Exploitation of genetically modified inoculants for industrial ecology applications

The major growth seen in the biotechnology industry in recent decades has largely been driven by the exploitation of genetic engineering techniques. The initial benefits have been predominantly in the biomedical area, with products such as vaccines and hormones that have received broad public approval. In the environmental biotechnology and industrial ecology sectors, biotechnology has the potential to make significant advances through the use of genetically modified (GM) microbial inoculants that can reduce agri-chemical usage or remediate polluted environments. Although many GM inoculants have been developed and tested under laboratory conditions, commercial exploitation has lagged behind. Here, we review scientific and regulatory requirements that must be satisfied as part of that exploitation process. Particular attention is paid to new European Union (EU) regulations (Directives) that govern the testing and release of genetically modified organisms and microbial plant protection inoculants in the EU. With regard to the release of GM inoculants, the impact of the inoculant and the fate of modified genes are important concerns. Long term monitoring of release sites is necessary to address these issues. Data are reported from the monitoring of a site 6 years after release of GM Sinorhizobium meliloti strains. It was found that despite the absence of a host plant, the GM strains persisted in the soil for at least 6 years. Horizontal transfer and microevolution of a GM plasmid between S. meliloti strains was also observed. These data illustrate the importance of assessing the long-term persistence of GM inoculants. This revised version was published online in August 2006 with corrections to the Cover Date.     

Regulatory requirements for licensing medicinal products of biotechnology

The recent and rapidly developing application of biotechnology which leads to the discovery of new therapeutic substances has raised a new set of safety issues for consideration by industry and regulatory bodies. The experience which already exists in the assessment of the safety and quality of biological products can contribute significantly to the approaches which are evolving with this new range of products. Industry and regulatory bodies should both resist the temptation to introduce testing programmes and requirements without a sound scientific rationale. This paper reviews some of the issues which should be considered when embarking on the safety evaluation of products derived from biotechnology.     

Biosimilars: a regulatory perspective from America

Biosimilars are protein products that are sufficiently similar to a biopharmaceutical already approved by a regulatory agency. Several biotechnology companies and generic drug manufacturers in Asia and Europe are developing biosimilars of tumor necrosis factor inhibitors and rituximab. A biosimilar etanercept is already being marketed in Colombia and China. In the US, several natural source products and recombinant proteins have been approved as generic drugs under Section 505(b)(2) of the Food, Drug, and Cosmetic Act. However, because the complexity of large biopharmaceuticals makes it difficult to demonstrate that a biosimilar is structurally identical to an already approved biopharmaceutical, this Act does not apply to biosimilars of large biopharmaceuticals. Section 7002 of the Patient Protection and Affordable Care Act of 2010, which is referred to as the Biologics Price Competition and Innovation Act of 2009, amends Section 351 of the Public Health Service Act to create an abbreviated pathway that permits a biosimilar to be evaluated by comparing it with only a single reference biological product. This paper reviews the processes for approval of biosimilars in the US and the European Union and highlights recent changes in federal regulations governing the approval of biosimilars in the US.     

Biosafety management and commercial use of genetically modified crops in China

As a developing country with relatively limited arable land, China is making great efforts for development and use of genetically modified (GM) crops to boost agricultural productivity. Many GM crop varieties have been developed in China in recent years; in particular, China is playing a leading role in development of insect-resistant GM rice lines. To ensure the safe use of GM crops, biosafety risk assessments are required as an important part of the regulatory oversight of such products. With over 20 years of nationwide promotion of agricultural biotechnology, a relatively well-developed regulatory system for risk assessment and management of GM plants has been developed that establishes a firm basis for safe use of GM crops. So far, a total of seven GM crops involving ten events have been approved for commercial planting, and 5 GM crops with a total of 37 events have been approved for import as processing material in China. However, currently only insect-resistant Bt cotton and disease-resistant papaya have been commercially planted on a large scale. The planting of Bt cotton and disease-resistant papaya have provided efficient protection against cotton bollworms and Papaya ringspot virus (PRSV), respectively. As a consequence, chemical application to these crops has been significantly reduced, enhancing farm income while reducing human and non-target organism exposure to toxic chemicals. This article provides useful information for the colleagues, in particular for them whose mother tongue is not Chinese, to clearly understand the biosafety regulation and commercial use of genetically modified crops in China.     

