Publicly-funded biobanks and networks in East Asia

With the enactment of the Nagoya Protocol, international competitions to secure biological resources are intensifying. Biobanking is one of the many attempts to preserve biological resources and their information for the use in future research and development. Asian countries, especially China, Japan, and Korea are very active in biobanking activities under the strategic plans coordinated by their governments. They also proactively established networks for biobanks of Asia to facilitate resource and expertise sharing. Biobanks of these countries should furthermore standardize operating procedures and diversify funding sources for establishing stable operation systems.


Background
Since the adoption of the Convention on Biological Diversity (CBD) in 1992, biological resources have been increasingly considered as exclusive possessions of their originating countries rather than common assets of mankind. International competitions to secure bioresources have recently been overheated with the enactment of the Nagoya Protocol on access to genetic resources and benefit sharing (ABS) in 2014. According to the CBD provision, biological resources are genetic resources and organisms in parts or their entireties with actual or potential uses and values for mankind. They are more than simple collections of organisms-they are the source of academic and industrial advancement and exploitation.
Biobanking is one of the many attempts to conserve ecologically and scientifically valuable biological resources and their associated information for the advancement of life sciences. Biobanks both accept and provide viable (often culturable and replicable) organisms or their parts and information on their molecular and physiological characteristics. Since its first appearance in a scientific literature in 1990s (Hewitt and Watson 2013), the term "biobank" was often used narrowly to describe a repository of human specimens. As more scientists, policymakers, and other stakeholders of biobanks expanded the range of its definitions, the word now also accommodates non-human organisms, such as plants, animals, fungi, and bacteria. In recent online surveys, biobanking stakeholders concurred in including different organisms in the biobanking realm and further agreed that biobanks should follow standard operating procedures and distribute materials for scientific use (Hewitt and Watson 2013). Broader definitions of the term are also reflected in international guidelines and numerous national regulations, such as the guidelines of Organisation for Economic Cooperation and Development (OECD) and the laws of several European countries (Hewitt and Watson 2013).
Biobanking activities were recorded in Europe as early as 1890s (Day and Stacey 2008). Since then, numerous institutes were established in Europe and led the effort of conserving and distributing biological resources. For culture collections, European institutes outnumber the institutes of other continents by far in terms of volume and diversity of their collections. However, Japan, Korea, and China have recently seen a rapid increase in the new deposits. In terms of the numbers of new deposits, yearly aggregated amount of the three countries are comparable to the European aggregate (Smith et al. 2013).
In this paper, we observe the status of biobanks in Asian countries, with emphases on three East Asian countries, China, Japan, and Korea. Despite the recent rise of Asian countries in the biobanking field, lack of coordination may have precluded international scholars to identify and have access to Asian biobanks. Through this paper, we identify public biobanks of Asian countries and explain how they operate. Furthermore, we present major networks of Asia-Pacific biobanks and their functions.

