Note: This document does not represent the final determinant in an overall Administration budget decision-making process. The programs presented in this report will have to compete for resources against many other high-priority Federal programs. If these programs compete successfully, they will be reflected in future Administration budgets.

Cover Illustration: Syntenic map of oats, triticeae, maize, sorghum, sugarcane, foxtail millet, and rice indicating close relationships among the genomes of grass species. Courtesy of Dr. M. Gale of John Innes Center, Norwich, United Kingdom.
 

The IWG on Plant Genomes was assisted greatly by James Tavares, Office of Energy Research; James Edwards, Machi Dilworth, and Keelin Kuipers, National Science Foundation; Judy St. John, Agricultural Research Service; and Sally Rockey and Ed Kaleikau, Cooperative State Research Education, and Extension Service.

Why a National Plant Genome Initiative

Initiative Goals and Objectives

                    Operating Principles

Public Issues

Cost Estimates for Achieving Five-Year Objectives

            Sidebars: Scientists Discover a New Class of Genes
                            The Genetic Assault on Plant Disease

Appendix A (Gibbons Memorandum)

Appendix B (Meetings)

Appendix C (NSF Program Announcement)

ABSTRACT
 
 

The Need for a National Plant Genome Initiative: Recent scientific advances made through our nation' s investments (private and public sector) in studying DNA structure and function in humans and model organisms have resulted in a new biological paradigm for understanding the traits of organisms. Through the National Plant Genome Initiative (NPGI), this paradigm can be extended to improving the useful properties of plants that are important to humanity. Solutions to many of our nation' s greatest challenges can be met through the application of plant-based technologies. For example, the revitalization of rural America will come from a more robust agricultural sector; reductions in greenhouse gasses can be achieved from the production of plant biofuels for energy; chemically contaminated sites can be rehabilitated economically using selected plants; and worldwide malnutrition can be greatly reduced through the development of higher yielding and more nutritious crops that can be grown on marginal soil.

The Initiative' s Goals: The long-term goal is to understand the structure and function of genes in plants important to agriculture, environmental management, energy, and health. Reaching this goal will require a sustained commitment from the Federal government working in collaboration with other nations and with the private sector. The Initiative' s short-term goals, to be achieved over the next five years, focus on building a plant genome research infrastructure by:

• completing the sequencing of the model plant species Arabidopsis;
• participating in an international effort to sequence rice;
• developing the biological tools (e.g., physical maps, ESTs, mutants) to study complex plant genomes (e.g., corn, wheat, soybean, cotton);
• increasing our knowledge of gene structure and function of important plant processes;
• developing the appropriate data handling and analysis capabilities; and
• ensuring this new information will be accessible to the broader community of plant biologists (e.g., growers, breeders, physiologists, biotechnologists) and maximizing the training opportunities that will arise from the Initiative.

• The Initiative should be viewed as a long-term project, governed by a plan that will be updated periodically.
• All resources, including data, software, germplasm, and other biological materials should be openly accessible to all.
• The Federal portion of the Initiative should be coordinated by an NSTC interagency working group with USDA, NSF, DOE, NIH, OSTP, and OMB representation.
• All awards should be made on a competitive basis with peer review.
• Partnerships with the private sector and with other nations are vital for success.

        The Interagency Working Group (IWG) for Plant Genomes was appointed on May 16, 1997, by Dr. John Gibbons, Assistant to the President for Science and Technology, in response to a request from the Senate VA, HUD and Independent Agencies Appropriations Subcommittee (see Appendix A). The charge was to identify science-based priorities for a national plant genome initiative and to plan for a collaborative interagency approach to address these priorities. The IWG consisted of representatives from the Department of Agriculture (USDA), National Science Foundation (NSF), National Institutes of Health (NIH), Department of Energy (DOE), Office of Science and Technology Policy (OSTP), and the Office of Management and Budget (OMB). The National Science and Technology Council (NSTC) Committee on Science provided oversight for the IWG.

        Over the past eight months, the IWG has benefited from the deliberations of several scientific meetings related to plant genome research (see discussion of these meetings in Appendix B). These meetings with scientists in the field of genomics research provided valuable insights that assisted the IWG in responding to its charge and verified the wide interest in and support for a coherent Federal program in plant genomics. The IWG also convened informal meetings with representatives of three groups interested in a plant genome initiative: agribusiness, academia and crop producers.

