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 Wof 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 6078–6080 ͉ PNAS ͉ April 18, 2006 ͉ vol. 103 ͉ no. 16 www.pnas.org͞cgi͞doi͞10.1073͞pnas.0602531103 Downloaded by guest on September 28, 2021 RETROSPECTIVE 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.