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Opening Discussion

Yoshiyuki Sakaki, Akiyoshi Wada, Yoshiki Hotta
Ten years at GSC, the institute that began a new era of genomics

GSC-RIKEN Genomic Sciences Center-was founded at the beginning of the genomic age, and now, in 2007, moves into its tenth year. GSC has been the flagship institute for Japanese genome research, and has contributed to the Human Genome Project, a project comparable in stature to the Apollo program. Let us listen to what Yoshiyuki Sakaki, Akiyoshi Wada and Yoshiki Hotta have to say about the past 10 years at GSC, about how GSC has presented itself to the world, and about plans for the future.

Akiyoshi Wada
RIKEN Science Advisor

Graduated from the Department of Chemistry, the University of Tokyo in 1952, got a degree of Doctor of Science. After serving as a Professor in the Faculty of Science, the University of Tokyo and as a Dean of the Faculty of Sciences, he became Director of GSC in 1998, following which he assumed Director of GSC in 2004.  And he assumed his present position in 2008.

Yoshiyuki Sakaki
President, Toyohashi University of Technology

Completed a doctoral course in the Department of Biochemistry and Biophysics at the University of Tokyo in 1971, and got a degree of Doctor of Science. After serving as Professor at the Institute for Medical Sciences, the University of Tokyo and as Project Director at GSC, and  Director of GSC in 2004,  he assumed his present position in 2008.

Yoshiki Hotta

President, Inter-University Research Institute Corporation,
Research Organization of Information and Systems

Completed a doctorate course in the Medical School of the University of Tokyo in 1968, graduating as a Doctor of Medical Science. After serving as a professor in the School of Science, the University of Tokyo, he took up the post of Director-General of the National Institute of Genetics in 1997. He then assumed his present position in 2004.

[Facilitator] Fuji Nagami

Science Communication Director, Associate Professor
Tohoku Neuroscience Global COE, Tohoku University

After completing the coursework for a doctorate in the Graduate School of Arts and Sciences at the University of Tokyo in 2002, Mr. Nagami took up a position in the same year at the National Museum of Emerging Science and Innovation. He has been responsible for science communication at JST since 2006, engaged in, among other things, the creation of "Science Agora". And he assumed his present position in 2008.

Trials and Tribulations on the Road to Founding GSC

Nagami: If we could start by looking back over the sequence of events and aims in the run-up to establishing GSC, as well as the problem points that you encountered along the way.

Wada: The first thing I can tell you is that GSC was not created because it had suddenly become necessary, although doing things that way was common in those days in Japan. Although I graduated from the chemistry department of Tokyo University, while I was studying abroad at Harvard University I met Watson and Pauling, who were at that time working on biopolymers, and I came across the new concept of considering life to be pieces of molecular equipment operating in a material world. I then began to consider as best I could at the time what it was that linked matter and organisms. After that, while working as an assistant professor and professor in the physics department of Tokyo University, I came to believe that it was necessary to create a giant machine that could take in the vast quantities of information contained within organisms in one huge batch. I thought that it would be difficult for there to be any consistent progress in biology when targeting something as complex as a living organism unless we could create a machine that could carry out this processing. At that point, we already knew that the genetic information of organisms was written as DNA, so after some deliberation, we decided to set ourselves the goal of reading a vast amount of this information, believing it to be the interface between life science and material science. That, for me, was the starting point for founding GSC.

Nagami: Only Dr. Wada could have thought of an idea like reading the DNA of an entire genome at a large-scale genomics center at a time in the age when biology was carried out on such an individualized basis in discrete laboratories. Your ideas and efforts then bore fruit in 1998, in the shape of the national center, GSC. Could you explain why at that point you chose to create groups covering five territories, including protein analysis and accumulation of cDNAs, and didn't just focus on reading DNA?

Wada: At that time, there was already a major effort underway in United States to read the genome, and that effort had already overtaken Japan. Just as I was thinking that Japan shouldn't lose out in this situation, Yoshiyuki Sakaki (the present Director of GSC) and Nobuyoshi Shimizu (at present, a Keio University professor) and others began work to read the partially decoded genome. I immediately asked Professor Sakaki to collaborate. However, thinking that simply by reading the genome we would not gain a comprehensive understanding of life as piece of working equipment, and after numerous discussions, I decided to cover five territories of research, including protein analysis and informatics. Having said that, there were some heated discussions and serious amounts of hard work involved in acquiring the budget for founding the center.

Nagami: Dr. Sakaki, how did you feel upon starting up one group out of those five territories?

