Annotated Bibliography Entry

Reference: Pew 2003
Title:  Future Fish? Issues in Science and Regulation of Transgenic Fish
Authors: Pew Initiative on Food and Biotechnology
Publisher:  Pew Initiative on Food and Biotechnology, 1331 H Street, Suite 900, Washington, DC 20009 USA.
Publication details: January 2003. 72p.

Summary
            US Regulatory Approaches
Development, Status, and Economic Implications
            Environmental Issues
          Food Safety Issues
          Regulating Transgenic Fish
          Summary
Main Report Table of Contents

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Summary

Over the past decade, genetic engineering has emerged as one of the most powerful transforming technologies known to this generation. Scientists can now transfer the beneficial traits of a particular gene from one organism to another in far less time than needed in traditional breeding and with more precision. The application of genetic engineering to agriculture already makes it easier for farmers to grow certain crops and reduces the use of certain pesticides. But this technology has also triggered debate among scientists, philosophers, environmental advocates, public health officials, business leaders, and regulators over a range of issues—from environmental safety and ecological impacts to the ethics of altering a genome.

As society wrestles with these difficult issues, developers continue to apply the technology to create new varieties of organisms across different kingdoms of life, moving from bacteria to plants and, now, to animals. In recent years, scientists have applied genetic engineering for a wide variety of purposes to a host of animals traditionally used as food sources, including cows, pigs, and fish. For example, scientists may soon be able to transform pigs to the point they could be a new source for human organs and cows could be engineered to produce proteins essential to the production of human pharmaceuticals. However, at this time, these products remain research possibilities rather than commercial realities. Only one animal—genetically modified fish—is thought likely to come to market in the near future.

The potential benefits of animal biotechnology will become a reality only if the US and other regulatory systems can review these products in a comprehensive manner that merits public confidence and gives product developers a clear pathway to the marketplace.    

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US Regulatory Approaches

In the mid-1980s, federal policy declared that biotechnology products would be evaluated under the same laws and regulatory authorities used to review comparable products produced without biotechnology. However, as scientists develop new varieties of organisms through genetic engineering that confound conventional categorization, regulators are increasingly pressed to develop creative interpretations of existing laws to address the unique issues raised by these products. For example, the Food and Drug Administration (FDA) has indicated its intention to use its authority to approve “new animal drugs” under the Federal Food, Drug, and Cosmetic Act (FFDCA) as the basis for regulating transgenic fish. The FDA argues that the genetic construct used to create transgenic fish meets the legal definition of a new animal drug as a substance “...intended to affect the structure or function of the body of man or other animals.” This use of the new animal drug application process may have some advantages. Some note that the FFDCA provides the FDA with adequate legal authority to assess food safety and to require mandatory pre-market approval of genetically modified fish—a regulatory feature currently not applied to existing agricultural biotechnology products such as genetically modified plants. However, others question whether or not the FFDCA gives the agency adequate legal authority to address the environmental and ecological issues unique to genetically modified fish.

Future Fish? Issues in Science and Regulation of Transgenic Fish describes some of the products that could be created through the application of genetic engineering to aquaculture as well as the potential environmental and food safety issues associated with such products. The report also analyzes the process through which regulators plan to evaluate transgenic fish. By consolidating both the scientific and regulatory issues concerning genetically modified fish in this report, the Pew Initiative on Food and Biotechnology hopes to facilitate a robust discussion about genetically modified fish and the adequacy of the regulatory process through which they may be brought to market.

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Development, Status, and Economic Implications

The first reports of the application of genetic engineering to animals appeared in the 1980s. Since then, there has been a burst of genetic modification activity in aquaculture research and development. Fish make attractive candidates for genetic modification for several reasons. One is that they produce eggs in large quantities and those eggs develop outside the fish’s body. (In contrast, cows and pigs produce fewer eggs at a time, and once scientists insert novel DNA they must re-insert the altered egg into the animal.) A second, equally compelling reason is that aquaculture is one of the fastest growing food-producing sectors globally. Since 1984, commercial aquaculture has expanded at an annual rate of almost 10 percent, compared with a 3 percent growth rate for livestock meat and 1.6 percent rate of growth for capture fisheries (FAO 2000). In the U.S. alone, sale of aquaculture products has grown from $45 million in 1974 to over $978 million in 1998 (National Agricultural Statistics Service 2000).

