AquAdvantage Research Articles

120 Gene editing: From the general public perspective

Abstract The public controversy around genetically engineered (GE) products, aka genetically modified organisms (GMO), has been ongoing for almost 40 yr fueled in part by well-funded misinformation campaigns disseminated by activist organizations. Polls reveal that public perception of GE animals is generally negative, with biomedical applications being more positively perceived than agricultural applications. Opposition to GE animals is often conflated with opposition to use of animals in research in general, as well as opposition to aspects of intensive animal agriculture. In general, concerns about animal biotechnology are influenced by views around the moral status of animals, the boundary between “natural” and “unnatural,” and perceived risks and benefits of GE animals to health and the environment (personal and cultural characteristics); the purpose of the application (e.g., disease resistance > fast growth), the method(s) being used, and the motivation of the research group making the genetic modification (public or private); and the species being modified (animal characteristics). There were three factors that aggravated opposition to GE products including 1) a lengthy and expensive regulatory step uniquely associated with commercializing products developed using that breeding method, 2) competing business interests (e.g., organic, non-GMO project) that were able to monetarize fear around the method to extract value (rent seeking) and selling their value-added (more expensive) product that avoided the use of GE, and 3) there is a mandatory labeling requirement to track/differentiate products produced with (or without) that breeding method to enable value-added marketing. Even so, when GE products that people wanted were allowed to reach the market (e.g., Impossible Burger with GE heme, GloFish, AquAdvantage salmon), they met with commercial acceptance. Now it has been suggested that the public will similarly reject animal products derived from gene edited (GnEd) animals, but that idea has only recently been put to the test as such food products were not previously available. A 2022 Japanese paper noted that with regard to GnEd food (gene knock-out tomatoes and fish) there was a “gap between anticipated and actual public response”. They noted that “even though there were some petitions against the use of genome-editing made by consumer groups; they did not develop into a mass mobilization, and media coverage was mostly positive.” These GnEd food products were developed by startups from Japanese universities, required no unique regulatory step before commercialization or mandatory labeling with Japanese regulatory agencies transparently sharing a summary of the information and notification on their websites, and businesses were encouraged to share information on products to respect The right of consumers to know. Successful commercialization of GnEd animal products has so far occurred in countries (e.g., Argentina, Brazil, Japan) where regulations treat simple GnEd products with no “foreign DNA” to be “non-GMO” and analogous to conventional breeding.

RNA-Seq Analysis of the Growth Hormone Transgenic Female Triploid Atlantic Salmon (Salmo salar) Hepatic Transcriptome Reveals Broad Temperature-Mediated Effects on Metabolism and Other Biological Processes.

This study examined the impact of rearing temperature (10.5, 13.5 or 16.5°C) on the hepatic transcriptome of AquAdvantage Salmon (growth hormone transgenic female triploid Atlantic salmon) at an average weight of 800 g. Six stranded PE libraries were Illumina-sequenced from each temperature group, resulting in an average of over 100 M raw reads per individual fish. RNA-sequencing (RNA-seq) results showed the greatest difference in the number of differentially expressed transcripts (1750 DETs), as revealed by both DESeq2 and edgeR (q < 0.05; fold-change > |1.5|), was between the 10.5 and 16.5°C temperature groups. In contrast, 172 and 52 DETs were found in the 10.5 vs. 13.5°C and the 13.5 vs. 16.5°C comparisons, respectively. Considering the DETs between the 10.5 and 16.5°C groups, 282 enriched gene ontology (GO) terms were identified (q < 0.05), including “response to stress”, “immune system process”, “lipid metabolic process”, “oxidation-reduction process”, and “cholesterol metabolic process”, suggesting elevated temperature elicited broad effects on multiple biological systems. Pathway analysis using ClueGO showed additional impacts on amino acid and lipid metabolism. There was a significant positive correlation between RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) results for 8 of 9 metabolic-related transcripts tested. RT-qPCR results also correlated to changes in fillet tissue composition previously reported in these salmon (e.g., methionine and lysine concentrations positively correlated with hsp90ab1 transcript expression), suggesting that rearing temperature played a significant role in mediating metabolic/biosynthetic pathways of AquAdvantage Salmon. Many transcripts related to lipid/fatty acid metabolism (e.g., elovl2, fabpi, hacd2, mgll, s27a2, thrsp) were downregulated at 16.5°C compared to both other temperature groups. Additionally, enrichment of stress-, apoptosis- and catabolism-relevant GO terms at 16.5°C suggests that this temperature may not be ideal for commercial production when using freshwater recirculating aquaculture systems (RAS). This study relates phenotypic responses to transcript-specific findings and therefore aids in the determination of an optimal rearing temperature for AquAdvantage Salmon. With approval to grow and sell AquAdvantage Salmon in the United States and Canada, the novel insights provided by this research can help industry expansion by promoting optimal physiological performance and health.

