Guidelines first published by the NIH in 1976 address the safe conduct of laboratory research involving the construction and handling of rDNA molecules and organisms containing rDNA. They are advisory in nature, rather than legally binding. However, all federal agencies that support or conduct rDNA research agreed to abide by the NIH Guidelines and require institutional compliance as a condition of funding. Thus, failure to comply may result in the suspension, limitation, or termination of financial support for rDNA research at the institution. The current version of the NIH Guidelines can be accessed on the Internet⁴.

The NIH Guidelines discuss risk assessment and recommend containment measures for various biological experiments. They set forth facility specifications and practices for conducting experiments classified according to four levels of biosafety containment; a fifth class encompasses experiments that are exempt. Although originally focused on rDNA microorganisms, the NIH Guidelines have undergone numerous revisions and now cover plant, animal, and human gene therapy research to accommodate the wide range of federally funded research projects.

The Guidelines were expanded in 1994 by the addition of Appendix P, Physical and Biological Containment for Recombinant DNA Research Involving Plants. The term "plants" includes, but is not limited to, mosses, liverworts, macroscopic algae, and vascular plants including terrestrial crop, forest, weed, and ornamental species. Recommended containment conditions for experiments involving plants together with plant-associated microorganisms or small animals in which any organism may be genetically modified are also found in Appendix P.

Plant-associated microorganisms include those known to cause plant disease, such as viroids, virusoids, viruses, bacteria, and fungi, as well as protozoa, and microorganisms that have a benign or beneficial association with plants, such as certain Rhizobium species. Microorganisms that are modified with the objective of fostering an association with plants are similarly subject to the terms of Appendix P. Plant-associated small animals include those arthropods that: (1) are in obligate association with plants; (2) are plant pests; (3) are plant pollinators; or (4) transmit plant disease agents, as well as other small animals such as nematodes for which tests of biological properties necessitate the use of plants. Microorganisms associated with such small animals (e.g., pathogens or symbionts) are included.

Appendix P describes practices for conducting experiments to construct, use experimentally, and propagate genetically engineered plants. It specifies physical and biological containment measures and management protocols applicable to each of four biosafety levels designated BL1-P, the lowest level of containment, through BL4-P, the highest level.

federal regulation; however, the following brief summary provides the broad context for regulatory review of transgenic plants associated with testing in the environment and commercialization. More complete information about these agencies and their roles with respect to products derived from biotechnology, with links to the laws, rules, and regulations that they administer, can be accessed at the US Regulatory Oversight in Biotechnology site on the Web⁵.

USDA/APHIS

The USDA's Animal and Plant Health Inspection Service (APHIS) has authority under the Federal Plant Pest Act to protect US agriculture from pests and diseases. Under the Coordinated Framework, this authority was extended to cover rDNA-containing plants and other potential plant pests. USDA also regulates veterinary biologics such as recombinant vaccines. The Plant Protection and Quarantine division is the lead regulatory office for GMOs. APHIS also adheres to international standards created by the International Plant Protection Convention. Any introduction of a GMO, defined as importation, interstate movement, or release to the environment, requires either notification to APHIS or application for a release permit, depending on the nature of the plant and the genetic modification made to it. APHIS has an extensive biotechnology Web site describing their regulations⁶.

EPA

The EPA regulates the use of two categories of GMOs. The first encompasses novel microorganisms (formed by deliberate combinations of genetic material from different taxonomic genera) that contain or express new combinations of traits and are intended for commercial use as biofertilizers, biosensors, waste treatment or pollutant degradation, or for commodity or specialty chemical production. The second category consists of plants and microbes producing pesticidal substances, such as plants expressing insect control proteins derived from Bacillus thuringiensis (Bt). More information on these topics is available through the EPA's Toxic Substances Control Act Biotechnology Program⁷and their Biopesticides Program⁸.

FDA

Commercial products modified by genetic engineering for human and animal consumption,

food additives, human and veterinary drugs are subject to regulation by the FDA. Their oversight does not apply to the R&D phases of product improvement. Nevertheless, developers are expected to consult with the FDA during the development phase for guidance on what types of data will be needed at the time of product safety review. An overview of the FDA's policies on food and feed from GM plants can be found on the Internet⁹.

Table 1 shows a concise overview of USDA's, EPA's and FDA's overlapping regulatory authorities.