Given such demand, it is not surprising that the majority of aquaculture biotechnology research and development efforts to date have focused on improving production. Scientists have modified at least 14 fish species—including varieties of carp, trout, salmon and channel catfish—so they will grow 2 to 11 times faster than their non-modified counterparts. Increased growth means reaching marketable size sooner and therefore reducing overhead costs for fish farmers. A growing number of reports indicate such transgenic fish also show better gross food conversion (i.e. the increase in fish weight per unit of food fed), creating another cost efficiency for fish farmers. In other research, scientists are exploring the use of the human interferon gene to improve disease resistance in carp, which could reduce the amount of antibiotics needed to keep fish healthy and reduce the costs incurred from losses due to disease.

Current research efforts are not, however, limited to improving fish farm productivity. In an attempt to identify new sources for the production of pharmaceutical substances, scientists have engineered tilapia with a human gene that makes the fish capable of producing a compound essential to the production for Factor VII, a substance vital to the clotting of human blood. Scientists have also tried to improve the cold tolerance of goldfish, so that this popular ornamental fish could thrive in different climates than its non-modified counterpart. Scientists have altered some marine microorganisms to reduce their dependence on light so they might live in unique environments.

While improving aquaculture efficiency could lower costs and generate economic benefits to producers and consumers, global supply and demand combined with consumer acceptance will largely determine whether these benefits will be realized. Such an analysis is beyond the scope of this report.

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Environmental Issues

Conventional aquaculture practices have raised a number of environmental issues including, but not limited to, pollution and the impacts on wild fish populations should fish escape from fish farms. The application of genetic engineering to aquaculture adds significant new dimensions to these existing concerns, especially the multiple possibilities related to gene flow and the ecological disruption associated with escapes.

Gene Flow
One of the larger environmental concerns raised by transgenic fish is the possibility that a transgenic species raised in open water pens will escape and spread novel traits into the ecosystem by breeding with wild relatives, a biological process known as “gene flow.”

Gene flow between transgenic or conventionally bred fish and wild populations is an environmental concern because it may present a threat to natural biodiversity. Some researchers believe that the genetic differences introduced to a transgenic fish may impact its net fitness, a scientific term meaning an organism’s ability to survive and pass its genes to future generations. The concept—which factors in characteristics such as the juvenile and adult viability of a fish, the number of eggs produced by a female, and the age at which a fish reaches sexual maturity—provides a useful barometer for discussing some gene flow scenarios.

According to one scientific model, if a transgenic fish escaped and mated with wild

·        Purge Scenario – When the net fitness of a transgenic fish is lower than that of its wild relatives, natural selection will quickly purge from the wild population any novel gene(s) introduced by the transgenic fish. In theory, evidence of the novel trait will disappear from subsequent generations.

·        Spread Scenario – When the net fitness of a transgenic fish is equal to or higher than the net fitness of a wild mate, gene flow is likely to occur and the genes of the transgenic fish will spread through the wild population. This means evidence of the transgenic genome would persist in subsequent generations.

·        Trojan Gene Scenario –When the net fitness of a transgenic fish is altered such that the fish has enhanced mating success but reduced adult viability (i.e. chances of surviving long enough to mate), introduction of that fish into the wild population could result in a rapid decline of the wild population. Essentially mating success would ensure the spread of the novel gene throughout the population, but the inability to survive would reduce the population size of subsequent generations and potentially lead to extinction.

