Genetically Modified Organisms Risk Assessment Research Articles

Integration of omics analyses into GMO risk assessment in Europe: a case study from soybean field trials

In Europe, genetically modified organisms (GMOs) are subject to an authorization process including a mandatory risk assessment. According to the respective guidance by the European Food Safety Authority (EFSA), one of the pillars of this GMO risk assessment is a comparative analysis of the compositional and agronomic characteristics. This targeted approach has been criticized for its limitations, as it only considers pre-determined compounds, being insufficient to assess a comprehensive range of relevant compounds, including toxins and anti-nutrients, on a case-specific basis. Strategies based on advanced untargeted omics technologies have been proposed as a potential broader approach to be implemented into the initial step of the risk assessment framework. Here, we provide an example of a step-by-step omics analysis based on systems biology approach to fit into the context of European GMO regulation. We have performed field trial experiments with genetically modified (GM) Intacta™ Roundup Ready™ 2 Pro soybean containing both cry1Ac and cp4epsps transgenic inserts and analyzed its proteomic profile against the non-GM counterpart and reference varieties. Based on EFSA’s comparative endpoint-by-endpoint approach, the proteomics analysis revealed six proteins from the GMO outside the 99% tolerance intervals of reference varieties (RVs) in the equivalence test. Interestingly, from the near-isogenic (non-GM) comparator we found as many as ten proteins to be outside of the said RVs’ equivalence limits. According to EFSA’s statistical guidelines, differences found in metabolite abundance between a GMO and its non-GM comparator would not be considered biologically relevant as all compounds of concern remained within the equivalence limits of commercial RVs. By assessing the proteomic and metabolomic data through our proposed systems biology approach, we found 70 proteins, and the metabolite xylobiose as differentially expressed between the GMO and its non-GM comparator. Biological relevance of such results was revealed through a functional biological network analysis, where we found alterations in several metabolic pathways related to protein synthesis and protein processing. Moreover, the allergenicity analysis identified 43 proteins with allergenic potential being differentially expressed in the GM soybean variety. Our results demonstrate that implementation of advanced untargeted omics technologies in the risk assessment of GMOs will enable early and holistic assessment of possible adverse effects. The proposed approach can provide a better understanding of the specific unintended effects of the genetic modification on the plant’s metabolism, the involved biological networks, and their interactions, and allows to formulate and investigate dedicated risk hypotheses in the first place. We draw conclusions on a detailed comparison with the comparative assessment according to EFSA and provide scientific arguments and examples on how the current comparative approach is not fit for purpose.

Biosafety of GM Crop Plants Expressing dsRNA: Data Requirements and EU Regulatory Considerations.

The use of RNA interference (RNAi) enables the silencing of target genes in plants or plant-dwelling organisms, through the production of double stranded RNA (dsRNA) resulting in altered plant characteristics. Expression of properly synthesized dsRNAs in plants can lead to improved crop quality characteristics or exploit new mechanisms with activity against plant pests and pathogens. Genetically modified (GM) crops exhibiting resistance to viruses or insects via expression of dsRNA have received authorization for cultivation outside Europe. Some products derived from RNAi plants have received a favourable opinion from the European Food Safety Authority (EFSA) for import and processing in the European Union (EU). The authorization process in the EU requires applicants to produce a risk assessment considering food/feed and environmental safety aspects of living organisms or their derived food and feed products. The present paper discusses the main aspects of the safety assessment (comparative assessment, molecular characterization, toxicological assessment, nutritional assessment, gene transfer, interaction with target and non-target organisms) for GM plants expressing dsRNA, according to the guidelines of EFSA. Food/feed safety assessment of products from RNAi plants is expected to be simplified, in the light of the consideration that no novel proteins are produced. Therefore, some of the data requirements for risk assessment do not apply to these cases, and the comparative compositional analysis becomes the main source of evidence for food/feed safety of RNAi plants. During environmental risk assessment, the analysis of dsRNA expression levels of the GM trait, and the data concerning the observable effects on non-target organisms (NTO) will provide the necessary evidence for ensuring safety of species exposed to RNAi plants. Bioinformatics may provide support to risk assessment by selecting target gene sequences with low similarity to the genome of NTOs possibly exposed to dsRNA. The analysis of these topics in risk assessment indicates that the science-based regulatory process in Europe is considered to be applicable to GM RNAi plants, therefore the evaluation of their safety can be effectively conducted without further modifications. Outcomes from the present paper offer suggestions for consideration in future updates of the EFSA Guidance documents on risk assessment of GM organisms.

