Daniel E. Koshland Jr., the UC Berkeley molecular biologist who revised scientists' notions of how enzymes work, remodeled the Berkeley biology department into one of the nation's best and, as editor, refashioned Science into the leading scientific journal in the world, died Monday at the Kaiser Permanente Medical Center in Walnut Creek, Calif., after a massive stroke. He was 87.
"Dan Koshland was a rare bird," said Nobel laureate Joseph L. Goldstein of the University of Texas Southwestern Medical Center in Dallas. "His career in science was exemplified by a distinction achieved by only a handful of scientists who are held in universally high esteem by their colleagues because of their human qualities of honesty, kindness, unselfishness, originality and wisdom. And in Dan's case, there was also wit.
F. Scott Fitzgerald's dictum, 'There are no second acts in American lives,' Dan accomplished the impossible," Goldstein said. "He performed three acts in one lifetime, all of them class acts: the visionary biochemist, the tireless institution-builder and the eloquent public communicator. It's indeed a sad day that the curtain has fallen."
An heir to the Levi Strauss jeans fortune, Koshland was probably one of the wealthiest academic scientists in the country, with a net worth estimated by Forbes magazine at nearly $800 million in 1997. But he spread his wealth liberally, with generous donations to fund a science museum in Washington, D.C., named after his late wife, a new science center at Haverford College in Pennsylvania, where his sons studied, a science library at Berkeley and a fellowship program at the Weizmann Institute in Israel, among others.
Members of his family, he said, "were told we were extremely lucky and had an obligation to share the benefit of our education and our wealth with others," he told the Jewish Bulletin.
As a newly minted, 31-year-old PhD., Koshland struggled with finding a job before landing in the biology department at Brookhaven National Laboratory on Long Island in 1951. The problem was that he was a biochemist in an era when traditional biologists ruled the roost, and his specialty made him an odd duck at Brookhaven.
His postdoctoral fellowship at Harvard University had interested him in the mechanism of the action of enzymes, the 5,000 or so proteins in the body that carry out the chemical reactions of life.
For more than 100 years, the behavior of enzymes had been explained by the "lock-and-key" mechanism developed by pioneering German chemist Emil Fischer. Fischer thought that the chemicals undergoing a biological reaction fit precisely into enzymes like a key into a lock.
But Koshland's work suggested that this view was too rigid — that enzymes sometimes had to change their shape to accommodate the chemicals and that this shape change could be part of the catalytic reaction. He called it the "induced fit theory," but in the late 1950s traditional journals weren't interested in publishing his first paper about it.
"Nowadays, it seems pretty obvious," Koshland said later. "But at the time it was a pretty wild theory. I had a really hard time publishing it."
One researcher wrote that "The Fischer Key-Lock theory has lasted 100 years and will not be overturned by speculation from an embryonic scientist."
Even after he got the paper accepted by the Proceedings of the National Academy of Sciences, it was a full decade before other scientists recognized its validity.
After what he intended to be a one-year stint at Brookhaven turned into 14, Koshland and his wife, Marian, an immunologist, were offered positions at Berkeley in 1965. Nine years later, he became chairman of the department of biochemistry and began a large-scale reorganization of the biology faculty.
In what he described as "one of the high points of my life," he pruned and merged the 11 small departments — with more than 200 faculty members — into three new ones that reflected changes in the field, especially the emergence of genetic engineering and the new focus on gene and protein interactions.
The reorganization was accompanied by a fundraising campaign that built two buildings and renovated a third.
"People thought the reorganization was impossible, and I think no one else could have pulled it off," said Berkeley molecular biologist Robert Tjian. "Berkeley was his true love, and it has lost one of its great champions."
Other universities soon reorganized their own departments, using the model developed by Koshland.
In recent years, Koshland was a leader of the campus' $400-million Health Sciences Initiative, arguing for the need to renew campus infrastructure to support scientific research. In 1992, Berkeley honored him by naming a new biology research building Koshland Hall.
In 1984, he was named editor of Science, which Goldstein described as "a good, but stodgy, journal." For a decade, he commuted between the coasts, spending one week of every month in Washington and the rest at his lab in Berkeley. Airplanes, he said, were a great place to write his editorials — "no telephones."