        The major challenges facing mankind in the 21st Century are the need for increased food and fiber production, a cleaner environment, and renewable chemical and energy resources. Plant-based technologies can play a major role in meeting each of these challenges. In order to reap the benefits of plant-based technologies, however, we must greatly expand our understanding of numerous fundamental aspects of plant biology and how these relate to desirable economic or environmental genetic traits. Therefore, the IWG recommends the development of the National Plant Genome Initiative (NPGI) as described in this report.
 
        The complete genetic makeup of any organism is known as its genome. The study of genomes, also known as genomics, consists of mapping, sequencing, and analyzing genomes to determine the function of genes. Information and knowledge gained from genomics will be used to improve the useful traits of plants through genetic engineering and new breeding strategies. Genomics has already had significant impact in agriculture with genetically-engineered plants comprising ten percent of the current U.S. corn crop. Similar, or greater, acreage of genetically engineered crops are anticipated for cotton and soybean. However, the total number of plant traits that have been genetically engineered is few, reflecting the limitations in our knowledge of fundamental plant processes. Fortunately, the genes that code for plant traits and processes appear to be nearly identical across a wide range of species. New technologies to exploit this finding are being developed constantly. Thus the time from fundamental discoveries about plant genomes to the final application of that information is relatively rapid.

        The study of plant genomes is providing growing evidence of the value of comparative genomic analysis. Comparative genomics uses genetic information gleaned from one species to help decipher that of another. For example, comparative genomics can be used to help determine gene content and order, patterns of gene expression during development, or how a particular gene has been conserved throughout evolution from the simplest to higher organisms. The ability to determine the physical organization and expression patterns of genes from many plant species will allow the best leveraging of available resources through comparative genome analysis.
 

Goal Statement
 
        The ultimate goal of genomics is to understand the structure and function of every gene in an organism. With the intent of exploiting that knowledge for the betterment of society, the NPGI will pursue this goal by focusing on plant species important to agriculture, environment, energy and health. This increased emphasis on the plant genome will radically change fundamental plant science research and its application to agriculture, forestry, energy, and the environment, as well as to the production of pharmaceuticals and other plant-based industrial chemicals and materials.  

Scientific Objectives

        Genomics research can be divided into three components: 1) structural genomics—studies of the structure and organization of genomes; 2) functional genomics—studies that relate genome structure and organization to plant function at the cellular, organismal or evolutionary level; and 3) application of the genomic information and knowledge for development of improved plants and novel plant-based products for human uses. The plan recommended in this report focuses on the first two components as most relevant to the Federal investment and provides linkages to the third component.
 
                    · Sequencing the Arabidopsis thaliana and Rice Genomes

Operating Principles

            *    The National Plant Genome Initiative should be viewed as a long-term project, governed by a plan that will
                  be updated periodically, based on assessment of success in reaching critical milestones and of the rapidly changing
                  state of the art. (The end-user community should participate in the periodic updating of NPGI goals and
                  objectives.)

            *    Research resources including data, software, germplasm and other biological materials should be made openly
                  accessible as rapidly as possible.

            *    The National Plant Genome Initiative should be coordinated by an interagency working group composed of
                  representatives from DOE, NIH, NSF, USDA, OSTP and OMB, operating under the aegis of the National
                  Science and Technology Council (NSTC).

            *    All awards should be made on a competitive basis with peer review to ensure the highest scientific merit.

            *    International partnerships should be developed with each country financing its own program.

            *    Cooperation with the private sector should be encouraged.

Agency Coordination and Responsibilities

        Past and current interagency activities in plant biology research (USDA, NSF and DOE) and the Arabidopsis Sequencing Project (NSF, USDA, DOE, and NIH) have evolved rational procedures for full collaboration between the respective agencies. These procedures allow the agencies to maintain faithfulness to each agency's mission and provide sufficient budgetary independence to permit full accountability. Joint program announcements, proposal peer review and technical management will be foremost among the characteristics of the interagency interactions. Coordination of these activities should be handled under the aegis of an NSTC interagency working group.