A comprehensive review on genetically modified fish: key techniques, applications and future prospects

AbstractGenetically modified fish is a general term used for whole fish whose DNA has been artificially altered by directly integrating (or deleting) single or multiple genes to introduce or modify a targeted character. Different techniques have been performed to produce genetically modified fish. Importantly, the introduction of various types of fluorescent proteins has dramatically expanded the range of applications of genetically modified fish. Currently, genetically modified fish have been widely employed as experimental models for medical science, pharmacology and environmental toxicology. The commercial application of genetically modified fish in aquaculture is still up for debate, although the first commercialization of genetically modified fish, GloFish, was in 2003, and further, the United States and Canada approved the commercial production and sale of the AquAdvantage Salmon. In this review, we discuss the principles and developmental history of fish transgenesis via gene transfer and gene‐editing techniques, and their applications in diverse fields. Further, challenges and prospects associated with the genetically modified fish are discussed.

RRI and Corporate Stakeholder Engagement: The Aquadvantage Salmon Case

Declining public trust in science and innovation triggered the emergence and development of the responsible research and innovation (RRI) concept among policymakers and academics. Engaging stakeholders in the early phases of innovation processes has been identified as a major driver of inclusive, responsible, and sustainable development. Firms however have often adopted practices entirely opposite to those being advocated within the RRI framework, namely, reducing external interaction with stakeholders, focusing on exclusive communication with the scientific community and legal authorities while avoiding the social spotlight. We illustrate these practices, their causes and consequences using the case of the Aquadvantage salmon, the first genetically modified (GM) animal approved to petition for the United States (US) Food and Drug Administration (FDA) approval for human consumption. We find that such practices heighten the risk of social backlash, being undesirable from the perspective of both the organizations involved and society at large. Stakeholder engagement remains necessary in order to gain the minimum social acceptance required for contentious innovative products to enter the market. However, stakeholder engagement must be selective, focused on pragmatic organizations whose aims and interests are sufficiently broad to potentially align with corporate interests. Strategic stakeholder engagement offers a meeting point between the transformative aspirations of RRI framework proponents and legitimate business interests.

Bigger, stronger, better: Fish transgenesis applications and methods

Transgenesis has been applied to several species to benefit from them in different fields. As natural fish stocks decline and the world population increase, the application of transgenesis on commercial fish species takes more attention to reduce the limitations of aquaculture and meet the increasing food demand. Transgenesis has been applied to obtain a stable transgenic line with improved traits to date. In aquaculture, growth rate, cold resistance, and disease resistance of commercial fish species were enhanced by transgenesis and even one of them, AquAdvantage Salmon, took place markets in the North America. Also, transgenic fish were developed to evaluate the health impacts of chemicals in ecotoxicology and provide more options with new color variants in ornamental fisheries. Different approaches for generating transgenic fish have been performed successfully, but they still require some developments. More transgenic fish could take place in the market by developing more efficient techniques and informing consumers about these techniques to reduce their concerns. This review discusses the application fields of transgenic fish with examples and provides an overview of gene delivery techniques and transgenesis methods.

