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PART I Overview
NATIONAL PROGRAM FOR THE DEVELOPMENT OF BIOTECHNOLOGY Didin S. Sastrapradja Assistant II Minister for Research and Technology/ Chairman, National Committee on Biotechnology Biotechnology, which integrates several sciences, plays a significant role in development worldwide. Research in this field has moved rapidly, and its application has produced new biotechnologies or bioindustries. Many technological problems remain, however, in applying biotechnology. The government of Indonesia has determined that the development of biotechnology is a national priority. It will be utilized for supporting national development needs on an industrial scale in the areas of agriculture, health care, chemical manufacturing, food production, and environment. APPLICATION OF BIOTECHNOLOGY IN INDONESIA In Indonesia, biotechnology is part of the activities traditionally associated with the fermentation of solids or liquids to produce food and beverages. This traditional technology has several characteristics: small investment, labor intensive (using skilled and unskilled labor), small scale, low budget, and low value added. Currently, medium-scale industries using biotechnological techniques produce alcohol, beer, citric acid, monosodium glutamate, liquid sugar, and single-cell protein. Biomedical products for humans have been produced for decades in Indonesia at Biofarma in Bandung, but the production process used presently needs improvement by introducing recently developed, sophisticated technologies. Biomedical products for animals have also been produced in Indonesia, with the use, however, of old technological processes. BIOTECHNOLOGICAL RESEARCH IN INDONESIA In general, research is dominated by efforts to develop materials standards for use in the traditional fermentation processes; to develop Inoculum through Isolation, identification, and screening of domestic microbes; and to learn more about the variables of the fermentation processes. - 3 -
- 4 - Recently, research has been expanded to cover the sectors of health care, agriculture, and industry. This research has centered around the search for a microbial strain that produces a secondary metabolite, bioengineering (fermentation conditions, reactor design, the post-fermentation process, the computerized fermentation process), tissue culture, biogas, and waste processing. In the future, this research will be directed toward large-scale applications. Research units supporting biotechnology in Indonesia include: o The Agency for the Assessment and Application of Technology o Universities such as the University of Indonesia, Bogor Agricultural University, Bandung Institute of Technology, and Gadjah Mada University. These universities form the Inter-University Center of Biotechnology. o Research institutes under the Indonesian Institute of Sciences, including the National Institute of Chemistry, National Institute of Biology, and Center for Research and Development in Biotechnology at Cibinong (planned) o Research institutes under the Department of Agriculture, including the Sugar Research Institute in Pasuruan, Estate Crops Research Institute, and Food Research Institute. Organizations involved in the production of biotechnologies include the Biofarma in Bandung (state owned), Veterenary Farma in Surabaya (state owned), various food and pharmaceutical industries (privately owned), and the research institute in the Department of Health. NATIONAL PROGRAM ON BIOTECHNOLOGY The objectives of the national program on biotechnology are to formulate a national plan of action and policy; to promote the role of biotechnology in agriculture, health, and industry; and to encourage R&D in biotechnology and its application. The targets of the national program are: o To increase the number of industries based on the application of biotechnology to produce goods and services o To develop R&D capabilities in all fields of study related to biotechnology that could support a sustainable national bioindustry. Meeting these targets requires application of a four-stage program for technological transformation in biotechnology:
- 5 - o Stage 1. Transfer of technology where the development of bioindustries requires the direct assistance of foreign technologies. At this stage, biotechnology is imported for immediate production of high-value added goods and services. This simultaneously provides opportunities to understand the design and techniques of the imported biotechnology. o Stage 2. Technological integration of biotechnology to develop a new design or blueprint for the development of a new biotechnology. o Stage 3. Technological development of the new biotechnology to afford a comparative superiority in bioindustry. o Stage 4. Basic research to support the future development of biotechnology. Possible steps needed to develop biotechnology in Indonesia are: mobilization of the existing national capabilities in biotechnology, promotion of the utilization of existing biotechnological processes as well as R&D on new processes, and development of scientific and skilled manpower through special training and education. In undertaking these steps, the following should be kept in mind: o The limitation of resources, including facilities, manpower, and funding, in each institution. o The purpose and function of each institution such as basic research, application, and education. o The weakness of the private sector which will likely be the consumer and marketer of products created by the institutes. CENTER FOR RESEARCH AND DEVELOPMENT IN BIOTECHNOLOGY AT CIBINONG Because development of the "new" biotechnology requires a large capital investment and substantial well-qualified manpower, it is more economical with the present situation in Indonesia to establish a new, well-equipped, and well-funded research and development center for biotechnology (the Center for Research and Development in Biotechnology at Cibinong) than support the existing R&D institutes under various government organizations. The objectives of the Center are to develop the national capability to conduct research and development in the "new" biotechnology and genetic engineering and to provide the sophisticated facilities needed for this undertaking. In the long run, it is expected that the biotechnological approach can be utilized to increase and promote the economic value of natural resources for food, feed, medicines, chemicals, and energy.