        Opportunities for cooperation and coordination of research efforts must be taken in a context that acknowledges the responsibility of specific agencies to support their distinct missions. The development of the fundamental knowledge base in the plant sciences is central to the mission of the NSF. NSF's continued efforts in all of plant science will be critical in helping to build the needed linkages between gene sequence and gene function, which is the ultimate goal of any plant genome project.

        The plant genomics mission of the USDA likely will be part of the broader program defined as the Food Genome Initiative, which includes agriculturally important plants, animals, and microbes used as sources of food, feed, and fiber. The new knowledge and technologies generated by the coordinated NPGI will be widely applicable for development of improved crops for traditional and new uses. The plant component of the Food Genome Initiative is envisioned as encompassing the USDA participation in the NPGI.

        DOE's interest in plant genome research includes energy-related issues underlying the use of plants in the production of biomass, chemical feedstocks, and biodegradable environmentally- friendly materials. The DOE is also interested in opportunities to genetically improve the role of plants for mitigating environmental problems in soil, water, or the atmosphere. Dependent upon the addition of fiscal resources, the DOE is likely to build upon its strengths in the functional genomics of metabolic pathways. Since DOE is a major participant in the Human Genome Project, relevant technologies developed through this program will be transferred to support the goals of the NPGI.

        The NIH will continue its activities promoting human health by investing in the underlying critical technologies through the Human Genome Project, and it will have strong interest in comparative genomics and the genetics of potential pharmaceuticals and nutritional factors of plant origin.

        While USDA, NSF, DOE, and NIH have been identified as the key Federal agencies, other agencies will benefit from this research and may wish to participate in the proposed NSTC NPGI coordination working group.
 
 

International Coordination and Collaboration

        With over 40 plant species of economic importance in the United States alone, it is clear that our nation–or any single nation–does not have the resources (financial or human) to launch a major genome project for each. Therefore, we must use our resources strategically, including establishing collaborations with scientists from other nations. Ideally, these collaborations should be among scientists rather than governments. Each participating scientist/laboratory should be supported by his or her own government under the terms and provisions of its own funding authority. However, in order to advance the project in a coordinated and efficient manner, all participating laboratories need to adhere to a common framework for participation.  A key for success in international collaboration is open communication and free exchange of research results including data and experimental materials.

         Fortunately we have excellent models on which to base future international plant genome projects. In particular, the Arabidopsis thaliana and the Human Genome Projects provide clear indications of how we should proceed in entering into international collaborations. Plans also are well underway for a new international rice genome project. Scientists met on September 23, 1997 in Singapore to begin development of an operational framework for this project. A steering committee was appointed consisting of representatives from Japan, China, Korea, European Union, and the United States. The Rockefeller Foundation will provide support to facilitate the work of the steering committee.

Interactions with the Private Sector

        The large benefits of genomic science for both fundamental and applied research activities, combined with current laws and policies governing intellectual property rights and patenting, have prompted some companies to make substantial investments in plant genomics including DNA sequencing. It is believed that currently there are extensive collections of plant sequence data in the private sector. The traditionally highly cooperative interactions between the public and private research communities have permitted some public researchers access to this information with restrictions on future patent rights or open communication. The IWG' s discussions with representatives from four agribusiness firms indicated that motives for restricted access to the sequence data were to protect the companies' investments in genomics and, therefore, their competitive advantage. However, these companies appeared to want extensive interaction with the public research community to leverage the private sector research investment. In particular, these four agribusiness firms were interested in establishing proprietary arrangements with public sector scientists in the area of functional genomics.

         The IWG also met with representatives from various commodity and producer groups. In general, these groups were supportive of an extensive Federal role in plant genomics. These representatives expressed concern that support for genomics should not detract from other high priority projects. Such groups can play an important role in determining the expediency of particular applications and identifying areas in need of further research. In order to promote the development of specific applications, partnerships should be explored between Federally supported researchers and commodity or producer groups.