Genetic Engineering of Livestock: The Opportunity Cost of Regulatory Delay.

Genetically engineered (GE) livestock were first reported in 1985, and yet only a single GE food animal, the fast-growing AquAdvantage salmon, has been commercialized. There are myriad interconnected reasons for the slow progress in this once-promising field, including technical issues, the structure of livestock industries, lack of public research funding and investment, regulatory obstacles, and concern about public opinion. This review focuses on GE livestock that have been produced and documents the difficulties that researchers and developers have encountered en route. Additionally, the costs associated with delayed commercialization of GE livestock were modeled using three case studies: GE mastitis-resistant dairy cattle, genome-edited porcine reproductive and respiratory syndrome virus-resistant pigs, and the AquAdvantage salmon. Delays of 5 or 10 years in the commercialization of GE livestock beyond the normative 10-year GE product evaluation period were associated with billions of dollars in opportunity costs and reduced global food security.

Bioenterprise Media Strategy 2020

In 2012 and 2016, the first two strategic science-business media models were published (SBBMM 1.0 and 2.0). Since that time, there have been significant changes both to the media landscape and to the usage and capability of online and social media platforms. This paper seeks to describe the current bioindustry-relevant media landscape, to introduce a new media model, the Strategic Bioenterprise Media Model 2020 (SBMM 2020), which reflects this new landscape, and to present a mainstream submodel to support the latest opportunity for biotechnology media coverage: Mainstream Media. Examples are drawn from media coverage following the FDA approvals of Zulresso from Sage Therapeutics, Aimovig from Novartis and Amgen, and AquAdvantage salmon from AquAdvantage Technologies. The overall goal of this paper is to equip bioenterprise professionals with an understanding of media dynamics and the strategic potential it brings, ultimately contributing to bioenterprise success.

Impact of rearing temperature on the innate antiviral immune response of growth hormone transgenic female triploid Atlantic salmon (Salmo salar)

AquAdvantage Salmon (growth hormone transgenic female triploid Atlantic salmon) are a faster-growing alternative to conventional farmed diploid Atlantic salmon. To investigate optimal rearing conditions for their commercial production, a laboratory study was conducted in a freshwater recirculating aquaculture system (RAS) to examine the effect of rearing temperature (10.5 °C, 13.5 °C, 16.5 °C) on their antiviral immune and stress responses. When each temperature treatment group reached an average weight of 800 g, a subset of fish were intraperitoneally injected with either polyriboinosinic polyribocytidylic acid (pIC, a viral mimic) or an equal volume of sterile phosphate-buffered saline (PBS). Blood and head kidney samples were collected before injection and 6, 24 and 48 h post-injection (hpi). Transcript abundance of 7 antiviral biomarker genes (tlr3, lgp2, stat1b, isg15a, rsad2, mxb, ifng) was measured by real-time quantitative polymerase chain reaction (qPCR) on head kidney RNA samples. Plasma cortisol levels from blood samples collected pre-injection and from pIC and PBS groups at 24 hpi were quantified by ELISA. While rearing temperature and treatment did not significantly affect circulating cortisol, all genes tested were significantly upregulated by pIC at all three temperatures (except for tlr3, which was only upregulated in the 10.5 °C treatment). Target gene activation was generally observed at 24 hpi, with most transcript levels decreasing by 48 hpi in pIC-injected fish. Although a high amount of biological variability in response to pIC was evident across all treatments, rearing temperature significantly influenced transcript abundance and/or fold-changes comparing time- and temperature-matched pIC- and PBS-injected fish for several genes (tlr3, lgp2, stat1b, isg15a, rsad2 and ifng) at 24 hpi. As an example, significantly higher fold-changes of rsad2, isg15a and ifng were found in fish reared at 10.5 °C when compared to 16.5 °C. Multivariate analysis confirmed that rearing temperature modulated antiviral immune response. The present experiment provides novel insight into the relationship between rearing temperature and innate antiviral immune response in AquAdvantage Salmon.