Assessing the impacts of genetically modified microorganisms

The progression towards greater industrial sustainability involves the analysis of biotechnology as a means of achieving clean or cleaner products and processes. Because living systems manage their chemistry more efficiently than man-made factories, and their wastes tend to be recyclable and biodegradable, they can be expected to be more environmentally clean. Industry has begun to use enzymes instead of traditional catalysts in many industrial production processes. The future holds obstacles as well as opportunities for biotechnological applications. A greater ability to manipulate biological materials and processes will have significant impact on manufacturing industries. A growing proportion of biotechnologyderived processes and products is based on the use of genetically modified microorganisms. This extends the analysis from the aspect of cleanliness to the aspect of safety.     

The current state of GMO governance: Are we ready for GM animals?

Given the history of GMO conflict and debate, the GM animal future is dependent on the response of the regulatory landscape and its associated range of interest groups at national, regional and international levels. Focusing on the EU and the USA, this article examines the likely form of that multi-level response, the increased role of cultural values, the contribution of new and existing interest groups and the consequent implications for the commercialization of both green and red GM animal biotechnology.     

昆虫遗传转化品系的常用标记

遗传转化标记是将遗传修饰昆虫从野生型种群中分辨出来的根据,遗传转化昆虫的鉴定、转化品系的维持及其遗传稳定性的监测都依赖于可靠的标记系统,发展易于应用和监测的转化标记能够极大地促进害虫遗传防治的相关研究。用于遗传修饰昆虫的转化标记主要有昆虫眼睛颜色标记基因、抗药性标记基因和荧光蛋白标记基因等。非果蝇类昆虫首个遗传转化品系的鉴定是通过眼睛颜色突变而实现,但大多数昆虫物种没有可用的突变体或缺少相应基因的信息,从而限制了眼睛颜色标记的应用。抗药性基因标记虽然能够通过对转化昆虫进行集体选择而大幅度提高筛选转化体的效率,但由于其鉴定的准确性不高且存在安全性问题,未得到广泛应用。荧光蛋白标记基因的发展则显著拓宽了能够转化的昆虫种类。从水母分离的绿色荧光蛋白(GFP)经突变方法获得了多种不同荧光性质的突变体,经人为修饰后与适宜的强启动子构成转化标记载体,能够有效鉴定更多昆虫物种的遗传转化个体,其中应用较多的是增强型绿色荧光蛋白(EGFP)。此外,从珊瑚属海葵中分离得到的红色DsRed标记基因提供了多样化的红色荧光蛋白选择,在某些生物中DsRed与GFP联合应用的表现明显优于GFP突变体,所以其应用前景也非常广泛。本文着重从眼睛颜色、抗药性和荧光蛋白等3个方面阐述了标记基因的发展历史与现状,并对其今后的发展方向进行了展望。     

Regulatory science requirements of labeling of genetically modified food

This paper provides an overview of the evolution of food labeling in the USA. It briefly describes the three phases of agricultural development consisting of naturally occurring, cross-bred, and genetically engineered, edited or modified crops, otherwise known as Genetically Modified Organisms (GMO). It uses the Best Available Regulatory Science (BARS) and Metrics for Evaluation of Regulatory Science Claims (MERSC) to evaluate the scientific validity of claims applicable to GMO and the Best Available Public Information (BAPI) to evaluate the pronouncements by public media and others. Subsequently claims on health risk, ecological risk, consumer choice, and corporate greed are evaluated based on BARS/MERSC and BAPI. The paper concludes by suggesting that labeling of food containing GMO should consider the consumer’s choice, such as the food used by those who desire kosher and halal food. Furthermore, the consumer choice is already met by the exclusion of GMO in organic food.     

Regulatory options for genetically modified crops in India

The introduction of semi‐dwarfing, high‐yielding and nutrients‐responsive crop varieties in the 1960s and 1970s alleviated the suffering of low crop yield, food shortages and epidemics of famine in India and other parts of the Asian continent. Two semi‐dwarfing genes, Rht in wheat and Sd‐1 in rice heralded the green revolution for which Dr. Norman Borlaug was awarded the Nobel Peace Prize in 1970. In contrast, the revolutionary new genetics of crop improvement shamble over formidable obstacles of regulatory delays, political interferences and public misconceptions. India benefited immensely from the green revolution and is now grappling to deal with the nuances of GM crops. The development of GM mustard discontinued prematurely in 2001 and insect‐resistant Bt cotton varieties were successfully approved for commercial cultivation in 2002 in an evolving nature of regulatory system. However, the moratorium on Bt brinjal by MOEF in 2010 meant a considerable detour from an objective, science‐based, rigorous institutional process of regulatory approval to a more subjective, nonscience‐driven, political decision‐making process. This study examines what ails the regulatory system of GM crops in India and the steps that led to the regulatory logjam. Responding to the growing challenges and impediments of existing biosafety regulation, it suggests options that are critical for GM crops to take roots for a multiplier harvest.     

