Remembering Barbara Low

Barbara Low in California, 1947. Credit: Low estate.

Barbara Low, a former research fellow for Linus Pauling and an esteemed scientist, died earlier this year at the age of 98. Low spent most of her career as a researcher and professor at Columbia University’s Vageos College of Physicians and Surgeons. She is perhaps best known for her work with protein structures, particularly her work on the structure of penicillin and her discovery of the pi-helix.

Barbara Wharton Rogers was born in Lancaster, England on March 23, 1920 (she married in 1950 and changed her name thereafter). After receiving her B.A. from Somerville College – an Oxford women’s college – in 1942, she went on to earn an M.A. and D. Phil. from Oxford University. As a component of her education, Low learned the techniques of x-ray crystallography, a field within the chemical sciences that was emerging for women. A major reason for this trend was the fact that one of the leading crystallographers of the era, Oxford professor Dorothy Crowfoot Hodgkin, was banned from teaching to men, so instead she taught crystallography to women at Somerville.

Low was one of Hodgkin’s star pupils, and after Low received her B.A. in chemistry, Hodgkin became Low’s advisor for her graduate studies. It was during these years that Hodgkin and Low determined the structure of penicillin using x-ray crystallography. In 1964, Hodgkin was awarded the Nobel Prize in chemistry for her work determining the structures of various important biochemical substances, penicillin certainly among them.

Molecular model of Penicillin by Dorothy Hodgkin, c.1945. Credit: Luke Hodgkin

While she was working on her doctorate, Low spent a year at the California Institute of Technology as a research fellow, supervised by Linus Pauling. This was the start of what would become a fruitful and mutual working relationship between Pauling and Low. After leaving Caltech and graduating from Oxford, Low took a position as a research associate, and later as assistant professor of physical chemistry, at Harvard University. As her career advanced, Low kept in touch with Pauling and this connection proved beneficial on more than one occasion.

In the early 1950s, Low began to apply x-ray crystallographic techniques to a study of the structure of insulin. She did so during a period of much debate within the scientific community about the structure of various proteins. Pauling famously solved a piece of this puzzle in April 1951 when he published, “The structure of proteins: Two hydrogen-bonded helical configurations of the polypeptide chain” with collaborators Robert Corey and Herman Branson. In this paper, Pauling described for the first time the alpha helical structure of many proteins, a watershed moment that ushered in a whole new era of understanding across the discipline.

Barbara Low was, of course, also working on the structure of proteins, and she became particularly inspired to investigate the connection between structure and function after attending a lecture that Pauling gave at the Massachusetts Institute of Technology in March 1951. Low believed, as did Pauling, that the configuration of the folding of the protein was of more importance to its function than was the molecular make-up itself. Determined to apply this belief to her work on the structure of insulin, Low wrote several letters to Pauling asking him to verify the bond angle distances for the proteins about which he had lectured. Pauling gladly supplied Low with the requested data, even noting that he had double-checked the calculations as he was writing her back. Pauling also helped Low to secure scientific models for the structures that he had described.

Pi-helix diagram published by Low and Grenville-Wells, 1953

These data and models proved vital to one of Low’s most famous discoveries: the pi-helix. Like the alpha-helix, the pi-helix is a type of structure found in some proteins, though one that was not published by Pauling as part of his alpha-helix investigations. This failure may have been due to the pi-helix’ small size, which at the time of its discovery led some researchers to believe it to be an infrequent and rare structure. More modern day findings indicate however that the pi-helix is much more common than previously thought; present in about 15% of protein structures all told.

Low wrote about her discovery to Pauling shortly after the news was made public and received a mixed reply from her former mentor. At the beginning of his response, Pauling suggested that the pi-helix was most likely something that he “too ran across a while back” but acknowledged that Low’s structure was not “intermediate between the alpha helix and the gamma helix,” and thus both novel and genuine. The letter concludes with an admission from Pauling that his researchers may have “overlooked it” in their previous work.

Pauling’s hedging congratulations in this instance did not seem to negatively impact the duo’s relationship, and throughout their correspondence one intuits that the colleagues remained on friendly terms throughout the years. In many letters to Pauling, Low often concluded by giving her regards to Ava Helen. Low also developed a love for the comic Li’l Abner by way of Pauling, who had introduced her to the satirical strip at a dinner party in the early 1950s.

Pauling and Low were also, at times, involved in one another’s careers. When Pauling was denied a passport to travel to the Royal Society Meeting to attend the Protein Symposium in 1952, Low wrote to express her “shock” and to express how “shaken” she was that he had been treated this way. For his part, Pauling helped Low to secure grants and funding through multiple letters of support.

Pauling also provided assistance to Low as her research position at Harvard came to an end in June 1956 by putting her in contact with colleagues Detlev Bronk of Johns Hopkins University, John Kirkwood of Yale University, and DeWitt Stetten at the National Institute of Arthritis. While it is unclear how influential these contacts may have been in Low’s gaining her eventual position at Columbia, it is certainly worth noting that Stetten had recently left Columbia after having served there for nine years as an instructor of biochemistry.

However it came to pass, Low started at Columbia in 1956 as an assistant professor and was promoted to professor in 1966. She formally retired from Columbia in 1990, but stayed on as a lecturer until 2013. Like Pauling, Low was active both socially and politically, devoting significant time and energy to affirmative action activities at her institution. She passed away on January 10, 2019 at her home in the Bronx, New York.

David and Clara Shoemaker

David and Clara Shoemaker working in an x-ray laboratory at Oregon State University, 1983.

Husband and wife crystallographers David and Clara Shoemaker were, in many respects, an unlikely couple.

