Edward L. Korwek

Hogan & Hartson

555 13th Street, NW

Washington, DC 20004

elkorwek@hhlaw.com

Modern biotechnology has been and will continue to be used in agriculture in many different ways, as well as in aquaculture. The goal is to improve plant and non-human animals, and other organisms such as fish, for a variety of reasons. These reasons include producing pharmaceuticals and food, or both, by making plants, non-human animals, and fish healthier, or larger, or more nutritious. The focus of this article is on modern biotechnology-produced fish, whether or not the fish is used for human consumption, and on the environmental regulatory aspects of transgenic fish production. The development of non-food aquatic transgenic fish, such as goldfish, would be subject to similar laws as those used for food purposes.

Transgenic fish can pose many environmental challenges, because of the ease with which such organisms can escape, enter the environmental water ways, and potentially impact the environment, commerce, or other aspects of human and other animal or plant health and the U.S. economy. The applicability of many environmental laws often depends on what the harm, if any, is perceived that engenders regulation.

The area of modern biotechnology-based (e.g., recombinant DNA (R-DNA)-based) aquaculture has not been the direct subject of federal legislation, as is the case with most R-DNA-derived organisms. These organisms are sometimes inarticulately referred to as "genetically modified organisms" or "GMOs," although most agricultural crops and food animals are genetically modified in some way. Several federal statutes could be used or already are being used to regulate aquatic GMOs. In the food and drug area, the primary laws are the Federal Food, Drug, and Cosmetic Act (FFDCA) and the Virus Serum Toxic Act (VSTA). In the environmental area, a variety of laws are relevant or potentially relevant, in particular the National Environmental Policy Act (NEPA). A recent, expansive view of the range of federal regulation of transgenic aquatic organisms and other transgenics was published by the Council on Environmental Quality (CEQ) and the Office of Science and Technology Policy (OSTP) (CEQ/OSTP 2001).

In my view, genetic constructs to create transgenic fish for food or non-food uses will be primarily regulated by the Food and Drug Administration (FDA) under its drug authorities. Environmental-oriented statutes likely will have less relevance, except for NEPA.

New Drug and Biologic Regulation

Under the FFDCA, FDA has primary responsibility for ensuring the safety and proper labeling of human and other animal foods, as well as fish, except meat, poultry, and egg products. These last three products are primarily handled by the Food Inspection Safety Service of the United States Department of Agriculture (USDA). Most generally, the use of modern biotechnology or, in particular, transgenic nucleic acid constructs, in the production of non-human animals, as well as of fish, for the purposes of enhancing the nutritional value of such animals or increasing their growth rate, reproduction, or resistance to disease, typically are regulated as drugs under the FFDCA. If the change is to alter the germ line or somatic cells of animals (or fish) to, for example, enhance their nutritional value, such as the production of more omega 3 fatty acids, or to prevent disease through a non-immune-based mechanism, the genetic sequences would be and are being regulated as new animal drugs. On the other hand, germ line or somatic cell alteration that results in the production of antigens producing antibodies to a particular disease would be regulated as biologics by APHIS. The genetic constructs are drugs or biologics because they either affect the structure or function of animals or fish, or are intended to prevent disease, or both. Generally, the use of modern biotechnology to map the genome of non-human animals or fish are not considered new animal drugs or biologics.

The Center for Veterinary Medicine (CVM) has particular responsibility for non-human animal drugs, a category that includes fish. To the extent that a product acts primarily through the direct stimulation, supplementation, enhancement, or modulation of the immune system or immune response, it is regulated as a biologic by the Animal and Plant Health Inspection Service (APHIS) within USDA under VSTA. Although FDA has not published a formal policy on how the FFDCA applies to transgenic fish, it has, for example, published a document generally applicable to aquaculture entitled "Aquaculture Drug Use: Answers to Commonly Asked Questions" (CVM, 1995). Drugs used in aquaculture, like other drugs regulated by CVM, generally require investigational authorization to conduct clinical studies in animals; such studies are then used to support the approval of a new animal drug application (NADA). A similar scheme exists for animal biologics. Permits for investigation and licenses for commercialization are required by APHIS. Both of these APHIS and CVM systems can be used to regulate research and the commercialization activities involving fish, via the use of genetic constructs or events.

