Love at First Lab

Chemist Jacqueline Barton blazes a trail with innovative DNA research

By Photograph by Nancy Neil

In 2015, Jacqueline Barton ’74 became only the third woman to receive the Priestley Medal, the highest award given by the American Chemical Society. It was the capstone moment in a career that’s won her nearly every major prize in chemistry—a field long considered so male dominated that Barton never even considered the possibility of taking chemistry classes until she came to Barnard.

Barton grew up in New York City, where she attended the Riverdale Country School for Girls. “In those days, [girls] mostly took languages and arts classes, so I never took chemistry in high school,” she recalls. She did, however, take math classes—and excelled at them to such an extent that her teacher arranged for her to take calculus at the nearby boys’ school.

It was not until her time at Barnard that Barton was first exposed to the field that would become her life’s work. It was love at first lab. “I loved chemistry. I loved that it had the rigor and discipline of math, but at the same time the molecular world has beautiful colors and amazing three-dimensional architecture,” she says. Barton credits her Barnard professors, particularly Bernice Segal, then the chair of the chemistry department, with spurring her to work even harder. “[Segal] was just a very strong woman who could scare the heck out of you,” Barton recalls. “She had enormously high expectations—and you would rise to meet them.” After Barnard, Barton went on to get her PhD at Columbia. As a graduate student, she zeroed in on research—the chemistry of DNA—that helped inform her work over the next several decades.

How DNA is like a telephone wire

If you think of the DNA double helix as a kind of spiral staircase, Barton explains, then the DNA base pairs are the stair steps; they encode the information that makes you who you are. The nuclei of each of our cells are filled with 3 billion base pairs of information, and mutations or errors in those base pairs can cause serious problems. But damage to DNA is occurring all the time, whether through environmental exposure, personal habits, or just plain old aging. In order to deal with that damage, cells need a way to send out a kind of distress signal indicating that repair is needed—a kind of genetic work order, so to speak.

Barton was a professor at Columbia from 1983 to 1989; while there, she became interested in how DNA’s electrical properties were involved in that signaling process. “A stack of base pairs is somewhat like a stack of copper pennies, from a chemical standpoint,” she explains. “And you can pass a current through it, just as you’d be able to do with a stack of pennies.” With that in mind, Barton and her team made discrete DNA assemblies with probes attached at either end in order to observe current move through the helix. “We found that the electrons could flow over long molecular distances, but if any part of the stack was off, the electron flow would stop—just as it would in a stack of pennies if there was a misalignment that interrupted the connection,” Barton says. In other words, damage in any of the DNA base pairs would turn off the electron flow, serving as a sort of electrical signaling method for detecting damage or mismatches.

To put it another way, the DNA in our cells is a little bit like a telephone wire. “If two telephone repairmen can talk to one another through the line, they know it’s working,” Barton says. In our cells, if repair proteins can talk to each other across a particular region of DNA, then that section is functioning fine. If not, repairs are in order.

While Barton’s research has since won her many accolades and become widely accepted, in its early days it was considered controversial. Barton is grateful to those critics: “The skeptics pushed us to do more innovative experiments and to keep asking the next question. Even when people didn’t believe in us, which hurt a little bit, I always had confidence in our experiments. I knew that we just had to keep doing them.”

Barton and her team’s discoveries have the potential to make it easier to develop highly sensitive but affordable diagnostic tools to identify mutations, which can lead to conditions like cancer. “Some people have a predisposition to colon cancer, for example,” Barton explains. “That’s a result of mutations to their repair proteins. The next step is to see if we can design molecules that’ll help us fix that damage. This research is really helping us understand and address the source of cancerous transformation—and may also serve as a foundation for coming up with new therapeutics.” In 2001, Barton cofounded GeneOhm Sciences, which developed molecular diagnostic tests for detecting DNA mismatches. (In 2006, the company was acquired by BD Worldwide.)

A leader and a teacher

Even as Barton’s research was becoming widely recognized, she remained committed to teaching and mentoring students. After graduate school and a postdoc at Bell Laboratories and Yale, Barton taught at Hunter College and Columbia (where she was the first woman to receive tenure in the chemistry department), before moving across the country to join the faculty of the chemistry and chemical engineering division at the California Institute of Technology, where she is now the chair. Her husband, Peter Dervan, is also on the chemistry and chemical engineering faculty there. “The thing of which I’m most proud is that I’ve trained more than 25 women who are now in academic positions somewhere in the world, including Marisa Buzzeo ’01, assistant professor in Barnard’s chemistry department,” Barton says. “I care about that enormously—my graduate students are more important to me than any papers I write.”

“The skeptics pushed us to do more innovative experiments and to keep asking the next question. Even when people didn’t believe in us, which hurt a little bit, I always had confidence in our experiments. I knew that we just had to keep doing them.”

Barton has been recognized for her leadership and inspirational role within the field, as well as her groundbreaking research. Over the years she has been named a MacArthur Foundation fellow and was awarded a gold medal from the American Institute of Chemists. Barton was also the first woman to win several major honors, including the Alan T. Waterman Award from the National Science Foundation; the American Chemical Society Award in Pure Chemistry; and the Nichols Medal and Baekeland Medal of the American Chemical Society. “She combines path-breaking research with service to the chemical profession in many arenas,” Madeleine Jacobs, the executive director of the American Chemical Society, said when Barton won the Priestley Medal. “She has also been a superb role model, not just for young women but for all young scientists, in her ability to balance her professional and personal life.”

That ability to balance various aspects of her life is something that Barton is proud of as well. “My family is another very, very important thing in my life,” Barton says. Her own experience as an eminent scientist and devoted mother belies the often-repeated idea that women have to choose between career and family. “You absolutely can do both,” insists Barton. (Her daughter bucked the family trend by eschewing chemistry in favor of law, which she is studying at Yale, and her stepson is an MD, doing a fellowship in Seattle.)

In 2010, President Obama awarded Barton the National Medal of Science, the highest honor bestowed upon American scientists. Her husband had won the award three years earlier, and the pair of medals now sits on the family’s mantel. “When the president presented me with the award, he noted that we were perhaps the only married couple who both had [won the award], and how displaying them together might intimidate our houseguests,” she says with a laugh. (The family’s houseguests, often impressive scientists in their own right, haven’t seemed to have a problem.)

Barton advises young chemistry students—and students of all disciplines—to follow their passion. “Have fun!” she says. “Find the thing you love, and if it’s chemistry, enjoy it. Don’t be scared of it. Do it because you love it.” She sees plenty of opportunities for young chemistry students in today’s world, whether that means going into academics, biotechnology, industry, or government. “Chemistry is critically important,” she says. “It’s important in terms of the pharmaceuticals we take, the food we grow, the insulation in our homes, and so much else. We need bright young people to take us into the next generation of chemistry.”

Barton herself is living proof that taking the advice to follow your passion can lead to a rewarding life full of challenges and inspiration. “I have the best job in the world,” she says, a sense of wonder creeping into her voice. “I get to interact with these wonderful young people. I don’t have a boss. I think up these crazy experiments, and then people actually go and try them.” •

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