Note: This document does not represent the finaldeterminant in an overall Administration budget decision-making process.The programs presented in this report will have to compete for resourcesagainst many other high-priority Federal programs. If these programs competesuccessfully, they will be reflected in future Administration budgets.
Cover Illustration: Syntenic map of oats, triticeae,maize, sorghum, sugarcane, foxtail millet, and rice indicating close relationshipsamong the genomes of grass species. Courtesy of Dr. M. Gale of John InnesCenter, Norwich, United Kingdom.
The IWG on Plant Genomes was assisted greatly by James Tavares, Officeof 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.
The Need for a National Plant Genome Initiative: Recent scientificadvances made through our nation's investments (private and public sector)in studying DNA structure and function in humans and model organisms haveresulted in a new biological paradigm for understanding the traits of organisms.Through the National Plant Genome Initiative (NPGI), this paradigm canbe extended to improving the useful properties of plants that are importantto humanity. Solutions to many of our nation's greatest challenges canbe met through the application of plant-based technologies. For example,the revitalization of rural America will come from a more robust agriculturalsector; reductions in greenhouse gasses can be achieved from the productionof plant biofuels for energy; chemically contaminated sites can be rehabilitatedeconomically using selected plants; and worldwide malnutrition can be greatlyreduced through the development of higher yielding and more nutritiouscrops that can be grown on marginal soil.
The Initiative's Goals: The long-term goal is to understand thestructure and function of genes in plants important to agriculture, environmentalmanagement, energy, and health. Reaching this goal will require a sustainedcommitment from the Federal government working in collaboration with othernations and with the private sector. The Initiative's short-term goals,to be achieved over the next five years, focus on building a plant genomeresearch infrastructure by:
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 arequest from the Senate VA, HUD and Independent Agencies AppropriationsSubcommittee (see Appendix A). The charge was to identify science-basedpriorities for a national plant genome initiative and to plan for a collaborativeinteragency approach to address these priorities. The IWG consisted ofrepresentatives from the Department of Agriculture (USDA), National ScienceFoundation (NSF), National Institutes of Health (NIH), Department of Energy(DOE), Office of Science and Technology Policy (OSTP), and the Office ofManagement 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 meetingsrelated to plant genome research (see discussion of these meetings in AppendixB). These meetings with scientists in the field of genomics research providedvaluable insights that assisted the IWG in responding to its charge andverified the wide interest in and support for a coherent Federal programin plant genomics. The IWG also convened informal meetings with representativesof three groups interested in a plant genome initiative: agribusiness,academia and crop producers.
The major challenges facingmankind in the 21st Century are the need for increased food and fiber production,a cleaner environment, and renewable chemical and energy resources. Plant-basedtechnologies can play a major role in meeting each of these challenges.In order to reap the benefits of plant-based technologies, however, wemust greatly expand our understanding of numerous fundamental aspects ofplant biology and how these relate to desirable economic or environmentalgenetic traits. Therefore, the IWG recommends the development of the NationalPlant Genome Initiative (NPGI) as described in this report.
The study of plant genomesis providing growing evidence of the value of comparative genomic analysis.Comparative genomics uses genetic information gleaned from one speciesto help decipher that of another. For example, comparative genomics canbe used to help determine gene content and order, patterns of gene expressionduring development, or how a particular gene has been conserved throughoutevolution from the simplest to higher organisms. The ability to determinethe physical organization and expression patterns of genes from many plantspecies will allow the best leveraging of available resources through comparativegenome analysis.
Genomics research can bedivided into three components: 1) structural genomics—studies of the structureand organization of genomes; 2) functional genomics—studies that relategenome structure and organization to plant function at the cellular, organismalor evolutionary level; and 3) application of the genomic information andknowledge for development of improved plants and novel plant-based productsfor human uses. The plan recommended in this report focuses on the firsttwo components as most relevant to the Federal investment and provideslinkages to the third component.
Structural genomics research involves elucidating the structure andorganization of genomes. Research in this area could include the production,mapping, and sequencing of expressed sequence tags (ESTs) from a numberof plant species and the construction of physical maps (cloned and orderedsegments of the genome). Therefore, a primary step for the NPGI would beto develop physical maps for key plant species, including corn and othereconomically important species. In addition, it would be extremely usefulto have approximately 200,000 ESTs available for 10-12 species, such ascorn, soybean, wheat, barley, sorghum, cotton, tomato and pine. A few "exotic"(non-economically significant) species should also be considered in orderto search for useful genes not present or expressed in economically importantplants.
· Functional Genomics
Functional genomics research involves identification of functions forgene sequences, including determining expression patterns for pathwaysor networks of genes under specific environmental conditions or duringdevelopmental stages. Genes obviously important to plant production andproductivity, such as those coding for disease and stress resistance, seeddevelopment, grain-quality traits, and flowering time would be targetedby the NPGI. Also included would be those genes that regulate other genes(e.g., transcription factors, receptors, signaling factors); these aredifficult to identify by classical means, but are much more accessiblevia genomic technologies.