- 6 - In developing the Center, the following guiding principles will be observed: o The activities of the Center will be cross sectoral in character. o The program of the Center will become the focal point of a national network in biotechnology. o The Center's activities will produce information and products (prototypes) that are low volume/high value in character, with extensive market potential and usable for scaling-up studies. The functions of the Center will be to: o Develop and disseminate appropriate applications of modern biotechnology. o Act as a clearinghouse in biotechnology. o Offer its facility for internships and training in biotechnological research. o Develop and perform the detailed planning of biotechnological manufacturing plants. To realize its objectives, the Center will formulate selected research and development projects that support national programs in the fields of family planning, health care, food production, animal production, and the manufacture of pharmaceuticals and other biologically active compounds. Research will encompass microbiology, plant cell and tissue culture, genetic engineering, analysis, fermentation techniques, downstream processing, and lab-scale pilot studies. The Center will be located on 200 hectares of government land at Cibinong which is situated between Jakarta and Bogor. Pharmaceutical and food processing factories, related research laboratories (agriculture, biology, health, animal husbandry), and universities are located nearby. The following facilities are planned for the future: o Laboratory of applied microbiology and tissue culture o Laboratory of biochemistry and molecular biology o Processing laboratory o Laboratory of limnology o Supporting facilities (water treatment, greenhouses, workshop, staff housing). During the first and second five-year development phases, the Center will be funded by the government of Indonesia and foreign assistance. Starting with the third five-year development phase, however, the Center is expected to be gradually able to finance its
- 7 - activities through contract research and the provision of facilities as well as consultants in the field of biotechnology. It is expected that this ability will increase with time.
BIOTECHNOLOGY IN AGRICULTURE Charles C. Muscoplat Chairman, NRC Panel, and President, Molecular Genetics, Inc. Biotechnology will have a major impact on the future of world agriculture. Technologies such as embryo transfer and genetic engineering to produce new vaccines, drugs, antibiotics, and hormones for animal production; cell and tissue culture of important crop species; nitrogen fixation; and industrial fermentation will be key to increasing world agricultural productivity. Coupled with better farm management systems, better hygiene, conservation of natural resources, and development of new fertilizers and crop chemicals, these technologies can mean tremendous improvements in agricultural productivity. The goals of these new technologies must be to increase agricultural productivity; to provide for a stable, high-quality, nutritious food supply; to protect international trade by safeguarding our livestock and crops from disease and toxic substances; and to preserve natural resources and safeguard the environment. Increased agricultural productivity will help feed the hungry and will improve the economics of agriculture-based countries by substituting technology for subsidies and preserving financial resources which can then be used to benefit the population in other ways. The four technologies covered in this workshop are critically important to the advancement of world agriculture. Embryo transfer and techniques to improve animal production, plant cell and tissue culture, nitrogen fixation, and industrial fermentation can work together in a complementary fashion to improve agriculture. This paper briefly reviews each of these technologies and gives examples of how each technology can benefit world agriculture. EMBRYO TRANSFER AND ANIMAL PRODUCTION Perhaps one of the most exciting fields in biotechnology today is embryo transfer and animal production. Embryo transfer is becoming widely available, and in many parts of the world it is now a commercial reality. The advantage of the advances achieved recently in embryo transfer over classical breeding is the rapidity with which superior genetic traits can be established within a livestock population. Transfer of improved productivity genes into livestock germ plasm will - 8 -
