In molecules, one chemist sees art

One Tuesday morning this past January, So Young Lee walked into a lab on the fourth floor of Building 18 and discovered that her equipment had exploded. It was a minor explosion—thankfully, no one was hurt—but the chemical she had painstakingly made had splattered all over the walls, the ceiling, and the broken shards of the glass tube that once contained it.

This incident would cost her time and precious product—and she didn’t have the time to lose. Lee, a fourth-year PhD student in chemical biology, was partway through a three-week, 11-step process to synthesize a chemical she helped design: azido-(Z,Z)-farnesyl phosphoryl-ß-D-­mannose, or AzFPM for short.

Meant to help combat the tuberculosis bacterium, which kills more people each year than any other pathogen, AzFPM is the first molecule to target a specific carbohydrate in the bacterium’s cell wall that helps it evade the immune system. The molecule is designed to sneak inside tuberculosis, potentially offering scientists and pharmaceutical companies a new tool for studying the pathogen at a time when it is steadily gaining antibacterial resistance. 

But making AzFPM isn’t easy. Producing just a few milligrams takes weeks of patiently heating, purifying, and combining chemicals at just the right ratios and timing. So when Lee saw that a vacuum suction machine with a hairline crack had sent her invention flying, she put on PPE, stood on a stool, and began mopping up every last drop with a paper towel. 

“I’ve wiped the floor before,” she jokes, “but I’ve never wiped the ceiling.”

After giving what she’d managed to salvage a good wash with methanol, two rounds of filtering, and a purification for good measure, she moved on to the next step, using just half the product she would have had sans explosion.

For Lee, designing molecules is a logical extension of her creative side. Growing up in South Korea, she was doing calligraphy at age 10 and choreographing K-pop dances at age 15. In her early 20s, she began oil painting, designing intricate nail art, and baking cakes and macarons for her friends. 

She first became intrigued with the idea of creating molecules while attending the selective Seoul Science High School. A teacher told her class about synthetic organic chemistry, a field focused on designing novel, complex compounds, and Lee was hooked. “He was just talking about the beauty of designing molecules and ways to synthesize them,” she says. “That really caught my attention.”

This new interest led Lee across the world, to Stanford University. There she spent her undergrad years balancing difficult coursework and long hours synthesizing analogues of HIV drugs in an organic chemistry lab with waking up at 4:30 a.m. to film dance videos with her school’s K-pop group (a hobby through which she would meet her husband). In her sparse spare time, she learned new languages, becoming proficient in Italian and Mandarin on top of being fluent in Korean and English.

“I like to think of [organic chemistry] as a language,” Lee says. If you rely on memorization, “you know all the words and grammar, seemingly, but you can’t speak the language.” In other words, though she knows a vocabulary of chemicals and the “grammar” of how they react, it still took her time and practice to put everything together to form new molecules.  

In 2020, when she came to MIT for graduate school, Lee spent a virtual lab rotation with Laura Kiessling ’83, a chemist who helped pioneer the field of chemical biology. Unlike biochemistry, which is the study of the chemistry behind biological systems, chemical biology involves applying chemical tools to probe and manipulate biological systems, Lee explains. 

GRETCHEN ERTL

Chemistry department students and advisors rank each other in a matching process to determine which labs students join. Lee was thrilled to match into Kiessling’s lab, her top choice. Beyond being drawn to the creative possibilities of the field, she was also excited to be part of a lab made up mostly of women and people of color. 

When Kiessling recalls the matchmaking process, she says that Lee had an impressive synthetic chemistry background as well as an interest in working on biological systems. More than that, Kiessling was looking for what she calls “open-minded people willing to try crazy things.”

In her lab, everyone studies glycans—chains of sugar molecules that coat the outside of all living cells. Glycans are one of the main research subjects for scientists studying Mycobacterium tuberculosis, the tuberculosis-causing pathogen, which lives in a quarter of the global population. Its thick, glycan-filled cell wall dampens the body’s usual immune response, allowing the bacterium to go undetected. As a result, people can live years without knowing they’re infected—until tuberculosis launches a devastating attack on the body. The disease causes as many as 1.5 million deaths per year.

Today, most patients are given a “cocktail” of drugs targeting different aspects of the bacterium. But it’s becoming increasingly resistant to existing antibiotics, and designing new drugs is a public health priority. Lee’s work targeting M. tuberculosis’s distinct cell wall could be one key avenue to finding an effective treatment. 