Engineering cytokine receptors to control cellular functions

Cytokine receptors function as an interface between a cell and the extracellular milieu, and play a pivotal role in cell fate, because they recognize specific ligands via their extracellular domain and trigger signal transduction via their intracellular domain. Recent advances in unraveling the mechanism of cytokine receptor-mediated signal transduction have allowed us to engineer cytokine receptors with distinct functions, which have a potential for use in biotechnology. This paper reviews the history and current topics of receptor engineering.     

利用决策树方法建立转基因植物环境生物安全评价诊断平台

转基因技术及其产品是解决世界粮食问题的重要途径之一, 但是包括食品和环境安全在内的转基因生物安全评价是转基因技术及其产品商品化应用的前提和保证。现有的人为生物安全评价方法存在着一定的不足, 难以应对数量日益增加和内容日趋复杂的转基因产品的安全评价需求, 因此找寻一种客观和高效的评价方法势在必行。决策树(decision tree)方法是现今广泛使用的数据挖掘和分析的决策方法之一, 通过将需要解答问题的层层分解并分别解决, 最终得到理想的决策结果, 在处理复杂问题方面具有独特的优势。本文旨在通过介绍决策树的概念、特性、种类及其构建方法, 探索将决策树方法应用于建立转基因植物环境生物安全评价诊断平台的可行性, 并分析构建的诊断平台在高效、准确和客观地进行转基因植物环境生物安全评价, 以及对新一代转基因产品环境安全性的预测和普及环境安全知识等方面的优势, 为进一步推动转基因技术的发展和转基因产品的安全利用奠定基础。     

Detection of genetically modified organisms by electrochemiluminescence PCR method

With the development of biotechnology, more and more genetically modified organisms (GMOs) have entered commercial market. Because of the safety concerns, detection and characterization of GMOs have attracted much attention recently. In this study, electrochemiluminescence polymerase chain reaction (ECL-PCR) combined with hybridization technique was applied to detect the GMOs in genetically modified (GM) soybeans and papayas for the first time. Whether the soybeans and the papayas contain GM components was discriminated by detecting the Cauliflower mosaic virus 35S (CaMV35S) promoter. The experiment results show that the detection limit for CaMV35S promoter is 100 fmol, and the GM components can be clearly identified in GM soybeans and papayas. The technique may provide a new means in GMOs detection due to its simplicity and high efficiency.     

Renegotiating GM crop regulation. Targeted gene-modification technology raises new issues for the oversight of genetically modified crops