- 9 - be achieved by the end of this decade. Once new livestock genotypes are established, embryo transfer is the only practical way to disseminate the new germ plasm quickly worldwide. It will then be essential that countries with intensive livestock production become skilled in the techniques of embryo transfer. Techniques of molecular biology and genetic engineering are already a commercial reality and promise to be as important as plant cell and tissue culture, nitrogen fixation, and embryo transfer. Genetic engineering will allow the production of improved vaccines for infectious diseases such as foot-and-mouth disease and swine fever rinderpest. It will also soon provide an array of pharmaceutical products for increasing livestock productivity. Some examples are animal growth hormones for increased growth and milk production; fertility hormones for increased fecundity, ovulation, and conception as well as synchronization; and immune-modulating proteins such as interferons, interleukens, and related proteins necessary for disease resistance. Monoclonal antibodies will provide the tools needed for rapid diagnosis and detection of specific diseases as well as for specific passive antibody therapy. Another exciting use of the new technology will be the application of genetic engineering to aquaculture. PLANT CELL AND TISSUE CULTURE The process of culturing plant cells in vitro is becoming better understood and widely available. It involves the in vitro propagation of either plant embryonic or other plant organ system tissues. The main purpose of the technology is to introduce into agronomic plants altered genetic traits that provide some production advantage. Specifically, by exploiting somaclonal variation in plant cell culture, scientists can increase the genetic diversity of plants and widen the sources of germ plasm used for major crops. Currently, many crops are produced from very few or even single cultivars, thereby exposing producers to high risks that a single disease could destroy an entire crop species. Broadening the basis of genetic diversity will reduce risk as well as allow selection for improved traits. Advanced techniques of plant cell culture can be used to alter specific single-gene traits such as selection for resistance to various crop chemicals, thereby giving the producer a wider choice of products and procedures for each type of agricultural operation, or increasing specific amino acid production to improve the nutritional quality of plants. One of the most exciting areas of investigation currently is the selection of plants resistant to viral, fungal, or even insect diseases. In the future, agricultural crops developed by tissue culture techniques may contain a combination of improved traits such as improved nutritional quality for both livestock and humans or tolerance of crop chemicals or toxic soil chemicals (the aluminum toxicity encountered in Brazil and other parts of the world, for example).
- 10 - NITROGEN FIXATION Most crops require increased nutritional support through the application of chemical fertilizers. For the most part, these chemicals consist of potassium, phosphorus, and nitrogen. Potassium and phosphorus are taken from the ground through mining, whereas nitrogen fertilizers are manufactured from natural gas utilizing atmospheric nitrogen. Fertilizers have been the single most important factor in increasing crop production. In combination with improved germ plasm, herbicides, insecticides, and soil conservation, nitrogen-based fertilizers have significantly boosted agricultural productivity worldwide. Fertilizers add significant cost to crop production. In some parts of the world, nitrogen fertilizers are expensive, difficult to obtain, or simply unavailable for a variety of reasons. Theoretically, eliminating or reducing the need for nitrogen will improve both the economics and productivity of the important nonleguminous crops. Although the development of genetically engineered, nitrogen-fixing crops appears to be many years from being practical, such a development promises to be one of the most important advances in all of plant agriculture. Research is currently directed toward developing improved nitrogen-fixing bacteria, genetically altering plants, and developing plants better able to use conventional fertilizers. INDUSTRIAL FERMENTATION The fermentation process is vitally significant worldwide. Examples of industrial fermentation products of importance are single-cell proteins for nutritional supplementation, antibiotics, drugs, hormones, food products such as microbial rennens for cheese production, alcoholic beverages, and specialty chemicals. In addition, nearly all the genetically engineered products described above will be produced using the fermentation process. Thus, there is no doubt about the critical need to develop improved industrial fermentation processes. In addition to the uses listed above, the creative use of fermentation techniques may also partially solve the important problems of agricultural waste. For example, although the large amounts of waste by-products associated with animal, crop, and food production may not be suitable for commercial use as they are, it may be possible with fermentation techniques to convert these products into either useful end products or valuable intermediates. The important challenges facing fermentation engineers are how to design both new microbes that facilitate appropriate bioconversions and the fermentation apparatus and its operation. It will also be important to address the difficult problems associated with materials handling in the bioconversion of agricultural wastes into useful end products.
