State of Green Business

How genetically engineered salmon swims onto our plates

This story first appeared in bioGraphic, an online magazine from the California Academy of Sciences.

One day in 1992, a technology entrepreneur sat down for a meeting with two biologists studying the genes of fish. The scientists, Choy Hew and Garth Fletcher, were working on a method of purifying "antifreeze proteins" that would help Atlantic salmon (Salmo salar) survive so-called superchill events in the North Atlantic. Normally these salmon migrate out of the sub-zero ice-laden seawater of the far North Atlantic to overwinter in less frigid waters. Increasingly, though, such fish were being farmed, penned year-round in offshore cages, in near-Arctic waters to which they were not adapted. Fish farmers were looking for a way to keep the fish alive through the winter, and the antifreeze protein seemed like a possible solution.

As the meeting drew to a close, Fletcher and Hew showed Elliot Entis, the entrepreneur, a photo of two fish of equal age. One dwarfed the other. "I sat back down," Entis recalled recently.

Fletcher and Hew, it turned out, had not just been putting antifreeze proteins into Atlantic salmon. They also had figured out a way to add a growth hormone from Chinook salmon (Oncorhynchus tshawytscha), plus a fragment of DNA from the ocean pout (Zoarces americanus), an eel-like creature that inhabits the chilly depths off the coast of New England and eastern Canada. This genetic code acts like an "on" switch to activate the growth hormone. The result was a genetically engineered superfish that grew nearly twice as fast, on less food, as conventional salmon.

AquaBounty
<div class="wp-caption aligncenter"><p class="wp-caption-text">The rapid growth rate of a genetically engineered AquaBounty salmon (left) is obvious when compared to a non-<span class="caps">G.E.</span>&nbsp;salmon of the same age.</p></div>

Those salmon, grown and marketed by a company called AquaBounty Technologies founded by Entis, could be coming to United States grocery stores next year. And they could offer a way out of the deadly spiral of overfishing that is decimating wild fish stocks.

Open-ocean fishing for wild species is no longer sustainable; it hasn’t been for a long time. While some of the most damaging forms of industrial fishing have been outlawed over the years, a combination of continued overfishing, habitat destruction and warming oceans dramatically has reduced salmon populations. According to the Northwest Fisheries Science Center, of the 17 distinct populations of Pacific salmon, all are considered either "in danger of extinction" or "likely to become endangered." Atlantic salmon, too, have been battered by commercial overfishing, climate change and cross-contamination by farmed salmon and the resulting spread of disease; according to a 2001 WWF report, their population fell by more than 75 percent between 1984 and 2001.

At current rates, according to a 2006 article in the journal Science, the world will run out of all wild-caught fish by mid-century.

Genetically engineered fish could provide a solution, taking the pressure off wild stocks and reducing the energy and carbon emissions required to feed the world’s seafood appetite. Because AquaBounty’s salmon are sterile and raised in land-based tanks, they can’t breed with wild populations. And because they efficiently convert fish feed into edible protein, they offer a potential low-cost solution for nourishing not only affluent consumers in North America but hungry people in the developing world with little access to meat.

But there is something about genetically engineered fish that many find uniquely disturbing. In a 2013 poll by the New York Times, 75 percent of respondents said they would not eat genetically modified fish. (That number dropped to two-thirds for other forms of G.E. meat.) The nation’s largest grocery chains, including Safeway and Kroger as well as Whole Foods and Trader Joe’s, have signed a statement saying they will not sell genetically modified fish.

There is also a tangle of bureaucratic red tape to get through before G.E. fish finds its way into U.S.  grocery stores. The U.S.Food & Drug Administration approved AquaBounty salmon for sale more than two years ago, in November 2015. But an obscure rider attached to a budget bill by Alaska senator Lisa Murkowski the next month effectively blocked the FDA from allowing G.E. salmon into the U.S. That import ban still stands.

It’s a strange paradox: If you could get the fish here, you could sell them; but you can’t legally bring G.E. salmon into the country.

Undeterred, in June, AquaBounty, headquartered in Maynard, Mass., purchased a land-based fish farm near Albany, Indiana. If the import ban can be overturned, enabling the company to bring in transgenic eggs produced in Canada, AquaBounty could begin raising fish there sometime this year. That means the company’s salmon could be on sale in the U.S. by 2019, which would make it the first genetically modified animal food sold and eaten in this country.

Opposition, naturally, is fierce. But to AquaBounty CEO Ron Stotish, bringing superfish to global markets is not just a promising business opportunity; it also has the potential to change an industry.