        It is the responsibility of government funding agencies to ensure the continued advancement of fundamental plant science, which leads to a highly competitive environment for those industries and businesses directly or indirectly dependent on plants or plant production. Limitations in the availability of public funds have restricted the government's ability to support timely and extensive plant genome research. These limitations, combined with current patenting policies, have led to a significant investment by the private sector which now is unable to make the information freely available. While it is undesirable to duplicate private sector efforts, both philosophically and economically, the government must now act to provide critical data and research tools to the entire plant science community. Government officials, as representatives of the public research community, should continue to hold discussions with private industry in an effort to minimize current and future impediments to plant genome research.
 

        One legal issue that still requires considerable discussion concerns the intellectual property rights to genomic data. Increasing attention is being given to the nature of private sector involvement and its influence on biosciences research and development. Commercial entities founded on exploitation of the tools of biotechnology to manipulate life processes have proliferated over the past two decades, with significant holdings in the health, agricultural and, to a lesser degree, environmental sectors. Such companies have become major players in all phases of genomics, including plant genomics, with a particular focus on crops with the highest market value such as corn and soybeans, in the United States. Biotechnology companies face the challenge of a long product development cycle, making them particularly dependent on the ability to obtain enduring capital investment through the research, development, and manufacturing period preceding product marketing. A strong intellectual property portfolio is an attractive magnet to draw investors' attention to a young start-up firm, necessitating vigorous protection measures for this asset. International harmonization of patent laws will probably emphasize this role by encouraging the practice of filing patent applications early and often.

        A number of agricultural biotechnology companies are engaged in the systematic sequencing of ESTs, focusing their efforts on the corn and soybean genomes with the intent to discover genes coding for proteins that are important for enhancing growth and development, disease and pest resistance, and desirable nutritional or other properties. There is intense competition to obtain access to ESTs, either by sequencing them in-house, or by contract production or licensing. The ESTs have no inherent value except as tools for gene discovery. However, in today' s research environment, they are but a short step from marketable products.

        Much has been written about the patentability and patenting (not to be confused) of the products of genome research. Suffice it to say that it appears that ESTs are patentable subject matter in the view of the U.S. Patent and Trademark Office, as long as the patent application contains at least some evidence of known gene product function or discloses some other credible utility for the EST. Thus there is incentive in the private sector to rush to patent ESTs to prevent others from staking a claim to downstream products, or require others to license the patent-holder' s EST, once a product has been developed. Because of the long lag between patent application and issuance, no one knows whether a patent application has been filed claiming a particular gene sequence has been patented, and who owns that patent, until it issues. This increases the pressure to apply for patents on genes and gene fragments.

        Various research funding agencies have adopted practices for encouraging both commercial development of the results of government-funded research and the sharing of research tools. This led to some friction in the human genome research community early in the Human Genome Project. However, the presence of a concerted government project appears not to have detracted significantly from the myriad private sector activities such as subscription-accessible EST databases and partnerships or licenses based on genome information.

        The government, to date, has not been a significant contributor to the sequencing of plant ESTs. In designing a plant genome initiative, the IWG has adopted the principle that Federally funded resources, including data, software, germplasm and other biological materials should be openly accessible to all. This principle is grounded in the belief, borne out in the Human Genome Project experience, that open access to a common set of research tools will advance the whole field of plant genomics and is a sound investment of public funds. Cottage industry sequencing is slow and tends to focus on genes of specific interest. A more ambitious but ultimately more useful approach is one that culminates in gene and chromosome maps with markers at intervals permitting rapid and efficient gene searches. Creation of common maps reduces duplication of effort and enhances quality control through verification by multiple users. Rapid release of data and sharing of material is desirable and necessary to expedite research and its application to the development of useful new products.

        Open access to these resources can be accomplished with or without patenting. The preferred option supported by the IWG is not to attempt to patent early-stage research tools and to discourage plant genome initiative grantees or contractors from doing so. This is consistent with the policy adopted for the Human Genome Project and the proposal suggested by the National Corn Growers Association. Fears that disclosure of gene fragment sequence would render the full gene sequence or other downstream genome research products unpatentable have diminished, although not entirely. Nevertheless, the importance of providing information and materials to the plant genome research community as rapidly as possible should take precedence over other concerns as the optimal means for ensuring efficient incorporation into the body of scientific knowledge, necessary for development of new plant genotypes and other applications.