- 11 - CONCLUSION Many challenges are facing agriculture today In the form of ever-Increasing demands for agricultural production, diminishing natural resources, and concerns about the environment, transportation, international trade, and geopolitics. Farms are changing rapidly from single farmer operations to large industrial ones. The future will require complex management of scientific as well as financial and logistical support. Each of the technologies described above can provide agriculture with a significant advantage. But achieving excellence in each of these areas will not be easy. It will require cooperation at all levels of government, industry, and academia worldwide. Because research is becoming increasingly expensive and difficult, it is becoming more difficult to purchase the necessary high-technology equipment, to build the proper facilities, and to train quality scientists. It is thus wise to form collaborative arrangements among countries, governments, industries, and universities and thereby take advantage of different areas of expertise found in each country and organization. Such a step would also reduce the financial cost of worldwide agricultural development, facilitate scientific exchange, and promote the acquisition of new knowledge. It would, in addition, build worldwide agricultural and technological alliances which will extend beyond agriculture and may serve as the basis of broader cooperation. In the United States, cooperation is slowly developing among government, industry, and academic scientists. Regulatory agencies are becoming increasingly skilled at understanding and regulating products developed through new genetic technologies. Professional societies are beginning to facilitate greater scientific exchange among scientists on a global basis. It is important that this continue. It is also important that an efficient patent system be developed to protect inventions arising from biotechnology. Such protection will ensure that industries invest research monies in continued product development and improvement. In summary, the future of agriculture will be exciting. We must take care, however, to focus our efforts and financial resources carefully on a limited number of practical areas to avoid the dilution of effort that results in slower overall development.
THE BIOTECHNOLOGY INITIATIVE IN NORTH CAROLINA Richard J. Patterson President, North Carolina Biotechnology Center The North Carolina Biotechnology Center is the first state-established center of its kind in the United States and, like that of several of its successors in other states, its mission is economic development from biotechnology. In pursuing its mission, the Center recognizes that biotechnology is expected over time to have a greater and greater economic impact in the United States and around the world. In North Carolina, the aim is to develop the Center's resources and capabilities so that the state will directly benefit from biotechnology. HISTORY OF THE CENTER The North Carolina Biotechnology Center was established in 1981 under the Governor's Board of Science and Technology. The idea behind this initiative was that a state investment in biotechnology would, in the long term, provide a major economic benefit to the state. Earlier state investments in other technologies established a favorable climate in which to start the Center. The first steps in its establishment were to assess thoughtfully research in biotechnology, look at where the biotechnology industry was and where it saw itself going in the future, examine the economy in North Carolina and its resource base, and establish the ability to target and to focus the Center's activities. One of the first major undertakings was an inventory of researchers in biotechnology. This inventory characterized their expertise and identified the areas in which they were doing research. The first time this inventory was undertaken, it identified about 150 researchers in N.C. universities who were actively involved in biotechnological research. The second inventory, undertaken about a year and a half ago, identified more than 300 researchers in biotechnology or, it is estimated, about half of the manpower resource. Simultaneously, N.C. industries and companies that are either actively involved in biotechnology or likely to feel the impact of biotechnology were queried. This then identified the private sector element involved in biotechnology. - 12 -
- 13 - FUNDING Funding for the Biotechnology Center has increased gradually. Initially, funding was about $200,000 a year from the Governor's Board of Science and Technology. In 1983, the Center received its first direct funding ($500,000) from the state legislature. Because the legislature was becoming increasingly interested in this investment in biotechnology, it established a legislative study committee to examine where biotechnology was today and to learn where those with expertise saw it going in the future. The study committee conducted almost two years of hearings, involving experts in research, business, and finance. As the committee listened to testimony, it heard about biomedicine, crop and animal agriculture, and forestry and marine industries--all of which are very important to the economy of North Carolina. This combination represents many opportunities, and the challenge then was determining what level of investment was necessary for the state to benefit. At the end of the two years of testimony, the study committee recommended that North Carolina invest almost $70 million in biotechnology over a five-year period. As a result, the budget of the Biotechnology Center for 1985-1986 is $6.5 million. In 1984, the North Carolina Biotechnology Center was reorganized as a private corporation, giving it the flexibility to work with the private sector and with private and public universities and to pursue opportunities that were not possible when the Center was part of state government. RESOURCES The North Carolina Biotechnology Center is not building a research facility. Because the facilities of North Carolina research universities are extensive, the Center determined that the most effective way to marshal its resources and to have its desired impact was to invest in research activities in the universities rather than develop a separate activity that would possibly compete with the universities. The universities are key to the Center's efforts, and a major thrust of the Center is to increase their capabilities in biotechnology. This includes attracting new faculty. For example, North Carolina State University was recruiting a senior faculty member in plant molecular biology, which attracted a senior academician, Dr. William Thompson, from the Carnegie Institute in Stanford, California. Dr. Thompson left an attractive situation at Carnegie to come to North Carolina for scientific reasons. That is, North Carolina State University has an outstanding plant breeding capability, and he wanted to collaborate with plant breeders who understood crops as well as the traits on which a molecular biologist should be working.