Growth performance and nutrient utilization of growth hormone transgenic female triploid Atlantic salmon (Salmo salar) reared at three temperatures in a land-based freshwater recirculating aquaculture system (RAS)

This study examined the effect of rearing temperature on growth performance and nutrient utilization of AquAdvantage Salmon (growth hormone transgenic female triploid Atlantic salmon) reared in a land-based freshwater recirculating aquaculture system (RAS) at three temperatures (10.5 °C, 13.5 °C, 16.5 °C) from first-feeding to 1500 g. All fish were fed the same commercial diets, which were analyzed for proximate, amino acid, fatty acid and mineral composition, and daily feed consumption was recorded for the calculation of feed conversion ratios (FCRs). Whole-body samples were collected at 300, 500, 800 and 1500 g for proximate composition, and fillet samples were collected at 500, 800 and 1500 g for amino acid, fatty acid, and mineral composition. Fillet yield, astaxanthin concentration and DSM SalmoFan™ colour were determined at 1500 g. Results indicated that fish reared at 16.5 °C required more feed per unit of biomass gain, and were less efficient at depositing important nutrients such as omega-3 fatty acids, compared to salmon reared at 10.5 °C and 13.5 °C. With higher viscerosomatic index (VSI) and condition factor (K) scores at 16.5 °C, these fish also diverted more dietary energy to lipid deposition in the viscera instead of muscle tissue compared to the lower temperature treatments. Fish reared at 16.5 °C had lighter fillet colouration compared to salmon reared at 13.5 °C, and exhibited lower fillet yields than the colder temperature groups. Fish reared at 16.5 °C reached the end target weight (1500 g) in 36 fewer days compared to 13.5 °C and 93 fewer days in contrast to 10.5 °C. However, thermal-unit growth coefficient (TGC) results indicated that growth rate was higher in fish reared at 10.5 °C compared to 16.5 °C for the majority of the trial. Collectively, these results suggest that it is preferable to rear AquAdvantage Salmon at either 10.5 °C or 13.5 °C in freshwater RAS. The information generated from this study is the first to provide insight into the relationships between rearing temperature and nutrient utilization in AquAdvantage Salmon for commercial application.

A method to assemble DNA fragments mimicking junctions of transgenic elements: Application to the AquAdvantage salmon

The detection of transgenic animals in food and environmental samples will require the development of reliable screening assays. The identification of junction regions between genetic elements is the unequivocal way to prove the presence of transgene constructs. However, a sample from the transgenic organism or genetic construct is not always available for analysis. Here, we describe an easy-to-implement method to create junctions of genetic elements that can serve as DNA template or positive control for the development and validation of detection methods. The new methodology was successfully used to test several pairs of PCR primers intended for the detection of the first transgenic animal approved for human consumption (the AquAdvantage salmon). The junction region was created by the PCR amplification of a genetic element (antifreeze protein gene) with a tailed primer containing part of the adjacent element (growth hormone gene), yielding a PCR product with both regions fused. This strategy can be adapted to create junctions of genetic elements in any transgenic organism if reliable sequence data is available.

A new paradigm for regulating genetically engineered animals that are used as food

Over the past 20 years, transgenic or genetically engineered (GE) plants have been routinely approved for human consumption, with close to 80 varieties successfully navigating the regulatory process. This is in stark contrast to GE animals, where only one has been approved for human consumption: the AquAdvantage salmon (1). The different regulatory trajectories for GE plants and GE animals for food raises the following questions: Why are the two regulatory tracts so different in outcome? Are the differences between GE plants and animals for use as food more significant than the similarities? We suggest that the two situations are more similar than different, that their regulatory paths should be harmonized, and that the regulations for genetically modified animals should be altered on multiple fronts.

