The system for regulating transgenic crops in the U.S. is complex and evolving. We first describe the current system, then mention several studies or proposals that may affect how this system is modified. For additional information and links, a good starting point is the web site "United States Regulatory Agencies Unified Biotechnology Website" (http://usbiotechreg.nbii.gov/).

Transgenic crops are regulated at every stage in their development, from research planning through field testing, food and environmental safety evaluations, and international marketing. These are the major regulators of transgenic crops:

• Institutional Biosafety Committee
• Animal and Plant Health Inspection Service (APHIS) of USDA
• Food and Drug Administration (FDA)
• Environmental Protection Agency (EPA)
• State regulations
• International agreements

Most research institutions have an IBC, which monitors potentially hazardous biological research and ensures compliance with biological safety procedures. At Colorado State University, for example, researchers must notify IBC if planning to work with recombinant DNA in any form. Depending on the nature of the work, a Biosafety Level is assigned. For transgenic plants, the appropriate level would be BL1-P to BL4-P, depending on the potential risk of a specific transgene. Precautions required for these four biosafety levels are as follows:

BL1-P - Basic containment level. Restricted access to greenhouse; insect, weed, and rodent control mechanisms; screens recommended.

BL2-P - For agents of moderate potential hazard.BL1-P requirements, plus: Concrete floor; screens restricting movement of small insects, but not pollen; autoclave to sterilize transgenic material before removal. CSU's new plant biotechnology greenhouse is a BL2-P facility.

BL3-P - For agents of serious potential hazard. BL2-P requirements, plus: Collection and sterilization of liquid runoff; sealed windows; ventilation filters; Security fence; protective clothing.

BL4-P - For work with extremely hazardous agents, including certain exotic plant pathogens. Similar to BL3-P but even more stringent.

More details and interpretation of the NIH safety guidelines for transgenic plants and associated organisms is available at http://www.fpm.wisc.edu/biosafety/Base/PlantContainment.htm.

An informative guide to growing transgenic organisms in greenhouses has been written by Traynor et al. (2001).

Animal and Plant Health Inspection Service (APHIS) of USDA (http://www.aphis.usda.gov/brs/)

Under the Federal Plant Pest Act, APHIS must determine whether a transgenic plant variety is likely to become a pest, i.e., to have negative agricultural or environmental effects. The agency regulates the import, transportation, and field testing of transgenic seeds and plants through notification and permitting procedures, as explained below.

1. For most common crops, researchers simply notify APHIS of their intention to transport or field test a transgenic plant. Certain criteria must be met for the introduced gene, including:

   • stable integration in the plant's chromosomes

   • non-pathogenic to animals or humans

   • unlikely to be toxic to other non-target organisms

   • low risk of creating new plant viruses

2. For less common crops and for genes or traits posing a greater risk, researchers must file a formal application for permission to transport or plant the material.

Field testing, typically conducted in many locations and several years, requires procedures to minimize spread of the transgene and keep it out of the food supply.

To commercialize a transgenic plant, the researcher petitions APHIS for non-regulated status. This requires extensive data on the introduced gene construct, effects on plant biology, and effects on the ecosystem, including spread of the gene to other crops or wild relatives. After the crop is on the market, APHIS has the authority to halt its sale if there is evidence that the plant is becoming a pest. Does APHIS have the authority to regulate ALL transgenic plants, or only those deemed to have the potential to become plant pests? An April 2000 report by the National Academy of Sciences (http://books.nap.edu/catalog/9795.html; see NAS Committee Report) felt that some transgenic plants might not fall under APHIS's current regulatory oversight, and recommended that the agency clarify its scope of coverage.

Food and Drug Administration (FDA) (http://www.fda.gov/oc/biotech/default.htm)

The FDA has authority under the Federal Food, Drug, and Cosmetics Act to determine the safety of foods or food ingredients. FDA staff consult with the plant developer, review safety and nutritional data, and request additional data considered appropriate for each product. If the introduced gene is from a known allergenic source, then the transgenic food must be assessed for allergenicity. For example, if a gene from peanut (which causes allergic reactions in some people) were introduced into soybean, the FDA would require extensive allergenicity tests. Additional investigation may be required for transgenic crops if they involve:

• known toxicants

• altered nutrient levels

• new substances

• antibiotic resistance markers

At the end of the consultation and review process, FDA sends a letter to the developer stating that the agency is satisfied with the data regarding food safety of the product. Information on completed consultations, including the FDA's letter to the developer and the FDA's final memorandum, is available at http://www.cfsan.fda.gov/~lrd/biocon.html. After a product is on the market, FDA has authority to order its removal if the food is deemed unsafe.