· Technology Development
Continued technological development will be required in order to sustainrapid advances in plant genomics. In particular, technological advancesare needed in such areas as: analytical methods for mapping genes for complextraits; novel methods for analysis of genome organization and its effecton biological function; cost-effective sequencing technologies; and proceduresto analyze the total expression patterns of genes under specific conditions.Promising technological developments include DNA chips for the simultaneousanalysis of expression patterns of thousands of genes and strategies forcreating specific gene mutations for the rapid identification of gene function.Due to the sizable Federal investment in genomic technology by the HumanGenome Project, the NPGI should focus on the development of technologiesof specific use for plant genomics.
· Distribution and Use of GenomeData and Resources
The NPGI will generate extensive mapping and sequence data that mustbe analyzed and distributed. While much of the necessary computer softwareand databases have been and are being developed by the Human Genome Project,plant-specific tools and databases must also be developed. Along with thedistribution of genomic data, resources such as reference sequences, libraries,and germplasm must also be developed, maintained, and distributed. Plantgenome data should be integrated with data from other genome projects.
· Outreach and Training
The ultimate success of a plant genome initiative will be determinedby its impact on fundamental plant biology research and on the applicationof this research. In order to ensure rapid transfer of genomic informationand technologies to their end users, outreach activities should be an integralpart of the overall plan for the NPGI. Examples of outreach include mini-courseson how to access and utilize the data, tools, and resources of plant genomicsand workshops that bring together plant genome researchers with other plantbiologists or breeders. The NPGI also offers excellent training opportunitiesfor young scientists, including members of under-represented groups, toparticipate in the development and use of cutting-edge research technologies.
* The National Plant Genome Initiative should be viewed as a long-term project,governed by a plan that will
* Research resources including data, software, germplasm and other biologicalmaterials should be made openly
* The National Plant Genome Initiative should be coordinated by an interagencyworking group composed of
* All awards should be made on a competitive basis with peer review to ensurethe highest scientific merit.
* International partnerships should be developed with each country financingits own program.
* Cooperation with the private sector should be encouraged.
Past and current interagencyactivities in plant biology research (USDA, NSF and DOE) and the ArabidopsisSequencing Project (NSF, USDA, DOE, and NIH) have evolved rationalprocedures for full collaboration between the respective agencies. Theseprocedures allow the agencies to maintain faithfulness to each agency'smission and provide sufficient budgetary independence to permit full accountability.Joint program announcements, proposal peer review and technical managementwill be foremost among the characteristics of the interagency interactions.Coordination of these activities should be handled under the aegis of anNSTC interagency working group.
Opportunities for cooperationand coordination of research efforts must be taken in a context that acknowledgesthe responsibility of specific agencies to support their distinct missions.The development of the fundamental knowledge base in the plant sciencesis central to the mission of the NSF. NSF's continued efforts in all ofplant science will be critical in helping to build the needed linkagesbetween gene sequence and gene function, which is the ultimate goal ofany plant genome project.
The plant genomics missionof the USDA likely will be part of the broader program defined as the FoodGenome Initiative, which includes agriculturally important plants, animals,and microbes used as sources of food, feed, and fiber. The new knowledgeand technologies generated by the coordinated NPGI will be widely applicablefor development of improved crops for traditional and new uses. The plantcomponent of the Food Genome Initiative is envisioned as encompassing theUSDA participation in the NPGI.
DOE's interest in plant genomeresearch includes energy-related issues underlying the use of plants inthe production of biomass, chemical feedstocks, and biodegradable environmentally-friendly materials. The DOE is also interested in opportunities to geneticallyimprove 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 genomicsof metabolic pathways. Since DOE is a major participant in the Human GenomeProject, relevant technologies developed through this program will be transferredto support the goals of the NPGI.
The NIH will continue itsactivities promoting human health by investing in the underlying criticaltechnologies through the Human Genome Project, and it will have stronginterest in comparative genomics and the genetics of potential pharmaceuticalsand nutritional factors of plant origin.
While USDA, NSF, DOE, andNIH have been identified as the key Federal agencies, other agencies willbenefit from this research and may wish to participate in the proposedNSTC NPGI coordination working group.
With over 40 plant speciesof economic importance in the United States alone, it is clear that ournation–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 resourcesstrategically, including establishing collaborations with scientists fromother nations. Ideally, these collaborations should be among scientistsrather than governments. Each participating scientist/laboratory shouldbe supported by his or her own government under the terms and provisionsof its own funding authority. However, in order to advance the projectin a coordinated and efficient manner, all participating laboratories needto adhere to a common framework for participation. A key for successin international collaboration is open communication and free exchangeof research results including data and experimental materials.