Inclusion and Implementation of Socio-Economic Considerations in GMO Regulations: Needs and Recommendations

Socio-economic considerations are included in the regulatory frameworks on genetically modified organisms (GMOs) of many countries. This is a reflection of an increasing interest in and recognition of the necessity to consider a broader range of issues when conducting a GMO risk assessment. At the same time, there are discussions about how socio-economic considerations can be identified and how their assessment can be carried out. To provide an understanding of the advances achieved so far, we describe the state of the art of existing biosafety institutional frameworks, legislation and policies with provisions on socio-economic considerations. We analyse the scope of the socio-economic considerations that have been included, the methodological options taken and the role of participatory processes and stakeholders involvement in the GMO-related decision-making. Since many of the countries that have legislation for assessing socio-economic considerations lack implementation experience, we provide an analysis of how implementation has evolved in Norway with the intention to illustrate that the inclusion of socio-economic considerations might be based on a learning process. Norway was the first country to include broader issues in its GMO assessment process, and is at present one of the countries with the most experience on implementation of these issues. Finally, we emphasise that there is a great need for training on how to perform assessments of socio-economic considerations, as well as reflection on possible ways for inclusion of participatory processes.

Can Systematic Reviews Inform GMO Risk Assessment and Risk Management?

Systematic reviews represent powerful tools to identify, collect, synthesize, and evaluate primary research data on specific research questions in a highly standardized and reproducible manner. They enable the defensible synthesis of outcomes by increasing precision and minimizing bias whilst ensuring transparency of the methods used. This makes them especially valuable to inform evidence-based risk analysis and decision making in various topics and research disciplines. Although seen as a “gold standard” for synthesizing primary research data, systematic reviews are not without limitations as they are often cost, labor and time intensive and the utility of synthesis outcomes depends upon the availability of sufficient and robust primary research data. In this paper, we (1) consider the added value systematic reviews could provide when synthesizing primary research data on genetically modified organisms (GMO) and (2) critically assess the adequacy and feasibility of systematic review for collating and analyzing data on potential impacts of GMOs in order to better inform specific steps within GMO risk assessment and risk management. The regulatory framework of the EU is used as an example, although the issues we discuss are likely to be more widely applicable.

Maize pollen deposition in relation to distance from the nearest pollen source under common cultivation - results of 10 years of monitoring (2001 to 2010)

Abstract Background Information on pollen dispersal is essential for the risk assessment and management of genetically modified organisms (GMOs) such as Bt maize. We analyzed data on maize pollen deposition at 216 sites in Germany, Switzerland, and Belgium from 2001 to 2010. All data were collected using the same standardized sampling method. The distances between sampling site and the nearest maize field ranged from within the field to 4.45 km. Results Maize pollen deposition was negatively correlated with distance from the nearest pollen source. The highest pollen deposition was within the field, but depositions of several thousand pollen grains per square meter were recorded over the kilometer range. A power function model most accurately described the relationship between deposition and distance from the nearest pollen source, rather than the exponential model currently used in EU risk assessment and management, which underestimates exposure for distances greater than 10 m. Regression analysis confirmed the high significance of the power relationship. The large variation in pollen deposition at a given distance reflected the influences of wind direction and other meteorological and site conditions. Plausible variations of single values and the predicted mean pollen count at a given distance were expressed by confidence intervals. Conclusions The model described here allows estimations of pollen deposition in relation to distance from the nearest field; therefore, it will be valuable for the risk assessment and management of GMOs. Our results indicate that buffer zones in the kilometer range are required to prevent harmful exposure of non-target organisms to GMOs.