Korea
Prior to 1990, academic and clinical institutes in Korea primarily led the preservation efforts of biological resources. As worldwide interest in biological diversity and conservation heightened, the Korean government started to invest heavily in securing and utilizing biological resources for academic and industrial uses. In 1995, the Ministry of Science and Technology 1 initiated a federal project to support and foster 5 research resource centers (RRCs; Lee and Lee 2009). This project has expanded to encompass 31 RRCs and 4 core centers, collectively managed by a central organization, Korea National Research Resource Center (KNRRC).
Korean public biobanks are operated by collaborative efforts of six government ministries (National Science and Technology Council Steering Committee 2015). Ministries collectively establish yearly plans for biological resource management, in order to prioritize policies for biological conservation, reduce risk factors in biological diversity, uphold sustainable use of ecosystem services, and strengthen international collaboration on conservation and research efforts. Under these joint objectives, each ministry has established responsible agencies to manage and support subordinate biobanks in accordance with their ministerial focus and interest.
Human biobanks are administered by the three ministries, the Ministry of Health and Welfare (MOHW), the Ministry of Food and Drug Safety (MFDS), and the Ministry of Science, ICT, and Future Planning (MSIP). Korea Centers for Disease Control and Prevention (KCDC), under the administration of MOHW, launched the Korea Biobank Project (KBP) in 2008. Through this project, KCDC has planned to collect specimens from 200,000 patients and 300,000 general population (1st term, from 2008 to 2012) and to establish Korean Biobank Network for specimen distribution (2nd term, from 2013 to 2015; Cho et al. 2012). Until now, National Biobank of Korea (NBK), along with 17 regional biobanks of university hospitals and 2 network-affiliated hospitals, has accumulated human serum, plasma, DNA, and other specimens from 328,000 patients (as of December 2015). NBK also accommodates 1 Currently the Ministry of Science, ICT, and Future Planning (MSIP).
population-based specimens collected from 384,000 people as part of regional cohort studies (Centers for Disease Control & Prevention, Korea 2016).
MSIP administers exceptionally diverse biobanks, unlike other ministries, in addition to the human biobanks. In accordance with the ministerial goal to foster scientific research (Ministry of Science, ICT and Future Planning 2015), three institutes, the Korea Research Institute of Bioscience and Biotechnology (KRIBB), the National Science Museum, and the Korea National Research Resource Center (KNRRC), endeavor to secure diverse research resources, including biological and non-biological resources. KRIBB manages 1 human biobank and 5 biobanks of other organisms, including animals, plants, and microbes (Korea Research Institute of Bioscience and Biotechnology 2014). The institute has set up the International Biological Material Research Center (IBMRC) for international research collaboration and collection of novel specimens. The National Science Museum houses 700,000 specimens of 9100 terrestrial and marine species (Korean Bio-resource Information System 2015). KNRRC accommodates 31 diverse biobanks of biological and non-biological research resources. The center has established best practice guidelines and integrated resource inventory system for biobanks to ensure the quality of resources and their information. Additionally, KNRRC hosts seminars and forums to educate biobank directors, staffs, and other biobanking stakeholders.
Other federal ministries handle more specialized biobanks, consistent with their ministerial responsibilities. Under the Ministry of Agriculture, Food, and Rural Affairs (MAFRA), the National Institute of Agricultural Sciences (NAS) and the National Institute of Animal Science (NIAS) support crops and livestock research and preservation implemented by laboratories of universities, local governments, and government-funded organizations. Korea Forest Service, another important agency of MAFRA, manages plant, insect, and microbial resources via National Institute of Forest Science (NIFoS), Korea Forest Seed and Variety Center (NFSV), and Korea National Arboretum (National Science and Technology Council Steering Committee 2015). Ministry of Oceans and Fisheries (MOF) appointed 14 laboratories of universities and research institutes as marine bioresource banks. Marine Biodiversity Institute of Korea was established in 2014 for public exhibition and preservation of marine organisms. The institute has collected more than 400,000 specimens which are as diverse as bacteria, fungi, algae, and vertebrates. Ministry of Environment (ME) operates the National Institute of Biological Resources (NIBR) for wildlife conservation and protection of endangered species.
Federal ministries will continue the collaborative works for management of biological resources until 2020 as specified in the master plan laid out by the ministries in 2011. Table 1 lists publicly funded biobanks in Korea.