When Lee sets to work producing her molecule, she moves around the lab swiftly and decisively—pouring liquids into giant beakers, pulling out a flame torch to evaporate excess moisture that threatens her reactions, and taking measurements with an assortment of the lab’s precisely calibrated instruments. She is following steps that she devised three years ago, when she started trying to figure out how to alter an existing tuberculosis-­targeting chemical so that it could breach cell walls like a Trojan horse and reveal details about the sugars within. M. tuberculosis absorbs different kinds of sugars for different purposes. Lee wanted to zero in specifically on mannose-containing glycans, which the bacterium uses to build its cell wall. If Lee could see how it incorporates those glycans into its structure, that could help researchers develop new drugs that disrupt the building process and thus kill the cell. But Lee needed to hit a sweet spot when designing her molecule. It had to be complex enough to fool the tuberculosis bacterium into incorporating it just as it would incorporate mannose-containing glycans, yet simple enough to be made repeatedly in the lab. If the synthetic glycan were too generic, tuberculosis would use it for multiple functions, making it impossible to target the cell-wall-building process she’s studying.

Designing the synthetic route to producing the molecule took a year of troubleshooting—what Lee calls “part of the art.” After much trial and error, she figured out how to optimize the synthesis, running multiple stages at once since some take minutes and others last days. Lee estimates that she’s done the full synthesis around 30 times.

The final tuberculosis-targeting chemical, AzFPM, consists of synthetic sugars mimicking mannose-containing glycans. It’s so close in structure to these glycans that the bacterium incorporates it into the cell wall without noticing. 

Lee works with model organisms that are much less dangerous than M. tuberculosis, including M. smegmatis, which is genetically similar to the real pathogen, as well as C. glutamicum, a rod-shaped bacterium that helps with visualization. Though she found success with her C. glutamicum model, she relied on a colleague in the lab who is specifically trained to work with biosafety hazards for testing it in M. tuberculosis. 

To know if the molecule worked, Lee and her colleague had to track how M. tuberculosis used AzFPM. The molecule has a chemical handle, upon which Lee used a process called click chemistry (which won its inventors a Nobel Prize in 2022) to attach other molecules that fluoresce under certain lights. When she saw that the bacteria treated with her molecule glowed more than the nontreated bacteria, she knew that her molecule had successfully made its way into the cell wall. 

COURTESY OF SO YOUNG LEE

Lee and her collaborators are the first to track and photograph mannose-containing glycans in the tuberculosis cell wall. It’s a meaningful achievement: Visualizing how the bacterium uses such glycans might lead to new drugs that target and, ideally, dismantle those mechanisms, harming the pathogen and helping the patient.

Visualizing specific glycans in the tuberculosis cell wall has historically been difficult because, while amino acids and proteins have unique chemical structures, those of all sugars are nearly identical. Bacteria use more than 600 different kinds of sugars, and many differ not in their composition but in the 3D orientation of their atoms. 

“The molecules that she made and the way that she came up with the routes are really elegant,” says Kiessling, adding that existing antibiotics do not target mannose-­containing glycans: “They’re hard molecules to make.” 

As a synthetic chemist, Lee says, her job isn’t just to study what her new molecule reveals; it’s also to make enough of it for others to use in biological studies (at least one other MIT lab is already interested). Since publishing her results last year in the Journal of the American Chemical Society, Lee has focused on scaling up production from about 5 milligrams to 50—a 20th the weight of a dollar bill—in each synthesis cycle. 

“Synthesis fails constantly,” says Leah Pauline Weisburn, Lee’s former roommate and an MIT graduate student in theoretical chemistry. “It’s a lot of trial and error, and you just have to be resilient.”

Resilience is a common thread for Lee, who’s had to conduct some of her hardest syntheses while recovering from surgery following a hiking injury last year. It was also a theme in her work as MIT’s Women+ in Chemistry mentorship and outreach chair, a position she took on in addition to mentoring students from underrepresented backgrounds in science as part of the MIT Summer Research Program in 2022 and 2023.

GRETCHEN ERTL

Much of Lee’s passion for mentoring comes from her own challenging experiences. Early in college, she joined a lab where she felt she got inadequate guidance and support, which limited her ability to learn and ask questions. Worse, she didn’t realize there were people in the lab she could turn to for help. Eventually, she worked up the courage to switch labs and found a new community with guiding figures who had created an environment where she could not only learn but thrive. Now, Lee encourages her mentees to lean on departmental resources, other students in the lab, and her. 