        Just as in other aspects of genome science, plant genetics has a number of ethical, social, legal, and economic issues of interest to society. These issues are being addressed on a wide scale, both here in the United States and abroad. Most of these issues relate to the genetic engineering of crop plants, not to genomics research per se.

        Issues regarding public perception of plant biotechnology are widespread and varied. All indications are that genetic engineering of food products will result in safer, more nutritious foods. Even so, some groups have expressed concerns about the perceived safety and quality of these products, such as the possibility of allergic reactions, introduction of toxins, or altered nutritional value. On the positive side, along with safer and better quality food, these products are expected to provide benefits to the environment. Some of the potential benefits include a reduction in the use of pesticides when plants are genetically modified to kill insects or the ability to withstand other environmental threats, including drought or extreme temperatures.

        However, there is some public concern over potential adverse impacts of genetically modified plants on the environment, such as reduction in genetic diversity or possible increased use of pesticides and herbicides when plants are genetically engineered to withstand them. Other environmental concerns include the possibility of uncontrolled natural propagation of genetically modified organisms and the transmission of engineered genes to related varieties and species.

        These safety and environmental concerns have spurred debate over regulatory issues, such as under what circumstances genetically engineered products should be labeled as such and what kinds of regulatory controls should be placed on the distribution and use of these products. There is currently public debate in the United States and Europe over whether genetically engineered food products should be labeled and how such labeling would affect public attitudes toward these products. Differences in regulatory approaches can impact international trade; therefore, international harmonization of these approaches and developing consensus on biosafety issues also need to be addressed. In addition, there is growing concern that, due to the cost of technologies resulting from plant genome research, developing nations may have slowed or limited access to them.

        Another set of issues revolves around whether patenting the results of plant genomics research is the most appropriate way to protect private sector investment. This leads to concerns about intellectual property rights and the increasing amount of R&D conducted by the private sector, particularly by a few large companies. Concerns over the increasing amount of plant genomic information held in the private sector and restricted access to this information drive the need to consider the implications of public/private initiatives in making genomic information more accessible to all researchers. This is also an issue internationally, where significant amounts of crop germplasm may be held outside the country from which it was collected.

        Given the number and complexity of ethical, social, legal, and economic issues related to plant genomics, the committee recommends that they should be addressed by the NPGI. Policy options to consider include establishing a fund for research into societal aspects of plant genome research and establishing mechanisms to improve the flow of information to the public on these issues.

         Fiscal Year 1998 plant genome funds already appropriated to NSF ($40 million) will allow initiation of a number of research and infrastructure projects (see attached NSF program announcement in Appendix C). An additional investment of $280 million could be used to ensure that the nation will be in a position to fully exploit the plant genomics revolution by the end of this five-year period. This estimate is based on the following anticipated needs:
 

• $20 million to speed up Arabidopsis genome sequencing, so that the complete sequence will be available by the year 2000; this amount will be complemented by comparable expenditures in the remaining countries participating in the multinational coordinated Arabidopsis Genome Project (including the European Union, France, and Japan);

• $40 million to sequence approximately 20 percent of the rice genome sequence, with the remainder of the genome to be sequenced by other nations, principally Japan and the European Union;

• $30 million for EST projects for 20 major economically important species and 10 major classes of plants (cost based on an estimate provided by The Institute for Genomic Research at the NAS Colloquium "Protecting Our Food Supply: the Value of Plant Genome Initiatives");

• Up to $100 million for cDNA and related genomic sequencing of selected plant species, such as corn, wheat, soybean, sorghum, tomato, barley, pine, etc.;

• Up to $60 million to meet the infrastructural needs of plant genomic research; and

• Up to $150 million for functional genomics research.

Non-IWG Meetings Used to Gain Scientific Insight
 

• The first was organized by the National Academy of Sciences (NAS) Board on Agriculture and Board on Biology at the request of USDA. The meeting entitled, "Designing an Agricultural Genome Program," was held at the National Academy of Sciences (NAS), Washington, D.C., on April 29, 1997, and attended by about 60 invited participants. Four members of the IWG were in attendance.