Japan
Japan has extensive specimen collections of diverse organisms which often have been managed by small-sized laboratories of academic or governmental institutes. The Japanese government has recently reorganized the management and funding scheme for biobanks as the government heavily emphasizes quality management of biological resources. In 2015, the Cabinet Office of Japan established Japan Agency for Medical Research and Development (AMED) as a "control tower" for medical research and development (R&D; Japan Agency for Medical Research and Development 2015). Previously, medical research in Japan was administered by three different ministries, Ministry of Education, Culture, Sports, Science and Technology (MEXT), Ministry of Health, Labour, and Welfare (MHLW), and Ministry of Economy, Trade and Industry (METI; Sano 2015). Each ministry had implemented different funding schemes which added burdens to medical researchers. As a part of the national revitalization strategy in 2013, the Cabinet acknowledged the importance of medical R&D and decided to create a "headquarters of healthcare policy, " modeled after National Institutes of Health (NIH) of the United States (Hishiyama 2015; Japan Agency for Medical Research and Development 2015). This initiative was developed into the creation of AMED. While three ministries remain as key stakeholders, AMED now works as an integrated funding agency between researchers and ministries. The government anticipates that fast-tracked funding and clinical trial process will help researchers to engage more in research and develop novel treatments for Japanese population.
The Japanese government is currently interested in personalized treatments enabled by advance in genomic research. For collection of human specimens, MEXT and MHLW collaborate in managing human biobank networks of BioBank Japan (BBJ), National Center Biobank Network (NCBN), and Tohoku Medical Megabank Organization (ToMMo) biobank project (Furuta 2014). BBJ is a disease-oriented biobank which embarked in 2003 (Okamura et al. 2014). From its first cohort study (2003)(2004)(2005)(2006)(2007), DNA, serum, and medical records of 200,000 patients were collected. RIKEN Center for Integrative Medical Sciences (IMS) and the Institute of Medical Science at the University of Tokyo (IMSUT) have teamed up for genomic analyses of specimens and data management. These institutes are securing additional DNA specimens and medical records from 100,000 patients of the second cohort (2013)(2014)(2015)(2016)(2017)(2018). NCBN is also a network for disease-oriented biobanks, in collaboration of six centers specialized in different diseases, including cancer, neurology, cardiovascular diseases. While each center individually operates its own hospital and research institutes, they perform joint research through the shared platform among the centers. ToMMo biobank is a population-based institute, unlike the previous two networks, and created for the long-term study of people who suffered the 2011 Tohoku earthquake. With the support of the latest IT technology, this biobank aims to collect medical and genomic data of 150,000 individuals from 10,000 affected households with three generations (Matsui and Tashiro 2014). National BioResource Project (NBRP) is an initiative managed by AMED for integrated and standardized management of biological resources (Nagai et al. 2015). Under the supervision of MEXT, the program commenced in 2002 to upgrade biobanking systems and facilities scattered throughout Japan. The program is at its third phase (2012-2016) of 5-year term and recently faced management transfer to AMED along with the opening of the agency. NBRP currently supports 29 facilities handling specimens and living organisms for scientific research. The project also emphasizes genome-enabled research to enhance the values of collected resources and specimen databases to better serve researchers.
For agricultural conservation efforts, Genebank Project has been implemented by the National Institute of Agrobiological Sciences (NIAS), under the supervision of the Ministry of Agriculture, Forestry and Fisheries (MAFF; National Institute of Agrobiological Sciences 2014; NIAS Genebank 2015). NIAS has accumulated 215,000 plant, 28,000 microbe, and 1000 animal accessions through the project and established online databases to provide their data to researchers. The project also aims to strengthen international cooperation and secure foreign genetic resources through exchange programs, joint research, and symposiums.
National Institute of Technology and Evaluation's Biological Resource Center (NBRC) of METI specializes in collection and preservation of microorganisms. NBRC provides services of domestic and international distributions and patent deposits and online databases for microbes with industrially useful properties (National Institute of Technology and Evaluation 2015b). The BRC also hosted the first meeting of Asian Consortium for the Conservation and Sustainable Use of Microbial Resources (ACM) and has strived to build cooperative relationships with other Asian countries (Asian Consortium For the Conservation and Sustainable Use of Microbial Resources 2015a; National Institute of Technology and Evaluation 2015a).
In summary, the Japanese government aims to strengthen life science research by the establishment of a dedicated funding agency and strategic support on biobanks handling useful resources for industrialization. Table 2 lists government-funded biobanks in Japan.

