Issues in the Regulation of Genetically Engineered Plants and Animals

QUICK SUMMARY

A range of options exists to enhance the regulatory review process to address new challenges future products of agricultural biotechnology are likely to present, although opinions vary about the need for change, according to Issues in the Regulation of Genetically Engineered Plants and Animals, a report by the Pew Initiative on Food and Biotechnology.

Introduction

Over the last quarter century, the rapid development of modern biotechnology (see Figure 1.1) has led to the creation of new varieties of plants and animals containing novel traits that would be difficult or impossible to achieve through traditional breeding. Biotechnology is a powerful tool that has the potential to deliver many benefits. Products have been developed or are being developed that can improve the agronomic performance of food crops (such as delivering higher yields or increased disease resistance), provide new consumer benefits (such as healthier oils and vegetables with longer shelf lives), provide new ways to make valuable industrial and pharmaceutical chemicals in plants and animals, and deliver environmental benefits (such as a reduction in the use of pesticides). Regarding fish and livestock, biotechnology has the potential to improve animal health, reduce the costs of production, and improve the quality of food derived from these animals.

Scientific reviews have generally found that the risks posed by biotechnology products do not differ in kind from the risks posed by their conventionally produced counterparts (GAO 2002; NRC 1987). In some ways, genetic engineering is more precise than conventional breeding, because scientists know what genetic material is being introduced and generally understand the functions of the expressed proteins. However, genetic engineering greatly expands the range of genetic material available for modifying plants and animals. Genetic engineering can introduce substances into food that have never been in the food supply before, and can give plants and animals new traits that have not previously been introduced into specific environments.

Concerns have therefore been raised about the potential of genetic engineering to introduce new toxins and allergens into food and to reduce essential nutrients (FDA 1992). Concerns have also been raised about potential adverse effects on the environment from the introduction of novel genetic traits, which could inadvertently be passed on to related wild plants or animals, reducing biological diversity and disrupting ecological systems (NRC 2002b). Plants that have been engineered to express substances to repel pests have raised concerns due to their possible impact on organisms other than the targeted plant pests and the possibility that the pests may become resistant to the pesticidal substances over time (NRC 2000).

The question of how best to regulate genetically engineered (GE) food and other products of agricultural biotechnology has been debated for nearly as long as the technology has existed. Since 1986, biotechnology products have been regulated under a Coordinated Framework of laws administered primarily by three agencies—the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA), and the U.S. Department of Agriculture (USDA).¹ The central premise of the Coordinated Framework was that the process of biotechnology itself poses no unique risks and that products engineered by biotechnology should therefore be regulated under the same laws as conventionally produced products with similar compositions and intended uses. A second and no less important conclusion was that existing laws were adequate to meet regulatory needs.

Under the Coordinated Framework and related agency regulations, the first generation of genetically engineered crops has been introduced and commercialized. Today, a significant percentage of the corn, cotton, and soybeans in the United States is grown from genetically engineered varieties.² For the most part, this first generation of agricultural biotechnology products consists of single-gene, single-trait modifications made for agronomic purposes, primarily to make crops pest resistant or herbicide tolerant. The adequacy of the Coordinated Framework has been a matter of disagreement from the beginning. Some have criticized the regulatory system in general (McGarity and Hansen 2001; Alliance for Bio-Integrity et al. v. Shalala, 116 F. Supp.2d 166 (D.D.C. 2000); Hansen 1999; Hopkins, Goldburg, and Hirsch 1991; Krimsky et al. 1989). Specific risk assessments and product approvals made by the agencies have also been the subject of criticism (NRC 2000, 120-125; UCS 1994). Others have argued that the regulatory system has worked well; they point to the absence of any evident food safety or environmental problems (NRC 2002b; Chassy et al. 2001; NRC 2000; Smith 2000) and the general scientific consensus that GE products are no riskier than their conventionally produced counterparts. Still others have argued that GE foods are over-regulated under the Coordinated Framework and should be afforded no greater review than conventional foods (Miller and Conko 2003).

