A Bright Future Writ Microscopically

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The Korea Research Institute for Bioscience and Biotechnology
Friday, August 28th, 2009

There is an aesthetic particular to Korea: the most interesting places are to be found nestled on the side of a mountain. In traditional Korea, Confucian academies, Buddhist temples, and beautiful hidden gardens are subtly positioned in unassuming places in the slopes of hills. The Korea Research Institute of Bioscience and Biotechnology (KRIBB) is a treasure of the same caliber, but with a modern technological spin. KRIBB is a peerless research center located in Daejeon's legendary Daedeok Valley where the hard questions of biology - like the cure for cancer and the source of biofuel - are being tackled and bit by bit surmounted each day; and it is nestled in the folds of the gentle slope of a pine-covered mountainside.

 

Quiet Pride

KRIBB front gate

The front gate of KRIBB

One finds a quiet pride in KRIBB's researchers. "The history of KRIBB is the history of biotechnology in Korea," said Choi Jin-sun, manager of the International Cooperation Department, when asked about the most significant aspect of the Institute. "We have a 24 year history in Korea." The response is understated, but it says everything. Since the mother of KRIBB, the Genetic Research Center, was established in 1985 as a spin-off of the Korea Advanced Institute of Science and Technology (KAIST), small groups of dedicated scientists have been working around the clock in these laboratories. Now, KRIBB is emerging as a major player in Asia, the foremost research center for bioscience and biotechnology, with the support of the Korean government under the umbrella of the Korea Research Council of Fundamental Science and Technology.

KRIBB excels in the three areas that count: publications, patents, and products. Its researchers publish over 300 articles per year in an astonishing range of disciplines, and register almost 400 patents. Recent efforts in commercialization have produced over 80 companies and commercialized numerous discoveries, making KRIBB the envy of lumbering government labs around the world where technology gathers dust.

KRIBB is going global at the same time. It has established branch research centers in Costa Rica and China and has more planned. These centers are focused on collecting biological samples, an activity instrumental to maintaining KRIBB's reputation as one of the top institutes for identifying new biodiversity. It also works together with Pfizer on drug development and has joint research projects with Japan. Access to diverse genetic data translates into real power in biotechnology.

There are good reasons that KRIBB's experts talk with such confidence. KRIBB has many achievements. One example is the discovery of a leading compound for fighting against super-bacteria, developed by KRIBB team member Dr. Kim Won-gon in 2008. Antibiotic-resistant bacteria were found to be especially susceptible to a new compound generated by KRIBB's own microbial community of actinomycetes, an invaluable weapon in the fight against nosocomial infections. This discovery is probably due to KRIBB's place at the top of the list of institutes finding novel bacteria species for three years in a row.

 

Strong Foundation

KRIBB campus

KRIBB's campus is filled with the biodiversity that it seeks

Understanding KRIBB's achievements requires us to look at its foundations. The best and the brightest of Korea's educational system have come to work on biotechnology projects in the well-lighted rooms of this attractive compact campus. They were drawn here because the infrastructure and support is so strong. KRIBB received W106 billion (US $85 million) from the government in 2008, and supplemented that with W59 billion (US $47.3 million) of its own revenue. It also receives a small fraction of funds from privately-funded projects, royalties, and other sources. With this money cushion, each division of the Institute has room enough to incubate and husband a great number of possible ideas. It supports approximately 175 researchers, 45 engineers, and another 45 technicians in accomplishing a wide variety of research activities. It would be hard to find another institute that has such a variety of fields working so close together. That generates collaboration and mutual stimulation on a large scale.

 

Solid Hope

DNA decor

KRIBB's biological focus is reflected in the decor around the Institute

One has a sense of a solid hope for the future here at KRIBB. The world of the future looked at through the eyes of KRIBB is bright and sweepingly transformed. It will be a world in which cancers can be easily identified and prevented through genetic markers. Carefully engineered nanotechnology medicines will search out and destroy disease-causing agents at the nanoscopic level. As a person ages, the effects on his body will be identified immediately and slowed, or even reversed, extending the lifetimes of everyone and allowing them to age gracefully. The environment itself will be monitored for disease-causing agents, which can be neutralized before they ever come into contact with people.

Sitting down with members of the KRIBB community is enthralling. They envision a world in which the human genome will be completely understood, with the genetic markers that make the Korean population susceptible to stomach and liver cancers easily identifiable. New organs, or even limbs, will be re-grown in the lab to match the patient perfectly. As part of that push, KRIBB is forming a thick global network between institutes with an in-depth understanding of all the ins and outs of proteins to tackle this challenge- a project that will make the cracking of the human genome seem like child's play. KRIBB is at the center of the drive.