Environmental protection goals, policy & publics in the European regulation of GMOs

One of the most divisive debates in modern agriculture concerns the use of genetically modified organisms (GMOs). In Europe, the policy debate over GMOs has been met with a persistent attempt to retreat into “sound science” as a potential unifying force. However, environmental risk assessment as an aid to regulatory decision-making is inherently entangled with questions of environmental ethics. This is particularly manifested in the setting of environmental protection goals. For the risk assessment of GMOs, the European Food Safety Authority has presented an inconsistent position on environmental protection goals. There is, however, an emerging trend for biodiversity conservation to be enfolded within an ecosystem services frame, and for ecosystem services to be reduced to biological terms. How environmental protection goals are understood, articulated and used to define risk assessment and shape regulatory decision-making is a significant factor in the entrenched debate over the regulation of GMOs in Europe. In negotiating this territory, I suggest that the attempt to enforce a strict divide between nature and culture or social and ecological systems in Europe’s risk assessment of GMOs is emphatically counter-productive, for both robust science and considered ethical action.

EFSA’s scientific activities and achievements on the risk assessment of genetically modified organisms (GMOs) during its first decade of existence: looking back and ahead

Genetically modified organisms (GMOs) and derived food and feed products are subject to a risk analysis and regulatory approval before they can enter the market in the European Union (EU). In this risk analysis process, the role of the European Food Safety Authority (EFSA), which was created in 2002 in response to multiple food crises, is to independently assess and provide scientific advice to risk managers on any possible risks that the use of GMOs may pose to human and animal health and the environment. EFSA's scientific advice is elaborated by its GMO Panel with the scientific support of several working groups and EFSA's GMO Unit. This review presents EFSA's scientific activities and highlights its achievements on the risk assessment of GMOs for the first 10years of its existence. Since 2002, EFSA has issued 69 scientific opinions on genetically modified (GM) plant market registration applications, of which 62 for import and processing for food and feed uses, six for cultivation and one for the use of pollen (as or in food), and 19 scientific opinions on applications for marketing products made with GM microorganisms. Several guidelines for the risk assessment of GM plants, GM microorganisms and GM animals, as well as on specific issues such as post-market environmental monitoring (PMEM) were elaborated. EFSA also provided scientific advice upon request of the European Commission on safeguard clause and emergency measures invoked by EU Member States, annual PMEM reports, the potential risks of new biotechnology-based plant breeding techniques, evaluations of previously assessed GMOs in the light of new scientific publications, and the use of antibiotic resistance marker genes in GM plants. Future challenges relevant to the risk assessment of GMOs are discussed. EFSA's risk assessments of GMO applications ensure that data are analysed and presented in a way that facilitates scientifically sound decisions that protect human and animal health and the environment.

A comparative evaluation of the regulation of GM crops or products containing dsRNA and suggested improvements to risk assessments

Changing the nature, kind and quantity of particular regulatory-RNA molecules through genetic engineering can create biosafety risks. While some genetically modified organisms (GMOs) are intended to produce new regulatory-RNA molecules, these may also arise in other GMOs not intended to express them. To characterise, assess and then mitigate the potential adverse effects arising from changes to RNA requires changing current approaches to food or environmental risk assessments of GMOs. We document risk assessment advice offered to government regulators in Australia, New Zealand and Brazil during official risk evaluations of GM plants for use as human food or for release into the environment (whether for field trials or commercial release), how the regulator considered those risks, and what that experience teaches us about the GMO risk assessment framework. We also suggest improvements to the process.

Risk assessment of Genetically Modified Organisms (GMOs)

EFSA's remit in the risk assessment of GMOs is very broad encompassing genetically modified plants, microorganisms and animals and assessing their safety for humans, animals and the environment. The legal frame for GMOs is set by Directive 2001/18/EC on their release into the environment, and Regulation (EC) No 1829/2003 on GM food and feed. The main focus of EFSA's GMO Panel and GMO Unit lies in the evaluation of the scientific risk assessment of new applications for market authorisation of GMOs, and in the development of corresponding guidelines for the applicants. The EFSA GMO Panel has elaborated comprehensive guidance documents on GM plants, GM microorganisms and GM animals, as well as on specific aspects of risk assessment such as the selection of comparators. EFSA also provides special scientific advice upon request of the European Commission; examples are post-market environmental monitoring of GMOs, and consideration of potential risks of new plant breeding techniques. The GMO Panel regularly reviews its guidance documents in the light of experience gained with the evaluation of applications, technological progress in breeding technologies and scientific developments in the diverse areas of risk assessment.

