Arthur Kornberg MD (father)/Roger Kornberg (son) Both Won Nobel Prizes

 

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Arthur Kornberg (1918 – 2007) – He and his son are the sixth father and son to win Nobel Prizes

 

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Roger Kornberg, left, the Nobel Laureate in Chemistry for 2006, pauses after a press conference to listen to his father Arthur Kornberg, the 1959 Nobel Laureate in Medicine

 

Arthur Kornberg was an American biochemist who, together with Dr. Severo Ochoa of New York University, won the Nobel Prize in Physiology or Medicine in 1959 for their discovery of “the mechanisms in the biological synthesis of deoxyribonucleic acid (DNA)“. Kornberg was also awarded the Paul-Lewis Award in Enzyme Chemistry from the American Chemical Society in 1951, L.H.D. degree from Yeshiva University in 1962, as well as National Medal of Science in 1979. Kornberg’s primary research interests were in biochemistry, especially enzyme chemistry, DNA synthesis/replication, and studying the nucleic acids which control heredity in animals, plants, bacteria and viruses.

 

Born in New York City, Arthur Kornberg was the son of Jewish parents Joseph and Lena (n?e Katz) Kornberg, who emigrated to New York from Austrian Galicia (now part of Poland) in 1900 before they were married. His paternal grandfather had changed the family name from Queller (also spelled Kweller) to avoid the draft by taking on the identity of someone who had already completed military service. Joseph worked as a sewing machine operator in the sweat shops of the Lower East side of New York for almost 30 years, and when his health failed, he opened a small hardware store in Brooklyn, where Arthur assisted customers at the age of nine. Joseph spoke at least six languages although he had no formal education.

 

Arthur Kornberg was educated first at Abraham Lincoln High School and then at City College in New York City. He received at B. Sc. in 1937, followed by an M.D. at the University of Rochester in 1941. Kornberg had a mildly elevated level of bilirubin in his blood – jaundice due to a hereditary genetic condition known as Gilbert’s syndrome – and while at medical school he took a survey of fellow students to discover how common the condition was. The results were published in Kornberg’s first research paper in 1942. His internship was at Strong Memorial Hospital in Rochester, New York, between 1941-1942. After completing his medical training he joined the armed services as a Lieutenant in the United States Coast Guard, serving as a ship’s doctor in 1942. Rolla Dyer, the Director of National Institutes of Health, had noticed his paper and invited him to join the research team at the Nutrition Laboratory of the NIH. From 1942 to 1945, Kornberg’s work was the feeding of specialized diets to rats to discover new vitamins. The feeding of rats was boring work, and Kornberg became fascinated by enzymes. He then transferred to Dr Severo Ochoa’s laboratory at New York University in 1946, and took summer courses at Columbia University to fill out the gaps in his knowledge of organic and physical chemistry while learning the techniques of enzyme purification at work. He became Chief of the Enzyme and Metabolism Section at NIH from 1947-1953, working on understanding of ATP production from NAD and NADP. This led to his work on how DNA is built up from simpler molecules. In 1953 he became Professor and Head of the Department of Microbiology, at Washington University in St. Louis, until 1959. Here he continued experimenting with the enzymes which created DNA. In 1956 he isolated the first DNA polymerizing enzyme, now known as DNA polymerase I. This won him the Nobel prize in 1959.

 

In 1960, Kornberg received an LL.D. again from City College, followed by a D.Sc. at the University of Rochester in 1962. He became Professor and Executive Head of the Department of Biochemistry, Stanford University, Stanford in 1959. In a 1997 interview with Sally Smith Hughes, Arthur Kornberg (referring to Josh Lederberg) stated: “Lederberg really wanted to join my department. I knew him; he’s a genius, but he’d be unable to focus and to operate within a small family group like ours, and so, I was instrumental in establishing a department of genetics [at Stanford] of which he would be chairman.“

 

Kornberg’s mother died of gas gangrene from a spore infection after a routine gall bladder operation in 1939. This started his lifelong fascination with spores, and he devoted some of his research efforts to understanding them while at Washington University. From 1962 to 1970, in the midst of his work on DNA synthesis, Kornberg devoted half his research effort to determining how DNA is stored in the spore, what replication mechanisms are included, and how the spore generates a new cell.

 

The Arthur Kornberg Medical Research Building at the University of Rochester Medical Center was named in his honor in 1999. Until his death, Kornberg maintained an active research laboratory at Stanford and regularly published peer reviewed scientific journal articles. For several years the focus of his research was the metabolism of inorganic polyphosphate. The “Kornberg school“ of biochemistry refers to Arthur Kornberg’s many graduate students and post-doctoral fellows, i.e., his intellectual children, and the trainees of his trainees, i.e., his intellectual grandchildren. Kornberg’s intellectual children include I. Robert Lehman, Charles C. Richardson, Randy Schekman, William T. Wickner, James Rothman, Arturo Falaschi and Ken-ichi Arai.