"We are providing technology to improve food production and make it sustainable," Stotish said. This, he said, will put society in a better position "to address the global food security issues we’ll face as the world’s population approaches 10 billion."

Eager to see how AquaBounty got to this point and what the future of fish farming might look like, I travel to the company’s hatchery at Bay Fortune, on Prince Edward Island. The island — known as PEI  forms an arc in the southern Gulf of St. Lawrence, just off the coasts of New Brunswick and Nova Scotia. Driving out from Charlottetown to the far eastern peninsula, we pass small, picturesque fishing villages and tidy farms flying Canadian flags. AquaBounty’s lab and hatchery is a metal-sided, two-story building, painted the cheery shade of ocean blue that has become the company’s trademark color. Belying the research and engineering under way inside, the exterior looks more like a roadside warehouse than a lab for mad fish science.

Inside, in big green fiberglass tanks, swim the salmon: conventional and transgenic in separate tanks, each fish individually microchipped. Called "AquAdvantage Salmon" in the company’s marketing materials, the G.E. fish are more than twice the size of conventional fish at 12 months of age  around 2.2 pounds compared to 0.7-0.9 pounds for the regular salmon.

This is Fletcher and Hew’s innovation, pictured in the photo they showed to Entis 25 years earlier. Entis, whose father ran one of the first companies to import farm-raised salmon from Norway, had seen a revolution in the making: "The first thing I thought was, 'My God, these guys don’t know what they’re sitting on.' To raise fish in half the time, that has enormous implications. I pretty quickly realized that this is the kind of massive breakthrough that could be critically important to an entire industry."

What Entis didn’t realize at the time was just how long it would take to bring that breakthrough to market — nor that he would no longer be there to see it through. Along the way, both Entis and Fletcher — who joined the company in 1994 — were ousted.

In 2012, the company’s primary investor, Kakha Bendukidze, a biologist and entrepreneur who had served as minister of economy in the former Soviet Socialist Republic of Georgia, lost patience and pulled out. AquaBounty was close to collapse before receiving a $6 million investment in 2012 from Intrexon Corp., a synthetic biology company.

Today, AquaBounty’s fish are available in Canadian grocery stores. Five tons were sold there in 2016 without being labeled as such. Canada has no law that requires labeling of genetically modified seafood.

Back in the Bay Fortune hatchery, the transgenic fish patrol the tanks ceaselessly, the only sound the occasional splash as one breaks the surface, thinking we might have food. The salmon are stippled and banded in endless shades of gray, silver and black, with occasional flashes of green. Evolved to travel hundreds of miles from their freshwater spawning grounds to the open ocean and back, these fish will live out their existences in these tanks, fed by constantly circulating filtered freshwater, never leaving this building.

Facility manager Dawn Runighan shows me the miniature tanks where the baby fish are raised, and the grow-out area where they reach maturity. There are big bags of fish feed, and canisters of sperm lined up like old-fashioned milk tanks. In another room are tubular incubators containing the eggs that will become superfish. If I were expecting a high-tech sanctum where Faustian scientists use supercomputers to meddle with the building blocks of nature, what I found was more quotidian: a few technicians in rubber boots moving equipment around and checking water levels. Much of the space in an adjoining room is taken up by an elaborate, three-phase filtration system that includes settling tanks, "bio-beads" impregnated with organisms that remove ammonia and organic matter from the water and finally an ultraviolet-light filter to finish the cleansing process. "It’s basically a wastewater treatment plant, with fish," cracked Runighan.

Alexi Hobbs/AquaBounty
<div class="wp-caption aligncenter"><p class="wp-caption-text">Young AquaBounty salmon spend their first weeks of life in these early grow-out tanks at the facility in Bay Fortune, Prince Edward Island.</p><p></p></div>

Upstairs is a lab where quality control and R&D on the company’s proprietary gene technology take place. A white-coated technician dips a pipette and fills tiny tubes in a rack. These will go into a machine that multiplies copies of a specific sequence of DNA for later analysis. No actual gene-splicing goes on at Bay Fortune. In fact, none has gone on for 13 generations of AquaBounty salmon, dating back to a single ancestor fish that reproduced and died in 1992. Each descendant carries a copy of the genetic construct that combines the Chinook growth hormone gene with the promoter gene from the ocean pout.

"Today," said company spokesman Dave Conley, "we are in the business of breeding fish."