Targeted genetic modification, which enables scientists to genetically engineer plants more efficiently and precisely, challenges current process-based regulatory frameworks for genetically modified crops.In 2010, more than 85% of the corn acreage and more than 90% of the soybean acreage in the USA was planted with genetically modified (GM) crops (USDA, 2010). Most of those crops contained transgenes from other species, such as bacteria, that confer resistance to herbicides or tolerance to insect pests, and that were introduced into plant cells using Agrobacterium or other delivery methods. The resulting ‘transformed'' cells were regenerated into GM plants that were tested for the appropriate expression of the transgenes, as well as for whether the crop posed an unacceptable environmental or health risk, before being approved for commercial use. The scientific advances that enabled the generation of these GM plants took place in the early 1980s and have changed agriculture irrevocably, as evidenced by the widespread adoption of GM technology. They have also triggered intense debates about the potential risks of GM crops for human health and the environment and new forms of regulation that are needed to mitigate this. There is also continued public resistance to GM crops, particularly in Europe.Plant genetic engineering is at a technological inflection pointPlant genetic engineering is at a technological inflection point. New technologies enable more precise and subtler modification of plant genomes (Weinthal et al, 2010) than the comparably crude methods that were used to create the current stock of GM crops (Fig 1A). These methods allow scientists to insert foreign DNA into the plant genome at precise locations, remove unwanted DNA sequences or introduce subtle modifications, such as single-base substitutions that alter the activity of individual genes. They also raise serious questions about the regulation of GM crops: how do these methods differ from existing techniques and how will the resulting products be regulated? Owing to the specificity of these methods, will resulting products fall outside existing definitions of GM crops and, as a result, be regulated similarly to conventional crops? How will the definition and regulation of GM crops be renegotiated and delineated in light of these new methods?Open in a separate windowFigure 1Comparing traditional transgenesis, targeted transgenesis, targeted mutagenesis and gene replacement. (A) In traditional transgenesis, genes introduced into plant cells integrate at random chromosomal positions. This is illustrated here for a bacterial gene that confers herbicide resistance (Herb^r). The plant encodes a gene for the same enzyme, however due to DNA-sequence differences between the bacterial and plant forms of the gene, the plant gene does not confer herbicide resistance (Herb^s). (B) The bacterial herbicide-resistance gene can be targeted to a specific chromosomal location through the use of engineered nucleases. The nucleases recognize a specific DNA sequence and create a chromosome break. The bacterial gene is flanked by sequences homologous to the target site and recombines with the plant chromosome at the break site, resulting in a targeted insertion. (C) Engineered nucleases can be used to create targeted gene knockouts. In this illustration, a second nuclease recognizes the coding sequence of the Herb^s gene. Cleavage and repair in the absence of a homologous template creates a mutation (orange). (D) A homologous DNA donor can be used to repair targeted breaks in the Herb^s gene. This allows sequence changes to be introduced into the native plant gene that confer herbicide resistance. Only a single base change is needed in some instances.Of the new wave of targeted genetic modification (TagMo) techniques, one of the most thoroughly developed is TagMo, which uses engineered zinc-finger nucleases or meganucleases to create DNA double-stranded breaks at specific genomic locations (Townsend et al, 2009; Shukla et al, 2009; Gao et al, 2010). This activates DNA repair mechanisms, which genetic engineers can use to alter the target gene. If, for instance, a DNA fragment is provided that has sequence similarity with the site at which the chromosome is broken, the repair mechanism will use this fragment as a template for repair through homologous recombination (Fig 1B). In this way, any DNA sequence, for instance a bacterial gene that confers herbicide resistance, can be inserted at the site of the chromosome break. TagMos can also be used without a repair template to make single-nucleotide changes. In this case, the broken chromosomes are rejoined imprecisely, creating small insertions or deletions at the break site (Fig 1C) that can alter or knock out gene function.TagMo technology would, therefore, challenge regulatory policies both in the USA and, even more so, in the [EU]…The greatest potential of TagMo technology is in its ability to modify native plant genes in directed and targeted ways. For example, the most widely used herbicide-resistance gene in GM crops comes from bacteria. Plants encode the same enzyme, but it does not confer herbicide resistance because the DNA sequence is different. Yet, resistant forms of the plant gene have been identified that differ from native genes by only a few nucleotides. TagMo could therefore be used to transfer these genes from a related species into a crop to replace the existing genes (Fig 1D) or to exchange specific nucleotides until the desired effect is achieved. In either case, the genetic modification would not necessarily involve transfer of DNA from another species. TagMo