“I try to find that balance between holding their hand but also letting them grow as an independent researcher,” she says. She has found that sharing her own experiences builds trust and camaraderie between herself and her mentees.

When giving talks to K–12 girls about chemistry, Lee makes sure to share her passion for art as well as science. She also emphasizes that “people that look like you and like the things that you do can also be scientists.”

Her attitude has impressed Kiessling, who recalls an organic chemistry retreat where Lee mentioned her love of nail art when asked to share a fun personal fact. “A few years ago, people wouldn’t want to admit that they cared about their appearance, much less their nails,” says Kiessling, who points out that organic chemistry is a historically male-dominated field. To her, Lee’s pride in her hobbies doesn’t just reveal her artistic side but also signals a shift toward more inclusivity in chemistry—a shift that she says strengthens the science being done.

Today, Lee is looking ahead to her dissertation. While she’s not sure whether she’ll land in academia, the pharmaceutical industry, or biotechnology after MIT, she knows her creativity will lead her in a direction where she can continue to grow.

“There’s an art to organic chemistry,” she says, “and that’s why I still do it.” 

Not just another band from Boston

In 1976, Tom Scholz ’69, SM ’70, was a 29-year-old product design engineer working at Polaroid on audio electronics and tape-recording technology, with 11 patents under his belt. But few colleagues knew what Scholz did after hours, why he often came in late, or why he was, in his own words, “a horrible employee.” 

For five years, Scholz had been painstakingly crafting music and lyrics, and perfecting phenomenally complex sound production, in the makeshift basement recording studio at his apartment in Watertown, Massachusetts—playing all his own instruments and mixing them on an analog 12-track recorder until they sounded as natural as a band that had played together for years. He got a friend, local musician Brad Delp, to record the lead vocals, mixing that in too. After finally picking up a contract with CBS’s Epic Records, he recruited some more friends from the Boston music scene to be the “faces” for an album with the working title Boston. When it came time to choose a name for the band, someone at the studio suggested using the same one. Having grown up in Toledo tuning in to Boston’s WBZ radio at night to hear British rock bands, Scholz readily agreed. 

COURTESY OF TOM SCHOLZ

“Honestly, I thought the recording I made in 1976 was going to be forgotten by the beginning of 1977,” he says. He was just hoping to get the song on the radio so he could get gigs in local clubs with a song people recognized. “I actually didn’t realize there was anything serious happening with my album until I was working in my back room [at Polaroid]—I had a secret back room, sort of like a boiler room, in the bowels of the building in Tech Square—and somebody comes running and says, ‘Hey! Your song’s playing in the drafting department!’” he recalls. He raced off to hear it but only caught the tail end. And that kept happening until finally, several months after “More Than a Feeling” hit the Top 10, he heard it all the way through on the radio.Still, Scholz didn’t quit his day job until Boston became a national arena headliner. 

Donald Thomas Scholz, a teenage fan of model airplanes, junker cars, basketball, and classical music, matriculated at MIT in 1965 to study mechanical engineering. Competition was brutal, he understood: “When I showed up for my freshman orientation, they sat us all in a large assembly area and put up a chart showing everyone’s SAT scores … I thought, ‘Now I’m in trouble.’” Scholz was so sure he’d flunk out that by the end of his first semester he’d already applied to transfer—but then he discovered he’d gotten a 4.8 average and decided to stay. In fact, he performed so well that MIT offered him a scholarship for a one-year master’s in mechanical engineering. His thesis project—a pair of simple A-frame hoists that made it possible to assemble prefabricated homes without a crane—led to his first patent, in 1972.

“The things I was exposed to at MIT were the basis for absolutely everything,” he says. “I use things I learned at MIT in the engineering department every day of my life—numerous times, every day.” MIT’s encouragement of blue-sky thinking would also stick with him. “It made me a little less fearful about looking like a fool when I tried new things because some of them aren’t gonna work,” he says. “I learned how to learn when I went to MIT, and I tried not to stop.”

Scholz didn’t pick up a guitar until he was 21, after getting hooked on bands like the Kinks and the Yardbirds. He dove into learning to play and soon became fascinated by what analog processors and amplifiers could do to the sound. As an MIT junior, he used an electric piano to compose an instrumental piece that eventually became the song “Foreplay” on Boston’s debut album. At the time, he was living in a fourth-floor Allston apartment: “I had had enough [understanding] of dynamics and so forth to understand how sound can transfer through a wood floor. The three nurses that lived below us were extremely patient with me because I usually wrote between 12 and two in the morning, and every time I pounded on those keys they felt it through the ceiling—and never complained. I think they felt sorry for me because I had to go to MIT.”