The introduction of the first generation of GE crops did not occur without controversy. In Europe, the food safety crisis caused by “mad cow disease,” while unrelated to GE food, raised broad concerns among EU consumers about the safety of the food supply and the competence of government regulators, contributing to widespread consumer wariness about GE food (Pringle 2003, 103). The resulting rejection of GE crops and market demand for non-GE varieties has become a major challenge for farmers, grain processors, grain shippers, food manufacturers, and others in industry (Shadid 2001; Shoemaker et al. 2001). Incidents in the United States have also illustrated the challenge of managing GE crops. In 2000, traces of StarLink, a GE variety of corn not approved for food use, were discovered in numerous food products. While the highly publicized incident caused no documented harm to human health, product recalls and trade disruptions cost industry hundreds of millions
of dollars (Lueck 2000).

Today, biotechnology developers are poised to bring the next generation of agricultural biotechnology products to market (Monsanto 2003; PIFB 2001). (See Figure 1.2) While some new crop varieties will continue to deliver benefits primarily to farmers in the form of increased pest resistance or herbicide tolerance, others will represent a significant departure from the first generation. The next generation of GE crop varieties will likely include a wider range of desirable agronomic traits, including drought tolerance. Food crops may be modified with traits to improve freshness, taste, and nutrition. Plants could also be modified for nonfood purposes, such as the manufacture of pharmaceutical or industrial chemicals.

The next generation of agricultural biotechnology also includes animals. In some cases, transgenic animals could be modified to include traits that improve the production offood; examples include faster-growing fish and disease-resistant cattle. In other cases, animals will be modified to produce industrial or pharmaceutical products, and even to grow organs for human transplantation. Many of these genetic modifications will be substantially more complex than the singlegene, single-trait modifications of the first generation of GE crops. The new products are expected to enter into the regulatory review process in the next two to ten years and could pose novel issues for the regulatory agencies.

When the federal agencies first proposed the Coordinated Framework nearly 20 years ago, they acknowledged the need to periodically reassess the regulatory system to ensure that it is keeping pace with the rapid development of the technology (OSTP 1984).³ The impending introduction of the next generation of agricultural biotechnology products has led to a renewed interest in examining the adequacy of the current regulatory system for such future products.

In evaluating the adequacy of a regulatory system, the purposes of the system must initially be considered. The primary purpose of any regulatory system is to protect againstharm by assessing and managing the risks of potentially harmful products and activities. At the same time, a regulatory system should provide a clear pathway to the market for safe and useful products. Over the years, Congress has passed numerous laws to ensure the safety of food, drugs, pesticides, chemicals, and other substances that could pose risks to health or the environment. While the primary goal of a regulatory system is to prevent harm, the public trust generated by an effective and credible regulatory system also has considerable importance for commerce. Regulation can provide assurance to consumers that they can rely upon the agency's independent expertise and purchase products without concern. These commercial benefits can be lost, however, if consumers lack confidence in the integrity and competence of the regulatory system. For this reason, many interested parties, including the biotechnology industry, have consistently acknowledged the importance that a credible, rigorous regulatory system has in ensuring the market acceptance of its products.⁴

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REPORT

Regulating Genetically Engineered Plants for Environmental Protection

Two federal agencies are responsible for assessing and managing environmental risks concerning genetically engineered (GE) plants: the Animal and Plant Health Inspection Service (APHIS) of the U.S. Department of Agriculture (USDA), and the Environmental Protection Agency (EPA). To date, more than 50 GE products have been reviewed by these agencies and received sanction for commercial use.¹ These products have been limited in scope; most are crops that have been rendered either insect resistant (through the insertion of Bacillus thuringiensis (Bt) genes, which have pesticidal properties) or herbicide tolerant. Their use has become widespread in the United States.²

The regulatory and scientific environment in which APHIS and the EPA operate is dynamic and has been rapidly evolving. In a recent report, the National Research Council (NRC) of the National Academy of Sciences stated:

The committee finds that APHIS and other regulatory agencies charged with assessing the safety of transgenic plants face a daunting task. This is so in part because environmental risk assessment of transgenic plants is new and in part because the social context in which regulatory decisions about transgenic organisms must now be made is dramatically different from the one in which these agencies have been accustomed to working (NRC 2002b).

This chapter describes and analyzes a variety of issues relating to the regulatory system governing GE crops and environmental protection. It contains four main sections. The first provides a summary of the key issues in play. The second describes in detail the existing regulatory system involved in managing the environmental impacts of GE plants and microorganisms. The third section delves further into the key issues and concerns regarding the existing system. And the fourth and final section offers several possible means for addressing those issues and concerns, if policy makers determine that changes are needed.