The institute will develop bacteria and other microbes for biotechnology applications, getting the microscopic little guys to produce substances like biodiesel that modern civilization needs. Relevant data about the human genetic code, and that of millions of other species, will be digitized. The data will be used to create algorithms and applications that can accurately simulate diseases, and the cures for those diseases. Also, plant breeding and protein synthesis will first be worked out digitally, and the results of those digital experiments will be applied in the real world. The efficient and cost-effective production of clean biodiesel will make energy cheaper and environmentally safe.

Biological systems contain an incredible amount of information, and arranging all that information will be easy with the new bio-information systems developed at KRIBB. The international bio-infrastructure being put together here will allow biologists around the world to instantly collect, preserve, and distribute biological resources. They will be able to analyze and process the information and biomaterials on hand using tried and tested processes stored on-line in readily available formats. With this type of technology at their disposal, the pace of biological progress will increase dramatically.

 

Four Divisions

There are four major divisions to KRIBB, each concerned with a major area of research. The Division of Translation Research unravels the mysteries of the genetic code, proteins, and cell regeneration. The Division of Bio-Convergence Technology focuses on applications related to nanotechnology, aging, the brain, and bio-monitoring. The Division of Biosystems Research focuses on using biological systems in industry and adapting them to changing environmental conditions. And the Division of Bio R&D Infra is building up the computer networks and expertise necessary to manage the increasingly large amount of information created in biology today. Each Division is further broken up into several research centers. Detailing their work would fill a book or two, so it is better to focus on one program in each division to give a sense of the whole.

 

Translation Research

Yoo Hyang-sook

Dr. Yoo Hyang-sook, director of the FHCRC-KRIBB Collaboration Center

The most notable project in the Division of Translation Research is the FHCRC-KRIBB Collaboration Center directed by one Dr. Yoo Hyang-sook. An animated woman with a drive that leaves fellow researchers in the dust, Dr. Yoo has worked for the last ten years in conjunction with the Fred Hutchinson Cancer Research Center (FHCRC) on a project to find markers which can identify cancerous cells in the liver. Dr. Yoo commands a budget of US$50 million per year to nail down the genetic markers. "You need the markers, not only for genetic diseases, but acquired changes can be detected if you have the right markers," she explains. "But the problem is we don't have the right markers to detect exactly the progression of disease. So we are looking for good markers that can be used for the early diagnosis of cancers." There has been some noteworthy progress, and some markers have been identified, but the continuing problem is the specificity, or sensitivity, of the markers. Some may mark too eagerly or not eagerly enough, while others may mark non-disease-related areas within the body. "We want markers that are very specific to a certain disease, and also specific with regards to sensitivity," she explains. The markers used now have a 70-80% specificity rate, but that does not satisfy Dr. Yoo's sense of perfection.

Dr. Yoo did not start out the project ten years ago focused on genetic markers. She built this research center from the ground up, starting with the first viable gene bank in Korea specifically for the Korean genetic makeup. She explained that a gene bank consists of the entire genetic code of humans broken up into genes and inserted into plasmids which are also inserted into E. coli bacteria. These bacteria are then labeled based on which gene they hold, and are kept alive indefinitely with the gene they contain. Then, whenever a researcher needs to study a gene, he or she can take a sample from the appropriate batch of E. coli bacteria. Dr. Yoo let show a bit of pride when she detailed the project, "We built that gene bank ourselves. Nobody else in Korea could have done that. So once we built it, we must maintain it, and give out the needed genes for free to anyone who has a research project." Such a gene bank was the first step towards a mature biotechnology research community and KRIBB is one of a small number in the world that has what it takes. Without a local gene bank, researchers in Korea would have to order all their genes from overseas. There are gene banks located in other parts of the world, but the unique benefit of a gene bank located in KRIBB is that it provides Korean genes on demand. This collection allows KRIBB to study genetic dispositions to disease from a Korean, and, by extension, Asian perspective. In an age of customized genetic drug development, such resources are essential.

Bio-convergence Technology

KRIBB building

The architecture at KRIBB can sometimes be imposing

Tucked away in another corner of KRIBB is the Integrative Omics Research Center, a part of the Division Bio-convergence Technology. Here Dr. Hoe Kwang-lee spends long hours developing bio-therapeutics products. Dr. Hoe has an innovative approach to understanding fission yeast. He deletes genes from the genome of fission yeast and one by one determines their function. Dr. Hoe's project is 99% complete and currently under review by distinguished researchers around the world. A part of the project involves cooperation with researchers at Rockefeller University, something Dr. Hoe considers to be a mutually beneficial strategy. Since all parties involved in the collaboration share the results of their research, their projects now proceed exponentially faster than was the case before. His only regret is that they cannot share information even more completely. Dr. Hoe has brought a Daejeon-based biotech company into the project as well. He shares his findings with Bioneer and in exchange Bioneer pays royalties back to KRIBB.