 

On November 21, 1943, Kornberg married Sylvy Ruth Levy, also a biochemist. She worked closely with Kornberg and contributed significantly to the discovery of DNA polymerase. The day after he was awarded the Nobel prize, she was quoted in a newspaper as saying “I was robbed.“ Arthur and Sylvy Kornberg had three sons: Roger David Kornberg (1947), Thomas B. Kornberg (1948), and Kenneth Andrew Kornberg (1950). Roger is Professor of Structural Biology at Stanford University, and the 2006 laureate of the Nobel Prize in Chemistry. Thomas discovered DNA polymerase II and III in 1970 and is now a professor at the University of California, San Francisco. Kenneth is an architect specializing in the design of biomedical and biotechnology laboratories and buildings.

 

When he was in his eighties, Kornberg continued to conduct research full-time at Department of Biochemistry at Stanford. He died on October 26, 2007 at Stanford Hospital from respiratory failure.

 

Roger D. Kornberg wins the 2006 Nobel Prize in Chemistry

 

 

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Roger David Kornberg (born April 24, 1947) is an American biochemist and professor of structural biology at Stanford University School of Medicine. Kornberg was awarded the Nobel Prize in Chemistry in 2006 for his studies of the process by which genetic information from DNA is copied to RNA, “the molecular basis of eukaryotic transcription.“ “Kornberg“ was born in St. Louis, Missouri, the eldest of three sons of biochemist Arthur Kornberg, who won the Nobel Prize in 1959, and Sylvy Ruth (Levy), also a biochemist. He earned his bachelor’s degree in chemistry from Harvard University in 1967 and his Ph.D. in chemical physics from Stanford in 1972. He became a postdoctoral fellow at the Laboratory of Molecular Biology in Cambridge, England and then an Assistant Professor of Biological Chemistry at Harvard Medical School in 1976, before moving to his present position as Professor of Structural Biology at Stanford Medical School in 1978. His closest collaborator has been his wife, Professor Yahli Lorch. He has two younger brothers: Thomas B. Kornberg (b. 1948) -biochemist who was the first person to purify and characterize DNA polymerase II and DNA polymerase III; and Kenneth Andrew Kornberg (b. 1950) – architect specializing in the design of biomedical and biotechnology laboratories and buildings.

Some Background of the Science

All organisms are controlled by their genes, which are coded by DNA, which is copied to RNA, which creates proteins, which are sequences of amino acids. DNA resides in the nucleus. When a cell expresses a gene, it copies (transcribes) that gene’s DNA sequence onto a messenger RNA (mRNA) sequence. mRNA is transported out of the nucleus to ribosomes. The ribosomes read the mRNA and translate the code into the right amino acid sequence to make that gene’s protein. The DNA is transcribed to mRNA by an enzyme, RNA polymerase II, with the help of many other proteins. Using yeast, Kornberg identified the role of RNA polymerase II and other proteins in transcribing DNA, and he created three-dimensional images of the protein cluster using X-ray crystallography. Polymerase II is used by all organisms with nuclei, including humans, to transcribe DNA.

 

 

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X-ray crystallography shows the arrangement of water molecules in ice, revealing the hydrogen bonds (1) that hold the solid together. Few other methods can determine the structure of matter with such precision (resolution).

 

Kornberg and his research group have made several fundamental discoveries concerning the mechanisms and regulation of eukaryotic transcription. While a graduate student working with Harden McConnell at Stanford in the late 1960s, he discovered the “flip-flop“ and lateral diffusion of phospholipids in bi-layer membranes. While a postdoctoral fellow working with Aaron Klug and Francis Crick at the MRC in the 1970s, Kornberg discovered the nucleosome as the basic protein complex packaging chromosomal DNA in the nucleus of eukaryotic cells (chromosomal DNA is often termed “Chromatin“ when it is bound to proteins in this manner, reflecting Walther Flemming’s discovery that certain structures within the cell nucleus would absorb dyes and become visible under a microscope). Within the nucleosome, Kornberg found that roughly 200 bp of DNA are wrapped around an octamer of histone proteins.

 

Announcement of Roger Kornberg’s winning of Nobel Prize sent out by Stanford University:

 

The Royal Swedish Academy of Sciences awarded Roger Kornberg, PhD, of the Stanford University School of Medicine, the 2006 Nobel Prize in Chemistry for his work in understanding how DNA is converted into RNA, a process known as transcription. In 2001 Kornberg published the first molecular snapshot of the protein machinery responsible – RNA polymerase – in action. The finding helped explain how cells express all the information in the human genome, and how that expression sometimes goes awry, leading to cancer, birth defects and other disorders.

