U.S. regulatory framework for genetic biocontrol of invasive fish

This paper provides an overview of the U.S. regulatory framework governing genetic biocontrol efforts for invasive fish. Genetic biocontrol refers to the intentional release of genetically modified organisms (GMOs) into the environment to control a target population of a non-native species. The terms “genetically modified” and “genetically engineered” are often used interchangeably, despite the scientific distinctions. A GMO is an organism that has had its genetic material altered or modified by humans through any method, including conventional breeding. Genetic engineering, as defined by the Food and Drug Administration (FDA), is the use of recombinant DNA techniques to introduce new characteristics or traits into an organism. GE organisms are therefore a subset of GMOs. As this paper will discuss, existing laws focus on GE organisms raising significant questions as to whether organisms modified without utilizing rDNA techniques fall within the jurisdiction of any federal agency. Under the 1986 Coordinated Framework for Regulation of Biotechnology, three federal agencies have primary responsibility over biotechnology—the Environmental Protection Agency (EPA), the U.S. Department of Agriculture, and the FDA. Because the EPA has exempted biological control agents from regulation as pesticides and no fish species are currently considered plant pests, the FDA is the agency responsible for approving the use of genetically engineered fish for biocontrol. FDA regulates genetically engineered animals through its New Animal Drug Application (NADA) process. The NADA process presents several challenges to effective and transparent regulation of genetic biocontrol, including the FDA’s focus on drug safety, secrecy provisions potentially limiting disclosure of the results of environmental reviews, and the secondary role of the Fish and Wildlife Service, the federal agency with the most experience with invasive species management. In addition, relying on the NADA process creates a significant regulatory gap as NADA approval is only required for GE organisms. The regulatory framework for GMOs created for genetic biocontrol without rDNA technology is unclear and primary responsibility may fall to the states. Given its extensive experience with hatcheries, invasive fish species control, and environmental reviews, the Fish and Wildlife Service (FWS) is the more appropriate agency to review applications for genetic biocontrol. Efforts should be undertaken now, while genetic biocontrol is still in the theoretical stages, to increase the role of the FWS in the permitting process either through formal regulations or more informal mechanisms such as memorandum of understanding.     

Assessment of unanticipated unintended effects of genetically modified plants on non‐target organisms: a controversy worthy of pursuit?

A typical risk hypothesis addressed during the environmental risk assessment (ERA) of genetically modified (GM) plants for cultivation is that the novel traits intentionally introduced into GM plants do not adversely affect non‐target organisms (NTOs). However, genetic modification may potentially also lead to unintended changes in the GM plant which could raise safety concerns. Therefore, the European Food Safety Authority (EFSA) advocates the characterization of ecological interactions between the GM plant and representative NTOs as part of the ERA of GM plants for cultivation in the European Union. Yet, this requirement is not unanimously accepted by stakeholders. Here, we present EFSA's approach to assess potential adverse effects on NTOs and summarize some of the stakeholders' views, mostly opposing EFSA's position on scientific grounds.     

Protection goals in environmental risk assessment: a practical approach

Policy protection goals are set up in most countries to minimise harm to the environment, humans and animals caused by human activities. Decisions on whether to approve new agricultural products, like pesticides or genetically modified (GM) crops, take into account these policy protection goals. To support decision-making, applications for approval of commercial uses of GM crops usually comprise an environmental risk assessment (ERA). These risk assessments are analytical tools, based on science, that follow a conceptual model that includes a problem formulation step where policy protection goals are considered. However, in most countries, risk assessors face major problems in that policy protection goals set in the legislation are stated in very broad terms and are too ambiguous to be directly applicable in ERAs. This means that risk assessors often have to interpret policy protection goals without clear guidance on what effects would be considered harmful. In this paper we propose a practical approach that may help risk assessors to translate policy protection goals into unambiguous (i.e., operational) protection goals and to establish relevant assessment endpoints and risk hypotheses that can be used in ERAs. Examples are provided to show how this approach can be applied to two areas of environmental concern relevant to the ERAs of GM crops.     