New on the Menu: Genetically Modified Salmon

For the first time, the FDA has approved a genetically engineered animal as food—the AquAdvantage Salmon. The agency said the particular genetic modification introduced into the salmon meets the definition of a drug. The fish has a growth hormone gene from a Chinook salmon and a promoter sequence from another edible fish, the ocean pout, which activates the growth hormone gene. The result is an Atlantic salmon that reaches market size much more quickly than traditional farm-raised Atlantic salmon (http://1.usa.gov/1MEDh2k).

美国转基因三文鱼商业化的启示

The US Food and Drug Administration (FDA) announced on November 16, 2015 that the genetically modified AquAdvantage Salmon is as safe to eat as non-GMO salmons. This means that the genetically modified fish has finally been approved by the sole authority in this field-FDA-in the United States, and can now be legally marketed as food. It is worth noting that the world’s first institute to obtain a genetically modified fish was the Institute of Hydrobiology, the Chinese Academy of Sciences, whose research remains, even now, at the forefront of the researches in the world, but has not yet been commercialized. This is a fact that deserves out reflections. The current Chinese legislation on transgenic plants, animals and foods can no longer account for the emergence of new biotechnologies, especially the gene-edit technology. In July 2015, the US President’s Office of Science and Technology Policy sent a memorandum entitled “Modernizing the Regulatory System for Biotechnology Products” to the Department of Agriculture, FDA, and the Environmental Protection Agency, requiring them to produce a draft regulation in one year for further discussion. How to amend Chinese regulations and policies concerning China’s biotechnology industry needs the combined efforts of scientists, legal experts, and government officials, who should conduct comprehensive discussions of and make decisions on the industrialization of biotechnology.

Produire et vendre du saumon transgénique. Délimitations et démarcations d’une marchandise

La Food and Drug Administration américaine est sur le point de remettre son avis sur la commercialisation de l’ AquAdvantage Salmon , un saumon transgénique destiné à la consommation humaine. La création, en cours, de ce marché pose la question des opérations nécessaires pour définir une nouvelle entité bio-légale et pour assurer sa viabilité sur les marchés. Nous éprouvons ici le cadre conceptuel conçu par Javier Lezaun pour analyser la fabrique d’un nouvel objet de gouvernance, en étendant toutefois son usage à la fabrique d’un marché. Cet article explore ainsi les actes de délimitation et de démarcation de l’entité « saumon transgénique » nécessaires à son inscription dans l’architecture juridique américaine, mais aussi les opérations de démarcation issues d’une tension grandissante entre les promoteurs de ce projet et la société civile, toutes nécessaires à sa potentielle commercialisation sur les marchés américains.

IMPLICACIONES DE LA RECIENTE AUTORIZACIÓN DE COMERCIALIZACIÓN PARA EL CONSUMO HUMANO DEL SALMÓN MODIFICADO GENÉTICAMENTE

This article focus on the authorization for AquAdvantage salmon a key event in the process of making decisions about animal products genetically modified to be allowed to be marketed for human consumption purposes. This approval opens the door to new authorizations and it undoubtedly changes completely the relations between law and science, at least as far as biotechnology is concerned. However, to achieve public acceptance is necessary to show that, both health and environmental agency responsible for the evaluation of risks has made a detailed and comprehensive work, with sufficient transparency, which does not seem to be the case. A move that could limit the effect of this rejection of society to these products would be the establishment of a mandatory labeling on genetically modified salmon, similar to that prevailing in the EU for transgenic plants.

Capitalism and the Commodification of Salmon: From Wild Fish to a Genetically Modified Species