The regulatory review process must be equipped to address the issues raised in these scenarios, as well as other environmental concerns. Regulators also have to consider the consequences such scenarios might pose for wild fish populations—including commercially significant, threatened, or endangered species—as well as the ecosystems into which transgenic fish could escape.

For instance, academic scientists who study aquatic ecosystems note that the Purge Scenario seems benign, but negative effects could appear as the transgene works its way out of the gene pool. The generations of fish that evolve between the first mating, and the generation that is “clean” of traces of the transgene, might be particularly aggressive or upset the ecosystem by preying on a species that wild counterparts traditionally do not consume. Experts also note that the Spread Scenario could result in a homogenization of fish species and the loss of distinct wild populations through a phenomenon some ecologists refer to as “extinction through hybridization.” The Trojan Gene Scenario, however, is particularly troublesome because it could result in the loss of unique genes or cause decline of the wild fish population into which the transgenic fish is introduced. If the trojan genes are passed on to a threatened or endangered species, the added influence could greatly increase that species’ risk of extinction. A declining fish population would also have secondary impacts on other aquatic species that feed on, or otherwise depend on it. Populations unable to successfully switch to another food source, or those whose survival or reproduction depends directly on the declining population, would also suffer.

Lastly, genetic changes in a species may impact the resilience of fish communities (the interconnected groups of fish species and other aquatic organisms living in the same environment). Although scientific understanding about what drives the resilience of a fish community is evolving, the introduction of transgenic fish could lead to a resilience reduction that may be irreversible or difficult and expensive to undo.

Transgenic Fish as Invasive Species
Even if they do not breed with wild relatives, transgenic fish that escape into natural ecosystems could be an environmental nuisance by becoming an invasive species. This danger mainly arises for those transgenic fish endowed with new genes that improve such fitness traits as breeding capabilities and the ability to withstand harsh conditions. The establishment of a thriving transgenic fish population in an ecosystem where it has never existed could crowd out native fish populations. Scientists lack data on many ecosystem variables that would allow them to predict when and where a transgenic fish, even one clearly endowed with fitness traits, could likely become an invasive species.

Risk Mitigation
Developers of transgenic fish are attempting to reduce or eliminate both gene flow and invasive species risks by sterilizing transgenic fish. Sterilization is relatively easy and inexpensive but success rates are highly variable. In addition, sterilization does not necessarily neutralize environmental risks. Academic scientists note that an escaped, sterile fish might still engage in courtship and spawning behavior, disrupting breeding in wild populations. Waves of escaped sterile fish could also create ecological disruptions as each group is replaced by another equally strong group of transgenic sterile fish.

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Food Safety Issues

Genetic engineering adds a layer of complexity to food safety issues associated with conventional fish, both farmed and wild. It is important to note, however, that genetic engineering could potentially reduce certain fish-specific food safety dangers.

One important food safety issue involves the extent to which fish absorb and store environmental toxins, such as mercury, high levels of which could pose a danger to humans who eat the contaminated fish. Some scientists worry that discrete biological changes induced by the genetic engineering process might enable transgenic fish to absorb a toxin that conventional fish cannot absorb or to better tolerate higher levels of a toxin already known to cause concern. Either scenario could pose a risk to human health.

Allergies to conventional fish and shellfish are common in the general population. Some scientists have expressed concern that the genetic engineering process could increase the allergic potential of fish, particularly through the introduction of novel proteins that never before existed in the food chain. However, it is equally plausible that genetic engineering will permit scientists to remove the allergenic component from certain seafood, allowing people with allergies to seafood to consume foods they otherwise would have to omit from their diet. In fact, scientists at Tulane University have already identified the major allergens in shrimp that cause allergic reactions in some people and have begun to use genetic engineering to alter proteins so shrimp no longer induce such reactions. In time, researchers may determine that genetic engineering similarly allows them to address toxins and other food safety concerns unique to conventional fish.