It’s a messy business. At spawning time, conventional females are milked of their eggs by hand, a method that requires two fish wranglers per female — one to handle the fish and another to hold the container that collects the eggs. The technicians use the same squeeze technique to extract semen, or "milt," from the males.

To prevent uncontrolled reproduction of genetically engineered fish, AquaBounty produces only transgenic females for market. To avoid the possibility of male eggs being produced, the male fish that produce the milt are actually "neomales": female fish that have undergone a sort of piscine sex change. Exposed to testosterone when juveniles, they produce milt that contains only female sex chromosomes. This is a common technique in aquaculture. When the sperm from neomales is used to fertilize the eggs (also with female sex chromosomes), only female fish can result.

When combined, the eggs and milt produce fertilized eggs. The technicians place the developing embryos in a stainless-steel tube where they are subjected to high pressure. This renders all the embryos’ cells triploid, meaning they have three sets of chromosomes instead of two, which makes the fish incapable of reproducing — another biological barrier to the spread of transgenic salmon in the wild.

After a period of incubation at the Bay Fortune hatchery, the sterile, all-female transgenic embryos are flown to a rearing facility in the highlands of Panama, where the resulting salmon are grown to maturity before being re-imported into Canada. (According to Conley, Panama was selected because the president of the company at the time had contacts there and the cost of building a facility was far less than it would have been in North America.) Eventually, AquaBounty plans to produce market-ready fish at a new facility under construction at Rollo Bay, on Prince Edward Island, and at the Indiana facility — an existing fish production factory that belonged to a now-defunct aquaculture company.

The key fact about all of these places, existing and under construction, is their location: They are on land. Nearly all other aquaculture takes place in ponds, lakes or the sea — in pens designed to keep farmed fish in and wild ones out. Unlike fish produced using this conventional approach, AquaBounty salmon have no chance of escaping into wild habitats. That was key to the company’s application for approval by the FDA. But land-based aquaculture is expensive, and many previous attempts have failed. Finding cost-efficient ways to maintain water temperature and quality at levels needed to grow healthy fish — things nature does for free — is critical to AquaBounty’s business success.

Alexi Hobbs/AquaBounty
<div class="wp-caption aligncenter"><p class="wp-caption-text">Genetically engineered salmon grow up fast inside the AquaBounty facility on Prince Edward Island.</p><p></p></div>

"We saw the convergence of these two technologies: the improved biology of the fish, and the improved technology of contained aquaculture systems," said Stotish, a former pharmaceutical executive. He said the company has "altered the economics of growth and production."

Producing salmon in Indiana, Stotish pointed out, would eliminate the need for long-distance flights that carry frozen fish from overseas farms to the U.S. market. Producing fast-growing fish on land reduces the amount of food and energy required to grow a given volume of food, while also reducing the use of fungicides, antibiotics and pesticides that are prevalent in conventional aquaculture. AquaBounty’s scientists said they have devised a sustainable, environmentally friendly and economical way of producing high volumes of healthy seafood, without the environmental risks of conventional aquaculture.

Most scientists who have studied the matter concur — and believe that the significance of AquaBounty salmon extends far beyond the fishing industry. A 1992 article in Nature Biotechnology by Fletcher, Hew and five other scientists laid out the evidence behind the company’s claims, and since then those claims have been validated by a number of other studies. An article published in the journal Aquaculture in 2013 (by seven scientists independent of the company) concluded that transgenic AquAdvantage salmon had higher feed-conversion ratios, retained nitrogen more efficiently and achieved their target weight 40 percent faster than conventional Atlantic salmon fed the same diet.

"In 20 or 25 years we’re all going to be eating genetically modified animal products," said Eric Hallerman, a professor of marine biology at Virginia Tech who served on an expert panel that reviewed AquaBounty’s technology for the FDA application. "What’ll make it attractive to producers is the benefit to consumers."

That potential benefit has not allayed the concerns of the vocal movement opposed to GMOs in general and to genetically engineered "Frankenfish" in particular.

Humans have been consuming salmon virtually since we first arrived in North America, and salmon have become deeply intertwined with both the cultures and the ecosystems of the places where they thrived. Indeed, salmon in many ways shaped both the civilization and the environment of those places. And salmon have been an intensely managed food source all along.

"The anadromous fish resource was perhaps the most intensely managed and ecologically manipulated food resource among these aboriginal societies," wrote anthropologists Sean Swezey and Robert Heizer in a 1977 study.