“Somehow I had to make those two things coexist—you know, being a positive influence and making some awesome music that people would think was kick-ass rock and roll.”

In the six years between his master’s and the release of Boston, Scholz built and deployed increasingly complex homebrew gadgets to create the otherworldly music he heard in his head. His favorite musical device was what he named the “hyperspace pedal.” “You can play a note with vibrato forever,” is how he describes its effect. “You can make a chord go up and down by several octaves. More importantly, you can make sounds that NASA would be scared of from a rocket ship. And I used that to my heart’s delight recording all of the Boston albums.” 

At Polaroid, Scholz’s primary responsibility was creating audio tape for the Polavision instant video system. Although that ended up being sold without audio, his work was instrumental in helping him develop the musical devices that gave Boston its singular sound. During that period, Scholz says, Polaroid “was almost like an extension of MIT—it had the same sort of mindset,” which gave him the freedom to build and experiment. Nearly all his Polaroid patents involved audio recording and reproduction.

In 1977, Scholz repaired the 16×4 channel studio mixer he’d used to lay down all the instrument tracks for Boston’s debut album. A year later, he mixed their second album on an Auditronics 501 26×4 console.

Scholz’s nights were for producing music. As a neophyte but increasingly adept guitarist, he began renting time at expensive recording studios. When recording between midnight and 8:00 a.m. above a bar an hour’s drive from home became untenable, Scholz decided to build his “really awful but workable” basement studio in Watertown (where, at 6 foot 5, he had to duck to avoid hitting his head on the way down). “Without saying too much to the landlord … I built a couple of temporary walls, and used an awful lot of carpeting and sound-absorbing materials that I could scrounge up,” he remembers. “Because this was done on, of course, an extremely low budget. And I managed to keep the noise level down enough that I could record.”

That volume control took some of his MIT-nurtured ingenuity. Scholz had to record his multilayered guitar tracks “at very high amplifier output” to get the sound he wanted. “A hundred watts through the speakers that worked with that amp were just incredibly loud—not something you could use in the basement of a house, not even in a house, because people down the street and in the neighborhood would be complaining about it. I had to find a way to decrease the output of the amp without changing the sound appreciably.” To this end, two of his personal patents—for “Constant Volume Distortion Control” and the physical unit in which the distortion control was housed—became the basis for what he called the Power Soak attenuator, the first product sold by his company, Scholz Research & Design. 

Executives at Epic Records were not enthusiastic about marketing a record that had been produced and recorded in a basement. Scholz and his “just another band out of Boston” flew to LA to record the vocals. Then Scholz went home to Watertown and, at the Epic producer’s request, re-recorded most of the album—“in exactly the same place as the demo they didn’t want to use, with exactly the same equipment, as close as I could to the original performance,” he says. “And that’s what they decided was great, and ready to be released.” Boston went on to become one of the best-selling debut albums of all time. 

Boston last toured in 2017 and has sold more than 31 million records worldwide. Today, Scholz’s home studio lies fallow—not for lack of inspiration, but because it remains resolutely analog, and “unfortunately there’s almost no one left locally who can maintain or repair analog studio equipment.”

But he is still busy and engaged. He and his wife, Kim, operate the DTS Charitable Foundation, which he founded in 1987 to promote a “vegetarian lifestyle, and prevention of cruelty and suffering to animals both nonhuman and human” (he has been a vegetarian for decades). Knee injuries sidelined him from basketball a few years ago, but he does freestyle figure skating and plays “extreme croquet,” which is typically played on challenging terrain without the usual out-of-bounds rules. He has a pilot’s license, and one of his current passions is designing high-performance radio-­controlled airplanes. “I love it,” he says. He is mourning the loss of the “scary-fast red delta-wing airplane” that he built in 1972, flew for 52 years, and considers his favorite invention: “Unfortunately, it had an in-flight breakup earlier this year and was destroyed. I was quite crushed by that. So was the airplane, by the way.”

Scholz says he and Kim have slowly turned their house into a workshop and lab. “There is no ‘house,’” he says. “When we have someone coming over for dinner, we actually have to clear out space to have a table that we can all sit at together.” (A proclivity for making things runs in the family; his son, Jeremy Scholz ’05, majored in mechanical engineering at MIT.) Scholz does interviews in “what used to be the electronics area for troubleshooting and fixing all this stuff in my studio,” he says. “It’s become a drafting area and a radio-controlled-aircraft fabrication/assembly area, and I have a small shop in what was the furnace room.”