Problem formulation in the environmental risk assessment for genetically modified plants

Problem formulation is the first step in environmental risk assessment (ERA) where policy goals, scope, assessment endpoints, and methodology are distilled to an explicitly stated problem and approach for analysis. The consistency and utility of ERAs for genetically modified (GM) plants can be improved through rigorous problem formulation (PF), producing an analysis plan that describes relevant exposure scenarios and the potential consequences of these scenarios. A properly executed PF assures the relevance of ERA outcomes for decision-making. Adopting a harmonized approach to problem formulation should bring about greater uniformity in the ERA process for GM plants among regulatory regimes globally. This paper is the product of an international expert group convened by the International Life Sciences Institute (ILSI) Research Foundation.     

Genetically modified crops and aquatic ecosystems: considerations for environmental risk assessment and non-target organism testing

Environmental risk assessments (ERA) support regulatory decisions for the commercial cultivation of genetically modified (GM) crops. The ERA for terrestrial agroecosystems is well-developed, whereas guidance for ERA of GM crops in aquatic ecosystems is not as well-defined. The purpose of this document is to demonstrate how comprehensive problem formulation can be used to develop a conceptual model and to identify potential exposure pathways, using Bacillus thuringiensis (Bt) maize as a case study. Within problem formulation, the insecticidal trait, the crop, the receiving environment, and protection goals were characterized, and a conceptual model was developed to identify routes through which aquatic organisms may be exposed to insecticidal proteins in maize tissue. Following a tiered approach for exposure assessment, worst-case exposures were estimated using standardized models, and factors mitigating exposure were described. Based on exposure estimates, shredders were identified as the functional group most likely to be exposed to insecticidal proteins. However, even using worst-case assumptions, the exposure of shredders to Bt maize was low and studies supporting the current risk assessments were deemed adequate. Determining if early tier toxicity studies are necessary to inform the risk assessment for a specific GM crop should be done on a case by case basis, and should be guided by thorough problem formulation and exposure assessment. The processes used to develop the Bt maize case study are intended to serve as a model for performing risk assessments on future traits and crops.     

The Applicability of Habitat Evaluation Methodologies in Ecological Risk Assessment

Traditionally, ecological risk assessments (ERAs) have emphasized risks to individual organisms or populations of species. Although habitats may be a potential target for chemical stressors, and are considered in the framework for ERAs, the actual use of habitat evaluation methods in this process is limited. Habitats obviously represent an important entity to protect since damaged aquatic and wildlife habitats may be totally irretrievable over a human life span compared to deleterious biochemical and physiological changes which may be reversible within the life cycle of an organism, if exposure is terminated. Habitat methods have been largely used as management tools to evaluate impacts of planned water and land development projects. Habitat evaluation methods represent a structured, systematic and logical approach to determine changes to habitats because they consider important life requisites and environmental variables limiting to species. Their use in the ERA process will provide a means to differentiate habitat changes resulting from physical, chemical and/or biological factors or a combination of such factors. In addition, minimal and optimum habitat suitability can be determined for different habitat variables under different chemical exposure scenarios. The objectives of this paper are to review several available habitat evaluation methods and discuss their use in risk assessment. Particular emphasis is given to USFWS's Habitat Evaluation Procedures (HEPs) and the Instream Flow Incremental Method (IFIM).     

Ecological Risk Assessment for Terrestrial Ecosystems: The Summary of Discussions and Recommendations from the Adelaide Workshop (April 2004)

The Ecological Risk Assessment (ERA) workshop focused on the anthropogenic contaminants in the terrestrial environment, addressing various components of the ERA process. These included sources, exposure pathways, bioavailability, and toxicity to receptor organisms as well as risk communication. It was concluded that although the overseas experience on ERA for terrestrial ecosystems (e.g., International Standards or guidelines from the European Union and the United States) is very useful, it is not directly applicable to Australia due to the differences in receptor organisms, contaminants, soil, and environmental conditions. Workshop discussions stressed on the need for making ERA locally relevant (in terms of choice of receptor organisms, sampling strategy, and bioavailability considerations). The workshop discussions highlighted the need of better appreciation of both the similarities and the clear differences between aquatic and terrestrial ERAs. The availability of reliable data, problems with databases, estimation of bioavailability, and extrapolations from laboratory to field were noted among the key limitations. ERA—being inherently complex and involving a range of environmental compartments, target receptor, and exposure pathways—at a minimum requires a multidisciplinary approach to address the complexities. Bringing a multidisciplinary team together often proves a major challenge in ERA. The delegates called for continued efforts in this area and formation of a network or working group in Australia.     

