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Opening Interview: Let's Create Technologies that Contribute to the Society by Seeking Originality and Creativity - The Future Created by Biotechnologies and Industry-academia Collaboration -- Isao Karube + Kiyoshi Itao

Let's Create Technologies that Contribute to the Society by Seeking Originality and Creativity

Isao Karube

Born in Tokyo in 1942. He graduated from the Tokyo University of Fisheries having dreamt of becoming a sailorman. But he had to give up the dream because he found he gets seasick severely. After graduating from the Ph. D. course of the Department of Science and Technology, the Tokyo Institute of Technology, he did research at the University of Illinois as a visiting researcher, he served as a professor at the Resources Chemistry Laboratory at the Tokyo Institute of Technology. He was appointed Professor of Research Center for Advanced Science and Technology, the University of Tokyo in 1988. Since 1999, he is Director of Center for Collaborative Research, the University of Tokyo.

Since Prof. Karube developed the first biosensor in the world, he has also been known as "Karube of Biotechnology". His motto is "Originality that makes difference from other people".

He received Japan Academic Chemistry Award, Ichimura Academic Contribution Award, Honorary Doctoral Degree from the University of Lund, French Government's Contribution Medal and other awards. He has published many books including "Acquiring originality" by Nippon Keizai Sinbun, "Future of bioelectronics" by NTT Publishing Co., Ltd., "My methods of Intellectual Production and Technique to Think" by Mikasa Shobo Co., Ltd.

The future created by biotechnologies and industry-academia collaboration

Itao: Professor Karube, I understand that you have been very active in industry-academia collaboration in inventing and developing biosensors. When did you acquire such an attitude?

Karube: When I was a student actually. The Tokyo Institute of Technology where I studied valued practical learning because it had been a school for craftsman from the beginning. My mentor also asserted that a faculty of engineering at a university should study something practical. His mentor was Professor Yogorou Kato who discovered the ferrite. People thought that we must create something useful for the society.

The first research topic I was told to study when I joined the research group was to fabricate Vienna sausage skin artificially. There were several methods to make Vienna sausage skin. The method I studied was to do so electrically. When I collected protein to an electrode electrophoretically and removed the protein from the electrode, the skin was created at a speed of 10 m per minute to my surprise. I found the method for the first time and filed a patent. As a custom then, the patent was filed by my professor's name and I was not listed as an inventor unfortunately. But I learned that patents were very important and they create incentives. It was an episode when I was a master course student.

Itao: It's amazing that you did it when you were so young.

Karube: The paper I wrote on that work was accepted and published in a journal titled, "Industry and Engineering Chemistry" without being asked to revise. I remember that I was too happy to sleep that night. The editors told me that they corrected all the English mistakes because my English was hopelessly poor but the idea was excellent (laughter).

Itao: It was because of the originality in the paper, wasn't it?

Karube: One company purchased the technology to manufacture Vienna sausage skin that we developed but the technology has been stored without being used because the company earned money in pharmaceuticals and focused their business in that area only. I learned a lesson that even a good invention may not be developed to commercial products in a company.

Itao: How did your research activities move since then?

Karube: The experiences proved useful when I extended my research activities to investigating the mechanism of how protein molecules get attracted to the electrode. I actually obtained my doctoral degree with that topic. In the last chapter of my doctoral thesis, I proposed to wrap enzyme using the protein film because it is very thin and strong. I presented my idea at an international conference. It was a strange coincidence that the presentation was highly praised by Dr. Katzir, the fourth President of Israel who created Weizmann Institute of Science. Dr. Katzir was called a right-hand man of Mr. Weismann who is the father of Israeli nation- building. He received the first Japan Prize, by the way. Anyways, Dr. Katzir praised my work saying it was very interesting. That was the trigger to use the technology in sensors.

Itao: I see. That was the beginning of your sensor research activities.

Karube: After graduation, I went to the University of Illinois to study there for two years because the research on protein was necessary in the research on arterial sclerosis. I did research in basic medicine on how fat adheres to blood vessel walls in a research environment where everyone except me was a doctor. After I returned to Japan, I started to focus on sensor research fully. I did research in the environment field where I developed what is called BOD sensors. They are used in many applications today. In this sensor, microbes are captured in a film. They are arrayed like in a chip. When the sensor with an electronic device is contacted to water, the microbes emit signals. Contamination in the water may be detected this way. Since this was the first microbe sensor, it was recognized in the world instantly. An English magazine titled, "New Scientists" called me "The father of biosensors." I was called that way because Dr. Clarke in the US who proposed the concept of biosensor had been called "The mother." I extended the concept and developed the biosensor.