"Ecological manipulation" is a good description of today’s salmon market. Even the wild salmon fishery of Alaska is helped along by human intervention: Each year the Department of Fish and Game releases nearly 2 billion juvenile salmon spawned in hatcheries into the waters of Prince William Sound and southeast Alaska. In 2015 Alaskan fishermen caught 93 million hatchery-born salmon, more than one-third of the total harvest of 263 million. Salmon stocks in the northern Pacific have recovered since bottoming out in the 1970s; that would not have happened without the coastal hatcheries.

U.S. imports of salmon totaled 339,000 metric tons in 2016, worth more than $3 billion. The vast majority of that came from farmed Atlantic salmon raised in floating cages off the coasts of Canada, Chile, Norway and Scotland, and flown into the U.S. According to SINTEF, an independent research institute in Norway, accounting for feed, aquaculture and energy to freeze and transport the fish, 2.2 pounds of farmed salmon eaten in Paris or New York produces the equivalent of 6.4 pounds of CO2 emitted into the atmosphere. A 2016 paper in Aquaculture Engineering found that the carbon footprint of salmon produced in land-based closed systems, such as AquaBounty’s, is less than half of that of salmon produced in conventional fish farms in Norway and delivered to the U.S. by air.

AquaBounty
<div class="wp-caption aligncenter"><p class="wp-caption-text">The eyespots of developing embryos are clearly visible inside these fertilized salmon eggs.</p></div>

But carbon footprints don’t pack the emotional punch of cultural legacy. "The Coast Salish people have organized their lives around salmon for thousands of years," Valerie Segrest, project coordinator for the Muckleshoot Food Sovereignty Project, said in a 2017 statement. The group is based at the Northwest Indian College in Bellingham and works to preserve access to traditional foods. The Salish fear that G.E. salmon could wreak environmental havoc with native species, and that the combination of genetic engineering and aquaculture finally could overwhelm the traditional fishing methods that they still carry out. "Corporate ownership of such a cultural keystone is a direct attack on our identity and the legacy our ancestors have left us."

In July 2016, the Quinault Indian Nation joined a lawsuit put forth by environmental groups and recreational fishermen that March. It challenged the FDA approval, saying the agency "has not adequately assessed the full range of potentially significant environmental and ecological effects presented by the AquaBounty application." That lawsuit is still pending. Led by the Center for Food Safety, anti-GMO activists are concerned that G.E. salmon could threaten native species if some piscine Houdini escaped and spread its transgenic kind in the wild.

But scientists who have followed AquaBounty’s long road to regulatory approval believe that the quarter-century process signals a flawed and politicized approval mechanism. The delay "sends the message to the rest of the world that the science-based regulatory oversight as embodied in the FDA review process is subject to political intervention," testified the late Calestous Juma, of Harvard’s Kennedy School of Government, in a 2011 hearing before the House Agriculture Committee’s Subcommittee on Rural Development, Research, Biotechnology and Foreign Agriculture. "Furthermore, it signals to the world that the U.S. may cede its leadership position in the agricultural use of biotechnology."

According to the scientific panel that reviewed the evidence submitted by AquaBounty to the FDA, the genetically engineered salmon "is as safe as food from conventional Atlantic salmon, and … there is a reasonable certainty of no harm from the consumption of food from this animal."

The agency concluded that because AquaBounty salmon is "not materially different from other Atlantic salmon" — meaning it is nutritionally and chemically indistinguishable — no additional labeling was required.

In the early 2000s, William Muir, a professor of genetics at Purdue University and a pioneer in the risk analysis for G.E. fish, and his colleague Richard Howard developed a quantitative model to assess risks associated with the other major fear about G.E. salmon: escape.

In simple terms, Muir’s method quantifies the probability of an escaped transgenic fish interbreeding in the wild, and the level of harm it would cause if that should happen. The first part is itself the product of two factors: "the probability of the organism escaping into the wild, dispersing and becoming feral" and the ability of the new gene to spread.

If either of those terms is zero, according to the model, the risk of environmental damage from transgenic fish farming is zero. It’s a simple matter of multiplication. "If it can’t escape, then don’t worry about it," Muir said. "Or if it escapes and then can’t proliferate, don’t worry about it."

By raising the fish on land, in contained tanks, far from cold-water environments, AquaBounty has reduced the risk of escape to near zero (unlike conventional aquaculture, where the farmed fish can and often do escape into the wild). The second factor — the risk of an escaped fish spreading its genetic material — also should be zero, because AquaBounty produces sterile, triploid females. Even if these fish did escape, wild salmon couldn’t successfully breed with them, so they wouldn’t be able to reproduce and persist in the environment. In contrast, when a net pen containing conventional farmed salmon breaks, the escapees can overwhelm an environment with their sheer numbers, and because they’re fertile, they can interbreed and bring down the fitness of native salmon.