The Cartagena Protocol on Biosafety and living modified fish

The Cartagena Protocol on Biosafety is an international treaty under the Convention on Biological Diversity that promotes biosafety by establishing practical rules and procedures for the safe transfer, handling and use of living modified organisms (LMOs), with a specific focus on regulating transboundary movements of these organisms from one country to another. The Protocol includes the advance informed agreement procedure which sets rules on how Parties should take decisions regarding the transboundary movement of LMOs for intentional introduction into the environment, including living modified fish for biocontrol of non-native and invasive species. The advance informed agreement procedure places great emphasis on risk assessment and the Protocol includes an annex with general principles, methodological steps and points to consider when conducting a risk assessment. In recent years, the Parties to the Protocol have begun to develop guidance on risk assessment for specific types of LMOs although they have not, to date, specifically addressed living modified fish. Other relevant aspects of the Protocol include its provisions on unintentional and illegal transboundary movements; the handling, transport, packaging and identification of LMOs; and liability and redress.     

The status and causes of alien species invasion in China

Data of classification, origin, pathway and environmental impacts of invasive alien micro-organisms, invertebrates, amphibians and reptiles, fish, birds, mammals, weeds, trees, and marine organisms in terrestrial, aquatic and marine ecosystems of China, were analyzed, based on literature retrieval, field survey and consultation. Some 283 invasive alien species were recorded in China, including 19 invasive alien micro-organisms, 18 aquatic plants, 170 terrestrial plants, 25 aquatic invertebrates, 33 terrestrial invertebrates, 3 amphibians and reptiles, 10 fish, and 5 mammals. Of the invasive alien species, 55.1% originated from North and South America, 21.7% from Europe, 9.9% from Asia, 8.1% from Africa and 0.6% from Oceania. Many institutions and individuals in China lack adequate knowledge of ecological and environmental consequences caused by invasive alien species, with some ignorance of the dangerous invasion in the introduction of alien species. For instance, 50.0% of invasive alien plants were intentionally introduced as pasture, feedingstuff, ornamental plants, textile plants, medicinal plants, vegetables, or lawn plants, 25% of alien invasive animals were intentionally introduced for cultivation, ornament, or biological control, In addition, more efforts are being made in the introduction of alien species, and little attention is paid on the management of introduced alien species, which may cause their escape into natural environment and potential threats to the environment. There were also gaps in quarantine system in China. All microorganisms were unintentionally introduced, through timber, seedling, flowerpot, or soil; 76.3% of alien invasive animals invaded through commodity or transportation facility because of the failure of quarantine. Therefore, quarantine measures should be strictly implemented; and meanwhile the intentional introduction of alien species should be strictly managed and a system of risk assessment should be implemented.     

Genetically modified crops: success, safety assessment, and public concern

With the emergence of transgenic technologies, new ways to improve the agronomic performance of crops for food, feed, and processing applications have been devised. In addition, ability to express foreign genes using transgenic technologies has opened up options for producing large quantities of commercially important industrial or pharmaceutical products in plants. Despite this high adoption rate and future promises, there is a multitude of concerns about the impact of genetically modified (GM) crops on the environment. Potential contamination of the environment and food chains has prompted detailed consideration of how such crops and the molecules that they produce can be effectively isolated and contained. One of the reasonable steps after creating a transgenic plant is to evaluate its potential benefits and risks to the environment and these should be compared to those generated by traditional agricultural practices. The precautionary approach in risk management of GM plants may make it necessary to monitor significant wild and weed populations that might be affected by transgene escape. Effective risk assessment and monitoring mechanisms are the basic prerequisites of any legal framework to adequately address the risks and watch out for new risks. Several agencies in different countries monitor the release of GM organisms or frame guidelines for the appropriate application of recombinant organisms in agro-industries so as to assure the safe use of recombinant organisms and to achieve sound overall development. We feel that it is important to establish an internationally harmonized framework for the safe handling of recombinant DNA organisms within a few years.This is IMTECH Communication No. 038/2005.     