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Regulating Genetically Engineered Crops and Foods for Food Safety

Scientific reviews have generally found that the use of genetic engineering to modify food crops is unlikely to raise any unique food safety concerns that could not also be posed by conventional breeding techniques (NRC 1987 and 2000). While the nature of the risks is not unique, however, genetic engineering does enable plant breeders to use genes from virtually any other organism, dramatically expanding the genetic palette available. In some cases, the genetic material and its expressed proteins may not previously have been found in food. This wide range of genetic material, and the relative lack of experience with novel genes and their proteins, are the principal justifications that federal regulatory agencies use for their increased oversight of genetically engineered (GE) crops and foods (FDA 1992).

The Food and Drug Administration (FDA) and the Environmental Protection Agency (EPA) share responsibility for the safety of food derived from GE crops. The FDA has general responsibility for food safety issues that might be posed by food derived from GE crops (OSTP 1986). The EPA has responsibility for food safety regarding pesticidal substances produced by some GE crops to resist insects (40 CFR Parts 152 and 174).

This chapter reviews the federal regulatory system governing food safety, as it applies to GE crops and foods. It contains four sections. The first is a brief summary of some of the key issues under debate regarding the safety of food products derived from GE crops. The second describes the FDA's and the EPA's existing regulatory systems regarding food safety, and how those systems apply to GE products. The third section describes in detail the key issues and concerns regarding the existing regulatory system. And the fourth section outlines possible approaches—both administrative and legislative—for addressing those issues and concerns, should policy makers decide that reforms are needed.

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Regulating Genetically Engineered Animals

Numerous genetically engineered (GE) animals and products derived from those animals are currently under development in laboratories around the United States (NRC 2002a and 2004).¹ Only one, a transgenic ornamental aquarium fish, has been commercialized (Weiss 2003); no other GE animals nor products derived from them have yet been marketed. The first GE food animal to be commercialized may be a type of salmon that contains an introduced growth hormone (Martin 2003). Other GE animals under development include animals that:

• produce pharmaceuticals for animal or human use,
• contain other substances that can be processed into commercial products,
• are disease-resistant or have other desirable production attributes, or
• contain organs or tissues that can be transplanted into humans.

Some of these animals may be intended to enter the food supply (e.g., the faster-growing salmon), while others are intended for nonfood uses and may need to be kept out of the food supply (e.g., cows that produce human drugs in their milk).

No new laws have been codified to specifically address the regulation of GE animals. And, because GE animals are so new and are still largely being used only in research, the agencies likely to oversee them have not yet established clear overall or product-specific policies for regulating them under existing laws. Regulators, researchers, developers, and potential consumers are thus currently navigating in uncertain waters, and the discussion of regulatory policies in this chapter is necessarily somewhat speculative.

The Food and Drug Administration (FDA) may regulate GE animals under the new animal drug provisions of the federal Food, Drug, and Cosmetic Act (FDCA; 21 USC § 360b; CEQ and OSTP 2001). Nonetheless, it remains unclear exactly how this law would be applied to GE animals, and it is possible that other agencies, with other statutory authorities, may also play a role.

This chapter provides an analysis of the regulatory and policy issues regarding GE animals. The chapter contains four main sections. The first is an overview of some of the key issues under debate regarding GE animals. The second section describes the FDA's regulatory systems for new animal drugs and food safety and explains how these could apply to GE animals. The section also describes the animal and plant quarantine, animal welfare, and meat safety regulatory systems of the U.S. Department of Agriculture (USDA) and the potential roles each may play in creating a regulatory framework for GE animals. The third section describes in detail the key issues and concerns regarding the regulatory system for GE animals. And the fourth section outlines possible approaches—both administrative and legislative—for addressing those issues and concerns, should policy makers determine that change is needed.²

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Regulatory Coordination for Genetically Engineered Crops

While the previous chapters each focused on the regulatory systems of one or two federal agencies, this chapter is centered on the issue of coordination among the various agencies. In particular, it addresses possible approaches for improving coordination among the U.S. Department of Agriculture (USDA), the Food and Drug Administration (FDA), and the Environmental Protection Agency (EPA)—the three agencies with primary responsibility for genetically engineered (GE) plants, animals, and products under the 1986 Coordinated Framework (OSTP 1986). One possible approach for coordinating the regulatory systems governing GE plants is described in detail.

