report

AquAdvantage® Salmon: A Case Study in the Development and Approval of Transgenic Aquatic Organisms

One approach to the genetic improvement of aquatic organisms that has emerged as a discipline in its own right over the past two decades is transgenesis, the transfer of foreign genes into new hosts. C. Greg Lutz

ransgenic fishes (or mol- instantaneous gains in many types pacts of genetically modified aquat- result of many years of diligence vantage Salmon is an important step Since this would be the first GM ani- luscs or crustaceans) can of important production traits such ic organisms on natural systems. As and perseverance, and at many times in this direction.” mal suitable for human consumption be defined as possessing as growth, cold tolerance, or disease a result, resource managers, politi- in the process it seemed virtually In 1989, AquaBounty developed to be submitted for FDA approval, within their chromosomal resistance may be possible. The po- cians and bureaucrats are reluctant unattainable. Jack A. Bobo, Senior AquAdvantage® salmon, a genetically the company initially faced an uphill TDNA, either directly or through in- tential problems, however, are also to even attempt to develop proto- Vice President and Chief Com- modified Atlantic salmon (Salmo sal- battle in terms of generating scien- heritance, genetic constructs which impressive: labor- and capital-inten- cols for the use of these organisms munications Officer at Intrexon, a ar), by inserting a gene from the Chi- tific data required to meet regula- have artificial origins. The key word sive methodologies and consumer in situations where inadvertent re- US-based company nook (King) salmon (Oncorhynchus tory concerns, and subsequently to for researchers, producers and even distrust of genetically engineered leases could occur. and Aquabounty’s main shareholder, tshawytscha), coupled to DNA frag- encourage opponents to accept the consumers here is within the chro- products in many nations. Another One (and probably the only) stated “The U.S. Dietary Guidelines ments from the coldwater marine science in the decision-making pro- mosomal DNA: introduced con- major constraint to the widespread case study of transgenic organisms Advisory Committee encourages fish Ocean Pout (Zoarces americanus). cess. For some time now, the U.S. structs are incorporated into the tar- adoption of transgenic stocks in in aquaculture involves the com- Americans to eat a wide variety of This modification allows specimens Food and Drug Administration has get organism in such a way as to be aquaculture involves regulatory re- pany AquaBounty Technologies. In seafood —including wild caught and to reach smolt size and commer- been in ‘the final stages’ of review- expressed and passed along to sub- strictions on stocking and culture of a press release dated November 19, farmed— as part of a healthy diet cial size in half the time required ing AquaBounty’s dossier and applica- sequent generations. genetically modified organisms. Due the company announced that the rich in healthy fatty acids. However, by traditionally farmed salmon. For tion for approval of the AquAdvan- The potential pay-offs for uti- to a lack of performance data, it is FDA had approved the production, this must occur in an environmen- many years, AquaBounty has fought tage® salmon. lizing this type of technology in usually quite difficult to assess (or sale and consumption of its trans- tally friendly and sustainable man- to bring their genetically modified In anticipation of an FDA ap- aquaculture are high: rapid, almost even speculate on) the potential im- genic salmon. This approval was the ner. FDA’s approval of the AquAd- (GM) salmon to the marketplace. proval, some groups have expressed

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technologies. In the U.S., one final step before the FDA could issue a formal approval was the public com- ment process for the draft Environ- mental Assessment and preliminary In 1989, AquaBounty Finding of No Significant Impact. ® This was also completed in 2013. developed AquAdvantage After compiling all the responses, it salmon, a genetically was expected that an FDA approv- al or rejection would be released at modified Atlantic some point in 2014. salmon (Salmo salar). Politics, and opponents unwilling to allow the scientific review process to follow its proper course, put the status of AquAdvantage® salmon in ® limbo for several years. Due to the AquAdvantage fish will pose no genetic threat to wild salmon. Photo courtesy NOAA. delays in the regulatory approval of the product, the company almost depleted its initial capital. The com- pany reported net losses of $4.7 concerns about commercialization million for 2013, following losses of the product in spite of company of $4.4 million in 2012. Losses re- assurances that its salmon will com- ported for 2011 and 2010 were $2.7 ply with the sterility levels required million and $5.3 million, respective- by the FDA. The regulatory appli- ly. Nonetheless, financial prospects ® cation for AquAdvantage salmon have improved since Intrexon be- production includes a manufactur- came AquaBounty’s main sharehold- ing site for egg production in Can- er. Intrexon has a broad portfolio of ada, and a grow-out site in Panama. technology and bio-molecular ap- The agency’s approval would allow plications, and funded a short-term AquaBounty to send eggs to Panama, bridge loan to support operations and products harvested there could through mid-2015. then be imported and marketed in The company is banking on eco- the USA. The company assures they nomic and environmental incentives Closed containment design. Courtesy of DFO Canada. have taken all the necessary precau- tions in the design and production process to ensure a safe, healthy and environmental risk-free product. In 2013, Environment Canada determined that the company’s salmon would pose no significant threat to the environment or human health when produced in contained facilities, clearing the way for the egg production component of the com- pany’s plans. The agency reached this conclusion following a risk as- sessment conducted by the Depart- ment of Fisheries and Oceans Cana- da, involving a panel of independent scientific experts in the fields of transgenics and fish containment

A close view of salmon eggs and developing salmon fry. Courtesy of USFWS.