Itao: I understand that you developed many kinds of biosensors after that.

Karube: Yes, I developed many sensors including a fish freshness sensor, a lactic acid sensor and an alcohol sensor. The sensor applications related closely to our daily life are in medical fields. The blood sensor has been used in a medical check-up. Since blood travels around a human body in four minutes, we can determine which organ is ill if we check chemicals and enzymes in the blood. There are more than 2,000 kinds of enzymes in a human body and each of them can detect specific molecule. If we test blood using a sensor with the enzyme and analyze the signal from the sensor, we can determine what is happening in a human body.

I think equipment to test DNA and AIDS virus which are urgently needed will appear in the market in two or three years. It has been great that industry-academia collaboration worked well in the research stage. Such human network will be important in technological development from now on.

Itao: Which field are you focusing on these days?

Karube: One of the fields is environmental issues. Take algae for example. They absorb CO2 in the air well. I'm doing research to enhance their capability by using biotechnology and fix CO2 in algae. Some microbes adjust themselves in the air with very high CO2 concentration of 30 to 40%. They absorb CO2 and create carbohydrate or protein. It's like killing two birds with one stone to get protein from CO2.

Challenges in Industry-Academia Collaboration

Itao: Your pioneering activities promoted enacting the TLO law (Technology Transfer Promotion Law) in 1998. Since then, many TLOs (Technology Licensing Organization) have been established. CASTI (Center for Advanced Science and Technology Incubation: Located in Advanced Science and Technology Center of the University of Tokyo, this center files patents and transfers new technologies from the university to companies for researchers) which was established under your leadership is doing very well. What do you think are the challenges to make the best use of research achievements of universities in the society?

Karube: Thanks to TLOs, research achievements from universities became closer to real applications. Staff of TLOs bridge universities and companies by explaining contents of research activities to companies, the value of which hasn't been well understood by them. They also file patents and set licensing fee, which used to be burden, for university researchers. Industry-academia collaboration has been active in the US since 1980. By 1996, as many as 1990 venture companies were established, and 3.4 trillion yen of sales and 220,000 jobs were created.

One problem is that the National Public Service Law imposes many restrictions to national university professors when they collaborate with other groups and organizations.

Itao: If you lived in the US, you might be able to create a very promising company because you could be a university professor and a company president at the same time.

Karube: I wanted to become a director of a research laboratory in a certain city but I couldn't get permission. The government would have to compensate any damage I might cause because a laboratory director is responsible for the management. My health might also be a concern. Such were the reasons.

Itao: I believe that collaboration in work and human interactions would be beneficial in general.

Karube: You're right. The issues of public servants' ethic are important and I understand the background. But building up human network would be difficult if the Information Disclosure Law would prohibit even having dinner with relevant people.

Itao: Although Japanese researchers are excellent, Japan is behind the US due to poor economy situation. After all, it's the lack of social back-up system as in the US that allows such a situation even though individual researchers have willingness and materials to start a business.

Karube: There is a back up system in the US that a whole bunch of lawyers and accountants get together to help universities. We don't have such a network system in Japan.

Itao: In terms of competition with the US, America started to place emphasis on basic research when the Japanese government started to spend more money on basic research after being criticized for free ride on American technologies.

Karube: It seems that Japan has been tossed about by the US.

Itao: The Japanese government has been encouraging industry-academia collaboration but it is still questionable to me if whipping along the road would work. I'm interested in industry-academia collaboration myself because I'm also involved in research activities in practical topics. But I fear that it would fail again if they drive people too much toward industry-academia collaboration.

Karube: I fully agree with you. The main mission of a university is to accumulate knowledge. Of course we must try to get benefits from the knowledge but it's quite dangerous if everyone looks at doing business. A professor who devotes to research and tries to accumulate intellectual achievements and convey them to the next generation wouldn't have to worry about giving benefits back to the society. A university covering many research fields like the University of Tokyo would be able to accommodate two types of activities.

