Bugs in the System? ISSUES IN THE SCIENCE AND REGULATION OF GENETICALLY MODIFIED INSECTS . .. .. ... .... ...... ..................................... ......... ..... .... ... ... .. .. .. .. A Report Prepared by the Pew Initiative on Food and Biotechnology Pew Initiative on Food and Biotechnology 1331 H Street, NW, Suite 900 Washington, DC 20005 Telephone: (202) 347-9044 Fax: (202) 347-9047 Internet: www.pewagbiotech.org January 2004 © 2004 Pew Initiative on Food and Biotechnology. All rights reserved. No portion of this paper may be reproduced by any means, either electronic or mechanical, without permission in writing from the publisher. CTable of Contents T able of Contents I. Development and Status of Genetically Modified Insects 1 A. Introduction 3 B. History of GM Insect Development 6 C. Status of GM Insects 7 D. A Look at the Science: How GM Insects are Created 9 II. Potential Benefits of Genetically Modified Insects 11 A. Potential Agricultural and Environmental Benefits 13 i. Traditional Biological Control Programs 13 ii. GM Insects as Biological Control Agents 14 iii. Conventional Genetic Control Methods 15 iv. GM Insects and Genetic Control Methods 16 v. The Use of Paratransgenesis in Controlling Agricultural Pests 19 B. Potential Public Health Benefits of GM Insects 20 i. The Use of Transgenic Vector Insects to Control Disease Transmission 20 ii. The Use of Paratransgenesis to Control Disease Transmission 24 C. GM Economically Beneficial Insects 26 i. Honeybees 26 ii. Silkworms 26 III. Potential Concerns Posed by Genetically Modified Insects 27 A. Potential Environmental Concerns Related to GM Insects 29 i. Environmental Concerns of Biological Control Programs 32 ii. GM Insects as Biological Control Agents 34 iii. Gene Flow 34 a. Vertical Inheritance 35 1. Consequences of Vertical Inheritance 35 b. Horizontal Gene Transfer 36 1. Transposons 36 2. Transduction 37 3. Horizontal Gene Transfer between Gut Bacteria and Other Bacteria 37 4. State of Scientific Knowledge about and Consequences of Horizontal Gene Transfer 38 B. Public Health Concerns Raised by GM Insects 39 i. Gene Silencing 39 ii. Laboratory Versus the Field 39 a. State of Scientific Knowledge about Vector Ecology 40 iii. Drivers 41 iv. Effectiveness 42 C. Food-Safety Concerns Raised by GM Insects 43 D. Societal Issues 44 IV. Regulation of Genetically Modified Insects 47 A. Overview 49 B. Federal Regulatory Authority for GM Insects 52 i. Summary 52 ii. Agency Authority and Procedure 55 a. USDA Authority and Procedure 56 1. Overview 56 2. Scope Issues 58 i. Transgenic Plant Pests 58 ii. Insect Symbionts 59 3. Risk Considerations 60 4. Risk Management Tools 62 5. Transparency, Clarity, and Public Participation 63 6. Resources and Expertise 63 b. FDA Authority and Procedure 65 1. Overview 65 2. Scope Issues 66 i. Scope of Organisms Covered – New Animal Drugs? 66 ii. Symbiotic Microorganisms 67 3. Risk Considerations 67 4. Risk Management Tools 68 5. Transparency, Clarity, and Public Participation 69 6. Resources and Expertise 69 c. EPA Authority and Procedure 70 1. Overview 70 2. Scope Issues 71 3. Risk Management Tools 72 4. Transparency, Clarity, and Public Participation 73 5. Resources and Expertise 73 d. Public Health Service – Authorities 73 C. NIH Research Guidelines 74 i. Overview 74 ii. NIH and Institutional Biosafety Committees 76 a. Overview – Biosafety and Containment 76 b. Application of Guidelines to GM Insect Research 77 iii. Informed Human Subject Consent 78 D. International Issues 79 V. Conclusions 81 A. Authority: Scope of Organisms Covered and Risks Considered 83 B. Transparency, Clarity, and Public Participation 85 C. Adequacy of Risk Management Tools – Determining and Managing Risks 86 D. Efficiency and Coordination 87 E. Resources and Expertise 87 F. Guidelines for Field Trials and Environmental Releases 88 G. The International Context 88 VI. Selected References 89 VII. Appendix 107 A. Reviewers 109 Preface As biotechnology continues to develop, scientists are applying genetic engineering techniques to develop new varieties of plants, animals and microorganisms for a wide range of purposes. Our first report, Harvest on the Horizon, documented some of the diversity of biotechnology products under development for many purposes, ranging from increasing agricultural production to solving human health problems. In this report, we examine the promises and potential problems associated with the genetic modifi- cation of insects.1 Scientists are modifying insects for a number of purposes. One area of research involves the use of genetically modified (GM) insects to help solve agricultural pest problems. For example, scientists are attempting to modify insect pests that destroy crops in ways that weaken their ability to reproduce