Observational science in the environmental risk assessment and management of GMOs

The international debate over how to apply monitoring for increasing certainty of the safety of released genetically modified organisms (GMOs) is frozen on two alternatives: case-specific monitoring (CSM) and general surveillance (GS). The experience level for applying GS for monitoring potential adverse environmental effects of GMOs is limited. Using recent examples from the research literature outside of GMO environmental risk assessment (ERA) and management, we find a place for combined and case-appropriate uses of both monitoring strategies. Uncertainties about the kind and severity of potential adverse effects can be high in ERA. Monitoring of past and present status of indicators and identifying trends is critical for informing decisions on biological systems and for proving damage (CBD, 2012). GSapproaches are grounded in comparative observational science and have much to offer the regulator wanting to safely release a GMO into the environment. Risk assessment and risk management uses the best available science – and the best available understanding of the science – to maximize the potential of technology through its safe use. Where there is a long history of use of a technology or where risk assessment relies upon sciences with firm theoretical grounding for prediction, there may be confidence that potential adverse effects of a product have been identified. A quality ERA requires quality science (Traxler et al., 2001). Biology has its theories but biology is not yet a science based on theory, in the way for example that technical sciences and engineering and physics can be. Biology has no arm that can make prediction very far from empirical observation whether that be the observation and manipulation of living things (e.g., ecology) or computation of patterns in molecules (e.g., bioinformatics). Within these limitations to predictive power, even the ability to completely describe the living things in an environment (Daniel, 2004; Rohwer, 2003), how should a risk assessor and manager work?

What Risk Assessments of Genetically Modified Organisms Can Learn from Institutional Analyses of Public Health Risks

The risks of genetically modified organisms (GMOs) are evaluated traditionally by combining hazard identification and exposure estimates to provide decision support for regulatory agencies. We question the utility of the classical risk paradigm and discuss its evolution in GMO risk assessment. First, we consider the problem of uncertainty, by comparing risk assessment for environmental toxins in the public health domain with genetically modified organisms in the environment; we use the specific comparison of an insecticide to a transgenic, insecticidal food crop. Next, we examine normal accident theory (NAT) as a heuristic to consider runaway effects of GMOs, such as negative community level consequences of gene flow from transgenic, insecticidal crops. These examples illustrate how risk assessments are made more complex and contentious by both their inherent uncertainty and the inevitability of failure beyond expectation in complex systems. We emphasize the value of conducting decision-support research, embracing uncertainty, increasing transparency, and building interdisciplinary institutions that can address the complex interactions between ecosystems and society. In particular, we argue against black boxing risk analysis, and for a program to educate policy makers about uncertainty and complexity, so that eventually, decision making is not the burden that falls upon scientists but is assumed by the public at large.

The structuring of GMO release and evaluation in EU law

Genetically modified organisms (GMOs) and their behavior in the environment are complex and can only be assessed if the different components are distinguished. This article examines, how by EU law the real causation processes from the GMO release to various endpoints are dissected, individually analysed and then again viewed in their entirety. In addition, the articles includes, how the intellectual process of assessment is divided into the steps of tiered generation, shared submission and structured evaluation of relevant knowledge. The framework proposed for such an examination allows to identify strengths and weaknesses of GMO risk assessment in the EU.

Systemic risks of genetically modified crops: the need for new approaches to risk assessment

Since more than 25 years, public dialogues, expert consultations and scientific publications have concluded that a comprehensive assessment of the implications of genetic engineering in agriculture and food production needs to include health, environmental, social and economical aspects, but only very few legal frameworks allow to assess the two latter aspects. This article aims to explain the divergence between societal debate and biosafety legislation and presents approaches to bring both together. The article reviews the development of biosafety regulations in the USA and the EU, focussing on diverging concepts applied for assessing the risks of genetically modified organisms (GMOs). The dominant environmental risk assessment methodology has been developed to answer basic questions to enable expedient decision making. As a first step, methodologies that take into account complex environmental and landscape aspects should be applied. Expanding the scope of risk assessment, more holistic concepts have been developed, for example the Organisation for Econonomic Co-operation and Development (OECD) concept of systemic risks which includes socio-economic aspects. International bodies as the OECD, the Convention on Biological Diversity (CBD) and the European Union (EU) have developed the Strategic Environmental Assessment (SEA) as an instrument that includes the additional aspects of risk assessment as demanded by many stakeholders. Interestingly, there had been no attempts yet to link the existing frameworks of GMO risk assessment and SEA. It is recommended to adapt current models of SEA to assess the systemic risks of GMOs. It is also suggested to revise the EU GMO legislation to promote the inclusion of SEA elements.

