Barbara Low: Pioneer in X-Ray Crystallography

Columbia’s Barbara W. Low, DPhil, was part of an early wave of women who gained prominence in the field of X-ray crystallography, a technique that can reveal the 3-dimensional shape of a molecule by analyzing how X-rays bend around and bounce off the molecule in its crystallized form.

She was the last of a small cadre of women who rose to eminent positions in the male-dominated world of mid-20th century biomedical science, establishing a culture of inclusion that continues to shape other scientists' careers.

Low, professor emeritus of biochemistry & molecular biophysics at Columbia University Vagelos College of Physicians and Surgeons, died Jan. 10 at age 98, marking the end of both an extraordinary life and an extraordinary era in the field of structural biology. 

By a historical accident, the field of X-ray crystallography became a bastion of female empowerment in the early 1940s. "People think there are lots of women in crystallography, but there are not,” says Helen Berman, PhD, Board of Governors Distinguished Professor Emerita of Chemistry and Chemical Biology at Rutgers University. “What is different is that some of the earliest pioneers in crystallography were women." 

British scientist Dorothy Crowfoot Hodgkin led the charge. Trained as a crystallographer, Hodgkin was excluded from teaching men at Oxford University and relegated to Somerville College, the university's women's school. "So, she trained a whole slew of women crystallographers, who then trained other women," says Berman.

Low was one of Hodgkin's star students, graduating Somerville College with a B.A. in 1943, then pursuing graduate work at Oxford with Hodgkin as her adviser. The pair solved the structure of penicillin during World War II. 

That work "was a tour de force,” according to Columbia structural biologist Wayne Hendrickson, PhD, University Professor. “It was a huge undertaking at that time, and Low and Hodgkin pushed the technology of the day to new limits.” 

Penicillin is a small molecule by today’s standards, but in 1945 when the structure was revealed, it was the largest molecule that had been solved with X-ray crystallography. The knowledge of what the penicillin molecule looked like allowed chemists to synthesize new derivatives, sparking the creation of better antibiotics that were able to treat a wider range of infections.

Because the work was part of the war effort, much of it remained classified for decades. The penicillin structure was one of the accomplishments cited in Hodgkin's 1964 Nobel Prize.

After Oxford, Low moved to the United States, eventually settling at Columbia University Vagelos College of Physicians and Surgeons in 1956 as an associate professor. There, she cemented her reputation as both an innovative researcher and a demanding but dedicated mentor. 

Berman joined Low's lab as an undergraduate in the summer of 1962. "She said to me that my job was to screen one crystal every day, so I assumed that was a reasonable request and I did it," says Berman. "I later found out when I became a crystallographer that that was a pretty challenging thing to ask a kid to do."

In her Columbia lab, Low and her team made a series of major advances, ranging from early work on the structure of insulin to pioneering studies on neurotoxins. 

Low was also the discoverer in 1952 of a fundamental protein structural element called the pi helix. "This is a protein conformation well known to structural biologists. Originally it was thought to occur only rarely in proteins, but it is now known as a quite commonplace feature within conventional alpha helices,” Hendrickson says. “It's something that Linus Pauling, with whom she'd worked earlier, had missed in his famous discovery of the alpha helix.”

Low's high standards and patient mentoring shaped the careers of many young scientists. "She made a huge impression on me at that time, so much so that I decided that I wanted to do crystallography for my life's work," says Berman. 

Low's influence also extended across the institution. "On the University's affirmative action committee, she was very forceful in wanting Columbia to live up to its ideals of having a diverse faculty and workforce," says Arthur Palmer, PhD, professor of biochemistry & molecular biophysics.

Indeed, colleagues say Low would want to be remembered not only for her scientific accomplishments, but also for her dedication to diversity. "She was leading a charge that really improved the situation for women in science, and she suffered a lot of bruises for it," says Philip Bourne, PhD, professor and Stephenson Chair of Data Science in the Department of Biomedical Engineering at the University of Virginia and a former postdoctoral fellow in Low's lab.

Her seriousness was balanced by acts of immense generosity. Bourne recalls showing up in New York City for his postdoctoral fellowship: "When I first went there I had nowhere to stay, and she put me up in her basement." Berman, whose apprenticeship to Low grew into a lifelong friendship, also remembers her warmly: "For me as a young woman thinking I wanted to be a scientist, it was really great having her as a mentor. I'll always be grateful for that.”