Itao: A system that allows coexistence of many types of activities would be ideal. In such a system, many options are equally possible allowing one person to do business while other person to devote to research. We would want more varieties of options as in the US such as working for two days for what a professor would really like to do.

Karube: That's the reason why I don't think changing universities to independent administrative institution while retaining public servant status in professors wouldn't work. On the same token, I believe that the government must duly support 90% of research budget while establishing independent administrative institutions consisting of non-public servants. Universities with global competitiveness such as MIT, Harvard and other private universities spend research budget, 90% of which is covered by the government. A university should allow basic research and practical development under such a funding system.

Food Genomics Will Change Living and Life

Itao: Professor Karube, you have been involved in such research fields as clone technologies, gene therapy, food production by artificial recombination of genes and so forth. What do you think about the possibilities of such technologies?

Karube: I don't think human clone would be a reality because of the bioethics issues but such projects as organ regrowth will progress. A while ago, Embryo Stem (ES) cell was made in a human. Since the ES cell is a stem cell, it may developed to a nerve cell, a myocardium cell, and a blood cell if differentiated. It may be possible to produce organs and blood in a glass vessel in the future.

In gene therapy, curing cancer and inherited disease caused by genes are expected. But some researchers are skeptical about the effectiveness. In addition, it's important to establish social standards and penetrating informed concept before starting actual therapy.

Application of artificial gene recombination to food production is getting attention in Japan. In the US, genes immune to chemical herbicides have been introduced in crops so that only weeds can be removed and the crops are not affected. Another example is that a breed of tomato which shows strength to harmful insects or have good keeping has been created using this technology.

In case of soybeans, area under gene-rearranged crops exceeds 50% already. It means genes of one out of two soybeans are rearranged. As a scientist, I assert that gene-rearranged foods that are currently approved are safe because their safety has been confirmed. The safety check of such foods is still very important because the kinds gene-rearranged foods will be increasing.

Itao: I'm wondering if it's possible to produce farm crops in a controlled environment like industrial products making use of low-cost energy converted from industrial waste. Such plan has been discussed since years ago, but it became realistic thanks to the rapid technological progress that made computers much smaller and reduced cost significantly. Sensor technologies and data technologies are also available. Professor Moritoshi of Graduate School of Agricultural and Life Science, the University of Tokyo says that if gene-rearranged farm crops could be produced in such facilities, crops that can deter cancer and active oxygen could be achieved. To start a new industry-academia collaboration project in this field, I became the coordinator of the University of Tokyo Future Science Forum. We include highly functional foods as one of the goals.

Karube: I believe that "food genomics" should be studied. In this field, foods that are genetically favorable in human body are designed. In pharmaceutical sciences, researchers are studying medicines that match individual's genes and they call such study pharma genotics. Food genomics is my coinage from such an association.

There are three levels in functions of foods. The first function includes tastes and appearances. The second level is nutrition like plenty of vitamin and so forth. The third level is functions that change in the process of metabolism. They change to become favorable to the individual's gene type and constitution. I think the era in which we eat the same food is over. Since Professor Itao and I have different geno-types, I mean types of genes, each of us should eat something that matches each gene types.

Itao: That's interesting! An age of individual food is likely to come.

Karube: Genome in human DNA contains gene information regarding diseases the person is likely to suffer. Such diseases can be avoided by taking specially arranged meals that help prevent the diseases. I believe that a human being has a potential to live up to 120 years old. This will be a reality.

I am now making chips to study how genes are classified and how proteins are created in a body from genes. Food genomics won't be completed until human body constitutions will have been studies using the chips. I assume that the chips will be commercially available in three years.

Itao: In that case, how about your group will make biosensors and mine will make an environment to make highly functional vegetables (laughter)?

Karube: They calculate calories in meals in hospitals. In the future, patients will certainly eat genomic foods. Senior people will also eat them.

Itao: Using door-to-door delivery services.

Karube: Daily meals are delivered by door-to-door-services once the genome information is registered. The system should be very helpful for those who live by themselves. It's not fun to live long in sickness. Everyone wants to live long healthily.

Itao: Thank you very much for your inputs about nature interface forefront today. They are full of hopes.

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