• The second meeting was a NAS Colloquium, "Protecting Our Food Supply: The Value of Plant Genome Initiatives." This meeting was held in Irvine, California, on June 2-5, 1997. Approximately 85 attended the meeting (including three IWG members) and included many of the world' s top scientists in plant genomics. A report of that meeting will be forthcoming.

• The third meeting was the Gordon Research Conference on Plant Cell Genetics and Development in Henniker, NH, on June 8-13, 1997. This meeting had many of the same scientists present as speakers, including Ronald Phillips, who reviewed the history and potential of a plant genome program. A subgroup at the meeting was assembled by the Conference Chair, Jo Messing, Director, Waksman Institute, Rutgers University. Others attending were the leader of the Rice Genome Program in Japan, Takuji Sasaki, Tsukuba; the leader of the Arabidopsis Genome sequencing projects of Japan, Satoshi Tabata, Kazusa DNA Research Institute, Chiba Prefecture; a leader of the American Arabidopsis Genome Sequencing Project, Joe Ecker, University of Pennsylvania; the leader of the International Triticeae (wheat, barley, oats, rye, etc.) Mapping Initiative, Michael Gale, John Innes Center, Norwich, UK; and the Chair of the International Grass Genome Initiative (funded by USDA, NSF, and DOE), Jeff Bennetzen of Purdue University. This subgroup discussed the idea of an international consortium.

• The fourth meeting of direct benefit was between the IWG and the NSF Panel reviewing the NSF, USDA, and DOE Arabidopsis Genome Sequencing Project.

• On September 4, 1997, the IWG met with eight industry representatives to discuss the role of the private sector in plant genome initiatives. Attending the meeting were Scott Tingey and Barbara Mazur of DuPont Agricultural Products, Stephen Padgette of Monsanto Company, and Daniel Alexander and Eric Ward of Novartis Seeds Biotechnology Research Unit, and Anthony Cavalieri and Peter Fuller of Pioneer Hi-Bred International.

• The IWG invited several prominent plant scientists to a meeting on October 14, 1997, to discuss their views on the science components that should constitute a plant genome initiative. These scientists included Jeff Bennetzen, Department of Biological Sciences, Purdue University; Michael Freeling, Department of Plant and Microbial Biology, University of California, Berkeley; Susan McCouch, Department of Plant Breeding and Biometry, Cornell University; Joachim Messing, Rutgers University, Waksman Institute; Calvin Qualset, Genetic Resources Conservation Program, University of California, Davis; Athanasios Theologis, Plant Gene Expression Center, U.S. Department of Agriculture, ARS; Elliott Meyerowitz, Division of Biology, California Institute of Technology; Ronald Sederoff, Department of Forestry, North Carolina State University; and Randy Shoemaker, Department of Agronomy and USDA-ARS, Iowa State University.

• On December 2, 1997, the IWG met with the following representatives of several commodities groups: Kellye Eversole, National Corn Growers Association; Mary Kay Thatcher, National Farm Bureau; Krysta Harden and Mark Berg, American Soybean Association; Michael May, United Soybean Board; James Miller, National Association of Wheat Growers; Daniel Shaw, National Grain Sorghum Producers; Marvin Zutz, Minnesota Barley Research and Promotion Council; Jane Shay and Gerald Lacey, Minnesota Barley Growers; and Philip Walkin, Cotton Council.

Recent scientific advances made through our nation' s investments (private and public sector) in studying DNA structure and function in humans and model organisms have resulted in a new biological paradigm for understanding the traits of organisms. Through the National Plant Genome Initiative (NPGI), this paradigm can be extended to improving the useful properties of plants that are important to humanity. Solutions to many of our nation' s greatest challenges can be met through the application of plant-based technologies. For example, the revitalization of rural America will come from a more robust agricultural sector; reductions in greenhouse gasses can be achieved from the production of plant biofuels for energy; chemically contaminated sites can be rehabilitated economically using selected plants; and worldwide malnutrition can be greatly reduced through the development of higher yielding and more nutritious crops that can be grown on marginal soil. This report recommends a long-term goal, five year objectives, and managment principles for the NPGI. To accomplish the five year goals of the NPGI, at least $320 million could be used by the Federal government in a targeted manner to leverage existing plant genome activities in the public and private sectors. Current estimates of cost could be decreased with advances in technology