Critics of the FDA's regulation of transgenic foods believe that the voluntary nature of the consultation process between FDA and crop developers is inadequate. Although all companies to date have consulted extensively with FDA staff and presented large amounts of data on food safety satisfying FDA's concerns, the lack of a formal review and approval process prevents that data from being part of the public record, and may reduce consumer confidence.

In late 1999, the FDA held a series of three meetings to seek public comment on FDA's regulatory policies and on suitable means to provide information to the public about transgenic products in the food supply. Transcripts of the meetings are available at the FDA's web page on bioengineered foods, listed above. Additional information is available from FDA's Center for Food Safety and Applied Nutrition (http://vm.cfsan.fda.gov/~lrd/biotechm.html).

Environmental Protection Agency (EPA) http://www.epa.gov/pesticides/biopesticides/

EPA regulates transgenic plants that are engineered for pest resistance, e.g., Bt insect resistant corn or virus resistant squash. In EPA terminology, these plants contain "plant-incorporated protectants" (also known as "plant-pesticides"). EPA's authority to regulate transgenics is based on three laws:

1. The Federal Insecticide, Fungicide, and Rodenticide Act grants the authority to regulate the distribution, sale, use, and testing of plants and microbes containing pesticidal substances.

2. The Federal Food, Drug, and Cosmetics Act empowers EPA to regulate pesticide content of foods.

3. Under the Toxic Substances Control Act, EPA regulates commercial use of genetically engineered microorganisms, e.g., a bacterium that allows a plant to fix nitrogen or produce a novel chemical.

To implement its oversight of transgenic crops, EPA

• Examines data characterizing the plant-incorporated protectant, e.g., the biochemical nature of the product, its mode of action, and the time and tissues in which the product is expressed.

• Reviews environmental effects (both risks and benefits) of the proposed plant-incorporated protectant, including effects on non-target organisms and environmental fate.

• May require a "resistance management plan", measures to slow down development of resistance in the target pest.

• Determines whether the introduced gene or its product are toxic, typically based on toxicity testing in animals.

• Sets tolerance levels for pesticide residues, if there is evidence of toxicity. Because of lack of toxicity in plant-incorporated protectants evaluated to date, they have been exempt from this requirement.

• Regulates new uses of existing pesticides, such as use of herbicides together with herbicide-resistant transgenics.

Recent developments

OSTP proposes updates to U.S. regulatory system

In August 2002, the U.S. Office of Science and Technology Policy formally proposed several changes in the way USDA, FDA, and EPA regulate biotechnology-derived crops. The main points of the proposed actions are

1. To encourage biotech crop developers to submit protein safety information (especially concerning allergenicity and toxicity) at an earlier stage in the evaluation process than currently practiced.
2. To strengthen field testing protocols for certain types of biotechnology-derived products to minimize the potential for gene flow to seed and commercial production fields.
3. To establish procedures to address potential intermittent, low level presence in food or feed of new proteins that have not completed regulatory review.

Published in the Federal Register, Vol. 67, No. 149. FR Doc. 02-19746, Filed 8-1-02.

NAS Committee Report

In April 2000, a U.S. National Academy of Sciences panel released a report calling for changes in the regulatory process for transgenic crops. The report, authored by the Committee on Genetically Modified Pest-Protected Plants, National Research Council, is entitled "Genetically Modified Pest-Protected Plants: Science and Regulation" (http://books.nap.edu/catalog/9795.html). As indicated by the title, the report addressed only transgenic varieties engineered to protect plants from insects and diseases. Among the conclusions in the 261-page report:

• There is no evidence that foods produced from transgenic crops currently on the market are unsafe as a result of the inserted genetic material.