Obtaining an experimental authorization or permit and approving an NADA or a biological license for a new drug or biologic are activities subject to NEPA. Although a comprehensive discussion of the intricacies and extensive litigation involving NEPA are beyond the scope of this article, many applications of modern biotechnology, like other technologies, are affected by NEPA. NEPA requires an assessment of any major federal actions significantly affecting the quality of the human environment. Many federal agencies have published categorical exemptions and other requirements pertaining to NEPA. Generally, the authorization or permitting of new drug or biologic clinical investigations, or the approval for commercialization of an NADA or a biological license, involves NEPA. FDA is expected to publish a draft guidance document covering environmental assessments associated with transgenic salmon. Interestingly, USDA also has already developed in one instance an environmental assessment related to a USDA-funded research activity involving transgenic carp (Cooperative State Research Service, 1990). It is expected that NEPA will continue to play an important role pertaining to the environmental impacts of the approved commercialization of new drugs or biologics involving transgenic fish.

Environmental Oversight Beyond NEPA

In 1995, the Agriculture Biotechnology Research Advisory Committee (ABRAC), of which I was a member, helped develop the first confinement guidelines covering the research and development of transgenic fish and shellfish (ABRAC 1995). Some states have established regulations covering marine GMOs, although states generally have authority over aquatic resources and certain marine resources. State permits can be required for certain aquaculture activities. At the federal level, the Fish and Wildlife Service (FWS) has oversight of fresh water and the National Marine and Fisheries Service (NMFS) has oversight of marine water. The primary environmental oversight, other than that related to NEPA, is related to the introduction of invasive or non-indigenous organisms, although many other state and federal laws can apply depending on the nature of the activity involved. On the international scene, the Biosafety Protocol, in the process of ratification, although not by the U.S., will apply to living modified organisms (LMOs) in foreign commerce. Table I describes a few relevant environmental oversight mechanisms.

Table I

Key Environmental Laws and Other Related Oversight Mechanisms

Legal Mechanism	Fish Coverage	Activity Covered	Responsible Government Body	Damage Covered
Lacey Act	Species of wild animals, wild birds, fish (including mollusks and crustacea), amphibians, brown tree snakes, or offspring or eggs of any of the foregoing.	Importation or transportation and release, violation of another law, or treaty, or regulation of U.S.	U.S. Fish and Wildlife Service (FWS)	Injurious to human beings, interests of agriculture, forestry, horticulture, wildlife, or wildlife resources of U.S.
Endangered Species Act	All listed endangered or threatened species, including fish.	Almost any action affecting listed endangered or threatened species.	FWS	Almost any action pertaining to listed endangered or threatened species.
Nonindigenous Aquatic Nuisance Prevention and Control Act	Aquatic nuisance species, including fish.	Introduction into waters of U.S.	FWS	Nonindigenous species that threaten abundancy or diversity of native species, or ecological stability of infested waters or commercial agricultural, aqua-cultural, or recreational activities.
Executive Order 13112	Invasive species, including fish.	Prevent introduction of invasive species, detect and control such species.	All executive federal agencies	An alien species where introduction does or likely causes economic or environmental harm or harm to human health.
Biosafety Protocol (in the process of ratification)	Living modified organisms in international commerce (including fish).	International transboundary movement for intentional introduction into the environment.	Signatory countries (not the U.S.)	May have adverse effects on the conservation and sustainable use of biological diversity, taking into account risks to human health.

The bottom line, from a regulatory perspective, is that federal and state governments are becoming very creative in the exercise of their statutory authorities over GMOs. To understand the real impact of such a viewpoint, one need only to look at the Environmental Protection Agency’s current regulation of plant incorporated protectants, formerly called plant pesticides, under the Federal Insecticide, Fungicide, and Rodenticide Act and its regulation of microorganisms under the Toxic Substances Control Act.

References

ABRAC, U.S. Department of Agriculture. 1995. Performance Standards for Safely Conducting Research With Genetically Modified Fish and Shellfish. http.www.nbiap.vt.edu.

Center for Veterinary Medicine. 1995. Aquaculture Drug Use: Answers to Commonly Asked Questions.

Cooperative State Research Service, U.S. Department of Agriculture. 1990. Availability of an Environmental Assessment and Finding of No Significant Impact Relative to USDA Funding of Research on Transgenic Carp. 55 Fed. Reg. 48661.

Council on Environmental Quality and Office of Science and Technology Policy. 2001. Notice of Availability and Request for Comments. 66 Fed. Reg. 7905. http//www.whitehouse.gov/ceq or http//www.ostp.gov.