Science

Daniel Koshland Jr., 87; UC Berkeley molecular biologist

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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.

"By 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."

He wrote more than 200 editorials, often featuring interviews with the fictitious Dr. Noitall, a parody of scientists who think they know it all.

More important, he changed the culture at the journal, bringing in more scientifically trained people to evaluate and edit papers, encouraging more news coverage and actively soliciting scientific reports.

Koshland said he was surprised to find that most of the journal's editors had backgrounds in writing, not science. Previous editors had hoped to improve the journal by improving the quality of the editing. Koshland decided to improve it by being more selective of articles and improving the quality of submissions.

By the end of his tenure, only one in every 10 submissions was chosen for publication.

His emphasis on scientific news made the journal a "must-read" not only for researchers, but also for stockbrokers, businesspeople, legislators and their staffs. "All I have to do is say something unflattering about a congressman and I get a phone call from him," he said.

Daniel Edward Koshland Jr. was born in New York City on March 30, 1920. His parents were banker Daniel E. Koshland and the former Eleanor Haas, cousins who were both heirs to part of the fortune of Walter Haas, founder of Levi Strauss & Co. The family moved to San Francisco two years later when the senior Koshland joined the company, eventually becoming vice president, president and chairman during his 57-year tenure.

Koshland recalled his childhood as "a landscape of boredom from sea to shining sea." There was, he said, none of "the material that generates good novels: no broken homes, no misunderstood childhood, no criminal youth gangs, no disastrous liaisons."

His interest in science was sparked in the eighth grade when he read "Microbe Hunters" by Paul de Kruif and "Arrowsmith" by Sinclair Lewis. Fascinated, he took all the courses in science and mathematics available at his high school.

Enrolling at Berkeley, he majored in chemistry. One insight into his character was provided in an inorganic chemistry course taught by Wendell Latimer. Koshland had just finished a final when Latimer asked him if an A in the course would be sufficient because Koshland already had aced three previous exams.

As Latimer prepared to tear up his test, Koshland "reacted angrily," pointing out that he had studied hard for the exam. "You owe it to me to correct it," he told Latimer. He got his A.

Koshland received his bachelor's degree in 1941 and went to work for the Shell Oil Co. in Martinez, Calif. When World War II broke out, he tried to enroll in the Navy but was rejected because his eyesight was 20/400, making him "legally blind" as far as the Navy was concerned.

Shortly thereafter, he received a call from Latimer, inviting him to move to Chicago and join a mysterious venture known as the Manhattan Project, telling him that the work was "the most important job in the world." Koshland spent the bulk of the war in Oak Ridge, Tenn., purifying plutonium for the world's first plutonium-based atomic bomb.

While he was at Chicago, he met Marian Elliott, whom he affectionately called Bunny. They married in 1945 and were devoted to each other until her death from lung cancer in 1997.

After the war, he returned to the University of Chicago to earn his doctorate in biochemistry, graduating in 1949.

By the 1970s, his interests had turned from enzymology to the study of how bacteria respond to their environment, a response called chemotaxis. He thought that would be a simple type of memory that could be studied biochemically and genetically.

He showed that bacteria have a rudimentary form of memory that allows them to compare past and present, and he demonstrated that they detect chemicals in their environment by means of receptors on their exterior. These receptors, he discovered, are linked to molecules on the bacteria's interior that transmit the signals and change the organism's behavior.

More recently, he turned his attention to the emerging field of bioenergy, looking into the use of cyanobacteria to produce methane as a fuel source.

"Unlike most scientists at his stage of career, he showed a striking willingness to switch directions and tackle new fields with creativity and originality," Tjian said.

In 1998, he received the Albert Lasker Award for Special Achievement in Medical Science in recognition of his lifelong contributions to medical science. The Lasker award is often considered a precursor to the Nobel Prize. He received a wide variety of other awards as well.

After Marian's death, he reconnected with Yvonne Cyr San Jule, whom he first met in 1940 when they were undergraduates in a Berkeley bacteriology course. They were married in August 2000.

In addition to his wife, Koshland is survived by two sons, James of Atherton, Calif., and Douglas of Baltimore; three daughters, Ellen Koshland of Melbourne, Australia; Phyllis Koshland of Paris; and Gail Koshland of Tucson; two sisters, Francis K. Geballe of Woodside, Calif., and Phyllis K. Friedman of Hillsborough, Calif.; nine grandchildren and one great-granddaughter; three stepchildren; 12 step-grandchildren and 17 step-great-grandchildren.

A campus memorial service is planned for the fall.

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thomas.maugh@latimes.com

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