IN MEMORIAM

Daniel E. Koshland Jr.

Professor of Biochemistry, Emeritus

UC Berkeley

1920 – 2007

 

Daniel E Koshland Jr. was born in New York, New York, on March 30, 1920. His love affair with Berkeley began when he was an undergraduate here in the late 1930s. He developed a keen interest in chemistry and graduated in this subject in 1941. During the war years he took this interest in chemistry with him to Chicago and the Manhattan Project, in which he was a group leader. He received further training in organic and biochemistry at the University of Chicago, from which he received the Ph.D. degree in 1949, and at Harvard University, where he did postdoctoral work. From 1951 to 1965 he held an independent research position at Brookhaven National Laboratory. In 1965 Dan was lured back to Berkeley by the great biochemist/microbiologist Horace (Nook) Barker. He remained on the faculty at the University of California, Berkeley, until his death on July 23, 2007.

 

Dan’s work on enzyme catalysis and his initial formulation of the induced fit mechanism came in the late 1950s during his first independent research at Brookhaven. Dan told the story of how he arrived at this insight in a reminiscence published in Nature (“Crazy, but correct: How a non-conformist theory beat scepticism and got into the textbooks,” Nature, 432: 447 [2004]). Studies on the enzyme hexokinase led him to the conclusion that Emil Fischer's long established “lock and key” theory needed to be replaced by a concept that he called “induced-fit.” In this model, the interaction of an enzyme with its substrate resembles the fit of a hand in a glove, with a moderately flexible enzyme (the glove) fitting a moderately flexible substrate (the hand). The response to this model was unenthusiastic, and his first submission was rejected with the statement "The theory of Emil Fischer has been a cornerstone for 100 years and will not be overturned by the ideas of an obscure young biochemist from a young national laboratory." Other journals, however, agreed to publish his work. The theory also explained many other enzymatic phenomena, such as hormone action, feedback inhibition, cooperativity and receptor function, so its acceptance grew slowly, but steadily, and its progress was accelerated by X-ray crystallographic studies that revealed pictures of enzyme–substrate interactions exactly as predicted by the induced-fit theory. These early experiences led Dan to be a lifetime supporter of nonconformity in science.

 

In 60-plus years as a scientist in New York and at UC Berkeley, Dan published over 350 papers, of which more than 80 were in the Journal of Biological Chemistry. His most important papers dealt with three distinct research areas: mechanisms of enzyme catalysis and allostery, bacterial chemotaxis, and receptor signal amplification. More than most even highly accomplished scientists, Dan was fearless in pursuing his nose into new areas of biology. He challenged all around him to look for the new and he did so with a sense of delight in discovery. His work brought him numerous honors, awards, honorary degrees and honorary named lectureships, far too many to be listed here; perhaps the most notable were the National Medal of Science (1970) and the Albert Lasker Award for Special Achievement in Medical Research (1998).

 

Given Dan’s background in chemistry as a student of Latimer, Seaborg and Westheimer, it was natural that he served to bridge the life science and chemistry departments at Berkeley and in so doing influenced a generation of leaders such as Pete Schultz, Alex Pines, Carolyn Bertozzi, Robert Tjian and many others. Dan used chemistry and quantitative analysis to great advantage in his work on receptor/ligand signal amplification and bacterial chemotaxis. In an era of increasing emphasis on nucleic acids, Dan emphasized understanding molecular mechanisms through functional and structural analyses of proteins. Like any progressive biochemist of the twenty-first century, however, Dan was not reluctant to apply the tools of molecular genetics and genomics as they developed.

 

His work in bacterial chemotaxis blended the best of all of Dan’s skills. He and his students developed techniques to track bacteria swimming in gradients of attractants and repellents and discovered that bacteria sense a change in concentration over time, not in space. In 1981, Goldbetter and Koshland published a pioneering study on amplified sensitivity of biochemical responses controlled by protein phosphorylation and dephosphorylation. This idea and subsequent work on zero-order ultrasensitivity by LaPorte and Koshland have informed our understanding of complex pathways from cell cycle control to development. Dan also early on recognized the power of 3-D structural analysis and embraced X-ray crystallography and other structural methods.

 

Dan was more than a great scientist; he was a warm human being who took responsibility selflessly and seemingly effortlessly. As chair of the Department of Biochemistry (1973-1978) and later as chair of the Chancellor’s Advisory Counsel on Biology he oversaw a series of key hires, including Randy Schekman and Gerry Rubin. Around 1980, Dan and his wife Marian, a prominent immunologist on the Berkeley faculty, realized that without a dramatic change in Berkeley’s departmental structure, the University could not maintain excellence in research and teaching or stay competitive with its peer institutions. Thus Dan, together with a handful of faculty and endorsements from the chancellor and provost, led an unprecedented and sweeping reorganization of the biological sciences at Berkeley. This massive, some thought impossible, task culminated with the elimination of 12 traditional departments and the formation of three new realigned departments (molecular and cell biology, integrative biology, and plant and microbial biology). Dan considered the reorganization of Berkeley’s biological sciences one of the most rewarding accomplishments of his career. Dan’s service to the Berkeley campus was recognized by the Berkeley Citation in 1970 and by his selection as UC Alumnus of the Year in 1991.

 

The continued success of Cal in recruiting top students and faculty today stands as testimony to Dan’s vision. As part of this legacy, Cal recently completed a 280,000 square foot modern research facility (The QB3 Stanley Building for Quantitative Biology); and a second 200,000 square foot facility (The Li Ka Shing Center for Biomedical and Health Sciences) is just beginning construction. Both of these state-of-the-art facilities, along with many other research projects and programs, have been possible, not only because of Dan’s scientific vision but also directly as a consequence of his personal philanthropy. Dan and other members of the Koshland-Haas-Goldman-Friedman-Hellman families, heirs to the Levi-Strauss clothing empire, have a legacy in the Bay Area and especially at the University of California.

 

Dan’s sense of service extended to the nation. As the campus life science reorganization loomed, Dan assumed the position of the editor in chief of the Proceedings of the National Academy of Sciences, quickly infusing the academy journal with fresh energy, good judgment and aggressive recruitment of high quality papers. In 1985 he took on the even more ambitious role of editor of Science magazine and there transformed a somewhat staid and stale journal into a more vibrant and edgy science magazine that still enjoys top ranking today.

 

Through it all, Dan had two most enduring traits: wit and calm self-assurance. He had an uncanny ability to rescue a tense situation with humor and charm. Though he came from a privileged background, his tastes ran to the simple. He drove a beat-up car and dressed accordingly. Unlike many men of his level of accomplishment, Dan did not crave attention. He often said “It is very difficult to get things done if you worry about credit or popularity.” Those who followed his example learned to treat colleagues and associates (students, lab technicians, administrative assistants, etc.) with dignity, generosity and respect.

 

It was a terrible blow to Dan when his wife Bunny (immunologist Marian Elliott Koshland) died in 1997. But as fate would have it, Dan reunited with Yvonne, a wonderful lady he had dated during his college years at Cal. Yvonne and Dan had seven great years together. Dan is survived by Yvonne and by the five children that he and Bunny had raised.

 

 

Robert Tjian

G. Steven Martin