He still hopes to get his studio back up and running, “because I am still writing music, believe it or not, in what’s left of my brain,” he says. “And it’s very frustrating not to be able to go in and make the recording of what I hear.”

Scholz marvels that classical composers could hear everything in their heads. “You listen to Vivaldi or Bach, and you think, ‘How did he know that those violins were going to work together when they all came together at the same time?’ He could only play one,” he says. “Whereas I always had to record things, listen to them together, and then go back and … ‘Well, that was the wrong bass line! I’ll try a different one,’ and so on.”

He initially came up with this method of layering different recordings together to please himself. “When I first started doing this, I was a kid in my 20s—well, late 20s—and I was just trying to put some music down that I thought sounded good. I actually didn’t believe that anyone else would think it sounded great,” he says. When it took off commercially, he felt compelled to become a positive role model as well. “Somehow I had to make those two things coexist—you know, being a positive influence and making some awesome music that people would think was kick-ass rock and roll.” 

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“After the first album, I was suddenly placed in a position where I was a figure that people were going to emulate. Kids listened to this music,” he says. “I felt this enormous weight, that everything that I did and everything that I said and anything I put on an album was going to have a possible effect on someone.” 

While other rockers were cultivating wild personas, he focused on the connection between self-improvement, higher education, and Boston’s music and tried “to encourage people to do things that I thought were a good step for mankind,” he says. “So when someone 50 years later comes and says, ‘Oh, this song really helped me get through,’ it means the world to me.”

Scholz has always been true to himself and to his music, even in the days when he was being rejected by one record label after another. “Having failed miserably,” he says, “I thought, ‘You know what? I’m going to make one more demo, and it’s going to be just exactly the way I see it, and the way I want to hear it, and I’m going to play every single part.’ And that worked, oddly enough. It’s been a wild ride.” 

How a butterfly’s scales are born

A butterfly’s wing is covered in hundreds of thousands of tiny scales, like miniature shingles on a paper-thin roof. A single scale is as small as a speck of dust yet surprisingly complex, with a corrugated surface that helps wick away water, manage heat, and reflect light to give a butterfly its signature shimmer.

MIT researchers have now captured the moments when an individual scale begins to develop this ridged pattern. The researchers used advanced imaging techniques to observe the microscopic features on a developing wing as a painted lady butterfly emerged in its chrysalis.

COURTESY OF THE RESEARCHERS

Using a special microscopic technique to peer through an opening they created in the chrysalis itself, the team continuously imaged individual scales as they grew out from the wing’s membrane during a crucial time window in the butterfly’s development. These images reveal for the first time how a scale’s initially smooth surface begins to wrinkle to form microscopic, parallel undulations like the ridges in corduroy. The ripple-like structures eventually grow into more finely patterned ridges, which make many functions of the adult wing scales possible.

The transition to a corrugated surface is likely a result of “buckling”—a mechanical process by which a material bows in on itself as it is subjected to compressive forces or constrained within a confined space. In this case, as they confirmed with the help of a theoretical model describing the general mechanics of buckling, actin bundles—long filaments that run under a growing membrane and support the scale as it takes shape—pin the membrane in place like ropes around an inflating hot-air balloon.

“Buckling is an instability, something that we usually don’t want to happen as engineers,” says Mathias Kolle, an associate professor of mechanical engineering and coauthor of a study on the work. “But in this context, the organism uses buckling to initiate the growth of these intricate, functional structures.”

The team is working to visualize more stages of butterfly wing growth that could inspire advanced functional materials in the future.

“These materials would exhibit tailored optical, thermal, chemical, and mechanical properties for textiles, building surfaces, vehicles—really, for generally any surface that needs to exhibit characteristics that depend on its micro- and nanoscale structure,” Kolle says.

“We want to learn from nature, not only how these materials function, but also how they’re formed,” says Anthony McDougal, SM ’15, PhD ’22, an MIT postdoc and another coauthor. “If you want to, for instance, make a wrinkled surface, which is useful for a variety of applications, this gives you two really easy knobs to tune to tailor how those surfaces are wrinkled. You could either change the spacing of where that material is pinned, or you could change the amount of material that you grow between the pinned sections. And we saw that the butterfly is using both of these strategies.”

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.