technology would, therefore, challenge regulatory policies both in the USA and, even more so, in the European Union (EU). TagMo enables more sophisticated modifications of plant genomes that, in some cases, could be achieved by classical breeding or mutagenesis, which are not formally regulated. On the other hand, TagMo might also be used to introduce foreign genes without using traditional recombinant DNA techniques. As a result, TagMo might fall outside of existing US and EU regulatory definitions and scrutiny.In the USA, federal policies to regulate GM crops could provide a framework in which to consider the way TagMo-derived crops might be regulated (Fig 2; Kuzma & Meghani, 2009; Kuzma et al, 2009; Thompson, 2007; McHughen & Smyth, 2008). In 1986, the Office of Science and Technology Policy established the Coordinated Framework for the Regulation of Biotechnology (CFRB) to oversee the environmental release of GM crops and their products (Office of Science and Technology Policy, 1986). The CFRB involves many federal agencies and is still in operation today (Kuzma et al, 2009). It was predicated on the views that regulation should be based on science and that the risks posed by GM crops were the “same in kind” as those of non-GM products; therefore no new laws were deemed to be required (National Research Council, 2000).Open in a separate windowFigure 2Brief history of the regulation of genetic engineering (Kuzma et al, 2009). EPA, Environmental Protection Agency; FIFRA, Federal Insecticide, Fungicide and Rodenticide Act; FDA, Food and Drug Administration; FPPA, Farmland Protection Policy Act; GMO, genetically modified organism; TOSCA, Toxic Substances Control Act; USDA, United States Department of Agriculture.Various old and existing statutes were interpreted somewhat loosely in order to oversee the regulation of GM plants. Depending on the nature of the product, one or several federal agencies might be responsible. GM plants can be regulated by the US Department of Agriculture (USDA) under the Federal Plant Pest Act as ‘plant pests'' if there is a perceived threat of them becoming ‘pests'' (similarly to weeds). Alternatively, if they are pest-resistant, they can be interpreted as ‘plant pesticides'' by the US Environmental Protection Agency (EPA) under the Federal Insecticide, Fungicide, and Rodenticide Act. Each statute requires some kind of pre-market or pre-release biosafety review—evaluation of potential impacts on other organisms in the environment, gene flow between the GM plant and wild relatives, and potential adverse effects on ecosystems. By contrast, the US Food and Drug Administration (FDA) treats GM food crops as equivalent to conventional food products; as such, no special regulations were promulgated under the Federal Food Drug and Cosmetic Act for GM foods. The agency established a pre-market consultation process for GM and other novel foods that is entirely voluntary.…TagMo-derived crops come in several categories relevant to regulation…Finally, and important for our discussion, the US oversight system was built mostly around the idea that GM plants should be regulated on the basis of characteristics of the end-product and not on the process that is used to create them. In reality, however, the process used to create crops is significant, which is highlighted by the fact that the USDA uses a process-based regulatory trigger (McHughen & Smyth, 2008). Instead of being inconsequential, it is important for oversight whether a plant is considered to be a result of GM.How will crops created by TagMo fit into this regulatory framework? If only subtle changes were made to individual genes, the argument could be made that the products are analogous to mutated conventional crops, which are neither regulated nor subject to pre-market or pre-release biosafety assessments (Breyer et al, 2009). However, single mutations are not without risks; for example, they can lead to an increase in expressed plant toxins (National Research Council, 1989, 2000, 2002, 2004; Magana-Gomez & de la Barca 2009). Conversely, if new or foreign genes are introduced through TagMo methods, the resulting plants might not differ substantially from existing GM crops. Thus, TagMo-derived crops come in several categories relevant to regulation: TagMo-derived crops with inserted foreign DNA from sexually compatible or incompatible species; TagMo-derived crops with no DNA inserted, for instance those in which parts of the chromosome have been deleted or genes inactivated; and TagMo-derived crops that either replace a gene with a modified version or change its nucleotide sequence (Fig 1).TagMo-derived crops with foreign genetic material inserted are most similar to traditional GM crops, according to the USDA rule on “Importation, Interstate Movement, and Release Into the Environment of Certain Genetically Engineered Organisms”, which defines genetic engineering as “the genetic modification of organisms by recombinant DNA (rDNA) techniques” (USDA, 1997). In contrast to conventional transgenesis, TagMo enables scientists to predefine the sites into which foreign genes are inserted. If the site of foreign DNA insertion has been previously characterized and shown to have no negative consequences for the plant or its products, then perhaps regulatory requirements to characterize the insertion site and its effects on the plant could be streamlined.TagMo might be used to introduce foreign DNA from sexually compatible or incompatible species into a host organism, either by insertion or replacement. For example, foreign DNA from one species of Brassica—mustard family—can be introduced into another species of