David Shoemaker was born on May 12, 1920 in the tiny town of Kooskia, Idaho. Clara Brink was born on June 20, 1921 in Rolde, Holland. Both moved through their primary studies in orderly fashion and progressed to undergraduate work in chemistry – David at Reed College in Portland, Oregon, Clara at the University of Leiden.

In 1942 David received his bachelor’s degree from Reed and moved directly to the California Institute of Technology. Working under Linus Pauling, David quickly established himself as a promising doctoral candidate. His research was initially divided between Pauling’s expansive program of scientific war work and, later, a series of crystallographic investigations. While in Pasadena, David determined the structure of sixteen molecules, most notable among them threonine, an amino acid.

Upon receiving his Ph. D. in 1947, David – with the assistance of Pauling – was subsequently named a Guggenheim fellow, studying at both Oxford and the Institute for Theoretical Physics in Copenhagen. Aged 27, he was among the youngest of his era to receive a Guggenheim Fellowship.

Group photo of participants at the Conference on Current Problems of Physics. Copenhagen, Denmark. September 1947. Niels Bohr sits in the front row, far left. David Shoemaker is seated in the second row, fourth from right.

Group photo of participants at the Conference on Current Problems of Physics. Copenhagen, Denmark. September 1947. Niels Bohr sits in the front row, far left. David Shoemaker is seated in the second row, fourth from right.

Clara’s path through graduate studies was somewhat less smooth. She completed her undergraduate work at the University of Leiden in 1941, shortly before the Nazi occupation of the Netherlands and the subsequent closing of the university. Despite the turbulence of World War II, Clara was able to commence her graduate studies through the University of Utrecht, though much of her coursework was self-taught, conducted in her parents’ home. Despite these handicaps, Clara completed her doctoral examinations on time, in 1946, after which point she assumed an assistantship at the University of Utrecht and learned the techniques of x-ray crystallography, commuting one day per week to Amsterdam to study under the renowned crystallographer Caroline MacGillavry.

The years immediately following the close of hostilities were fruitful ones for both David and Clara. Having returned home from his Guggenheim trip, David was named a Senior Research Fellow at Caltech, where he solved the difficult structure of DL-serine and began the research program that came to define much of his (and Clara’s) career – a broad series of investigations into the structures of complex transition-metal phases. In the meantime, Clara became a full-time crystallographer, first studying crystal structures of monovalent ions at the University of Leiden and later working for one year at Oxford, where she conducted research on the crystal structure of vitamin B12 under Dorothy Hodgkin, the 1964 Nobel laureate in Chemistry.

In 1951 David was hired away from Caltech by the Massachusetts Institute of Technology, where he began investigating zeolite structures as an Assistant Professor. Two years later, dissatisfied with the working environment at the University of Leiden, Clara took a one-year leave of absence to work on transition metals at M.I.T. Her laboratory in Cambridge was run by David Shoemaker.

In 1954 David renewed Clara’s leave of absence for an additional year and by 1955 it was clear that Clara would not be returning to Europe – on August 5th, the couple was married. Shortly thereafter Clara transferred to Harvard Medical School to work under the biochemist Barbara W. Low. One year later, Clara gave birth to the couple’s only son. While caring for the newborn Robert, Clara worked from home on the International Tables of Crystallography.

The Shoemakers enjoyed a productive tenure at M. I. T. – David was promoted to full professor, began a lengthy service on the U. S. National Committee for Crystallography (including a three-year term as President) and published widely, including a textbook titled Experiments in Physical Chemistry, which would eventually run through six editions.

In 1970 David was elected President of the American Crystallography Association. That same year, the Shoemakers relocated to Oregon State University, where David had been hired to chair the Department of Chemistry. In reaction to the university’s nepotism guidelines, Clara arranged to work as Research Associate under Dr. Ken Hedberg – like David Shoemaker, a former graduate student of Linus Pauling. The arrangement lasted for several years until the university’s rules were relaxed.

Model of the crystal structure and superstructure of the K Phase, Mn77Fe4Si19. Model built by Clara B. Shoemaker, David P. Shoemaker and Ted E. Hopkins.

During his tenure as department chair, David oversaw two major building projects – the construction of a new chemistry laboratory facility and the renovation of the chemistry offices and research building. Over that same period of time, Clara trained several graduate students in techniques of x-ray crystallography, publishing papers with many of her protégés. The couple retired in 1984, though they continued to conduct important work on transition metal phases as well as the controversial topic of quasicrystals.

The Shoemakers remained close friends with Linus Pauling, though they did dispute certain of Pauling’s claims about the nature of quasicrystals. In 1995 David Shoemaker, himself in fading health, spoke of his long association with Pauling at a memorial conference organized at Oregon State University. David’s comments detailing his recollection of the discovery of the alpha-helix caused something of a stir in the audience, as the provenance of the alpha-helix work has long been a matter of some dispute.

David Shoemaker on the Discovery of the Alpha Helix

Afterward, Shoemaker offered this clarification:

My memory may have been faulty in claiming to have seen Pauling actually taping his cardboard amide linkages together to form a helix, but Professor William Lipscomb, in a talk that preceded mine, showed a drawing in Pauling’s own hand of an alpha-helix rolled out flat, showing what points the polypeptide chain joined together in the helix. The drawing was titled ‘alpha helix. First drawn March 1948. Linus Pauling.’ My visit to Oxford was from January to March 1948.

David Shoemaker died of kidney failure on August 24, 1995, some six months after the Pauling memorial conference. His wife Clara, a close friend of our department, passed away on September 30, 2009. Over the course of their professional association, David and Clara published thirty-six scientific papers together.

The David and Clara Shoemaker Papers are just one of the many collections held in the OSU Libraries Special Collections.