Fortunately we haveexcellent models on which to base future international plant genome projects.In particular, the Arabidopsis thaliana and the Human Genome Projectsprovide clear indications of how we should proceed in entering into internationalcollaborations. Plans also are well underway for a new international ricegenome project. Scientists met on September 23, 1997 in Singapore to begindevelopment of an operational framework for this project. A steering committeewas appointed consisting of representatives from Japan, China, Korea, EuropeanUnion, and the United States. The Rockefeller Foundation will provide supportto facilitate the work of the steering committee.
The large benefits of genomicscience for both fundamental and applied research activities, combinedwith current laws and policies governing intellectual property rights andpatenting, have prompted some companies to make substantial investmentsin plant genomics including DNA sequencing. It is believed that currentlythere are extensive collections of plant sequence data in the private sector.The traditionally highly cooperative interactions between the public andprivate research communities have permitted some public researchers accessto this information with restrictions on future patent rights or open communication.The IWG's discussions with representatives from four agribusiness firmsindicated that motives for restricted access to the sequence data wereto protect the companies' investments in genomics and, therefore, theircompetitive advantage. However, these companies appeared to want extensiveinteraction with the public research community to leverage the privatesector research investment. In particular, these four agribusiness firmswere interested in establishing proprietary arrangements with public sectorscientists in the area of functional genomics.
The IWG also met withrepresentatives 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 shouldnot detract from other high priority projects. Such groups can play animportant role in determining the expediency of particular applicationsand identifying areas in need of further research. In order to promotethe development of specific applications, partnerships should be exploredbetween Federally supported researchers and commodity or producer groups.
It is the responsibilityof government funding agencies to ensure the continued advancement of fundamentalplant science, which leads to a highly competitive environment for thoseindustries and businesses directly or indirectly dependent on plants orplant production. Limitations in the availability of public funds haverestricted the government's ability to support timely and extensive plantgenome research. These limitations, combined with current patenting policies,have led to a significant investment by the private sector which now isunable to make the information freely available. While it is undesirableto duplicate private sector efforts, both philosophically and economically,the government must now act to provide critical data and research toolsto the entire plant science community. Government officials, as representativesof the public research community, should continue to hold discussions withprivate industry in an effort to minimize current and future impedimentsto plant genome research.
One legal issue that stillrequires considerable discussion concerns the intellectual property rightsto genomic data. Increasing attention is being given to the nature of privatesector involvement and its influence on biosciences research and development.Commercial entities founded on exploitation of the tools of biotechnologyto manipulate life processes have proliferated over the past two decades,with significant holdings in the health, agricultural and, to a lesserdegree, environmental sectors. Such companies have become major playersin all phases of genomics, including plant genomics, with a particularfocus on crops with the highest market value such as corn and soybeans,in the United States. Biotechnology companies face the challenge of a longproduct development cycle, making them particularly dependent on the abilityto obtain enduring capital investment through the research, development,and manufacturing period preceding product marketing. A strong intellectualproperty portfolio is an attractive magnet to draw investors' attentionto a young start-up firm, necessitating vigorous protection measures forthis asset. International harmonization of patent laws will probably emphasizethis role by encouraging the practice of filing patent applications earlyand often.
A number of agriculturalbiotechnology companies are engaged in the systematic sequencing of ESTs,focusing their efforts on the corn and soybean genomes with the intentto discover genes coding for proteins that are important for enhancinggrowth and development, disease and pest resistance, and desirable nutritionalor 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 marketableproducts.
Much has been written aboutthe patentability and patenting (not to be confused) of the products ofgenome research. Suffice it to say that it appears that ESTs are patentablesubject matter in the view of the U.S. Patent and Trademark Office, aslong as the patent application contains at least some evidence of knowngene product function or discloses some other credible utility for theEST. Thus there is incentive in the private sector to rush to patent ESTsto prevent others from staking a claim to downstream products, or requireothers to license the patent-holder's EST, once a product has been developed.Because of the long lag between patent application and issuance, no oneknows whether a patent application has been filed claiming a particulargene 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 fundingagencies have adopted practices for encouraging both commercial developmentof the results of government-funded research and the sharing of researchtools. This led to some friction in the human genome research communityearly in the Human Genome Project. However, the presence of a concertedgovernment project appears not to have detracted significantly from themyriad private sector activities such as subscription-accessible EST databasesand 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 principlethat Federally funded resources, including data, software, germplasm andother biological materials should be openly accessible to all. This principleis 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 wholefield of plant genomics and is a sound investment of public funds. Cottageindustry sequencing is slow and tends to focus on genes of specific interest.A more ambitious but ultimately more useful approach is one that culminatesin gene and chromosome maps with markers at intervals permitting rapidand efficient gene searches. Creation of common maps reduces duplicationof effort and enhances quality control through verification by multipleusers. Rapid release of data and sharing of material is desirable and necessaryto expedite research and its application to the development of useful newproducts.