• Pest-resistant transgenic plants are useful in reducing the amount of chemical pesticides applied, and may therefore lead to greater biodiversity in some areas.

• Regulatory agencies (USDA, FDA, and EPA) should more closely coordinate their regulatory and approval activities, and should make the process more open to the public.

• Long-term impacts of transgenic crops on ecosystems and human health should be monitored.

• Two EPA categorical exemptions should be revoked: (1) for plants with viral coat protein genes to provide virus resistance; and (2) for plants transformed with genes from a sexually compatible plant. The panel felt that these categories of transgenic crops could have negative effects in some cases, and should not be exempted from a rigorous evaluation.

• Better methods of identifying potential allergens should be developed.

Clinton Administration initiatives on ag biotech regulation

A series of steps to strengthen science-based regulation of ag biotech products was announced by the Clinton Administration on May 3, 2000. These initiatives include:

1. A 6-month assessment of federal environmental regulations pertaining to agricultural biotechnology, to be conducted by the Council on Environmental quality and the Office of Science and Technology Policy.

2. A proposed requirement by the Food and Drug Administration (FDA) that it be informed at least 120 days before GM crops or products are placed on the market. This will replace the current voluntary consultation process. (On Jan. 17, 2001, FDA formally proposed this change in regulations.) (Food and Drug Administration Center for Food Safety and Applied Nutrition http://vm.cfsan.fda.gov/~lrd/biotechm.html)

3. Development of FDA guidelines for voluntary labeling of foods containing or not containing transgenic ingredients. (On Jan. 17, 2001, FDA formally proposed this guidelines.) (Food and Drug Administration Center for Food Safety and Applied Nutrition http://vm.cfsan.fda.gov/~lrd/biotechm.html)

4. An expanded competitive grants program by USDA and FDA on health and safety issues.

5. Improved public education activities on the nature of the US regulatory process.

USDA Committee Begins 2-Year Review

In March 2000, Secretary of Agriculture Dan Glickman convened a 38-member panel to review USDA's role in developing and regulating transgenic crops. The committee, which includes scientists, farmers, and representatives of consumer groups and seed companies, is expected to take two years to complete its assignment. Among the issues the panel will address are the use of "terminator" technology, developed by USDA to prevent unauthorized reproduction of transgenic seeds.

State regulation

In addition to federal regulation, some states require additional review and approval of transgenic crops at the state level. State agencies work together with APHIS to monitor transgenic field testing.

At present, Colorado does not require a separate state review of transgenic crop varieties. A description of Minnesota's regulation of transgenic crops is available at www.mda.state.mn.us/BioTech/regulations.HTM.

International agreements

In this age of global trade, international agreements can have a major impact on regulating the movement of products between countries. Two developments that may effect the import and export of transgenic crops and food are described below.

World Trade Organization (WTO) members have agreed to a wide range of policies aimed at creating and maintaining free and open international trade. For example, if a country blocks import of beef produced with growth hormones, an exporting country could file a protest with the WTO. WTO's position on transgenic food products has not been finalized, but will likely be very important in regulating the future trade in transgenic crops.

A landmark International Biosafety Protocol to regulate international trade of genetically modified organisms (GMOs) was approved by representatives of 130 countries at a meeting in Montreal, Canada in January, 2000. The agreement, an outgrowth of the Convention on Biological Diversity (Rio Earth Summit, 1992), was hailed as a step forward by both proponents and opponents of transgenic crops. The protocol still requires ratification by 50 nations before it goes into effect. Its major components are:

• International shipments that "may contain" transgenic food products must be so labeled. The exact nature of the genetic modification need not be specified, but the agreement calls for negotiations on more specific labeling requirements in the future. This labeling provision applies only to large-scale shipments, and does not affect labeling requirements on consumer products, which are determined by each country.

• Governments may use the so-called "precautionary principle" to bar import of a transgenic product even in the absence of conclusive evidence that the product is not safe. However, the protocol does not override other international agreements, including the WTO, which requires that import decisions be science-based.

• To assist countries in making import decisions, a database will be established to make available uniform information on transgenic crop varieties.

• Perhaps most importantly, the protocol establishes an international framework for regulating international trade in transgenic crops, and demonstrates that a balance can be found between different points of view in this often polarized debate.