Brassica. Alternatively, TagMo might be used to introduce foreign DNA from any organism into the host, such as from bacteria or animals into plants. Arguments have been put forth advocating less stringent regulation of GM crops with cisgenic DNA sequences that come from sexually compatible species (Schouten et al, 2006). Russell and Sparrow (2008) critically evaluate these arguments and conclude that cisgenic GM crops may still have novel traits in novel settings and thus give rise to novel hazards. Furthermore, if cisgenics are not regulated, it might trigger a public backlash, which could be more costly in the long run (Russell & Sparrow, 2008). TagMo-derived crops with genetic sequences from sexually compatible species should therefore still be considered for regulation. Additional clarity and consistency is needed with respect to how cisgenics are defined in US regulatory policy, regardless of whether they are generated by established methods or by TagMo. The USDA regulatory definition of a GM crops is vague, and the EPA has a broad categorical exemption in its rules for GM crops with sequences from sexually compatible species (EPA, 2001).Public failures will probably ensue if TagMo crops slip into the market under the radar without adequate oversightThe deletion of DNA sequences by TagMo to knock out a target gene is potentially of great agronomic value, as it could remove undesirable traits. For instance, it could eliminate anti-nutrients such as trypsin inhibitors in soybean that prevent the use of soy proteins by animals, or compounds that limit the value of a crop as an industrial material, such as ricin, which contaminates castor oil. Many mutagenesis methods yield similar products as TagMos. However, most conventional mutagenesis methods, including DNA alkylating agents or radioactivity, provide no precision in terms of the DNA sequences modified, and probably cause considerable collateral damage to the genome. It could be argued that TagMo is less likely to cause unpredicted genomic changes; however, additional research is required to better understand off-target effects—that is, unintended modification of other sites—by various TagMo platforms.We propose that the discussion about how to regulate TagMo crops should be open, use public engagement and respect several criteria of oversightGenerating targeted gene knockouts (Fig 1C) does not directly involve transfer of foreign DNA, and such plants might seem to warrant an unregulated status. However, most TagMos use reagents such as engineered nucleases, which are created by rDNA methods. The resulting product might therefore be classified as a GM crop under the existing USDA definition for genetic engineering (USDA, 1997) since most TagMos are created by introducing a target-specific nuclease gene into plant cells. It is also possible to deliver rDNA-derived nucleases to cells as RNA or protein, and so foreign DNA would not need to be introduced into plants to achieve the desired mutagenic outcome. In such cases, the rDNA molecule itself never encounters a plant cell. More direction is required from regulatory agencies to stipulate the way in which rDNA can be used in the process of generating crops before the regulated status is triggered.TagMo-derived crops that introduce alien transgenes or knock out native genes are similar to traditional GM crops or conventionally mutagenized plants, respectively, but TagMo crops that alter the DNA sequence of the target gene (Fig 1D) are more difficult to classify. For example, a GM plant could have a single nucleotide change that distinguishes it from its parent and that confers a new trait such as herbicide resistance. If such a subtle genetic alteration were attained by traditional mutagenesis or by screening for natural variation, the resulting plants would not be regulated. As discussed above, if rDNA techniques are used to create the single nucleotide TagMo, one could argue that it should be regulated. Regulation would then focus on the process rather than the product. If single nucleotide changes were exempt, would there be a threshold in the number of bases that can be modified before concerns are raised or regulatory scrutiny is triggered? Or would there be a difference in regulation if the gene replacement involves a sexually compatible or an incompatible species?Most of this discussion has focused on the use of engineered nucleases such as meganucleases or zinc-finger nucleases to create TagMos. Oligonucleotide-mediated mutagenesis (OMM), however, is also used to modify plant genes (Breyer et al, 2009). OMM uses chemically synthesized oligonucleotides that are homologous to the target gene, except for the nucleotides to be changed. Breyer et al (2009) argue that OMM “should not be considered as using recombinant nucleic acid molecules” and that “OMM should be considered as a form of mutagenesis, a technique which is excluded from the scope of the EU regulation.” However, they admit that the resulting crops could be considered as GM organisms, according to EU regulatory definitions for biotechnology. They report that in the USA, OMM plants have been declared non-GM by the USDA, but it is unclear whether the non-GM distinction in the USA has regulatory implications. OMM is already being used to develop crops with herbicide tolerance, and so regulatory guidelines need to be clarified before market release.In turning to address how TagMo-related oversight should proceed, two questions are central: how are decisions made and who is involved in making them? The analysis above illustrates that many fundamental decisions need to be made concerning the way in which