Biosystems Research

Oh Hee-mock

Dr. Oh Hee-mock, director of the Biosystems Research Group

"Imagine our division as the unit that handles a wide range of bio-resources such as enzymes, bio-materials, and bio-energy," explained Dr. Oh Hee-mock. Dr. Oh heads the Environmental Biotechnology Research Center, the largest division at KRIBB with 40 regular staff members. If one includes students, Ph.D. candidates, and post-doctoral staff involved in the project, the number goes up to 220. Dr. Oh's offices can be reached by following winding passageways chockablock with centrifuges, refrigerators, and cell culture cabinets. His work is quickly outgrowing the facilities that house it, and he expressed hope that he would move to better facilities soon.

Dr. Oh has his finger on the pulse of Korea, standing in the thick of Korea's push for green technology. He spends his days investigating panoply of algae to find those best at producing biodiesel. This work has gained him attention beyond KRIBB's sheltered hillside and funding not only from the Korean government, but also from a venture company called Pro-bionics, run by a former KRIBB man, Dr. Park Yung-ha.

"We are not chemical engineers; our whole job is the development of strains, cultures, and methods," Dr. Oh noted. The chemical engineers are the algae themselves, and Dr. Oh's team simply figures out what they can do, nurtures them, and then points them in the right direction to do their stuff. Of course that process is not that simple, and it is his 17 years of uninterrupted work here that provides a wealth of experience to make it happen.

The crème-de-la-crème of bio-diesel-producing algae form a most condensed culture of algae that likes to crowd together. Algae are a good source for biodiesel because they have high oil content, grow fast, and do not require too much care.

"Over there you can see over one thousand algae that we have isolated from samplings in Korean waters," Dr. Oh explained. "There are so many different kinds of algae, so we are now testing to determine which ones are best." Like Dr. Yoo, Dr. Oh had also created an algae bank that gives out sample algae to researchers throughout the country. Dr. Oh's algae bank is the place to go for the algae critical for biodiesel research. And in an age of environmental and energy challenges, these green algae may be worth their weight in gold.

Bio R&D Infra

Jong Bhak

Dr. Jong Bhak, Director of the Korean BioInformation Center

Dr. Jong Bhak is a man with a mission. He is here in the northwest corner of KRIBB everyday in front of his array of monitors. Instead of the standard Petri dishes and centrifuges, his office is crammed with computers. His clipped and excited speech hints at a deep passion for the fusion of IT and BT.

"Programming. Every day we do programming. Twenty-four hours," replied Dr. Bhak, when asked about his research center. Dr. Bhak is the director of the Korean BioInformation Center. The purpose of this center is to make the storage, processing, and dissemination of biological information easier. That makes things smoother for everyone else in the institute, and throughout Korea. "We construct here was are known as pipelines, automated analysis modules of DNA sequences, protein sequences, RNA sequences, protein structures, and expression levels," said Dr. Bhak. If the gene bank stores genes inside bacteria, here the genes are stored electronically in computer code, in an online bank of sorts.

There are many research institutes and companies that can make good use of software like this, and they pay good money for it. But processing information from the genome is no simple task, the automation of such pipeline programs is essential for untangling that web of data. "The pipelines we develop are extremely specific, so it may be difficult to sell them now. But maybe in 3 years or 5 years time the information can be presented in a user-friendly format like a Windows program," Dr. Bhak suggests.

If the center appears to be on the margins of KRIBB, it is at ground zero in an emerging set of interlocking circles for global collaborative research. The BioInformation Center is developing a virtual pan-Asian research collaboration center online that will speed research and analysis in biological research centers around the globe. KRIBB has been working with Dr. Alp Malazgirt of the SolBridge International School of Business to formulate a new international strategy and Dr. Bhak is right in the middle of it.

Herein lays the remarkable strength of KRIBB. It is an unparalleled collection of experts in every field of biotechnology close enough to have lunch together and share ideas or results over coffee. At the same time, its units are parts of global collaborative networks. Dr. Bhak is on the front line of that expansion of global networks. He notes that traditionally researchers create and store their own data. It has taken time to convince people of the value of sharing data. "I feel we have a responsibility as scientists to collect data and share it in a database, but not everyone does that," Dr. Bhak explained.

The analysis of complex data can best be done by pooling resources globally and conducting analysis to a centralized office. But this is a new idea that will take some time for the biological research community to accept. Dr. Bhak's team is not waiting for the jury to come in, however. They are out there building their networks and winning people over, bit by bit.

E Pluribus Unum

Although the exterior of the KRIBB labs may appear tranquil, the inside is buzzing like a beehive. If there is going to be a breakthrough Korean biotechnology, its epicenter will be in Daejeon. The walls of KRIBB pulse with focused energy that puts a spring in the step of anyone who visits. Good things are happening there, and it's only a matter of time before this mountainside will no longer be able to hide them.

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