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Jack F. Kirsch
In Memoriam

Jack F. Kirsch

Professor of Molecular and Cell Biology and Chemistry, Emeritus

UC Berkeley

Jack F. Kirsch passed away on November 12, 2018 at home in El Cerrito, surrounded by his family. Jack was born on August 14, 1934 in Detroit, Michigan, the elder son of Louis and Laura Kirsch. He was always very proud of his undergraduate degree in physics from the University of Michigan, which he completed in 1956. Jack then pursued graduate studies in biochemistry at the Rockefeller Institute in New York (now Rockefeller University). His Ph.D. mentor was George Palade, who later was awarded the Nobel Prize in Physiology or Medicine (1974). His graduate work involved the beginnings of deconvoluting the complexities of protein biosynthesis. During his graduate studies, he spent time at Cambridge University, England and the Carlsberg Laboratory in Copenhagen, Denmark.

After completion of his Ph.D. in 1961, Jack took up postdoctoral work at Brandeis University with William (Bill) Jencks. We are certain that Jack would agree with the view that it was with Jencks that Kirsch developed his life-long research passion for enzymes and how they function. In a memoir for Jencks, Jack and fellow Jencks mentee John Richard wrote that Jencks “… provided the graduate students and postdoctoral fellows working in his laboratory with unique insights into catalysis not easily gleaned from focused chemical or enzymatic studies.” Jack forever retained and honed those unique insights into catalysis in all of his research. The physical-organic thinking woven into the Jencks lab involving linear free-energy relationships and the like would be a recurring theme in Jack’s research in Berkeley.

While doing postdoctoral work at Brandeis University, Jack met his wife, Birthe, and they were married in 1962. They then spent a year in Israel (1963-64), where Jack continued postdoctoral research at the Weizmann Institute working with Ephraim Katchalski-Katzir. In 1964, Jack joined the faculty at Berkeley as an assistant professor in what was then the Department of Biochemistry and would become a division within the Department of Molecular and Cell Biology. Jack would also hold an appointment in the Department of Chemistry. Jack rose through the ranks and was promoted to professor in 1974.

The main focus of Jack Kirsch’s research was in enzymology, but it also involved directed evolution of proteins and drug discovery. His early work at Berkeley was focused on proteases, enzymes that hydrolyze (break down) the peptide bonds in proteins. He captured and built on emerging themes in catalysis using chemical and biochemical approaches to discern the chemistry enzymes used to carry out this process. Eventually, he extended his efforts to include enzymes that use vitamin B6 (pyridoxal phosphate, PLP) and other hydrolases, including lysozyme and beta-lactamases, enzymes that are involved in penicillin resistance. As time and methodology moved on, so did Kirsch, by bringing site-directed mutagenesis and incorporation of unnatural amino acids into his research and mechanistic studies. Lysozyme became a focus of his work on enzyme engineering. In collaboration with his colleague Allan Wilson at Berkeley, Kirsch provided new insights into the molecular basis of enzyme-antibody interactions. His pervading and long-standing work was with the PLP enzymes. Kirsch and his family spent a sabbatical leave in Basel, Switzerland, where Jack contributed to the emerging X-ray structure and mechanistic analysis of the enzyme aspartate aminotransferase. With the deep understanding and intuition that resulted from this collaboration, Jack would become a world expert on the mechanism of PLP enzymes, publishing a definitive perspective in the Annual Review of Biochemistry in 2004. It is here where our understanding of enzyme catalysis would be much diminished without Kirsch’s contributions. The impact of his work is clear to the present day. The foundations of enzyme mechanism research were begun by physical organic chemists who used chemical models to dissect steps in catalysis. Kirsch’s postdoctoral mentor Bill Jencks was an essential part of that early work. Those methods could not be applied to labile proteins but Kirsch combined his rigor from his early days with the newly available modern methodology to produce a linear free-energy analysis in a PLP enzyme – a remarkable paper published in Science in 1989. Rigor permeated all of Kirsch’s work. He was highly critical, but no more so than with his own work. His investigations into enzyme catalysis serve as an example of how it should be done, and his contributions live on.

Kirsch was honored throughout his career. At the outset, his potential was recognized with prestigious fellowships from the Jane Coffin Childs Fund and the Helen Hay Whitney Foundation. As a Berkeley faculty member, he was awarded a Guggenheim Fellowship and a Doctor of Philosophy-Honoris causa, Uppsala University, Sweden. Of many prestigious lectureships, he was most proud of being named the Nathan O. Kaplan Lecturer at Brandeis University. In 2016, Jack was appointed to the Edward A. Dickson Emeriti Professorship in recognition of his exemplary continued contributions in teaching, research, and public service. Evidence of his commendable service record can be seen both internally and externally. His advice on review panels at the National Institutes of Health and other national and international boards serves as an example to us all. His Academic Senate service included membership over a total of nine years on multiple committees, including Berkeley Division committees on Student Affairs and Academic Freedom, the systemwide Committee on Academic Freedom, and the systemwide Assembly.

Jack did not shy away from controversy. Indeed, he was thrust into it upon his arrival at the Berkeley campus. The Free Speech Movement was underway, as was a difficult period for the Berkeley campus and the Regents. Though vulnerable as an assistant professor, Jack was outspoken in his support of the FSM and his opposition to the Vietnam War. His promotion with tenure had been approved at all campus levels but was held up at the final step of regental approval, though ultimately it took place. Jack spoke out when he thought something was right and spoke out just as strongly when something was wrong.

Jack Kirsch was dedicated to his family. Upon their arrival in the Bay Area, Jack and Birthe settled in Kensington, where they raised their sons, Gorm and Joshua. From 1971-72, Jack took a sabbatical year at the University of Göttingen Germany, during which he commuted biweekly to nearby Denmark, Birthe's native country, where she and the boys spent the year. The family also greatly enjoyed the aforementioned sabbatical year in Basel, Switzerland, in 1979-80. While delighting in his life's work in biochemistry, Jack was a man of diverse passions and interests. First and foremost, he cared for his family, entertaining them with puns and jokes of varying quality, while emphasizing the values of education, hard work, honesty, and integrity. Jack's other passions included birdwatching, Apple computers (proudly proclaiming his status as a "power user"), running (he completed three marathons), literature, theater, and classical music.

After Jack "retired" from the faculty and took emeritus status, he remained active with his scientific pursuits well into 2018. He continued his love of mentoring students and following the progress of their ongoing academic and professional careers. Jack also ventured into a new academic arena, offering a course in performing arts appreciation, with the goal of exposing non-arts students to the performing arts world, taking them to plays, concerts, and dance performances. He was enormously proud of this innovative course entitled “Sampling the Performing Arts at Berkeley.” It enriched his later life.

In 2004, Jack and Birthe moved from Kensington to El Cerrito, where they lived just down the street from Joshua, his wife Lucy, and grandsons Nicolas and Lukas. Jack and Birthe both volunteered at their grandsons' elementary school during this period and were actively involved in helping to raise the boys. Jack and Birthe supported numerous worthy causes over the years, including groups dedicated to environmental protection, local theater, education, and feeding the hungry, as well as political candidates and organizations who shared these values.

Jack touched the lives of so many people during his 84 years. He is survived by his wife, Birthe, sons Gorm (Geoff) and Joshua (Lucy), grandsons Nicolas and Lukas, brother Sheldon, and numerous nephews, nieces, cousins, and their extended families. He is sorely missed by them and by his many friends in the Berkeley community.

Judith P. Klinman
Michael A. Marletta

Photo credit: Mark Joseph Hanson