Sakaki: Ever since the discovery of the double helix structure of DNA, decoding genomic information has been a major theme in the life sciences. I am a graduate of the faculty of science, and I used to carry out research into microbial genes. However after I began working in the medical faculty of Kyushu University in 1977 my focus shifted to humans. DNA sequencing technology allowed us to analyze humans and E. coli in the same way, although for me personally, decoding the human genome was part of an inevitable process, along with discovering retrotransposons and genes responsible for genetic disease, and so on. When I met Dr. Wada at the 1987 corporate Hayashibara Mutual Aid Forum (Hayashibara Forum), the general drift was towards America playing the leading role in the human genome project, and Dr. Wada's perception that Japan ought to have a solid system for sequencing of the human genome really made a big impression on me. Kenichi Matsubara (at that time a professor at Osaka University, and presently the representative of DNA Chip Co. Ltd.) was appointed as leader of the Japanese efforts for the human genome project, and I was also involved from the outset. We put lots of effort into sequence analysis during the latter half of the 1990s, including setting up the international consortium for determining the DNA sequence of human chromosome 21. Those efforts were connected to the start-up of the Human Genome Research Group at GSC. I didn't think that decoding the genome would be the ‘be all and all end all', but I did think that without deciphering the genome there could be no genomic sciences.

The Human Genome Comes into Focus

Dr. Wada was the first person in the world to propose automated high-speed technology for deciphering DNA sequence, but it was in fact not Japan but the United States and countries in Europe that first realized its true importance. The US took a particularly positive attitude towards deciphering the human genome, declaring in 1985 that they intended to read all 3 billion human DNA base pairs in a human genome project. In 1998, the human genome organization (HUGO) was established through appeals from James Watson and Victor McKusick, who were to lead the project, and The International Human Genome Project began in earnest in 1990, under the cooperation of Japanese, European, and American researchers working on "The International Human Genome Project". The latter half of the 1990s saw a move into the long awaited sequencing age. At a meeting in 1996 in Bermuda, a decision was taken to split the task of sequencing the human genome between several countries. Japan was allocated human chromosome 21, and the Japanese team, consisting of Yoshiyuki Sakaki, Nobuyoshi Shimizu, and their colleagues, successfully sequenced the entire chromosome in 2000 with the collaboration of the German team. Around that time, America's private sector, Celera Genomics directed by Craig Venter, developed an ultra high speed technique for determining DNA sequence known as shotgun sequencing, and he began using this method to sequence the human genome independently of the other efforts. The international team, sensing an impending crisis due to the activities of Venter, revised part of their plan, and published a draft version of the human genome in 2001, followed by a complete version in April 2003. It was through these efforts that, for the first time, the human race held all of their genetic data in the palm of their hand.

Nagami: Dr. Hotta, I believe that you were able to view Dr. Wada's activities before he became busily involved with establishing GSC. What were your feelings at the time that Dr. Wada became the first director of the center?

Hotta: My research laboratory was adjacent to Dr. Wada's for around 20 years in the Physics Department. Since I had been a graduate of the medical school, and I viewed genes as a tool that could be used to understand how the brain is designed for its mysterious function. In other words, I saw genes as being on a par with electrodes in electrophysiology, or microscopes for histology. Just as I was thinking along these lines, Dr. Wada from the laboratory next door began saying that we needed to make DNA sequencing cheap and fast. Dr. Wada said to me, "Don't you think it would be great if we could determine sequence rapidly?" To which I replied, "Absolutely, it would be marvellous." He then asked me how much I could pay for reading a base pair for my research and I, thinking of my research budget in comparison to the length of the genes that we were deciphering, said "Probably about 10 yen per base or less". I remember, I was greeted by laughter and the reply "Well, that's not going to happen, is it?". That was about the extent of my knowledge about reading the genome at that time .

Nagami: What was it like after the establishment of GSC?

Hotta: When sequence data started to come out, I was somewhat puzzled. It made me think about questions like, "Up until now science has been beautiful by looking at a limited part of the whole complex picture and trying to imagine the rest, but now, without knowing what it really means, we are suddenly able to read the whole thing. What does this mean?" and "What kind of era is this, when we are able to read the entire genome?" However, sequencing a huge amount of DNA at a university lab would have been difficult, and, as I thought it was inappropriate to have graduate students working mostly on base sequence determinations, I thought it would be a good idea to set up an organization with a large-scale sequencing apparatus and staffs dedicated to the sequencing. With the establishment of GSC, I began to get some idea that the genomic age could well give rise to new breakthrough in science, but I was reluctant to be really involved in it by myself.