Metabonomics study of transgenic Bacillus thuringiensis rice (T2A-1) meal in a 90-day dietary toxicity study in rats

Rice is one of the most important staple foods in the world. The Cry2A gene was inserted into the rice genome to help the plant combat insects. As the unintended effects of the genetically modified (GM) organisms are the most important barriers to the promotion of GM organisms, we have carried out a useful exploration to establish a new in vivo evaluation model for genetically modified foods by metabonomics methods. In this study, the rats were fed for 90 days with the GM and NON-GM rice diets. The changes in metabolites of the urine were detected using (1)H-NMR. The metabonomics were analyzed to see whether the GM rice can induce the metabolite changes in the rats' urine when compared with the NON-GM rice group. The multivariate analysis and ANOVA were used to determine the differences and the significance of differences respectively, and eventually we concluded that these differences did not have a biological significance. The conclusion of the metabonomics was comparable with that from the traditional method. As a non-invasive and dynamic monitoring method, metabonomics will be a new way of assessing the food safety of GM foods.     

Statistical Issues in Ecological Risk Assessment

Ecological risk assessment (ERA) is concerned with making decisions about the natural environment under uncertainty. Statistical methodology provides a natural framework for risk characterization and manipulation with many quantitative ERAs relying heavily on Neyman-Pearson hypothesis testing and other frequentist modes of inference. Bayesian statistical methods are becoming increasingly popular in ERA as they are seen to provide legitimate ways of incorporating subjective belief or expert opinion in the form of prior probability distributions. This article explores some of the concepts, strengths and weaknesses, and difficulties associated with both paradigms. The main points are illustrated with an example of setting a risk-based “trigger” level for uranium concentrations in the Magela Creek catchment of the Northern Territory of Australia.     

Public perspectives on genetic biocontrol technologies for controlling invasive fish

Understanding people’s knowledge, attitudes, and concerns about genetic biocontrol can help researchers understand the challenges and opportunities that may be encountered during development of these technologies. This study conducted eight focus groups in the United States Great Lakes and Lake Champlain region to assess different stakeholders’ views about genetic biocontrol technology, factors affecting whether or not they support its use, and recommendations on how to proceed with its development. Stakeholders were excited about having a new invasive species control tool, but they were deeply concerned about potential unintended consequences. The primary concerns relate to ecological impacts, along with the cost of development and the possibility that such efforts will distract from other, ongoing control work. Participants made a number of recommendations to genetic biocontrol developers, including setting up regulatory systems, conducting independent cost benefit analyses and risk assessments, and engaging stakeholders throughout the development process.     

Environmental risk assessment of GE plants under low-exposure conditions

The requirement for environmental risk assessment (ERA) of genetically engineered (GE) plants prior to large scale or commercial introduction into the environment is well established in national laws and regulations, as well as in international agreements. Since the first introductions of GE plants in commercial agriculture in the 1990s, a nearly universal paradigm has emerged for conducting these assessments based on a few guiding principles. These include the concept of case-by-case assessment, the use of comparative assessments, and a focus of the ERA on characteristics of the plant, the introduced trait, and the receiving environment as well as the intended use. In practice, however, ERAs for GE plants have frequently focused on achieving highly detailed characterizations of potential hazards at the expense of consideration of the relevant levels of exposure. This emphasis on exhaustive hazard characterization can lead to great difficulties when applied to ERA for GE plants under low-exposure conditions. This paper presents some relevant considerations for conducting an ERA for a GE plant in a low-exposure scenario in the context of the generalized ERA paradigm, building on discussions and case studies presented during a session at ISBGMO 12.     

Exploitation of molecular profiling techniques for GM food safety assessment

Several strategies have been developed to identify unintended alterations in the composition of genetically modified (GM) food crops that may occur as a result of the genetic modification process. These include comparative chemical analysis of single compounds in GM food crops and their conventional non-GM counterparts, and profiling methods such as DNA/RNA microarray technologies, proteomics and metabolite profiling. The potential of profiling methods is obvious, but further exploration of specificity, sensitivity and validation is needed. Moreover, the successful application of profiling techniques to the safety evaluation of GM foods will require linked databases to be built that contain information on variations in profiles associated with differences in developmental stages and environmental conditions.     

