In Memoriam: PNAS Editor-in-Chief Nicholas R. Cozzarelli (1938–2006) hen Nicholas R. Cozzarelli possessed a sharp, analytical memory, became Editor-in-Chief of which perhaps explains why he initially the Proceedings of the Na- chose to study pre-law at Princeton. tional Academy of Sciences However, after some undergraduate ofW the United States of America (PNAS) research, he began falling in love with in 1995, he inherited a journal that in science, and he graduated magna cum many ways had remained unchanged laude in 1960 with a bachelor’s degree since its inception in 1914. Yet in just in biology. Afterward, he attended Yale over a decade, he had—through a com- University School of Medicine (New bination of visionary leadership and Haven, CT) but soon realized that, de- sheer force of will—transformed PNAS spite his talents, he did not want to be a and raised it to a higher level. That physician. After a year, he transferred to transformation can be seen throughout Harvard Medical School (Boston, MA) the journal, from cover to last page. to embark on a journey of research, Since 1995, PNAS has experienced a which began with his graduate studies in marked rise in the number of submis- the laboratory of E. C. C. Lin, examin- sions and published papers, an improve- ing the genes and pathways regulating ment in the quality and variety of Escherichia coli glycerol metabolism. published material, and the introduction After receiving his Ph.D. from Har- of an innovative hybrid open access vard in 1966, Cozzarelli moved to Stan- model. And through it all, Cozzarelli ford University (Stanford, CA), where orchestrated these changes by simply he conducted 2 years of postdoctoral being himself. ‘‘In his role of Editor-in- training under Nobel laureate Arthur Chief of PNAS, Nick exhibited the same Kornberg. At Stanford, Cozzarelli began Cozzarelli in his Berkeley laboratory during filming studying the complex beauty of DNA boundless energy, enthusiasm, dedica- for ‘‘porridge pulleys and Pi’’ produced by the tion, and uncompromising standards Mathematical Sciences Research Institute (Berke- synthesis, a process he would continue that characterized his own science,’’ says ley, CA). Photograph by George Paul Csicsery © to unravel throughout the rest of his Jack Halpern, Associate Editor of PNAS 2003. All rights reserved. academic career, first as a Professor of and Professor Emeritus of Chemistry at Biochemistry and Biophysics and Theo- the University of Chicago (Chicago). retical Biology at the University of Cozzarelli dedicated his career to the PNAS, for plucking it out of the halls Chicago, and then from 1982 on at the passionate pursuit of excellence, whether of the Academy and setting it squarely University of California, Berkeley. Un- in research, teaching, or service to the in front of the scientific community as raveling is perhaps an apt term, because scientific community. He spent 24 years a must-read publication,’’ says Diane a significant portion of Cozzarelli’s work as a professor at the University of Cali- Sullenberger, PNAS Executive Editor was aimed at understanding the struc- fornia, Berkeley, where he contributed since 1996. ture and mechanisms of gyrases and to- immensely to the understanding of how poisomerases, enzymes that control the Portrait of a Scientist proteins alter the topology of DNA. He coiling and knotting of DNA, to eluci- served as Chairman of the Molecular Much like the DNA he studied, Cozza- date how they influence the topology of Biology Department from 1986 until relli’s career followed a twisting and DNA to compact such an enormously 1989, Director of the Virus Laboratory turning path. He was born on March 26, long and tangled molecule into a man- from 1986 to 1990, and Director of the 1938, and was raised in Jersey City, NJ, ageable structure. Mathematics and Molecular Biology the son of Italian immigrants from the Using a combination of experimental Program from 1988 to 1996. Cozzarelli southern town of Castelnuovo di Conza. and mathematical approaches, Cozzarelli was elected to the National Academy of His father was a cobbler and his mother determined the conformations of super- Sciences in 1989, received the CIBA- edited telephone books. By the time he coiled and catenated DNA (1–3) and Geigy͞Drew Award in Biomedical Re- started kindergarten, his parents had highlighted the simple mechanism— search in 1990, became a fellow of drilled into him the belief that education passing the DNA through an