- 14 - PROGRAMS Monoclonal Lymphocyte Technology Center The Monoclonal Lymphocyte Technology Center is actually based in three universities: North Carolina State University, Duke University (private), and the University of North Carolina at Chapel Hill. Funding for the Center is provided by the National Science Foundation, sponsoring companies, and the North Carolina Biotechnology Center. Its present annual budget is about $675,000. The Technology Center's objective is to undertake basic research that is relevant and of particular interest to industry. Thus, the sponsoring companies are critical in selecting research projects for the Center and in monitoring their progress. Over time the number of sponsoring companies will likely increase, and there will be a turnover in projects as the frontiers of science change. As the needs of industry change, the basic research of industrial interests will take on a different complexion as well. Plant Molecular Biology Consortium The Plant Molecular Biology Consortium is also based at the "Triangle Universities": Duke University, North Carolina State University, and the University of North Carolina at Chapel Hill. A major activity of the Consortium is a fellowship program for graduate and postgraduate training. Funding is provided by the Biotechnology Center and companies that sponsor the fellowship program. These fellowships are used to attract the very best people in the country to these universities for graduate and postgraduate training. The Consortium also sponsors seminars which bring this group together monthly. The Biotechnology Center's competitive grants program is aimed at young scientists, or scientists moving into new fields, and at collaborative research--that is, collaborative research among university investigators and among university and industrial researchers. Since 1982, the Consortium has identified $16 of new research investment for particular research projects for each dollar of early investment. The resources of the entire state university system are drawn upon to conduct a peer review of research proposals for their scientific quality. This review process is important because it draws the Center much closer to the individual researchers in the fields that make up biotechnology. Biomaterials Engineering Program This program includes nine scientists at four different universities as well as one research institute funded by the Office of Naval Research. These individuals came together at a workshop sponsored by the Biotechnology Center and realized that they had
- 15 - several shared interests. By putting these interests together, these scientists were able to attract a $650,000 three-year grant. They meet monthly to share the results of their research, and they have now written two new grant proposals to take their research to an even higher level. Other Programs Bioprocess engineering is critical to biotechnology. Because U.S. research institutions are lacking in bioprocess and biochemical engineering, many have increased their efforts to develop a greater capability for bioprocessing research. North Carolina universities are committed to bringing their capability up to a level considered a center of excellence. Since most products of biotechnology are the result of some type of engineered process, this expertise is critical to commercial success. In the area of education-based activities, several state universities are now faced with a challenge; many do not have faculty qualified to teach their undergraduates or to conduct laboratories in molecular biology. Thus, the Biotechnology Center is working with these institutions to develop their educational capabilities in biotechnology. Another Center educational program conducts training in the two-year community college system. One institution has a program for training technicians in biotechnology, chemistry, and biology. This college involved industry extensively in developing this curriculum, which was accepted by the community college system. In the fall of 1985, the first students started courses. This curriculum could be offered at any community college, particularly if a business needed trained personnel. The Center is also addressing the need for better education in molecular biology in state primary and secondary schools, and it is supporting achievement of this goal through the science and math education initiatives being undertaken in North Carolina. INVOLVEMENT OF INDUSTRY One theme running throughout this discussion of the Center's activities is the involvement of industry. This involvement is very important in targeting the Center's programs, so that the activities undertaken are particularly relevant to the needs of industry and do not duplicate their efforts.