 

“I’m simply stunned. There are no other words,“ said Kornberg after the 2:30 a.m. call. “It’s such astonishing news.“ The scene at Kornberg’s house was one of controlled chaos, with nonstop telephone calls from well-wishers and media. Kornberg, who is also the Mrs. George A. Winzer Professor in Medicine, is the School of Medicine’s second Nobel Prize winner this week. On Monday, Andrew Fire, PhD, professor of pathology and of genetics, was a winner of the 2006 Nobel Prize in Physiology or Medicine for his work on RNA interference. Together the two awards serve as a clarion announcement of RNA’s arrival in the scientific and medical spotlight. “Roger has been one of my role models for many years,“ said Fire. “We did our post-docs at Cambridge in the same institute, and he’s been a tremendous help to me since I came to Stanford in 2003. Our fields are interestingly intertwined.“ Kornberg’s research, and latest award, is a family affair: his father Arthur Kornberg, PhD, was awarded the Nobel Prize in Physiology or Medicine in 1959 for studies of how genetic information is transferred from one DNA molecule to another. The Kornbergs are the sixth father-son team to win Nobel Prizes, in addition to one father-daughter team. “I have felt for some time that he richly deserved it,“ said the elder Kornberg after hearing about his son’s award. “His work has been awesome.“ Arthur Kornberg is the Emma Pfeiffer Merner Professor of Biochemistry, Emeritus, at the School of Medicine. He learned of the award from a nephew in LaJolla, Calif., who had been called accidentally by someone looking for Roger. “Roger Kornberg is one of our nation’s treasured scientists,“ said Philip Pizzo, MD, dean of the School of Medicine. “He has dedicated his life and career to using the powerful tools of structural biology to elucidate the molecular mechanism of transcription. His remarkable studies have been acclaimed for their elegance and technical sophistication as well as the unique insights they have yielded. His work has deepened our understanding of the ?message of life’ and how it contributes to both normal and abnormal human development, health and disease.“

 

Kornberg emphasized that the work required many contributions. “I am indebted to my colleagues,“ he said. “This is not something that I did alone, or even with a small number of people. It is the result of the hard work, insight and inspiration of very many exceptionally talented Stanford students and post-docs.“ Selective transcription of a cell’s tens of thousands of genes determines whether it becomes a neuron, a liver cell or a stem cell – and whether it develops normally or becomes a runaway cancer. The picture of RNA polymerase at work provided an atomic-level window into how the protein complex unzips and then re-zips the double-stranded DNA like a Ziploc bag after using the internal code to build a specific RNA molecule. It was a thing of beauty for biologists around the world. “We were astonished by the intricacy of the complex, the elegance of the architecture, and the way that such an extraordinary machine evolved to accomplish these important purpose,“ said Kornberg of the images he and his colleagues created. “RNA polymerase gives a voice to genetic information that, on its own, is silent.“ Learning how that voice is amplified – and shushed – through the selective expression of genes is a critical stepping stone to many areas of biological and medical research.

 

The path to the pictures involved a highly specialized field at the intersection of chemistry, biology and physics called crystallography. The technique, as much art as science, is the same one used by Francis Crick and James Watson to determine the double-stranded nature of DNA. In general, it involves evaporating a concentrated solution of a molecule until all that’s left are highly structured crystals somewhat like the crust of salt left behind by drying seawater. Extremely bright X-rays are then able to pinpoint the position of individual atoms and the data are used to produce a computer-generated representation of the molecule. Successfully crystallizing one molecule is a feat worth congratulating. Capturing the 10 subunits of RNA polymerase in action on the DNA was unthinkable. “It was a technical tour de force that took about 20 years of work to accomplish,“ said Joseph Puglisi, PhD, professor and chair of the department of structural biology at the School of Medicine. “Like other great scientists, Roger doesn’t quit. He’s stubborn. A lot of scientists would have given up after five years.“ Kornberg’s determination, coupled with his expertise in both crystallography and biochemistry, finally cracked the code. “I’m a biochemist and he’s a biochemist, but beyond that he’s a crystallographer, a structural chemist and a geneticist,“ said Arthur Kornberg. Roger Kornberg devised a way to first initiate the process of transcription in a test tube and then stall it by withholding one of the building blocks of RNA. Crystallizing the frozen complex showed the relative positions of the polymerase, the DNA template and the growing RNA strand.