8 » » 9 report FDA, 7,000 eggs from 20 families to be clearly marked at the point of salmon will hold the same nutri- were individually analyzed, using flow sale. Similarly, the U.S. Senate Ap- tional and biochemical properties cytometry. Of those 20 crossings 14 propriations Committee adopted an as conventional farmed salmon, so were found to be 100% triploid, and amendment sponsored by Senator apart from any stigma associated the overall average was 99.85%. In Lisa Murkowski of Alaska, requiring with a genetically enhanced product, addition, 100% of AquAdvantage® mandatory labelling of GM salmon. they may accept it and enjoy it like salmon are mono-sex (all female), A number of arguments against any other farmed salmon. so that they cannot establish re- AquAdvantage® salmon were pub- As has been shown in the case of productively active, self-sustaining licized in the resulting discussion, AquAdvantage® salmon, sound sci- populations. In many salmonid spe- none of which were scientifically ence is only a part of the regulatory cies, females are considered superior sound. At the time AquaBounty’s process when it comes to GM organ- (and more efficient from a bio-eco- CEO, Dr. Ronald Stotish, stated that isms. Future GMO applications sub- nomic perspective) in most produc- “The amendment appears to be an mitted to the FDA will be handled tion traits. Since sex in salmonids is attempt to usurp legal authority for on a case by case basis, and it is im- based on female homogameity (as is food labelling from the FDA where possible to predict their outcomes, Land-based production in Naimo Canada. the case with humans), which we can it has resided historically. More im- but now that AquaBounty’s applica- refer to here as an XX state, it is pos- portantly, it appears to be an attempt tion is finally approved it could give sible to produce all-female stocks by to utilize labelling as a weapon for hope to other GMO producers. mating normal female salmon with protection of economic interest.” XX ‘males’ produced through hor- Murkowski was widely considered PEI-Hatchery-Fish-Tanks. Courtesy of Aquabounty. to use GM salmon, due to its im- monal masculinization of normal to be acting to protect the interests proved growth and feed conversion XX fry. of wild salmon fisheries in her home to deal with resistance in the market- based RAS systems that are specially Dr. C. Greg Lutz has a B.A. in and Spanish by the ratio (FCR) characteristics. Studies Like all Atlantic Salmon, AquAd- state. ® Earlham College at Richmond, Indiana, a M.S. in Fisheries carried out by the company suggest vantage® salmon cannot breed with The relationship between price, place, at least initially. Presumably, designed for AquAdvantage salmon and a Ph.D. in Wildlife and Fisheries Science by the Loui- AquAdvantage® salmon will have a culture, the company estimates that siana State University. His interests include recirculating that producers may obtain a lower any of the five species of Pacific sustainability and consumer accep- system technology and population dynamics, quantitative lower production cost than tradi- producers could save up to $1-1.50/ and multivariate analyses and the use of web FCR (20-25%), and more efficient salmon, including Coho Salmon. tance presents a complicated balance ® based technology for result-demonstration methods. utilization of dietary protein. Both Therefore, the combination of trip- in the case of AquAdvantage® salmon. tional farmed salmon. By using land- kg. For end users, AquAdvantage would have direct environmental loidy, monosex populations and When one considers the overall envi- benefits. The company has also cit- natural reproductive incompatibility, ronmental impacts in terms of con- ed a number of other potential im- as well as multiple containment bar- tainment and conversion efficiency, provements to sustainability. Because riers built into culture centers, mean many of those criticizing these GM AquAdvantage® salmon will be raised that the reproductive interaction be- fish apparently have not considered only on land-based systems, this will tween AquAdvantage® salmon and that they may be “cutting off their hopefully contribute to increase the wild salmon stocks would be essen- nose to spite their face.” However, adoption of closed systems such as tially zero. No accidents like we saw those producers who want to work RAS. Additionally, scientific applica- in Jurassic Park. with a salmonid with accelerated tions incorporated into the product, AquAdvantage® eggs will be la- growth and reduced FCR will have as triploid, monosexed populations, beled as genetically engineered may be more easily transferred to Atlantic Salmon; this label will be conventional aquaculture species, in implemented on each batch to be order to protect both the environ- marketed. However, the company ment and the intellectual property has no power to control how cus- of genetic improvement companies. tomers and distributors will label The use of a more efficient, high- their final products. Opponents The percentage efficiency turnover fish such as AquAdvantage have focused on this aspect of the of triploid induction in salmon might be the key to making market chain as a means to pre- land-based salmon culture economi- vent the commercialization of fish general has been reported ® cally sustainable. like AquAdvantage . For example, to exceed 99% According to the company, vir- although voters in Washington re- tually all AquAdvantage® salmon are jected mandatory labelling of genet- triploids. The percentage efficiency ically modified organisms in 2013, of triploid induction in general has Rep. Cary Condotta introduced a been reported to exceed 99%. In the bill the following year that would re- validation study submitted to the quire genetically engineered salmon

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