"In my view, the risk of harm from G.E. salmon as developed and managed by AquaBounty is less than that of farmed salmon," said Muir, who is now retired.

Alison Van Eenennaam, an animal genomics and biotechnology specialist at the University of California, Davis, who served as a subject-matter expert for the scientific panel that evaluated AquaBounty’s FDA application, said that conventional farmed fish carry different, and arguably higher, risks. "Conventionally bred Atlantic salmon undergo no food safety tests, grow faster as a result of selective breeding, are fertile and are raised in ocean net pens where they can escape to the ocean and transmit/acquire diseases and parasites," she said.

Like most scientists who have examined the matter, Hallerman dismisses the claim that G.E. salmon pose a threat to existing fisheries: "This technology has been sitting on the shelf for way too long. People want more meat and this is a way to get it to them."

But not all scientists agree with this consensus. In 2013, after the FDA issued its draft environmental assessment of the AquaBounty breeding program, Anne Kapuscinski, a professor of sustainability science at Dartmouth College, and Fredrik Sundstrom, an assistant professor of ecology and genetics at Uppsala University in Sweden, submitted comments criticizing the agency’s finding of "no significant impact."

The two scientists wrote that they "found major scientific inadequacies" in the assessment. Among their many concerns was that while the risk of exposure to the open sea and harm to the marine environment from G.E. salmon is probably low at the existing PEI and Panama sites, those facilities are only the first of many probable hatcheries and production farms — and there is no guarantee that other locations will maintain the same standards.

"The future of G.E. fish farming will surely involve larger fish farms, with less confinement, in many different environments," wrote Kapuscinski and George Leonard, chief scientist at the Ocean Conservancy, in a 2015 opinion piece. The risks posed by those hypothetical future farms are harder to determine.

Meanwhile, Murkowski, whose legislation is at this point the only remaining legal obstacle for AquaBounty in the U.S., has said allowing G.E. salmon would amount to "messing with nature’s perfect brain food." In July, vowing to continue her "years-long fight against 'Frankenfish,'" Murkowski introduced the Genetically Engineered Salmon Labeling Act, which not only would require plain-English labels for G.E. salmon but also would mandate a review of the FDA’s procedures for approving AquaBounty’s fish. AquaBounty officials say they have no problem with labeling their fish, if regulations require it; but Murkowski’s bill, co-sponsored by senators from Washington and Oregon, effectively would maintain the ban on AquaBounty salmon in the U.S. market.

Ultimately, the future of AquaBounty’s superfish most likely will hinge more on marketing than on legal challenges. Will grocers carry the fish, and will consumers buy it? If the answer to those questions is yes, the sustained outcry over G.E. salmon ultimately will matter little. Muir pointed out that research on transgenic fish is proceeding worldwide, regardless of what happens with AquaBounty salmon in the U.S. market. Scientists in Cuba and the United Kingdom have engineered tilapia to add weight three times faster than normal fish. A mud loach developed in South Korea can grow up to 35 times faster than conventional varieties.

At the end of my visit to Bay Fortune, I sat in the small company kitchen with Stotish and the AquaBounty staff and enjoyed some smoked salmon, grown in AquaBounty’s indoor fish farm and prepared by a local chef. It was delicious. I could not have told it from conventional salmon.

Stotish hopes that Murkowski’s import ban will be dropped in an upcoming appropriations bill, should Congress ever manage to agree on a budget. He won’t say much about AquaBounty’s future plans for worldwide production, other than to mention that he’s talked to more than one Asian fish supplier who is interested in growing and marketing AquaBounty salmon. The U.S. market may be important to AquaBounty’s success as a company, but Stotish is working in other places where the opposition to G.E. seafood is less pitched and less political. In other words, whether AquaBounty ever gets to sell its fish in the U.S. ultimately may be moot, in terms of the future of G.E. aquaculture.

Meanwhile, AquaBounty’s new indoor aquaculture facility at Rollo Bay, on PEI — two warehouse-sized buildings with enough space for more than 88,000 cubic ft of fish tanks — is nearing completion. It will supply 13 million to 15 million eggs a year when it reaches full capacity. The company expects to be producing eggs there by the second quarter of 2018.

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