Eric Hallerman
June, 2004

The GloFish, a fluorescent red zebrafish sold as a novel pet, has become the first transgenic animal sold to U.S. consumers. Its sale has produced regulatory controversies, a lawsuit, and profits for its proponent, Yorktown Technologies (Austin, TX). With the market plan calling for sales in a widening number of countries, continuing controversy seems likely.

What is a GloFish?
The GloFish is a trademarked transgenic zebrafish (Danio rerio) expressing a red fluorescent protein from a sea anemone under the transcriptional control of the promoter from the myosin light peptide 2 gene of zebrafish1. Produced and patented by a group at the National University of Singapore, exclusive rights for international marketing were purchased by Yorktown Technologies approximately a year-and-a-half ago. Yorktown produces GloFish through contracts with 5-D Tropical (Plant City, FL) and Segrest Farms (Gibsonton, FL), and began marketing them in the United States in December.

Issues posed
The prospect of commercial sales of GloFish raised a number of issues. Among them was the issue of whether GloFish pose an environmental hazard. Zebrafish, a tropical species native to south Asia, are sensitive to low temperature. Despite decades of production and use in the U.S., zebrafish have not established self-sustaining populations within the country. Laboratory tests1 showed that viability, reproductive success, and temperature tolerance of transgenics were equal to or somewhat less than those of the wild type. While preliminary, results supported the expectation that the modification would not increase invasiveness, and that environmental risk was small.

Commercialization of the GloFish in the United States poses regulatory uncertainty because existing biotechnology policy bases oversight on the use of the product. Sales of ornamental fishes are not federally regulated. The Food and Drug Administration asserts jurisdiction over genetically modified animals using the New Animal Drug Application process. After a brief internal review and interagency consultation, FDA's Center for Veterinary Medicine determined that "because tropical aquarium fish are not used for food purposes, they pose no threat to the food supply. There is no evidence that these genetically engineered zebra danio fish pose any more threat to the environment than their unmodified counterparts which have long been widely sold in the United States. In the absence of any clear risk to the public health, the FDA finds no reason to regulate these particular fish2." Alan Blake, CEO of Yorktown Technologies, also made contact with the U.S. Department of Agriculture, the U.S. Fish and Wildlife Service, and the Environmental Protection Agency, which expressed no regulatory concerns regarding GloFish.

States generally have lead authority on fisheries issues. California is the only state that forbids the possession, sale, and transport of genetically modified fishes. Yorktown asked for an exemption, but on December 3, the California Fish and Game Commission voted not to approve sale of the fish. Explaining the decision, Commissioner Sam Schuchat wrote, "Creating a novelty pet is a frivolous use of this technology. No matter how low the risk is, there needs to be a public benefit that is higher than this3." Many California consumers were unhappy with the Commission's decision. Following appointment of a new commissioner and a change of mind by a continuing commissioner, on April 1 the Fish and Game Commission reversed their earlier decision by a 3-1 vote4. They asked for an updated recommendation from the Department of Fish and Game and will hold public hearings before making a final decision. The final vote of the Commission is expected near the end of June. If approved, GloFish would become available for sale in California by the end of July.

Commercialization of GloFish sparked legal action to force the FDA to exert regulatory oversight and block further sales. On January 14, the Center for Technology Assessment (CTA) and Center for Food Safety (CFS) filed a lawsuit in the Federal District Court in Washington, D.C. challenging FDA's implementation of the Federal Food, Drug, and Cosmetics Act (FFDCA), National Environmental Policy Act (NEPA), and Administrative Procedures Act regarding procedures by which FDA allowed commercialization of GloFish5. CTA and CFS allege that FDA inaction poses harm to the enjoyment of natural waters, harm to carnivorous fishes, increased exposure to antibiotic-resistant bacteria and viruses due to elements in the expression vector used to produce GloFish, and aesthetic injury from viewing genetically engineered GloFish in aquaria. CTA and CFS asked the court to declare that FDA has regulatory authority under FFDCA, "absence of a clear risk to public health" is not the appropriate regulatory standard, and FDA action was not compliant with NEPA, and to enjoin FDA from allowing further sales of GloFish. The lawsuit is currently pending.

Future prospects
Future prospects for the GloFish include marketing additional color lines in a wider range of markets. Not only red, but also green and yellow fluorescent proteins have been introduced into stable transgenic lines, yielding green, yellow, and orange fish.

Commercialization of fluorescent zebrafish has gone forward in several countries and is stymied in others. Fluorescent green zebrafish developed in Taiwan have been sold in Taiwan, Malaysia, and Hong Kong. Singapore confiscated attempted imports of the fish. Despite this, Yorktown Technologies is considering other markets, including parts of Asia and Latin America. Extensive information requirements suggest that GloFish will not be marketed in Canada or the European Union in the near future. Despite these regulatory challenges, according to Blake, "The GloFish venture is a profitable one, and the company looks forward to continuing to provide a safe and enjoyable product for many years to come."

Issues posed by commercialization of GloFish will be with us for years to come. Approval for commercializing other transgenic fishes, including Atlantic salmon expressing an introduced growth hormone (GH) gene, has been sought. GH-transgenic tilapia, channel catfish, and rainbow trout are on the regulatory horizon, and a wide range of other transgenic fishes are under development. Marketing of fluorescent zebrafish may spur efforts to develop other transgenic ornamentals, such as goldfish and koi carp. Transgenic zebrafishes also are under development for biomoni-toring—expression of fluorescent protein genes under the control of estrogen-inducible or stress response promoters would indicate exposure of caged zebrafish to environmental pollution6.

Literature Cited

1. Gong W et al. (2003) Development of transgenic fish for ornamental and bioreactor by strong expression of fluorescent proteins in the skeletal muscle. Biochemical and Biophysical Research Communications 308: 58-63.

2. U.S. Food and Drug Administration. (2003) FDA statement regarding Glofish.

3. Schuchat S. (2003) Why GloFish won't glow in California. San Francisco Chronicle.

4. Thompson D. (2004) California reconsiders nation's only bio-pet ban. Associated Press,

5. Center for Food Safety and International Center for Technology Assessment. (2003) Complaint to Federal District Court.

6. National University of Singapore. (2004) Zebrafish as pollution indicators.

Eric M. Hallerman
Department of Fisheries and Wildlife Sciences
Virginia Polytechnic Institute and State University