Contributions from scientific research to the risk assessment of GMOs. Lessons learned from a symposium held in Brussels, Belgium, 21–22 October 2010

In many domains, risk assessment is a defined methodology aimed at determining and quantifying risks associated with a specific activity, including the identification and characterization of potential hazards and their probability of occurrence. It relies on the gathering and interpretation of scientific and technical data and must be carried out in a scientifically sound and transparent manner. With regard to the use of genetically modified organisms (GMOs), risk assessment relies primarily on the results of research and studies aiming at evaluating the potential impacts of GMOs on the environment and/or human health. Given the increasing number of GMOs tested or commercialized worldwide and the development of new types of GMOs, new and up-to-date scientific information generated by basic or applied research in various fields can strengthen the risk assessment and/or provide answers to potential knowledge gaps identified during risk assessment. The gathering of data obtained from scientific research relevant to the risk assessment, as well as the implementation of new research activities resulting from the identification of potential knowledge gaps, would be facilitated by regular exchanges of views between experts involved in risk assessment/evaluation and scientists involved in basic or applied research (from public institutions or companies). As this interaction could be of mutual benefit and could also serve to inform competent authorities and policy-makers, platforms bringing together these communities are considered of relevance.

A Precautionary Approach to Genetically Modified Organisms: Challenges and Implications for Policy and Science

The commercial introduction of genetically modified organisms (GMOs) has revealed a broad range of views among scientists and other stakeholders on perspectives of genetic engineering (GE) and if and how GMOs should be regulated. Within this controversy, the precautionary principle has become a contentious issue with high support from skeptical groups but resisted by GMO advocates. How to handle lack of scientific understanding and scientific disagreement are core issues within these debates. This article examines some of the key issues affecting precaution as a legal standard and as an approach to the use of science in decision-making processes. It is pointed out that there is a need for reflection over the level of scientific evidence required for applying the precautionary principle as well as who should have the burden of proof when there are uncertainties. Further, an awareness of the broader scientific uncertainties found in GMO risk assessment implies that a precautionary approach must be elaborated: both for acknowledging uncertainties and for identification of scientific responses. Since precaution is an important issue within the sustainable development framework, it is suggested that sustainability can provide a normative standard that can help to reveal the influence and negotiate the importance of the various forms of uncertainty. Wise management of uncertainties and inclusion of normative aspects in risk assessment and management may help to ensure sustainable and socially robust GMO innovations at present and in the future.

The US’ Food and Drug Administration, Normativity of Risk Assessment, GMOs, and American Democracy

The process of risk assessment of biotechnologies, such as genetically modified organisms (GMOs), has normative dimensions. However, the US' Food and Drug Administration (FDA) seems committed to the idea that such evaluations are objective. This essay makes the case that the agency's regulatory approach should be changed such that the public is involved in deciding any ethical or social questions that might arise during risk assessment of GMOs. It is argued that, in the US, neither aggregative nor deliberative (representative) democracy ought to be used to make such determinations. Instead, participatory (deliberative) democracy should be the means by which members of the polity decide which normative concerns ought to underlie FDA's assessment of GMOs. This paper uses a hypothetical case involving a new GM seed to make that argument.

GMO risk assessment around the world: Some examples

All over the world, authorities responsible for the assessment and surveillance of foods and feeds derived using gene technology and the environmental impacts of genetically modified organisms (GMO) have chosen specific strategies to assess their safety. Although different regulatory frameworks are in place, almost all adopted risk assessment strategies are based on a common set of principles and guidelines. Here we provide some examples of these strategies and we compare them to highlight areas where an international consensus exists. Our hope is that even if limited, this short review can represent a first step towards the recognition of an international consensus and a broader dialog on GMOs regulation worldwide.