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Regulating Transgenic Fish

US Regulatory system  
In 1986, federal regulators adopted the Coordinated Framework for Regulation of Biotechnology, which reflected the policy decision that no new laws were needed to regulate the then-anticipated biotechnology products. Instead, the framework directed three principal agencies—the Food and Drug Administration, the Department of Agriculture, and the Environmental Protection Agency—to coordinate the regulation of biotechnology products under existing laws, despite the fact that those laws were enacted prior to the development of biotechnology and reflected widely different regulatory approaches and procedures. At that time, federal regulators stated that the assumption that existing laws were adequate to deal with the then-anticipated products of agricultural biotechnology would need to be revisited as the technology developed. Today, nearly sixteen years later, scientists continue to use biotechnology to develop new varieties of organisms such as transgenic fish that do not fall neatly within existing legal constructs, and federal regulators are increasingly challenged to address new issues within existing legal frameworks.

Thus far, government officials have not fully articulated a specific regulatory framework for transgenic fish. While a number of federal laws would or could apply, it is unclear whether existing statutes provide the tools and authorities needed to fully address all of the food safety and environmental concerns.

The Food and Drug Administration (FDA) clearly plays a primary role in the regulation of food safety. The Federal Food, Drug, and Cosmetic Act (FFDCA), the primary regulatory statute enforced by the FDA, provides several approaches through which the FDA could assert jurisdiction over transgenic fish. At this time, agency officials have stated that the biological material used to transform a genetically modified fish, and the product expressed by the fish’s transformed genetic construct, both fall under the legal definition of a “new animal drug.” Therefore, the FDA has indicated it will use the same process to regulate transgenic fish that it currently uses to review a new animal drug.

While using its legal authority to require approvals of new animal drugs creates some challenges for the FDA, in some respects it is not as much of a legal stretch as it may first appear. For example, the agency already has the authority to review a conventional drug that would increase growth hormone levels in fish. Therefore, one could perceive the FDA’s regulatory approach as simply applying the same regulatory scrutiny to another method—genetic engineering—designed to achieve the same end result: a faster growing fish.

One way to evaluate the FDA’s new animal drug application process is to examine how it measures against five elements often thought to be part of an adequate regulatory review system:

·        Legal authority. It is unclear if the FDA has the comprehensive legal authority needed to address all the food safety and environmental issues associated with transgenic fish. Of the several approaches through which the FFDCA allows the FDA to assert jurisdiction over transgenic fish, the new animal drug approach gives the FDA comprehensive powers to ensure food safety. For instance, before transgenic fish are allowed on the market, a developer will have to prove that the food derived from the transgenic fish is safe for humans to consume. But the FFDCA contains no provisions expressly dealing with environmental risks, particularly those presented in this report: harm to a species’ center of origin, decline in fish community resilience, or gene flow. In addition, it is uncertain whether the FDA’s interpretation of the law to include genetic modification as a new animal drug would withstand legal challenge.

·        Adequacy of risk management tools. The new animal drug approach gives the FDA a great deal of authority before and after product approval. The developer must prove the safety of a product before it is allowed on the market and the FDA can restrict the use of the product with labels, conditions of use, and post-approval monitoring. The FFDCA also requires developers to report adverse effects discovered post-approval and, if necessary, the FDA can stop the marketing of a product. Theoretically, the new animal drug approach seems to provide the FDA with adequate tools to manage some of the risks associated with transgenic fish. But if the FDA’s authority to regulate transgenic fish as new animal drugs is ever successfully challenged and the agency is required to use another approach, the benefits of the new animal drug approach may be lost.

·        Transparency, clarity and public participation. These three elements are the backbone of public confidence in the safety of an approved product. Together, they mean the public has access to, and understands, the information used to determine if a product is fit for approval. It also means that before an agency makes an approval decision, the public can provide input. In the case of the new animal drug laws, however, the application and approval process is entirely confidential and closed until the FDA grants approval. While this legal requirement protects trade secrets and confidential business information, when applied to transgenic animals it prevents public consideration of, and input into, important policy questions such as: What is an acceptable level of environmental risk? How does FDA know it is safe for people to eat transgenic fish? This lack of transparency could become a major challenge to an agency hoping to retain public confidence in its decision-making process as well as to the developers who need that confidence to ensure a market for their products.

