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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

The Future of Life Science

Nagami If you look back over the history of life science, you can see that major events like the rediscovery of Mendel's law, the discovery of the double helix structure of DNA, and the sequencing of the entire human genome happen every 50 years or so. What do you think biology, with its roots in the genome, will be aiming for in the long term?

Hotta In my opinion, no matter what the aims are, it will be essential that the science and technology of informatics and computers make progress quickly enough to keep up with the vast amounts of complex information that are going to be produced. The first thing is to make sure all the research results are accumulated in databases that work harmoniously and correctly. These databases should conform to minimal requirement and format so that all can be linked and become a large and comprehensive "Life Science Database". We need to develop a kind of common platform - with an operating system (OS) - like function - on which researchers could make a new program or combine different tools to make an integral use of the complex and large-scale experimental data. However, I don't know whether the people who will develop such a new kind of research will necessarily be biologists. We may need help from people in totally different fields. When molecular genetics first started, it was not biologists, but physicists who really pushed the discipline forward. I have the feeling that the same thing may happen all over again.

Wada That's an interesting point. Just what kind of people are going to be the torchbearers for this discipline in the future?

Hotta They may well be mathematicians, or information scientists. Not just average mathematicians, but true geniuses. I am imagining mathematicians who could really jump into experimental sites and quickly understand the entire production or processing of data on-site. If they do so without losing mathematical genius, they will tell biologists what sort of things might be possible in the future. Biologists of today often rely on their intuition in order to decide what should be done next, but this is no more efficient when you are dealing with vast amounts of data. Our brain is no more sufficient to make judgments based on logical foundations related to so many data and knowledge. Invention of a new mathematical or informatics framework is wanted to bring about a breakthrough in biology.

Wada I get the feeling that analysis of the stimulus-reaction responses of cells that are operating on the basis of the genome is being neglected at present. I believe that comprehensive analysis of how the 200 or so kinds of human cell react to stimulus-responses may be essential in future biology research. I think it would be useful if we could make a chip or something similar that had as many as a million holes into which cultured cells could be inserted.

Nagami What are your opinions regarding the contribution of GSC and biology to society?

Sakaki I think Dr. Hotta has his own personal theory of a hierarchy within biology, taken from the old Japanese hierarchy of samurai, farmers, artisans, and merchants.

Hotta The hierarchy I was talking about refers to research fields within biology. When I was younger, I started to work in classical genetics such as that on fruit flies or nematode worms. Thanks to the introduction of modern molecular tools, the field is now really at the maturation stage, as being the top, noble "samurai," class. The papers produced from that kind of research have to be perfect, and all the possible experiments have to be done to confirm the logics before being accepted by a good journal. They are almost works of art. Then similar technologies became applicable to mice, ignoring some imperfections. Although the wording is a little off, I viewed that kind of research as producing a kind of "farmer-level" papers using incomplete, but yet very interesting data. The noble class researchers frowned at it, but a revolution inevitably arrived, and the farmers have gotten more attention than the samurai. Just as I was mourning the loss of samurai-level papers, along came a merchant class, who turned biology into a commercial business.

Wada Where does that leave the artisan class?

Hotta They are represented by technology. Although the merchants stepped forward, thinking they would profit considerably from science, it turned out that technology held the key to success. Therefore, the current stage is characterized as the transition from artisan to businessman.

Yoshiyuki Sakaki

Sakaki That is a very interesting line of thought. The kind of social contribution that springs to mind is using research results to understand the mechanisms of disease and develop treatment strategies. Also, I believe that it may be possible to gain a thorough understanding of the life strategies of all the world's organisms, and then apply this knowledge to environmental protection measures, the development of foodstuffs, and drug discovery. I'm sure there must be a great many organisms on the face of this planet that are carrying out unimaginable chemical reactions and producing unknown substances. If we can better understand these mechanisms, we will undoubtedly find things that will have major benefits for our way of life or for industry.

Wada Absolutely. Development basically occurs when disparate elements are discovered, then more knowledge is gained about the interactions between these elements, and then larger networks are found. One element has already been found, in the shape of the genome, and the next step is to investigate the interactions between genomes and networks. I think it will be highly profitable to analyze unknown life phenomena, as well as intestinal flora, soil bacteria and so on.

Hotta In a sense, I feel that biology is following the same path as physics. Application of physics is found everywhere; for example in X-rays and electronics. But they were originally started as "samurai" science, and now are found everywhere in our daily lives and produce money for some people. I wonder if biology won't go the same way. In order for this to happen for the best of ourselves, technology and commercialism are not enough.

Akiyoshi Wada

Wada However, don't you think that the samurai-level research will also be important as a discipline in the future? Inquiry into grand questions concerning the nature of the universe, matter, life, and human beings is important, but it is basically not being pursued by the biology community. When thinking about applications or social contribution, there has got to be some kind of large aim backing it up. If there isn't, we can't expect young people to get involved.

Sakaki I think you're absolutely right. Not only is it interesting to look at the evolution of humans and of human behavior from the samurai viewpoint, but those points are also very interesting for the general public, and although they are grand questions, I think they may become extremely important themes.

Wada In physics it is acceptable to look only at short-range interactions, but in biology, whether you look at evolution of organisms or the life of individual organisms, there are extremely long-range and large-scale interactions at work. That is precisely why I think mathematics is going become so important, particularly network theory.

Yoshiki Hotta

Hotta And, even more precisely, new mathematical frameworks may be needed, such as group theory, that can be used to classify and categorize complex networks. The so-called theoretical biologists are using algebra and differential equations to simulate biological processes, but other mathematical methods are also needed for the visualization of extremely complex and vast data through the use of well-deigned coordinates. I hope that kind of a new "theoretical biology" will emerge from the genome and related studies. Simulation is amusing but not enough.

Nagami Do you think that the mechanisms of society will be able to cope with breakthroughs in biology that you foresee?

Sakaki The first question that will arise is that of applying genomic information to medical care. It is said that in 10 years, it will be possible to read anybody's genome in a few days for a 1000 dollars. There are as yet various questions as to how that information should be used. Take for example snips (SNPs-single nucleotide polymorphisms). There is a lot of research currently being carried out into snips, but although they can give information about disease risk for whole populations, it is difficult to use them to get information about disease risk for individuals. I think that if it is not shown that the genome information that can be obtained is of real merit to the individual, the concept of reading someone's genomic information will not be accepted by society. Once there has been discussion in society as to the positives and negatives of obtaining an individual's genomic information, and the rules of its use, the care to be given after diagnosis, necessary legislative revisions, and whatever else is needed, and once the necessary changes and arrangements have been made, then we can start to give something back to society.

Hotta I would be very happy if results from the genome biology could bring cost reductions in medical care. That is unfortunately the exact opposite of the current situation, in which the development of a new technology leads to a new diagnostic device or drugs, pushing up the cost of medical care astronomically. Medical care is already going bankrupt, so it would be a superb social contribution if research based on the genome could bring about a reversal of this trend.

Wada Just as everybody has said, there are various ways to use research results. However, what I would like all of you here at GSC to do is keep in mind that the genome is the soul of 3.8 billion years of survival wisdom, and to probe and understand this wisdom to find the essence of life.

Nagami Thank you all very much for your time today.

(Written by Naoko Nishimura, Science Writer)