转基因作物的食用与环境安全性问题及其对策

自转基因技术研发和商业化生产以来,针对转基因作物的食用安全性和环境安全性问题一直是公众争论的焦点。面对全球粮食安全形势的严峻压力,如何使公众对转基因技术及其产品的客观性保持一种科学性的认识,是摆在各国(特别是发展中国家)政府和科学家面前不可忽视的课题。本文从食品和环境两个方面简要介绍了转基因作物的安全性问题,旨在还原转基因技术的科学真实性,并简要提出转基因作物的安全性对策。     

Testing pollen of single and stacked insect-resistant Bt-maize on in vitro reared honey bee larvae

The ecologically and economic important honey bee (Apis mellifera) is a key non-target arthropod species in environmental risk assessment (ERA) of genetically modified (GM) crops. Honey bee larvae are directly exposed to transgenic products by the consumption of GM pollen. But most ERA studies only consider responses of adult bees, although Bt-proteins primarily affect the larval phases of target organisms. We adopted an in vitro larvae rearing system, to assess lethal and sublethal effects of Bt-pollen consumption in a standardized eco-toxicological bioassay. The effects of pollen from two Bt-maize cultivars, one expressing a single and the other a total of three Bt-proteins, on the survival and prepupae weight of honey bee larvae were analyzed. The control treatments included pollen from three non-transgenic maize varieties and of Heliconia rostrata. Three days old larvae were fed the realistic exposure dose of 2 mg pollen within the semi-artificial diet. The larvae were monitored over 120 h, until the prepupal stage, where larvae terminate feeding and growing. Neither single nor stacked Bt-maize pollen showed an adverse effect on larval survival and the prepupal weight. In contrast, feeding of H. rostrata pollen caused significant toxic effects. The results of this study indicate that pollen of the tested Bt-varieties does not harm the development of in vitro reared A. mellifera larvae. To sustain the ecosystem service of pollination, Bt-impact on A. mellifera should always be a crucial part of regulatory biosafety assessments. We suggest that our approach of feeding GM pollen on in vitro reared honey bee larvae is well suited of becoming a standard bioassay in regulatory risk assessments schemes of GM crops.     

Risk-Based Approaches to Managing Contaminants in Catchments

Risk-based methods promise improved decision-making for managing of contaminants, such as salinity, sediments, nutrients, and toxicants, that can adversely affect the ecological condition of aquatic ecosystems. Two aspects of ecological risk assessment (ERA) and management—stakeholder involvement and more quantitative approaches to risk analysis—are particularly challenging. Stakeholder involvement is crucial both in the risk assessment process and the development, acceptance, and implementation of a risk management plan. Additionally, a number of quantitative approaches (particularly Bayesian approaches and multi-criteria decision-making) have been identified as having the potential to include expert-based inputs into risk-based decision-making. These offer promise for better inclusion of stakeholder knowledge and preferences into the decision-making process, and for improving the links between stakeholder inputs and potential risks to the ecological condition of the system. A major challenge for ecologists and natural resource managers is to make the ERA process more quantitative. Most ERAs conducted to date have been qualitative assessments that suffer from a number of deficiencies, the most serious being the lack of transparency and a reliance on subjective judgments. This article argues that the most productive way forward may be to use Bayesian methods to couple existing process-based models, empirical relationships based on good data, and expert opinion, to make the analysis of ecological risks more robust, consistent, and repeatable.     

生态风险研究述评

生态风险(ＥｃｏｌｏｇｉｃａｌＲｉｓｋ,ＥＲ),指一个种群、生态系统或整个景观的正常功能受外界胁迫,从而在目前和将来减小该系统健康、生产力、遗传结构、经济价值和美学价值的一种状况[20]。生态风险评估(ＥｃｏｌｏｇｉｃａｌＲｉｓｋＡｓｓｅｓｓｍｅｎｔ,ＥＲＡ)指受一个或多个胁迫因素影响后,对不利的生态后果出现的可能性进行的评估。美国环保局(ＥＰＡ)把这种尚不为人们所重视的领域叫做生态风险评估[20,48]。随着新技术和新方法的应用,ＥＲＡ的研究领域迅速扩展。早期的生态风险评估主要是针对人类健康而言的,也就是人类健康风险…