At present, the Coordinated Framework is expected to serve as a regulatory safety net under which all plant-based products are subject to pre-market oversight by at least one federal agency, and sometimes by two or three agencies (OSTP 1986). For example, for plants that produce pesticidal substances (called “plant-incorporated protectants,” or PIPs), three agencies are typically involved.

1. The USDA's Animal and Plant Health Inspection Service (APHIS) reviews plants for their potential effects on agriculture and the environment under the Federal Plant Pest Act (formerly 7 USC § 150aa et seq.), now subsumed by the Plant Protection Act (PPA; 7 USC § 7701 et seq.), and also under the National Environmental Policy Act (NEPA; 42 USC § 4321 et seq.).
2. The EPA reviews the potential effects on human health and the environment of pesticidal substances produced by plants, under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA; 7 USC § 136 et seq.) and the pesticide residue provisions of the federal Food, Drug, and Cosmetic Act (FDCA; 21 USC § 346a).
3. The FDA reviews the food and feed safety and nutritional aspects of whole foods, and any other nonpesticidal substances that might be added to plants through genetic alteration, under the food safety provisions of the FDCA (21 USC § 301 et seq.).

While agencies have worked to increase cooperation and coordination, issues remain. In particular, the system can present challenges for small companies and public researchers, who often face multi-agency reviews with little or no comprehensive guidance on who must be talked to and when. Also, the interested public is left largely in the dark about how any given GE product is proceeding through the regulatory review process, particularly given that some agency guidance is unclear or lacking and some key decisions are made via informal, private consultations. Due to this lack of transparency, it is nearly impossible to track a GE product from the initial phases of regulation (e.g., a field trial) through to commercialization (e.g., a GE food set to enter the food supply) via the information provided by the agencies on their respective web sites. Product characterizations and the timing and substance of posted data vary widely. And there is no single, authoritative source of information about specific products undergoing regulatory review. Also, technology developers often claim confidentiality for large portions of submissions, making it difficult for third parties to make independent assessments, particularly prior to commercialization (NRC 2000, 177-178; 2002b, 178).

The regulatory system can also appear to be unpredictable. Many procedures for product review and safety assessment are not spelled out in formal regulations, policies, or guidelines. Given the diversity of products under development and the rapidly advancing state of the science, the agencies have elected to develop their review procedures largely through case-by-case assessments of individual submissions. For those not directly involved in the process, attempting to determine what was done and why, or whether a similar process will be followed in the future, can be difficult. In the case of APHIS and the FDA, it is not clear how newer products that incorporate pharmaceuticals and vaccines into crops are being reviewed. Moreover, it is not clear that like reviews are conducted in the same manner or with comparable rigor by different agencies (e.g., ecological risk assessments by APHIS and the EPA (NRC 2000, 165-166, 170-171; 2002b, 178) and allergenicity assessments by the
FDA and the EPA complement one another (NRC 2000, 168-169)).

In general, the agencies appear to have avoided overlapping reviews and responsibilities through understandings reached in the development of the Framework and through interagency memoranda of understanding (USDA and EPA, no date). The substance of these understandings is not readily available to the public, however, and the possibility of redundancies exists, particularly in the review of PIPs by the EPA and APHIS. This chapter reviews options for achieving greater coordination among the agencies that regulate GE plants and GE plant products, should policy makers decide that such change is needed.

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Appendices

We at the Pew Initiative on Food and Biotechnology (PIFB) would like to thank the individuals listed below for contributing to our understanding of the regulatory issues surrounding agricultural biotechnology. These individuals include members of the Stakeholder Forum on Agricultural Biotechnology: Nearly 100 outside legal, scientific, and policy experts provided assistance to the Forum's efforts through briefings, presentations, research, analysis, and informal discussions; and those who took part in a joint meeting with the National Research Council. We would also like to give special notice to Jennifer Thomas-Larmer, whose wordsmithing abilities and understanding of regulatory issuesmade her the ideal editor of this report.

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Personal Communications Cited
James V. Aidala, former Assistant Administrator, Office of Prevention, Pesticides, and Toxic Substances, Environmental Protection Agency. September 16, 2003.
Thomas Bundy, Deputy Assistant General Counsel (Retired), Regulatory Division, Office of General Counsel, U.S. Department of Agriculture. November 30, 2003.