Nobel laureate Arthur Kornberg dies at 89

- By Mitzi Baker

L.A. Cicero

Arthur Kornberg (left) with his son, Roger, after Roger received the 2006 Nobel Prize in Chemistry. Arthur Kornberg received the Nobel Prize in Physiology or Medicine in 1959 for his work elucidating DNA assembly.

Arthur Kornberg, winner of the 1959 Nobel Prize for his work elucidating how DNA is built, died Oct. 26 at Stanford Hospital of respiratory failure. He was 89.

'Dr. Kornberg was one of the most distinguished and remarkable scientists in American medicine,' said Philip Pizzo, dean of the Stanford University School of Medicine. 'His towering contributions have continued virtually up until the time of his death. Without doubt, his legacy will certainly live on for many, many generations to come.'

Kornberg, professor emeritus of biochemistry at the School of Medicine, shared the Nobel Prize in Physiology or Medicine with Severo Ochoa, , who at that time was at New York University. Kornberg was honored for the test-tube synthesis of DNA, the blueprint of heredity, and Ochoa for the synthesis of RNA, the genetic message derived from DNA. Although James Watson and Francis Crick had put forward a formal model of how DNA is replicated in the early '50s, Kornberg discovered the actual chemical mechanism by which the huge amount of DNA that comprises a chromosome gets constructed in the cell.

'There have got to be tens of thousands of people around the world today whose eyes are tearing up with the news that he's gone,' said Paul Berg, the Robert W. and Vivian K. Cahill Professor of Cancer Research Emeritus and winner of the 1980 Nobel Prize in Chemistry for his work with recombinant DNA. 'He was an extraordinary scientist. His accomplishments might be called legendary. The style in which he did his science was inspirational.'

Kornberg and Ochoa turned to enzymes to solve basic biology problems. Along the way, they discovered new enzymes that create the building blocks of DNA and RNA, as well as the enzyme that Kornberg named DNA polymerase that assembles those building blocks. These basic studies ended up paving the road to the creation of recombinant DNA and genetic engineering, as well as providing the basis for many drugs currently used to treat cancer and viral infections.

Kornberg, who lived in nearby Portola Valley, liked to refer to his scientific career as a 'love affair with enzymes.'

One of his sons inherited his love of enzymes. Roger Kornberg, PhD, who was just 12 when he accompanied his father to the Nobel Prize ceremony in Stockholm, went on to study the enzymes that create RNA as a professor of structural biology at Stanford. Father and son returned to Stockholm 47 years later - to attend the award ceremony for Roger Kornberg, who was awarded the 2006 Nobel Prize in Chemistry.

Spyros Andreopoulos, who arrived at Stanford in 1963 to direct the medical school's news bureau, said he gathered his courage to ask Kornberg to meet with him. 'I was scared. Someone had warned me that Nobel laureates behaved like God-like princes,' said Andreopoulos. 'To my surprise, he was entirely unpretentious. Our first meeting was the beginning of an enduring friendship in which he let me share his challenges and triumphs.'

Kornberg was born in Brooklyn on March 3, 1918. He attended the New York public schools, then earned his BS degree in chemistry and biology from the City College of New York in 1937. He attended the University of Rochester, where he earned his MD in 1941.

Stanford News Service Arthur Kornberg's work in DNA synthesis

Arthur Kornberg's work in DNA synthesis led to creating recombinant DNA and genetic engineering.

After a yearlong internship in internal medicine, he served as a commissioned officer in the U.S. Public Health Service. He was first assigned to the Navy as a ship's doctor, and then as a research scientist at the National Institutes of Health in Bethesda, Md., from 1942-53.

During this time, he studied enzymology at New York University School of Medicine in 1946 with Ochoa and in 1947 at Washington University School of Medicine in St. Louis with Carl Cori, MD, and Gerti Cori, MD, who shared the Nobel Prize for Physiology or Medicine that year.

Upon returning to the NIH from his sabbatical, he organized and directed the enzyme and metabolism section of the National Institute of Arthritis and Metabolic Diseases. He became medical director, but resigned in 1953 to return to St. Louis as the chair of microbiology at Washington University School of Medicine.

In 1959, he came to Stanford as the chair of the new Department of Biochemistry, at a time of great change for the school as it was moving its entire shop from San Francisco to Palo Alto, aspiring to become a great research institution. On the heels of scientific advances stimulated by wartime research, the medical community began to appreciate a new approach, beyond treating patients, that explored why and how disease happened.

This philosophy fit right in with Kornberg, who remained chair of the department for 10 years. 'He helped bring some important people to Stanford and during that first period when he was chairman we came to be known as probably the premier department in the country,' said Berg.