TagMo-derived products will be regulated and, more broadly, what constitutes a GM organism for regulatory purposes. These decisions are inherently values-based in that views on how to regulate TagMo products differ on the basis of understanding of and attitudes towards agriculture, risk, nature and technology. Neglecting the values-based assumptions underlying these decisions can lead to poor decision-making, through misunderstanding the issues at hand, and public and stakeholder backlash resulting from disagreements over values.Bozeman & Sarewitz (2005) consider this problem in a framework of ‘market failures'' and ‘public failures''. GM crops have exhibited both. Market failures are exemplified by the loss of trade with the EU owing to different regulatory standards and levels of caution (PIFB, 2006). Furthermore, there has been a decline in the number of GM crops approved for interstate movement in the USA since 2001. Public failures result from incongruence between actions by decision-makers and the values of the public. Public failures are exemplified by the anti-GM sentiment in the labelling of organic foods in the USA and court challenges to the biosafety review of GM crops by the USDA''s Animal and Plant Health Inspection Service (McHughen & Smyth, 2008). These lawsuits have delayed approval of genetically engineered alfalfa and sugar beet, thus blurring the distinction between public and market failures. Public failures will probably ensue if TagMo crops slip into the market under the radar without adequate oversight.The possibility of public failures with TagMo crops highlights the benefits of an anticipatory governance-based approach, and will help to ensure that the technology meets societal needsAnticipatory governance is a framework with principles that are well suited to guiding TagMo-related oversight and to helping to avoid public failures. It challenges an understanding of technology development that downplays the importance of societal factors—such as implications for stakeholders and the environment—and argues that societal factors should inform technology development and governance from the start (Macnaghten et al, 2005).Anticipatory governance uses three principles: foresight, integration of natural and social science research, and upstream public engagement (Karinen & Guston, 2010). The first two principles emphasize proactive engagement using interdisciplinary knowledge. Governance processes that use these principles include real-time technology assessment (Guston & Sarewitz, 2002) and upstream oversight assessment (Kuzma et al, 2008b). The third principle, upstream public engagement, involves stakeholders and the public in directing values-based assumptions within technology development and oversight (Wilsdon & Wills, 2004). Justifications for upstream public engagement are substantive (stakeholders and the public can provide information that improves decisions), instrumental (including stakeholders and the public in the decision-making process leads to more trusted decisions) and normative (citizens have a right to influence decisions about issues that affect them).TagMo crop developers seem to be arguing for a ‘process-based'' exclusion of TagMo crops from regulatory oversight, without public knowledge of their development or ongoing regulatory communication. We propose that the discussion about how to regulate TagMo crops should be open, use public engagement and respect several criteria of oversight (Kuzma et al, 2008a). These criteria should include not only biosafety, but also broader impacts on human and ecological health and well-being, distribution of health impacts, transparency, treatment of intellectual property and confidential business information, economic costs and benefits, as well as public confidence and values.We also propose that the CFRB should be a starting point for TagMo oversight. The various categories of TagMo require an approach that can discern and address the risks associated with each application. The CFRB allows for such flexibility. At the same time, the CFRB should improve public engagement and transparency, post-market monitoring and some aspects of technical risk assessment.As we have argued, TagMo is on the verge of being broadly implemented to create crop varieties with new traits, and this raises many oversight questions. First, the way in which TagMo technologies will be classified and handled within the US regulatory system has yet to be determined. As these decisions are complex, values-based and have far-reaching implications, they should be made in a transparent way that draws on insights from the natural and social sciences, and involves stakeholders and the public. Second, as products derived from TagMo technologies will soon reach the marketplace, it is important to begin predicting and addressing potential regulatory challenges, to ensure that oversight systems are in place. The possibility of public failures with TagMo crops highlights the benefits of an anticipatory governance-based approach, and will help to ensure that the technology meets societal needs.So far, the EU has emphasized governance approaches and stakeholder involvement in the regulation of new technologies more than the USA. However, if the USA can agree on a regulatory system for TagMo crops that is the result of open and transparent discussions with the public and stakeholders, it could take the lead and act as a model for similar regulation in the EU and globally. Before this can happen, a shift in US approaches to regulatory policy would be needed.? Open in a separate windowJennifer KuzmaOpen in a separate windowAdam Kokotovich     

