Carolyn R. Bertozzi was shocked — and groggy — when she received the call from the Nobel Prize committee shortly before 2 a.m..
The Lexington native, Harvard University graduate, and daughter of an MIT professor was among three winners of the prize in chemistry awarded Wednesday for methods that enable scientists to unravel the inner workings of cells and led to a breakthrough discovery about the ability of cancers to evade the body’s immune defenses.
“I was asleep and the phone rang, so I had to shake it off and try and figure out what was going on. And then it seemed a bit surreal. You know, I was thinking it was some strange hallucination or dream or something,” Bertozzi said from her home in Palo Alto, Calif., where she is a professor at Stanford University. “But when I finally realized that, yes, I really was on the phone with the chair of the Nobel Committee and his colleagues and they were congratulating me, I just went into shock. I think I might have stopped breathing for a minute.”
Bertozzi, Morten Meldal from the University of Copenhagen in Denmark, and K. Barry Sharpless of Scripps Research in California were awarded equal shares of the prize. Meldal and Sharpless were recognized for their creation of a widely used technique called “click chemistry,” which allows scientists to efficiently, quickly, and selectively connect two chemical building blocks to create more complex molecules, including medicines.
Bertozzi, 55, was honored for taking click chemistry “to a new dimension” by discovering how to use it in living cells. The technique enables scientists to precisely manipulate cells with chemical tools to learn how they behave, either when healthy or diseased.
Laura Kiessling, a professor of chemistry at MIT, said Bertozzi’s work provided “a powerful new way” to monitor and isolate molecules from cells in ways that weren’t possible before. “It changed the way people think about doing science,” she said. “There have been further advances, but they all build on her work.”
Bertozzi pioneered the technique to better understand the importance of complex sugar molecules called glycans. Scientists had long suspected that glycans may be involved in cancer, but lacked good tools for studying their role in the disease.
Her first demonstration of click chemistry in cells, published in 2004, allowed Bertozzi to begin monitoring these glycans. That work led to a seminal paper in 2014 where she showed that many cancer cells decorate themselves with a particular kind of glycan that helps them suppress and evade the immune system’s sentinels that would normally attack a growing tumor.
“It’s really catalyzed a whole new field within medicine,” said Dr. Jim Broderick, chief executive of Palleon Pharmaceuticals, a Waltham-based biotech company that he cofounded with Bertozzi in 2016, based on her discovery. She remains a scientific adviser to the company.
Palleon is wrapping up an early clinical trial of a drug designed to make tumors more vulnerable to the immune system by unmasking their glycan disguise.
Another company, San Francisco-based Shasqi, to which Bertozzi is an adviser, is beginning an intermediate clinical trial that uses click chemistry directly in the body to keep the chemotherapy drug doxorubicin inactivated until it makes contact with a tumor. Chief executive and founder José M. Mejía Oneto said the approach allows the company to administer higher doses of chemo without the usual side effects.
“We are just scraping the surface of what can be done with this technology.”
Even though click chemistry is just starting to lead to therapeutic applications, scientists emphasize that Bertozzi’s contributions to fundamental science shouldn’t be minimized. Her work formed the cornerstone of a larger field called “bioorthogonal chemistry,” a term she coined to reflect chemical reactions performed inside of living organisms that don’t disturb their normal functions.
“So many scientists use these reactions to monitor things in cells,” even by people who aren’t chemists, Kiessling said. “It’s just become a tool that people can use broadly in many different fields.”
Bertozzi may live on the West Coast, but her heart remains with her hometown teams. She describes herself as a “rabid” Red Sox and Celtics fan and fondly recalls the time she had her photo taken with Larry Bird when he made an appearance at the Harvard Coop in the 1980s.
“Bet you Larry didn’t realize he was getting his picture taken with a future Nobel laureate,” she said with a chuckle. “My mom was such a huge fan. She dragged me and my sister there; we stood in line for like an hour.”
They took home an autographed poster of Bird that her mother “hung in the middle of her living room like it was a piece of art,” she recalled.
Bertozzi graduated from Harvard University in 1988 and during her college days played keyboards in a band with Tom Morello called Bored of Education. Morello later cofounded Rage Against the Machine.
“That might be the one thing that I’m best known for,” she said. “He recruited me into his band and we played college parties at Harvard and around the Boston area, and then he went off to become a superstar. And I wasn’t talented the way he was. So I think I made the right choice to go to grad school.”
Morello gave a shout-out to Bertozzi on Twitter on Wednesday.
Every time autumn rolls around, current and former researchers in Bertozzi’s lab have wondered if it would finally be the year that their beloved mentor won the Nobel Prize.
Mireille Kamariza, who was a graduate student in Bertozzi’s lab from 2012 to 2019, said that after her initial shock at hearing the news, her first thought was “it’s about time.”
As a young graduate student, Kamariza recalls a 30-minute meeting with Bertozzi turning into a three-hour discussion. “I felt like my ideas mattered, she has this uncanny ability to draw out the talents out of each person.”
Bertozzi, the daughter of MIT physics professor William Bertozzi, was “naturally enthralled by science,” according to a biography posted when she won the Lemelson-MIT prize in 2010. Her mother was the late Norma Bertozzi, a Davis scholar who graduated cum laude with a degree in French from Wellesley College in 1998.
Her father “encouraged her and her sisters to explore technological tools from his projects and demonstrations,” her biography states.
The Nobel Prize is a capstone to Bertozzi’s dozens of research and teaching accolades. She has received the prestigious MacArthur Fellowship, known as the “genius grant,” and in 2010 became the first woman to receive the Lemelson-MIT Prize, a top award for invention. This year, she was one of three recipients of the Wolf Prize in Chemistry, an international award “for achievements in the interest of mankind and friendly relations amongst peoples,” and will also receive the Wistar Institute’s 2022 Helen Dean King award, which recognizes “outstanding women in biomedical research.”
As news of her Nobel spread, Bertozzi quickly became a point of local pride in Lexington, where she graduated from Lexington High School in 1984. Her honor was noted on Twitter by Suzie Barry, a fellow 1984 graduate and member of the town’s select board.
Sharpless is a 1963 graduate of Dartmouth College and has taught at both Harvard and MIT. He was also awarded the 2001 Nobel for Chemistry, one of only five people to win the award twice in their lifetime.
John Ellement and Shannon Larson of the Globe staff contributed to this story.
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