·        Resources and expertise. Even if one could stretch the FDA’s new animal drug application authority to include the necessary environmental assessments, it is unclear if the agency has the staff and resources needed to do so. A number of agencies—including the Fish and Wildlife Service and the National Marine Fisheries Service—possess expertise that the FDA may lack. Although the FDA has indicated it may need to consult with these agencies, it has yet to announce a clear framework for how it will involve them on a consistent basis. Additionally, resource limitations may hamper the FDA’s ability to ensure that developers follow any special conditions under which it approves use of a product.

·        Efficiency and coordination. The expertise to deal with food safety and environmental risks associated with transgenic fish is spread over several agencies. In 2001, the Council on Environmental Quality and the Office of Science and Technology Policy published case studies that provide informal guidance as to how these agencies might work together. No other official or formal explanation of the agencies’ approach to these issues has been made public. In the absence of a clear statement of how these authorities and agencies will work together, it is difficult to judge whether the regulatory system for reviewing transgenic animals is efficient, sufficient and well coordinated.

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Summary

In summary, the application of genetic engineering to animals could provide numerous benefits, including the possibility of a safer, cheaper food supply and the creation of new sources for scarce pharmaceutical resources. But, as demonstrated by the current plan to regulate transgenic fish, it is unclear if regulators have the tools they need to adequately evaluate these new products, and there is reason to wonder if innovation is getting ahead of our ability to manage it. Without a clearly articulated and transparent road map to guide agency review and approval, it will remain difficult for developers to bring products to market and even more difficult to assure the public that the next generation of agricultural biotechnology products are undergoing a regulatory review process that includes a careful, thorough, and rational consideration of risks and benefits.

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Pew 2003. Future Fish? Issues in Science and Regulation of Transgenic Fish.

 

Full Report Table of Contents

I. Development, Status, and Economic Implications 1

A. Introduction 3

B. A Look at the Science: How Transgenic Fish Are Created 8

C. What It Could Mean: Possible Economic Implications 10  

II. Environmental Issues 11

A. Introduction: Conventional Aquaculture and Transgenic Fish 13

B. Pollution 14

C. Impacts on Fisheries 16

D. Gene Flow: Impacts on Genetic Diversity and Health of Wild Fish 17
a. Conventional and Transgenic Aquaculture Fish 17
b. Escape 18
c. Examining Gene Flow – Net Fitness Parameters 19
d. Gene Flow – the “Purge” Scenario 20
e. Gene Flow – the “Spread” Scenario 21
f. Gene Flow – the “Trojan Gene” Scenario 22
g. Gene Flow – Potential Environmental Consequences > 23

E. Exotic Species Invasion 25
a. Establishment of an Invasive Species 25
b. Consequences of Exotic Species Invasion 26

F. Risk Mitigation: Use of Sterile Fish to Reduce Risks of Gene Flow and Exotic Species Invasion 27

III. Food Safety Issues 29

A. Toxic Compounds 31

B. Allergens 32

C. Hormones 33

D. Possible Future Advantages 34 

IV. Regulation 35

A. Overview 37

B. Potential Legal Authorities for Regulating Transgenic Fish and Aquatic Organisms 39
a. Food Safety: Potential Legal Authorities 39
b. Environmental Impacts: Regulatory Approaches 42

C. Policy Issues: FDA’s New Animal Drug Approach to Transgenic Fish 47
a. Legal Authority 47
b. Adequacy of Risk Management Tools 50
c. Transparency, Clarity, and Public Participation 50
d. Resources and Expertise 55
e. Efficiency and Coordination 56

V. Conclusion: Regulatory Policy Issue 57

VI. Selected References 61

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Web site: http://pewagbiotech.org/research/fish/