enzyme- AAAS in 1999, and became a member was the key to success, Cozzarelli said bridged break—by which topoisomerase of the American Academy of Arts and in an interview for the Howard Hughes operated (4–6). He also discerned the Sciences in 2000. Medical Institute (HHMI) ‘‘Ask a Scien- mechanism of how some drugs, the Cozzarelli’s career was cut short when tist’’ feature in 2000 (www.hhmi.org͞ quinolones and coumarins, can effec- tively kill cells by trapping DNA gyrase he died on March 19, 2006, at the age askascientist͞meet-scientist͞scientists͞ in an intermediate form that induced of 67, from complications related to cozzarelli.html; accessed March 20, breaks in double-stranded DNA, thus treatment for Burkitt’s lymphoma. His 2006). Cozzarelli took this belief to turning this enzyme into a poison of death is a loss for both the research and heart, and his scholastic excellence replication (7–9). This unexpected dis- publishing communities, but he has left earned him a full scholarship to Prince- covery was once noted by Cozzarelli as a legacy of uncompromising scientific ton University (Princeton, NJ). one of his proudest achievements, and achievement, advancement toward inter- Linda Cozzarelli, his wife, remembers one that continues to have immense disciplinary and multidisciplinary work, that her husband had always had dis- clinical impact. These discoveries are and a revitalized journal positioned to criminating tastes and a good eye for meet the challenges of the 21st century. detail, which fostered a refined appreci- ‘‘Nick is known for revolutionizing ation for both art and wine. He also © 2006 by The National Academy of Sciences of the USA

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perceived negatively because, as Brown notes, ‘‘his heart was always in the right place.’’ One of Cozzarelli’s earliest challenges was to improve the editorial and peer review policies of PNAS. To address the scientific community’s concerns about ensuring rigorous peer review, as well as to allow nonmembers of the Academy to publish in PNAS, Cozzarelli immediately added the then-controversial Track II direct submission system. In this system, any author could submit work directly to PNAS without sponsorship from an Academy member. Establishing this new feature was the ‘‘watershed mark’’ of Coz- zarelli’s early years at PNAS, Fulton says. Direct submissions trickled in to PNAS in December 1995. By the end of the following year, 1,700 manuscripts were submitted under the new system. The year after that, the number jumped to 2,200. In 2005, 8,700 direct submis- sions were received, constituting nearly 80% of the journal’s submissions. From right to left: Cozzarelli; his wife, Linda Cozzarelli; daughter, Laura Cozzarelli-Wood; and son-in-law, Brian Wood. Diversify and Modernize From his extensive work on the editorial boards of other journals, such as the but a fraction of his contributions, how- sure a strong future. Cozzarelli took the Journal of Biological Chemistry, Cozzarelli ever. ‘‘Nick’s contributions to research reins at a challenging time; PNAS was recognized the unique role that PNAS and science are far too many to enumer- struggling through a difficult period of possessed regarding its relationship with ate, but clearly his pioneering biochemi- transition. For some years, concerns had the members of the Academy. When cal studies of topoisomerases and the been raised that PNAS, although highly Cozzarelli started as Editor-in-Chief, 26 importance of DNA topology were pre- respected, was losing its luster as a pre- people sat on the PNAS Editorial Board, eminent,’’ says Robert Tjian, Professor mier scientific journal, notes Kenneth most of whom worked in the biological of Biochemistry and Molecular Biology Fulton, Executive Director of the Na- sciences. Cozzarelli began creating a at the University of California, Berke- tional Academy of Sciences and Pub- board that was more diverse and more ley, and member of the PNAS Editorial lisher of PNAS. The Academy had hired active. ‘‘Nick was fond of experiments and Board. a consulting group to develop recom- considered the Editorial Board a great Laboratory research was not all that mendations for the journal’s operations, experiment,’’ says PNAS Managing Editor Cozzarelli valued. In the HHMI ‘‘Ask a which included a major overhaul. Cozza- Daniel Salsbury. ‘‘He selected members to Scientist’’ interview, he offered the follow- relli was enthusiastic about the chal- have the breadth to cover the entire ing advice to young scientists: ‘‘Take as lenge of rebuilding a journal. ‘‘He was Academy and the depth to handle the little science as possible in college. As a tremendously excited about this oppor- work evenly,’’ Salsbury says. Today, more science major, take electives to develop tunity,’’ says Linda Cozzarelli. ‘‘He than 140 members serve on the PNAS skills in communication. If you are suc- always liked an upstream swim.’’ Editorial Board. cessful at science, your time will be spent Cozzarelli approached the challenges at Cozzarelli also wanted the PNAS pub- writing, reading, speaking, listening. Very PNAS with his trademark passion and lication record to echo this diversity. In little will be spent in the lab.’’ By his own headstrong commitment to ideals, quali- 1998, he set a goal for the journal to measure, Cozzarelli was successful at sci- ties he had developed since youth and had greatly increase the publication of papers ence, because his contributions extended successfully practiced throughout his ca- in the nonbiological sciences. He helped well beyond the laboratory. He was a reer. ‘‘He had a sincerity and complete encourage this direction through the es- skilled teacher who enjoyed sharing his commitment to whatever he was doing, tablishment of special features, the en- enthusiasm for science, making yearly vis- whether it was teaching, giving a lecture, couragement of recruiting by members, its to talk about science and mathematics or just through interactions in the lab,’’ and the hiring of recruiting editors, Sul- at the special education school where his recalls Patrick O. Brown, a member of the lenberger says. This inclusiveness reflected daughter, Laura Cozzarelli-Wood, taught. PNAS Editorial Board and a former grad- his personality. ‘‘He was well rounded as a He often collaborated with researchers in uate student of Cozzarelli’s. ‘‘It created a researcher and well rounded as a person, other disciplines, and in 1988 he founded great lab environment. It made everything and he wanted the journal to be the the Program for Molecular Biology and you were doing seem cutting edge and same,’’ Sullenberger says. Mathematics at Berkeley to foster inter- important,’’ he says. Cozzarelli developed Cozzarelli found ways to modernize the disciplinary research. a reputation for holding others to his own image of the journal as well. PNAS had exceedingly high standards. ‘‘He was an long been known as ‘‘the gray lady,’’ be- Charting a New Course especially tough interviewer,’’ says Fulton, cause of its cover’s muted gray color and In July 1995, Cozzarelli joined PNAS as ‘‘He would quiz people as if they were simple black-ink seal of the NAS. Cozza- Editor-in-Chief, recruited to build on graduate students defending their theses.’’ relli was in favor of more visually dynamic the journal’s solid foundation and en- Yet Cozzarelli’s tough nature was rarely covers that appealed to researchers and

Nuzzo and Zagorski PNAS ͉ April 18, 2006 ͉ vol. 103 ͉ no. 16 ͉ 6079 Downloaded by guest on September 28, 2021 the public. Starting in 1998, PNAS se- lected covers from eye-catching scientific images submitted by researchers. This move satisfied Cozzarelli on two levels, Sullenberger says, because it was a fresh look for the journal and also stirred inter- est among researchers. ‘‘He loved the fact that people compete to have their images on the cover,’’ Sullenberger says. ‘‘[I] witnessed with awe the way in which he transformed the journal and brought it into the 21st century,’’ says Charles M. Radding, Professor in the Department of Molecular Biophysics and Biochemistry at Yale University and a member of the PNAS Editorial Board. Radding notes, ‘‘Nick introduced the di- rect submission of manuscripts, raised the quality and reputation of the journal, and made headway in diversifying it. He suc- ceeded not only by virtue of his great in- tellect but also his outstanding leadership qualities.’’ Cozzarelli with his daughter, Laura Cozzarelli-Wood, teaching in Laura’s class. Access Granted Cozzarelli soon faced the highly charged issue of open access, an issue that would thought that a journal like PNAS would to do,’’ says Fulton, ‘‘when in fact they set PNAS apart from the crowd. In 2001, send a ripple through the scientific com- often wander and take detours. Nick a handful of scientists, including Brown munity if it took the initiative and started thought that being able to see that the and Michael Eisen, a computational biolo- an experiment,’’ Sullenberger says, ‘‘and it careers of successful scientists didn’t al- gist at the University of California, Berke- did.’’ ways progress along a straight line would ley, and Lawrence Berkeley National After the boycott was not upheld by the be helpful to young people who think they Laboratory (Berkeley, CA), began a pro- majority of its signatories, Brown and his might not be focused enough.’’ test against scientific journals that did not open access advocates decided to launch Perhaps it is fitting that the PNAS make their research articles freely avail- the Public Library of Science and form a Profiles add liveliness and humanity to the able online through open access 6 months new open access journal, PLoS Biology. journal, because those characteristics are after publication. By 2002, nearly 30,000 Brown called on Cozzarelli for advice. reflective of the man who guided it over scientists had signed a petition agreeing to Conversations with Cozzarelli, who served the last 11 years. Cozzarelli displayed a boycott closed-access journals. on the Editorial Board of PLoS, helped natural curiosity and was a magnet for Cozzarelli was intrigued by these devel- guide Brown in practical details as well as information, which resulted in countless opments. ‘‘He watched the boycott with philosophical questions. ‘‘He helped me brainstorming session and lively debates, an intellectual curiosity,’’ Sullenberger develop a more pragmatic as opposed to often made livelier by Cozzarelli’s strong- says, while keeping a ‘‘balanced perspec- idealistic perspective on open access,’’ says willed nature. ‘‘Nick relished trying to tive’’ on the open access movement. Brown. convince someone to see his point of Although he was aware that publishing view,’’ says Sullenberger. ‘‘He would research papers was a business that in- A Scholar and a Gentleman tackle an argument from different angles volved hard costs, Cozzarelli deeply be- Under Cozzarelli’s leadership, biographi- until he could get his point across,’’ she lieved that free and unfettered access to cal Profiles of newly elected Academy recalls. However, he was respectful even the scientific literature benefited science members were introduced in the journal in disagreements and would readily admit and society. For PNAS, he favored taking in 2003 and a new front section called ‘‘In when he was wrong. ‘‘Even people who small, yet pioneering steps to test these This Issue,’’ highlighting a few exceptional disagreed with him respected him principles. So, in addition to making all articles in each issue, was launched in greatly,’’ says Fulton. Cozzarelli also pos- PNAS content free online after 6 months 2005. Although he approached the addi- sessed an infectious joie de vivre that suf- and free immediately to more than 140 tion of nonresearch features in PNAS fused his research and his interactions developing countries, Cozzarelli intro- with caution—wanting PNAS to remain a with others. Says Halpern, ‘‘Those of us duced an open access option that permit- top-tier journal, not a magazine—he espe- who were privileged to be associated with Nick have lost a valued friend and ted authors to make their papers immedi- cially enjoyed the biographical Profiles. colleague.’’ ately free online by paying a nominal fee. ‘‘He felt that people view scientists as hav- Cozzarelli made it clear that he wanted ing perfectly defined career paths, and Regina Nuzzo and Nick Zagorski, PNAS to take a leadership role. ‘‘He that they always knew what they wanted Science Writers

1. Boles, T. C., White, J. H. & Cozzarelli, N. R. Acad. Sci. USA 78, 843–847. Cozzarelli, N. R. (1977) Proc. Natl. Acad. Sci. USA (1990) J. Mol. Biol. 213, 931–951. 5. Dean, F. B. & Cozzarelli, N. R. (1985) J. Biol. 74, 4767–4771. 2. Dro¨ge, P. & Cozzarelli, N. R. (1992) Methods Chem. 260, 4984–4994. 8. Sugino, A., Higgins, N. P., Brown, P. O., Peebles, Enzymol. 212, 120–130. 6. Dekker, N. H., Rybenkov, V. V., Duguet, M., Crisona, C. L. & Cozzarelli, N. R. (1978) Proc. Natl. Acad. 3. Vologodskii, A. V. & Cozzarelli, N. R. (1994) N. J., Cozzarelli, N. R., Bensimon, D. & Croquette, V. Sci. USA 75, 4838–4842. Curr. Opin. Struct. Biol. 4, 372–375. (2002) Proc. Natl. Acad. Sci. USA 99, 12126–12131. 9. Khodursky, A. B. & Cozzarelli, N. R. (1998) 4. Brown, P. O. & Cozzarelli, N. R. (1981) Proc. Natl. 7. Sugino, A., Peebles, C. L., Kreuzer, K. N. & J. Biol. Chem. 273, 27668–27677.

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