China
Human biobanking in China launched in 1994 with the establishment of immortalized cell lines from Chinese ethnic groups (Gan et al. 2015). As the Chinese government and academia saw growing importance of biological resources, biobanking activities in China have significantly expanded in the last decade. Disease-oriented biobanks are often affiliated with hospitals in major cities, like Beijing and Shanghai, and equipped with advanced medical equipment . Beijing Biobank of Clinical Resources (BBCR) is composed of 14 hospitals and considered as the largest clinical biobank network in China. The project team of BBCR aims for diverse management, standardized operation, and thirdparty supervision . With accumulated expertise on biobanking operation, BBCR also provides frameworks for constructing new biobanks. Shanghai also has a well-established biobank project, called Shanghai Biobank Network (SBN). Currently, SBN consists of 18 allied institutes  and preserves liver cancer tissue and rheumatism samples as key collections among other diverse specimens (Fan and Zhang 2011). Population-based biobanks in China collect specimens from various groups of population based on the unique objective of each biobank. The China Kadoorie Biobank (CKB) began in 2003 to collect medical data and blood samples from 510,000 individuals in 10 geographic regions for research on common chronic diseases among Chinese people. Other prominent population-based projects are the Guangzhou Biobank Cohort Study on elderly people and the Born in Guangzhou Cohort Study which will follow 1,000,000 pregnant women and their offspring for 20 years .
Like the preceding two countries, genetic resources of livestock and crops are actively managed by the Ministry of Agriculture (MOA). Chinese Academy of Agricultural Sciences (CAAS) is a major institute organizing and American Association for the Advancement of Science 2013). The dedicated funding helps the institute continues on long-term preservation of agricultural resources and conducts rigorous research. CAAS is running a longterm nationwide biobank of plant germplasms and 10 medium-term plant biobanks. The Ministry of Environment Protection (MEP) is mainly focused on maintaining biological diversity and protecting endemic and endangered species of China. The ministry endeavors to protect diverse organisms through a number of institutes, including the Southwest China Germplasm Bank of Wild Species (The Ministry of Environmental Protection of China 2014). This bank preserves plant seeds of 10,000 species, animal germplasms, macrofungi, and microorganisms. In addition, Chinese academic institutes now explore the cryopreservation option for cell lines of wild animals, such as Bengal tigers (Guan et al. 2010) and pandas (Yu et al. 2015).
The Ministry of Science and Technology (MOST) has established the National Science and Technology Infrastructure (NSTI) to raise research capacity by effective management of research resources (Ministry of Science and Technology of the People´s Republic of China 2006). NSTI aims to create a science and technology "infrastructure platform" which consolidates management system for effective use and sharing of biological resources and for prevention of wasted funding due to duplicated or unnecessary financial support. Under this project, an open database of biological resources in China is under development for improved sharing of resources and data (Xu 2007). One of the NSTI divisions is the National Infrastructure of Microbial Resources (NIMR) which collectively manages nine microbial resource centers. Each biobank has different characteristics and research emphasis as shown in their collections, either subjectspecific (e.g. agricultural, medical, or pharmaceutical) or site-specific (e.g. marine-oriented). China General Microbiological Culture Collection Center (CGMCC) is one of the NSTI-supported biobanks geared toward more general and comprehensive collections of microorganisms and managed by the Institute of Microbiology at Chinese Academy of Science (IMCAS).
In order to create an integrated and open platform for effective management of biological resources, the Chinese government created China National Genebank (CNGB). The Genebank consists of bioresource bank, bioinformatics database, and consortium system . Bioinformatics data are stored in cloud for various applications, such as healthcare and germplasm preservation (China National Genebank 2015). CNGB also engages in developing and providing standard operation procedures and training personnel for biobanking skills. The Genebank aspire to present a new biobanking model for the Chinese science communities and industries. Table 3 summarizes Chinese biobanks funded by the government. a Biobanks funded by the third phase of the National BioResource Project (NBRP). Some institutes, such as RIKEN BRC, have assumed numerous NBRP projects but they are listed separately as each project has a clear organizational structure and hosts its own website

Other Asian biobanks and Asian biobank networks
Biobanks of other Asian countries are also in active operations. Most Asian countries have nationally funded culture collections available to international scholars. Some countries, such as Taiwan and Malaysia have populationbased biobanking projects established to understand common and chronic diseases of their citizens. Table 4 is the partial list of Asian biobanks in Asia-Pacific. As numerous definitions of biobanks point out resource sharing as one of their key functions (Organisation for Economic Co-operation Development 2012; Hewitt and Watson 2013), networking is seemingly an indispensable element for most of the biobanks. Biobanks can improve their institutes and others by sharing their resources, data, and expertise through domestic and international networks. Generally, domestic biobanking networks in Asia are created or supported by governmental agencies for integrated management of specific resources, efficient funding, and support for research based on these resources. International networks are often more comprehensive in terms of resource types and aim for research cooperation at national-level. As domestic networks were described in previous section, we will focus on international networks in this section (Table 5).
Asian Network of Research Resource Centers (ANRRC) is a well-established network of Asian and Oceanian biological and non-biological resource centers. In 2009, the first meeting of ANRRC was held in Korea. Since then, the network grew to include 103 centers from 14 countries (Lee et al. 2016). Through the network, members share biobanking expertise and scientific technology and open the prospect for collaboration. The 2015 annual

Conclusion
Biobanking is the fundamental scientific effort to preserve and manage biological resources rapidly dissipating from the planet. In this paper, we have observed public biobanks of Asian countries, especially ones in China, Japan, and Korea. These biobanks are characterized by strategic operations orchestrated and assessed by their governments. Asian biobanks are also active in creating and utilizing networks for domestic and international collaboration. Recently, these three countries have enthusiastically partaken in the establishment of the International Standard for biobanks by TC 276 Biotechnology of the International Organization for Standardization (ISO).
In general, East Asian biobanks are heavily influenced by visions and plans of the governments as their financial resource is often solely dependent on governmental funding. Such fiscal system allows stable funding, however only for the defined period of time. Biobanks of Asia must consider diversifying funding sources by adding values to biological resources and offering additional services, such as data analyses, trainings, and software development as suggested by the OECD guideline for biological resource centers. Biobanks of Korea, Japan, and China have seen rapid growth in size over the last decade thanks to the substantial investment from governments. Now these countries should further focus on establishing stable and systematic resource centers and providing end-users with high-quality resources processed in compliance to international standards.