History and future of genetically engineered food animal regulation: an open request

Modern biotechnology resulted from of a series of incremental improvements in the understanding of DNA and the enzymes that nature evolved to manipulate it. As the potential impact of genetic engineering became apparent, scientists began the process of trying to identify the potential unintended consequences. Restrictions to recombinant DNA experimentation were at first self-imposed. Collaborative efforts between scientists and lawyers formalized an initial set of guidelines. These guidelines have been used to promulgate regulations around world. However, the initial guidelines were only intended as a starting point and were motivated by a specific set of concerns. As new data became available, the guidelines and regulations should have been adapted to the new knowledge. Instead, other social drivers drove the development of regulations. For most species and most applications, the framework that was established has slowly allowed some products to reach the market. However, genetically engineered livestock that are intended for food have been left in a regulatory state of limbo. To date, no genetically engineered food animal is available in the marketplace. A short history and a U.S.-based genetic engineer’s perspective are presented. In addition, a request to regulatory agencies is presented for consideration as regulation continues to evolve. Regulators appear to have shown preference for the slow, random progression of evolution over the efficiency of intentional design.     

Genetically modified soybeans and food allergies

Allergenic reactions to proteins expressed in GM crops has been one of the prominent concerns among biotechnology critics and a concern of regulatory agencies. Soybeans like many plants have intrinsic allergens that present problems for sensitive people. Current GM crops, including soybean, have not been shown to add any additional allergenic risk beyond the intrinsic risks already present. Biotechnology can be used to characterize and eliminate allergens naturally present in crops. Biotechnology has been used to remove a major allergen in soybean demonstrating that genetic modification can be used to reduce allergenicity of food and feed. This provides a model for further use of GM approaches to eliminate allergens.     

In the democracies of DNA: ontological uncertainty and political order in three states

This paper compares the regulation of biotechnology in Britain, Germany and the United States and shows that systematic differences have developed around four issues: abortion, assisted reproduction, stem cells, and genetically modified crops and foods. Policy choices with respect to these issues reflect the capacity of each nation's regulatory institutions to deal with the scientific, social and ethical uncertainties around biotechnology. National regulatory frameworks constitute an apparatus of collective sense-making through which governments and publics interpret biotechnology's risks and promises. Specifically, regulatory choices position the novel ontologies created by biotechnology either on the side of the familiar and manageable or on the side of the unknown and insupportably risky. The comparison shows that public responses to biotechnology are embedded within robust and coherent political cultures and are not ad hoc expressions of concern that very unpredictably from issue to issue.     

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.     

Scaffold-based bone engineering by using genetically modified cells

The first generation of clinically applied tissue engineering concepts in the area of skin, cartilage and bone marrow regeneration was based on the isolation, expansion and implantation of cells from the patient's own tissue. Although successful in selective treatments, tissue engineering needs to overcome major challenges to allow widespread clinical application with predictable outcomes. One challenge is to present the cells in a matrix to the implantation site to allow the cells to survive the wound healing contraction forces, tissue remodeling in certain tissues such as bone and biomechanical loading. Hence, several tissue engineering strategies focus on the development of load-bearing scaffold/cell constructs. From a cell source point of view, bone engineers face challenges to isolate and expand cells with the highest potential to form osseous tissue along with harvesting tissue without extensive donor site morbidity. A major hurdle to tissue engineering is de-differentiation and limited ability to control cell phenotype following in vitro expansion. Due to early successes with genetic engineering, bone tissue engineers have used different strategies to genetically alter various types of mesenchymal cells to enhance the mineralization capacity of tissue-engineered scaffold/cell constructs. Although the development of multi-component scaffold/osteogenic cell constructs requires a combination of interdisciplinary research strategies, the following review is limited to describe the general aspects of bone engineering and to present overall directions of technology platforms, which include a genetic engineering component. This paper reviews the most recent work in the field and discusses the concepts developed and executed by a collaborative effort of the multi-disciplinary teams of the two authors.     

分选酶的研究进展及其在生物技术中的应用

分选酶(sortase)普遍存在于革兰氏阳性细菌中,是一类膜结合的转肽酶,负责将表面蛋白共价结合到细胞壁的肽聚糖上。由于其独特的作用机制,分选酶在生物技术领域具有广阔的应用前景,可应用于革兰氏阳性菌的表面展示、蛋白质工程等。     

Preclinical development of monoclonal antibodies

The development of mAbs remains high on the therapeutic agenda for the majority of pharmaceutical and biotechnology companies. Often, the only relevant species for preclinical safety assessment of mAbs are non-human primates (NHPs), and this raises important scientific, ethical and economic issues. To investigate evidence-based opportunities to minimize the use of NHPs, an expert working group with representatives from leading pharmaceutical and biotechnology companies, contract research organizations and institutes from Europe and the USA, has shared and analyzed data on mAbs for a range of therapeutic areas. This information has been applied to hypothetical examples to recommend scientifically appropriate development pathways and study designs for a variety of potential mAbs. The addendum of ICHS6 provides a timely opportunity for the scientific and regulatory community to embrace strategies which minimize primate use and increase efficiency of mAb development.