IN MEMORIAM

Nicholas R. Cozzarelli

Professor of Molecular and Cell Biology

Berkeley

1938–2006

Nicholas R. Cozzarelli was born March 26, 1938 in Jersey City, New Jersey and his life typifies an American success story. His parents were immigrants from Castel Nuevo di Conza in southern Italy. His father was a shoemaker, and his mother edited telephone books and encouraged their son to take seriously the advantages of study. Nick attended Princeton University on a full scholarship, intending to prepare for a career in law. His curiosity and thirst for fundamental knowledge developed as his career path transitioned  from  classical professional trades to scholarship. He became fascinated by science and graduated with an A.B. in biology, Magna Cum Laude, in 1960. He began medical school at Yale University, but switched after a year to graduate training at Harvard Medical School. He studied glycerol metabolism with E. C. C. Lin and earned a Ph.D. in biochemistry in 1966. Nick received his postdoctoral training from Arthur Kornberg, the discoverer of DNA polymerase and a Nobel Prize winner, at Stanford University School of Medicine. Nick purified T4-phage-induced DNA ligase, which stitches DNA strands together, deriving its energy from the hydrolysis of ATP. Nick’s ligase was used by Mehran Goulian in the construction of enzymatically synthesized DNA of the bacterial virus fX174. This DNA was able to enter host cells and yield progeny virus particles. The popular press called this phenomenon “synthesis of life in the test tube” and “the greatest scientific achievement of 1968,” ahead of the first heart transplant.

 

From 1968 to 1982 Nick was on the faculty of the University of Chicago. There he studied enzymes called topoisomerases, which can unwind the DNA double helix, promoting DNA replication, repair and transcription into RNA. He discovered a class of topoisomerases that unwind two turns of the DNA helix in a single step. Nick proposed that these “type II topoisomerases” break both strands of DNA transiently and pass part of the DNA molecule through the enzyme-bridged transient double break. He also showed that quinoline antibiotics, such as ciprofloxacin, inhibit type II topoisomerases. These antibiotics are widely used, not only to block bacterial infections, but also to kill cancer cells.

 

Cozzarelli joined the faculty at the University of California, Berkeley in 1982, and was appointed a professor in the Department of Molecular Biology. This department was one of several to join in the establishment of the present Department of Molecular and Cell Biology. Soon after arriving at Berkeley, Nick took on the job of departmental graduate adviser and caused a notable rise in the spirits of the graduate students as a result of his attention to their individual needs, strengths and problems. From 1986 to 1989 he chaired the department and was known for the extra time and care that he put into the writing of cases for faculty promotions. He was head of the Virus Laboratory, a state-funded organized research unit, from 1986 to 1989.

 

Cozzarelli was one of the first scholars to understand the importance of interdisciplinary collaborations and worked to build academic structures to facilitate such cross-fertilization. In 1988 he founded and directed the National Science Foundation’s Program in Mathematics and Molecular Biology. This program encouraged collaboration between mathematicians and molecular biologists and helped to explain the pattern of knotting and unknotting of DNA molecules that occurs in the presence of type II topoisomerases.

 

As a professor and mentor Nick’s teaching of introductory molecular biology for graduate students was universally admired. He chose classic and recent papers for students to read and to analyze in detail. The students never felt overloaded with work, but they were inspired as they were transformed from novices to near-experts. When they moved to Berkeley, Nick and his wife Linda bought a large, artistically inspired house near the campus, where they frequently entertained faculty and students. Especially appreciated were the receptions for as many as 50 prospective graduate students. The refreshments always showed Nick and Linda’s excellent taste in food and wine.

 

Cozzarelli was elected to the National Academy of Sciences in 1989, received the CIBA-Geigy/Drew Award in Biomedical Research in 1990, became a fellow of the American Association for the Advancement of Science in 1999, and was elected a member of the American Academy of Arts and Sciences in 2000. 

 

In 1995 Nick was invited to become editor-in-chief of the Proceedings of the National Academy of Sciences (PNAS). This prestigious journal had at least two problems. First, it only accepted articles communicated by members of the Academy. Second, it had the same gray cover on every issue. Nick initiated a system in which any author could submit an article to the Proceedings and have it edited by an appropriate Academy member. He also changed the cover, so that it gave an idea of the most exciting articles that appear in each issue. He favored the dissemination of the journal to the general public at minimal or no cost at the earliest possible time.  Testimony given by many academy members including the former president of the Academy Bruce Alberts and PNAS staff members provide evidence for the comment that Cozzarelli was the best editor of the Proceedings since its inception in 1915.

 

Nick died on March 19, 2006 from the complications of treatment for Burkitt’s lymphoma. After his death, his department sponsored a memorial symposium and dinner in his honor. Former students, postdoctoral fellows and collaborators came from around the world to present their research and recollections of Nick. A current student, Paul Pease, presented some of the current research of Nick’s lab, which is arguably his best. Paul had studied single molecules of a molecular motor, called FtzZ, from the bacterium Escherichia coli, that when tethered to a structure at the plane of cell division pumps newly replicated DNA from one part of the cell to another. This motor binds to E. coli DNA and uses the energy of hydrolysis of ATP to move in a single direction along the DNA molecule. When tethered this translocation machine becomes a “DNA pump”. An asymmetric nucleotide sequence, found in many copies on E. coli DNA, determines the direction of movement of the motor. The symposium and dinner brought forth many fond recollections. James Bliska, a former graduate student and now professor at the State University of New York at Stony Brook, recalled that Nick was a model thesis advisor. “His devotion to science and no-nonsense style of mentoring was inspirational. His record of scientific excellence set a high standard that all of his students sought to achieve. He was also a tremendous communicator, in both his speaking and writing style. The University of California, and the scientific community as a whole, has lost one of the best graduate advisors ever with Nick’s passing.” Michael Carey, a former graduate student and Professor at the University of California, Los Angeles, recalled that “graduate school is an impressionable time in one’s life. What you learn and how you learn it strongly influences your individual style and path through science. To this day I still hear Nick’s voice. I use his phrases—good science, blast ahead, make a contribution, and I base my scientific decisions on guiding principles laid out in his training. He gave all of his students the freedom to pursue what interested them most, while providing the intellectual environment and resources that allowed us to be successful.”

 

Nick is survived by his wife Linda, daughter Laura Cozzarelli-Wood of Towson, Maryland, and brothers, Francis, of Buffalo, New York and Angelo of Buffalo Grove, Illinois.

 

Michael Botchan

Richard Calendar

Richard Harland