Open access to these resourcescan be accomplished with or without patenting. The preferred option supportedby the IWG is not to attempt to patent early-stage research tools and todiscourage plant genome initiative grantees or contractors from doing so.This is consistent with the policy adopted for the Human Genome Projectand the proposal suggested by the National Corn Growers Association. Fearsthat disclosure of gene fragment sequence would render the full gene sequenceor other downstream genome research products unpatentable have diminished,although not entirely. Nevertheless, the importance of providing informationand materials to the plant genome research community as rapidly as possibleshould take precedence over other concerns as the optimal means for ensuringefficient incorporation into the body of scientific knowledge, necessaryfor development of new plant genotypes and other applications.
Just as in other aspectsof genome science, plant genetics has a number of ethical, social, legal,and economic issues of interest to society. These issues are being addressedon a wide scale, both here in the United States and abroad. Most of theseissues relate to the genetic engineering of crop plants, not to genomicsresearch per se.
Issues regarding public perceptionof plant biotechnology are widespread and varied. All indications are thatgenetic engineering of food products will result in safer, more nutritiousfoods. Even so, some groups have expressed concerns about the perceivedsafety and quality of these products, such as the possibility of allergicreactions, introduction of toxins, or altered nutritional value. On thepositive side, along with safer and better quality food, these productsare expected to provide benefits to the environment. Some of the potentialbenefits include a reduction in the use of pesticides when plants are geneticallymodified to kill insects or the ability to withstand other environmentalthreats, including drought or extreme temperatures.
However, there is some publicconcern over potential adverse impacts of genetically modified plants onthe environment, such as reduction in genetic diversity or possible increaseduse of pesticides and herbicides when plants are genetically engineeredto withstand them. Other environmental concerns include the possibilityof uncontrolled natural propagation of genetically modified organisms andthe transmission of engineered genes to related varieties and species.
These safety and environmentalconcerns have spurred debate over regulatory issues, such as under whatcircumstances genetically engineered products should be labeled as suchand what kinds of regulatory controls should be placed on the distributionand use of these products. There is currently public debate in the UnitedStates and Europe over whether genetically engineered food products shouldbe labeled and how such labeling would affect public attitudes toward theseproducts. Differences in regulatory approaches can impact internationaltrade; therefore, international harmonization of these approaches and developingconsensus on biosafety issues also need to be addressed. In addition, thereis growing concern that, due to the cost of technologies resulting fromplant genome research, developing nations may have slowed or limited accessto them.
Another set of issues revolvesaround whether patenting the results of plant genomics research is themost appropriate way to protect private sector investment. This leads toconcerns about intellectual property rights and the increasing amount ofR&D conducted by the private sector, particularly by a few large companies.Concerns over the increasing amount of plant genomic information held inthe private sector and restricted access to this information drive theneed to consider the implications of public/private initiatives in makinggenomic information more accessible to all researchers. This is also anissue internationally, where significant amounts of crop germplasm maybe held outside the country from which it was collected.
Given the number and complexityof ethical, social, legal, and economic issues related to plant genomics,the committee recommends that they should be addressed by the NPGI. Policyoptions to consider include establishing a fund for research into societalaspects of plant genome research and establishing mechanisms to improvethe flow of information to the public on these issues.
Fiscal Year 1998 plantgenome funds already appropriated to NSF ($40 million) will allow initiationof a number of research and infrastructure projects (see attached NSF programannouncement in Appendix C). An additional investment of $280 million couldbe used to ensure that the nation will be in a position to fully exploitthe plant genomics revolution by the end of this five-year period. Thisestimate is based on the following anticipated needs:
Non-IWG Meetings Used to Gain Scientific Insight
Recent scientific advances made through our nation's investments (privateand public sector) in studying DNA structure and function in humans andmodel organisms have resulted in a new biological paradigm for understandingthe traits of organisms. Through the National Plant Genome Initiative (NPGI),this paradigm can be extended to improving the useful properties of plantsthat are important to humanity. Solutions to many of our nation's greatestchallenges can be met through the application of plant-based technologies.For example, the revitalization of rural America will come from a morerobust agricultural sector; reductions in greenhouse gasses can be achievedfrom the production of plant biofuels for energy; chemically contaminatedsites can be rehabilitated economically using selected plants; and worldwidemalnutrition can be greatly reduced through the development of higher yieldingand more nutritious crops that can be grown on marginal soil. This reportrecommends a long-term goal, five year objectives, and managment principlesfor the NPGI. To accomplish the five year goals of the NPGI, atleast $320 million could be used by the Federal government in a targetedmanner to leverage existing plant genome activities in the public and privatesectors. Current estimates of cost could be decreased with advances intechnology
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