On February 25, 2013, the U.S. Food and Drug Administration (FDA) closed the public comment period for the environmental assessment of the AquAdvantage Salmon. Their review of the first genetically modified animal for human consumption concluded with a “finding of no significant impact.” Numerous fishermen, consumer safety advocates, public health officials, ecologists, and risk assessment experts submitted comments that directly challenged this finding. Despite the opposition, it is very likely that the FDA’s approval of this genetically engineered salmon and precedent-setting regulatory process is imminent.… The aquaculture industry and corporate investors are championing this recent development in food biotechnology. They propose that this “invention” will yield ecological benefits, such as preserving wild salmon, while enhancing efficiency.… Unfortunately, the discussion of fisheries and oceans is constrained by ideological justifications that prevent a comprehensive assessment.… [The alternative approach presented here focuses on] how the logic of capital has shaped production and commodification processes. It also highlights how the most recent case of biotechnology in relation to salmon serves the needs of capital by increasing control of biological and ecological systems in order to better conform to economic dictates. The genetic modification of salmon is part of a biological speedup, whereby natural processes are transformed to achieve faster rates of return in the food marketplace.This article can also be found at the Monthly Review website, where most recent articles are published in full.Click here to purchase a PDF version of this article at the Monthly Review website.

Risk Assessment of Genetically Modified Food and Neoliberalism: An Argument for Democratizing the Regulatory Review Protocol of the Food and Drug Administration

The primary responsibility of the US Food and Drug Administration (FDA) is to protect public health by ensuring the safety of the food supply. To that end, it sometimes conducts risk assessments of novel food products, such as genetically modified (GM) food. The FDA describes its regulatory review of GM food (of both the plant and the animal variety) as a purely scientific activity, untainted by any normative considerations. This paper provides evidence that the regulatory agency is not justified in making that claim. It is argued that the FDA’s policy stance on GM food is shaped by neoliberal considerations. The agency’s review of a genetically engineered animal, the AquAdvantage salmon, is used as a case study to track the influence of neoliberalism on its regulatory review protocol. After that, an epistemic argument justifying public engagement in the risk assessment of new GM food is outlined. It is because risk evaluations involve normative judgments, in a democracy, layperson representatives of informal epistemic communities that could be affected by a new GM food should have the opportunity to decide the ethical, political or other normative questions that arise during the regulatory review of that entity.

Education in the age of biocapitalism: optimizing educational life for a flat world

Introduction: Biopolitics and Education: A Return to the Question of Life in Schools PART I: ORIGINS OF EDUCATIONAL BIOCAPITAL 1. Learning to be Homo economicus on the Plantation: A Brief History of Human Capital Metrics 2. Schooling for Value-Added Life: The Making of Educational Biocapital PART II: PROMISSORY FUTURE(S): LEARNING THE SCIENCE OF LIFE 3. Engineering Promissory Future(s): Rethinking Scientific Literacy in the Era of Biocapitalism 4. Learning about AquAdvantage(R) Salmon from an ANT: Actor Network Theory and Education in the Postgenomic Era PART III: GOVERNING STUDENTS FOR A FLAT WORLD AND ALTERNATIVES 5. The Biomedicalization of Kids: Psychotropic Drugs and Biochemical Governing in High Stakes Schooling Epilogue: Alternative Futures of Education: Exiting Education for Biocapital

The Tragedy of the Commodity and the Farce of AquAdvantage Salmon®

The US Food and Drug Administration is expected to approve AquAdvantage Salmon as the first genetically modified animal for human consumption. The genetic modifications allow the proprietary fish to grow at a rate twice as fast as a wild salmon, leading to greater ‘efficiency’ in terms of reduced costs and reduced time to market. This article provides an analysis of the ways in which AquAdvantage Salmon exemplifies capitalist market forces controlling and guiding the terms of salmon recovery and conservation. The authors trace historical developments within the salmon industry to demonstrate how capitalist commodity production has impacted fishing communities. They reject the oft-cited ‘tragedy of the commons’ hypothesis offered to explain fisheries crises. In its place, they offer the conceptual framework of the ‘tragedy of the commodity’ to explore how capitalist market forces and complicit state regulations amplify rather than resolve global environmental problems.

Transgenic salmon: a final leap to the grocery shelf?

Despite being caught up in regulatory proceedings for 15 years or more, AquAdvantage salmon, the first animal genetically engineered (GE) for food purposes, continues to raise concerns. Are any of these concerns scientifically justified?