first term, he wrote the bill that made Cambridge the first city in New England to abolish the requirement that new construction include a certain number of parking spaces, which can make housing prohibitively expensive to build. He also played a key role in pushing through amendments to an existing law that pave the way for taller buildings to be built for affordable housing, among other initiatives.

TOAN TRINH

“I don’t know that he always gets a ton of the credit, but he’s probably been one of the most, if not the most, prominent councilors on a lot of the housing issues that have been worked on over the last term,” says Cambridge city manager Yi-An Huang, an appointed official who works with the city council.

Azeem worked to update Cambridge’s Building Energy Use Disclosure Ordinance (BEUDO) so that it requires large nonresidential buildings, like those on MIT and Harvard’s campuses, to reach net zero emissions by 2035. He also helped pass the “specialized stretch energy code,” which requires all new construction and major renovations to rely entirely on electricity or be wired to transition to such a system in the future, and advocated for the buildout of 25 miles of protected bike lanes in the city. But while he’s pushing for more affordable housing, he’s also working to block a proposal that would ban lab development in Cambridge. Although its proponents say the ban is meant to preserve space for housing, he says a lot of developments include both lab space and housing, so it’s not one or the other. And he sees the research that goes on in the city’s labs as essential to its economic vibrancy.

He credits his success in part to being “really good at the boring technical stuff,” as he puts it. “I write my own policy and I go through all the details of the bills,” he says, noting that not every local politician is willing or able to do that. “There’s lots of stuff that people just don’t enjoy doing, and if you can find a way to enjoy it, then there’s lots of work to be done.”

Huang says Azeem’s tendency to pore over every detail makes him stand out, as do his “listening very well” and his collaborative approach. “He’s impressively in the weeds on policy,” he says. “He does his homework and understands the issues and really grapples with the nuance.”

A lifetime to go

Though young people are notorious for skipping local elections, Azeem sees his experience as a testament to the remarkable power of hyperlocal politics—and to why his peers shouldn’t sit them out. 

“[The city council] has a roughly $1.25 billion budget. Divide that by nine [council members], and it’s over $100 million per person. Each of us gets elected on 2,000-ish votes. So it’s almost $60,000 per vote. That’s your impact,” he says. “I lost by 100 votes in my first election and won by 200 in my second. If you had taken the person who came in 10th, and replaced them with me, more than 100 million dollars would have gone in a different direction than they did. That’s crazy to think about: 200 citizens decided where $100 million went.”

In his second term, Azeem hopes to influence where another $100 million–plus will go. He already has ideas for bills that he thinks will increase public transit options, help Cambridge fight climate change while adapting to its impact, make it easier for citizens to afford basic necessities like housing, and make streets safer for cyclists, pedestrians, and all citizens. 

He acknowledges that public service is not always the easiest choice to make as a young person. Despite his remarkable work ethic and ambition, Azeem is still a twentysomething who wants to enjoy his life. Going out with his friends for a night of dancing can be a bit odd when it ends with people approaching him and asking, “Are you my city council member?” He even got recognized once when he was using a dating app.

From Sharma’s perspective, the best way to understand Azeem’s seemingly boundless drive is through the lens of “immigrant psychology,” which Sharma in many ways shares. “When I was starting this new company, he wanted to join,” he recalls, “and I was like, ‘How will you do all of this? Starting a new company is demanding. You cannot do both that [and be on city council]. He said, ‘I will do whatever needs to be done. I just don’t want to waste my life.’” 

With reelection in the bag, and with a fresh influx of funding at Tandem, Azeem is finding himself in a more stable position than he’s been in for a long time, which is affording him new space to think about the future. He’s grateful that he’s been able to both work in local politics and be part of two successful startups, but he knows that down the line he may have to choose one path or the other.

He hasn’t decided yet which will win out. But what he does know for sure is that he wants to leave a legacy he can be proud of—and he’ll be happy to let his work speak for itself.

“A lot of people feel like they need to be in the spotlight because they feel like they’re the ‘main character,’” he says. “But five to 10 years from now, when I’m looking back, I just want to see that the things I did are still around and having a positive impact.”