Identification of potentially hazardous human gene products in GMO risk assessment

Genetically modified organisms (GMOs), e.g. viral vectors, could threaten the environment if by their release they spread hazardous gene products. Even in contained use, to prevent adverse consequences, viral vectors carrying genes from mammals or humans should be especially scrutinized as to whether gene products that they synthesize could be hazardous in their new context. Examples of such potentially hazardous gene products (PHGPs) are: protein toxins, products of dominant alleles that have a role in hereditary diseases, gene products and sequences involved in genome rearrangements, gene products involved in immunomodulation or with an endocrine function, gene products involved in apoptosis, activated proto-oncogenes. For contained use of a GMO that carries a construct encoding a PHGP, the precautionary principle dictates that safety measures should be applied on a "worst case" basis, until the risks of the specific case have been assessed. The potential hazard of cloned genes can be estimated before empirical data on the actual GMO become available. Preliminary data may be used to focus hazard identification and risk assessment. Both predictive and empirical data may also help to identify what further information is needed to assess the risk of the GMO. A two-step approach, whereby a PHGP is evaluated for its conceptual dangers, then checked by data bank searches, is delineated here.

White clover (Trifolium repens) and associated viruses in the subalpine region of south-eastern Australia: implications for GMO risk assessment

Over the past several years, increased emphasis has been placed on conducting comprehensive ecological-risk assessments of virus-resistant genetically modified organisms (GMOs) prior to their release into the environment. In this paper we report on the first stage in our assessment of the level of risk posed by virus-resistant transgenic Trifolium repens L. (white clover) to native plant communities in south-eastern Australia. We investigated the distribution, abundance and phytosociological characteristics of naturalised T. repens populations in two areas in the subalpine region of New South Wales (NSW) and the Australian Capital Territory (ACT), and determined the distribution and abundance of Alfalfa mosaic virus, Clover yellow vein virus and White clover mosaic virus in 31 populations of white clover in this region. We found that T. repens is a significant component of Poa grasslands and Eucalyptus–Poa woodlands in the subalpine region, but is absent or rare in Eucalyptus species forests and Carex–Poa species bogs. Clover yellow vein virus was by far the most common virus in the study area, being present in 18% of T. repens plants across a wide range of plant communities. Alfalfa mosaic virus and White clover mosaic virus were each recorded in only one white-clover population growing in a native plant community. We conclude that white clover is a significant constituent of subalpine grasslands and woodlands in the region studied, and that of the viruses investigated, Clover yellow vein virus is the most abundant and widespread.

Assessment of GM Crops in Commercial Agriculture

The caliber of recent discourse regarding genetically modified organisms (GMOs) has suffered from a lack of consensus on terminology, from the scarcity of evidence upon which to assess risk to health and to the environment, and from value differences between proponents and opponents of GMOs. Towards addressing these issues, we present the thesis that GM should be defined as the forcible insertion of DNA into a host genome, irrespective of the source of the DNA, and exclusive of conventional or mutation breeding. Some defenders of the commercial use of GMOs have referred to the scientific work of GMO critics as "junk science." Such a claim is false and misleading, given that many papers critical of both the utility and safety of GMOs have been published in peer reviewed journals by respected scientists. In contrast, there is a dearth of peer reviewed work to substantiate the frequently heard assertions of either safety or utility in GMOs. The polar- ity, which now characterizes much of the public discourse on GMOs, reflects not simply scientific disagreement, but also disagreement in underlying value assumptions. Value differences strongly affect the assessment of both benefit and harm from GMOs. The concept of substantial equivalence occupies a pivotal position in the GMO risk assessment process that is used in both Canada and the US. A GMO judged to be substan- tially equivalent to a conventional product - as have all submissions to date - is presumed to be safe enough for commercialization. The conclusion of safety - from both human health and environmental perspectives - should be based on scientific evidence, corroborated by actual experimentation. However, regulators infer safety largely from assumptions-based reasoning, with little or no experimental validation. The judgement of safety because of substantial equivalence is a dubious argument by analogy.