Toward innovative research: Lessons from the Kornbergs July 23, 2007 Yasuda Auditorium Introduction by Ken-ichi Arai

Kornberg Family Photo in 2006, Stockholm Dear Arthur, Roger, Tom, Ken, welcome to Tokyo! Kornberg Family Photo in 1959, Stockholm Roger Ken Sylvy Arthur Tom

Sylvy discovered the enzyme that makes huge polyphosphate chains. Her high intelligence led to key insights at many stages of our work on replication. For the Love of Enzymes The Odyssey of a Biochemist Arthur published books; DNA Replication, For the Love of Enzymes, Golden Helix (Inside Biotech Ventures).

This book is a modern-day “Book of Five Rings” that replaces the medium of Swordmanship with that of , particularly enzymology. In relating his story, Kornberg never avoids the difficult question of why? Joining the Enzyme Hunters: Arthur’s Mentors

Gerty & Carl Cori in 1947

Gerty had no faculty appointment until 1947 when she shared the Nobel Prize Severo Ochoa in 1955 with Carl. I had come to the Cori laboratory to solve the major problem in I went to New York to meet Ochoa. He biochemistry, the mechanism of aerobic agreed to take me and I started as his phosphorylation. first postdoctoral student a month later. Arthur Kornberg Network

S. Ochoa NYU, USA A. Kornberg O. Hayaishi Stanford, USA Kyoto A. Kornberg, Y. Kaziro, O. Hayaishi, R.& T. Okazaki C. Weissmann K. Ueda, K. & N. Arai Y. Nishizuka, K. Ueda, T. Honjo H. Okayama, T. Shimizu

P. Berg Stanford, USA C. Weissmann Y. Kaziro R.&T. Okazaki Zurich, Swiss IMSUT H. Okayama Nagoya R. Mulligan T. Tadatsugu, K.& N. Arai , S. Nagata S. Nagata, A. Miyajima, T. Yokota DNAX California, USA K.& N. Arai, A. Miyajima, T. Yokota, K. Matsumoto Human Network in Life Science Ochoa-Kornberg network extends to Japan via Kaziro, Hayaishi & Okazakis

Yoshito Kaziro Ochoa & Shimazono (Kaziro’s mentor in Japan) were close friends.

Yoshiaki Miura

Severo Ochoa, Arthur, Paul Berg

International Symposium in Honor of Yoshito Kaziro in 1989 Severo Ochoa & Sumio Shimazono The Enzyme Section, NIH in 1952 Osamu Hayaishi Arthur

Osamu Hayaishi, later to become the doyen of biochemistry in Japan had come from Osaka, and was working with me at NIH as a postdoctoral fellow. He later moved with me from NIH to Washington University to become an assistant professor, the first appointment I made as a chairman of the new department of microbiology. The Microbiology Department, Washington University, St. Louis in 1956 R. Lehman Arthur P. Berg D. Hogness

The Stanford Biochemistry Department began to coalesce in 1953 while I was still in St. Louis. I left Bethesda for St. Louis on January 21, inauguration Day of President Eisenhower. DNA Synthesis, Chromosome & Replication Fork

The ability to manipulate and alter DNA fired a revolution that forever changed the nature of biology. Arthur is a primary architect of this revolution. Prior to Arthur, genetic information and later DNA were imbued by biologists with almost vitalistic aura. Arthur demonstrated that DNA is a molecule synthesized by enzymes, like all other chemical constituents of the cell. Stanford University Department of Biochemistry in 1980 Arthur N.& K.Arai

I have been fortunate in my family life-at home and in the laboratory. The Biochemistry Department at Stanford seems strange to most people-a small faculty, together for over thirty years, sharing resources communally and focusing on single subject, DNA. Arais at Stanford in 1977 Paul Berg visited Japan in 2006 S.Watanabe Department of Biochemistry

Paul & Stanford/DNAX Alumni I.&A.Miyajima

H.Okayama Reiji & Tsuneko Okazaki When Reiji and Tsuneko left my laboratory in 1963, they returned to Nagoya University where they made their epochal discovery “Okazaki Fragments” & “semidiscontinuous replication” Biochemistry Department, Stanford in 1963 Arthur & Sylvy with Okazakis in 1975 Arthur Reiji & Tsuneko

!"#$%&'%()#*)+,#"-%./+/0"1*%2033 Astonishing Machines of Replication

RNA priming & Primosome

The Locomotive that starts DNA chains

DNA Polymerase III holoenzyme & Replisome The Super Sewing Machine under the Fig Leaf of the replication fork At Biochemistry Department Stanford in 1980

At DNAX in 1985

Arthur Roger

Arthur Kornberg, Paul Berg, Charles Yanofsky established DNAX with Alex Zaffaroni combining molecular biology, cell biology and . DNAX shed light on cytokine network and signaling through receptors

Arthur Hugh McDevitt Gene Hunters and the Golden Age industry in

Double helix Genetic code Arthur Kornberg DNA polymerase DNA polymerase Discovery Splicing 1959 Nobel Prize Ribozyme

Cloning Sequencing PCR Paul Berg Innovation SELEX Gene targeting 1980 Nobel Prize

Translational

Researc h Genome Diagnosis Genomic Drugs Gene Therapy Alejandro Zaffaroni New Products Cell Therapy DDS, DNA chip Regenerative Entrepreneuer Medicine

Arthur trained a school of scientists who focused on and discovered many of the enzymatic activities on DNA. It is these enzymes that allow modern “genetic engineering”. Roger Kornberg

Roger proposed Nucleosome structure of chromatin in 1970s Nucleosome

At Stanford

Our children were often with us in the lab after school let out and often weekends.When asked at age nine what he want for Christmas, Roger said “A week in the lab.” Roger Kornberg

With Summer Students in 1996, Stanford

Roger will give a lecture on in 2006, Stockholm Eukaryotic Transcription tomorrow at Tetsumon Auditorium Tom Kornberg

Tom’s talent for music and devotion to the cello from the age of eight precluded any special attention to science. At sixteen, he was selected for the Juilliard School. At my urging, Tom also enrolled as a full- time student at Columbia College. At UCSF

M. Sato

Tom will talk about Developmental Biology tomorrow at Yayoi Auditorium Ken Kornberg

Ken’s early exposure to biochemistry was evident when at the age of eight. But science was not to be his profession. Ken did not escape science entirely. As an architect, he specializes in the design of laboratories and buildings for research in biomedical science and biotechnology.

With Vietnam delegation Ken will give a talk on Designer Laboratory this afternoon. We thank Arthur & Carolyn for coming to Japan At their home in Portola Valley with Ken

Arthur will give a talk on Inorganic Polyphosphate tomorrow afternoon At IMSUT. We thank all members of Kornberg Family and wish you to have pleasant time in Japan!