The department in its early days 'had many surprising features, most of them carefully planned by Arthur Kornberg,' said Robert Baldwin, PhD, professor emeritus of biochemistry. 'The most surprising features of the department were that general laboratory space was shared by everyone, so that students and postdocs from the various research groups were mixed together in common laboratories, and research grants were also shared.'

The outstanding feature of the department, said Baldwin, was the strong spirit of cooperation among the faculty. This spirit lasted for decades. The original members of the department - Baldwin, Berg, David Hogness, Dale Kaiser and Robert Lehman - stayed together as a cohesive unit for nearly 50 years until retirement. They trained generations of students and postdoctoral fellows who are among the leaders in biomedical research today.

In 1988, Kornberg moved to emeritus status at Stanford, but he continued to run a lab until his recent hospitalization.

Although DNA replication held Kornberg's attention for years, in 1991 he switched his focus to return to an early interest of his: poly P, a long chain of phosphates. This polymer is found in every bacterial, plant and animal cell. Kornberg was convinced the molecule was critical in the evolution of Earth's first cellular organisms. He thought the ancient cells used poly P to shuttle metals in and out, and as a simple way to regulate enzyme activity.

Kornberg once said that he thought poly P might equal DNA in importance. He spent the last 16 years of his life outlining functions for poly P that include response to stresses, and motility and virulence in some major pathogens. He concluded that the enzymes that create poly P might be manipulated as a completely different type of antibiotic.

Kornberg was devoted to bridging the gap between basic research and its ultimate practical payoffs, and to encouraging the government to support scientists in studying science for curiosity's sake rather than for any potential financial benefits. The payback, he said, will come as a natural extension of the scientific process.

'No matter how counterintuitive it may seem, basic research has proven over and over to be the lifeline of practical advances in medicine,' he said in a 1977 publication, Basic Research, the Lifeline of Medicine. 'Without advances, medicine regresses and reverts to witchcraft.'

Toward the end of advancing medicine, Kornberg was a founder of the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto, and a member of its policy and scientific advisory boards. He also served on the scientific advisory boards of Regeneron Pharmaceuticals Inc., Maxygen, and XOMA Corp., and was also a member of the board of directors of XOMA Corp.

Beyond winning the Nobel Prize, Kornberg earned a number of other honors, including the National Medal of Science in 1979, the Cosmos Club Award in 1995 and the Gairdner Foundation Award, also in 1995. He served as the president of the American Society of Biological Chemistry in 1965, held memberships in the National Academy of Sciences, the Royal Society and the American Philosophical Society, among others. He was also awarded honorary degrees from 12 universities since 1960.

In addition to research, and teaching graduate, medical and postdoctoral students, Kornberg wrote several books: Enzymatic Synthesis of DNA in 1961, DNA Synthesis in 1974, DNA Replication in 1980 and its second edition in 1992. He wrote a scientific memoir, For the Love of Enzymes: The Odyssey of a Biochemist, in 1989. The Golden Helix: Inside Biotech Ventures, published in 1995, provides his insider's view of biotechnology.

Germ Stories, Kornberg's last book, is scheduled to be available in bookstores Nov. 15 and is written for children. When his sons were small, he often told them stories about germs, ranging from the bacteria he used as research material to those that inhabit the stomach, good and bad. Andreopoulos recalled Kornberg saying that he hoped someone would be able one day to share with children the essence and wonder of bacteria through his stories - and with the scheduled publication of his book, his wish was granted.

Kornberg is survived by his wife, Carolyn Frey Dixon Kornberg, whom he married in 1998. He was previously married to Charlene Walsh Levering Kornberg, who died in September 1995. Previous to that, he was married to Sylvy Ruth Levy Kornberg, his wife of 43 years who died in 1986. Sylvy worked full-time in Kornberg's laboratory and contributed significantly to his studies of DNA replication during the 1950s.

Kornberg is also survived by three sons and eight grandchildren. His sons are Roger Kornberg; Thomas Kornberg, PhD, professor and vice-chair of biochemistry and biophysics at the University of California-San Francisco, and Kenneth Kornberg, an architect and founder of Kornberg Associates, specializing in laboratory design.

'He is beloved by his family, friends and the Stanford community,' said Pizzo.

Burial arrangements are private. Stanford University will host a celebration of Kornberg's life and legacy; details will be released as they become available.

In lieu of flowers, the family requests that contributions be made to the Dr. Arthur Kornberg Memorial Fund at the School of Medicine or to a charity of the donor's choice.

Contributions to the memorial fund should be sent to: Stanford University Office of Medical Development, 2700 Sand Hill Road, Menlo Park, CA 94025.

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