 

“Professor Kornberg’s seminal research on transcription has been an exceptional contribution to the body of knowledge in fundamental biology,“ said Stanford University President John Hennessy. “His work settled long-open questions about how genes communicate the information needed to make proteins and will help us understand a variety of diseases that can be caused by a failure in the transcription process. For the second time this week, a colleague’s achievement reminds us of the unique role universities have in advancing basic knowledge. We are proud to claim Professor Kornberg and his father Arthur as members of the Stanford family. I offer Roger warm congratulations on behalf of the entire university community.“

 

Prior to beginning his work studying the molecular mechanism of transcription, Kornberg discovered the nucleosome, the basic unit from which all chromosomes are made. In 1974, as a junior scientist at Cambridge University, he proposed that the massive amounts of DNA contained in every cell could be compactly stored by wrapping it in its condensed form – the chromosome – around eight histone protein “spools“ to form nucleosome “beads.“ Kornberg and his wife and collaborator Yahli Lorch, PhD, associate professor of structural biology at Stanford, were instrumental in identifying the nucleosome as fundamental to transcription. Since then, it has been recognized that disruptions involving the nucleosome underlie many cancers and other diseases.

 

“Roger was a scientist from the beginning; He never showed any other interest,“ said his brother, Thomas Kornberg, PhD, a professor of biochemistry at the University of California-San Francisco. “Both my parents had fine scientific minds and taught by example how to approach questions and problems in a logical, dispassionate way,“ Roger Kornberg once said. “Science was a part of dinner conversation and an activity in the afternoons and on weekends. Scientific reasoning became second nature. Above all, the joy of science became evident to my brothers and me.“ Kornberg was able to indulge his scientific bent early as a high school student working in the laboratory of Paul Berg, a colleague of his father’s at Stanford who won the Nobel Prize in Chemistry in 1980. The senior Kornberg said his son’s winning did not come entirely out of the blue. He had mentioned the chemistry prize yesterday in a conversation with his son, who had just returned from a trip to Jerusalem. “I talked to him at length and couldn’t help but discuss this possibility – I know he’s been shortlisted in previous years,“ said the elder Kornberg. “He dismissed it, saying it was a possibility but he didn’t expect it, but that’s the way it goes.“ Arthur Kornberg said he had not imagined decades ago, when his son first began his career as a biochemist, that there would be a second Nobel laureate in the family. “Of course not,“ he remarked. “But nature is so broad, profound and mysterious – one doesn’t know where it leads. And I would say among the people I know – and I have trained many hundreds – he has the clearest vision, sense of purpose and direction.“ Pizzo paid tribute to the contributions of both father and son to Stanford. “Arthur Kornberg played a major role in transforming the Stanford University School of Medicine into a research-intensive powerhouse,“ Pizzo said. “He was clearly productive in both his professional life and his private life – since he is the father of remarkably talented children, including Roger – who has sustained a legacy of brilliance and commitment to science and the deepening of our understanding of human life.“

 

Roger Kornberg received his undergraduate degree in chemistry from Harvard in 1967 and his doctorate in chemistry from Stanford in 1972, studying the motion of lipids in cell membranes. He was a postdoctoral fellow and member of the scientific staff at the Laboratory of Molecular Biology in Cambridge, U.K., from 1972 to 1975. He joined Harvard Medical School in 1976 as an assistant professor in biological chemistry. Kornberg returned to Stanford in 1978 as a professor in structural biology. He served as department chair from 1984 until 1992. Kornberg is an elected member of the National Academy of Sciences and of the American Academy of Arts and Sciences, and an honorary member of the Japanese Biochemical Society. He is editor of the Annual Reviews of Biochemistry. He has written more than 180 peer-reviewed journal articles. His previous honors and awards include the Eli Lilly Award (1981), the Passano Award (1982), the Harvey Prize (1997), the Gairdner International Award (shared in 2000 with Robert Roeder), the Welch Award (2001) and the Grand Prix of the French Academy of Sciences (2002). “One of the benefits of the recognition of work such as ours is that it encourages continued support of fundamental issues like this one,“ said Kornberg. “Many of the major advances in human health have their origins in the pursuit of basic biological knowledge.“ His funding sources agree. “Through decades of elegant, state-of-the art studies in biochemistry and structural biology, Roger Kornberg has revealed the mechanism underlying how cells transcribe genetic information,“ said Jeremy M. Berg, PhD, director of the National Institute of General Medical Sciences, which has funded Kornberg’s research since 1979. “This knowledge sheds light on a fundamental process that is key to health and disease. The achievement also demonstrates the power of innovative approaches to probe the many complicated molecular assemblies essential to life.“ Despite the kudos, wining such a prestigious award can create complications: Kornberg was scheduled to fly to Pittsburgh this evening to receive the Dickson Prize in Medicine. When he called to cancel his flight, the Travelocity operator wanted to know the reason for the cancellation. There was a pause, and a gulp. “Well,“ he said. “I just won the Nobel Prize in Chemistry.“ There’s no word yet as to the operator’s response, but perhaps he can roll the ticket over to his upcoming trip to Sweden. “I’m looking forward to being in Stockholm, where we have many friends,“ said Arthur Kornberg, remembering his own award 47 years ago. “They put on a great party.“

 

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