or that make them less harmful to crops. Alternatively, scientists are work- ing to use biotechnology to make more effective predators of agricultural pests. For beneficial insects like honeybees that produce food or that provide important natural services such as pollination, sci- entists are using biotechnology to make them more disease- and pest-resistant. A major area of research involves using biotechnology to make insects much less effective vectors (organisms that transmit diseases) of animal and human diseases, such as malaria and Chagas’ disease. Some of the approaches being explored involve the direct genetic modification of the insect (transgenesis), while other approaches involve modification of the symbiotic microorganisms carried by insects (para- transgenesis). The potential to reduce or even end age-old endemic insect-borne diseases without the use of potentially environmentally harmful chemical pesticides is a powerful vision. As with other biotechnology applications, however, potential risks must be weighed against these potential dramatic benefits. A recent report from the National Academy of Sciences raises some environmental issues, expressing special concern about GM animals that can easily escape or breed with wild relatives. If the modified trait provides the genetically modified animal with a fitness advantage, it could disrupt ecosystems and lead to adverse results. 1 Throughout this paper, the term “insects” will be used to encompass not only the taxonomic class of insects, but also mites and other creatures the general public may refer to as ”bugs,” but which the scientific community would refer to as “arthropods.” In the broadest sense, “genetic modification” can refer to changes in the genetic makeup of organisms, including hybrids (offspring of parents from different species or sub-species). The focus of this paper is on GM insects where genetic material from a separate organism has been inserted into the heredity material (chromosomes) of an insect through recombinant DNA techniques (transgenesis). Additionally, some research is being carried out to genetically modify the microbes associated with the gut or reproductive systems of pest insects. This type of genetic modification has been termed “paratransgenesis” because, although the insect itself has not been modified, its microbial inhabitants have been. Discussion of microorganisms in this paper is limited to the use of them in paratransgenesis; direct modification of pathogen microorganisms will not be discussed. The term “GM insects,” then, will be used to include both transgenic and paratransgenic insects, and transgenic and paratransgenic will be used when necessary to differentiate specifically between the two. Environmental concerns are especially critical for some GM insects, particularly those planned for some biological and disease control uses. These GM insects differ from most other genetically mod- ified organisms created to date in one very important respect: they are intended for permanent establishment in the environment and, in the case of those GM insects intended for population replacement, the new genetic trait has to be “driven” into the wild population to work at all. In other genetically modified organisms, scientists generally want to contain the GM variety to prevent the genetic trait from moving into related organisms. In contrast, some GM insects will not only be expected to survive in the wild, but also to pass their genes to the wild population. The potential to “recall” these GM insects, if unanticipated adverse results occur, will be difficult if not impossible. Because insects play valuable roles as predators, prey, recyclers, pollinators, and more in ecosystems throughout the world, scientists must carefully weigh the risks and benefits of their proposals for using GM insects. Careful regulatory scrutiny will be needed to prevent possible environmental, public health, agri- cultural, and food safety risks from GM insects. In addition to these primary functions, a secondary critical function of an effective and credible regulatory system is to create public confidence and trust that regulators are adequately addressing the potential risks of new technologies. Despite the potential substantial benefits of GM insects, public concerns about the possible negative impacts will need to be assuaged through credible and transparent regulatory processes. At the same time, researchers need a fair and effective regulatory system that establishes a reasonable and pre- dictable path through the regulatory review process. Since 1986, a central tenet of the U.S. regulatory system has been that the regulation of biotech- nology products should not differ from that covering comparable products made by conventional