This is a true Canadian tale of two genetically modified animals and the efforts to have them end up one day on our dinner tables.
The story starts in 1989 with Garth Fletcher and Choy Hew, two scientists at Memorial University who collaborated in creating a genetically modified Atlantic salmon that grew to market size in half the time of conventional salmon. The fish required less feed and promised to make salmon farming more profitable. At one year old, the largest specimen was 13 times bigger than the average Atlantic salmon. In 2010, Time magazine belatedly named it one of the best 50 inventions of that year, while Greenpeace activists nicknamed the transgenic wonder “Frankenfish.”
A decade after the fish was built, in 1999, University of Guelph biology professor Cecil Forsberg created a pig that was cleverly engineered so that its poop contained less phosphorus. Thus, any runoff from farms where the pigs were raised or from fields spread with their manure, as is often the practice, would be less polluting to the local watershed. The professor called this high-tech, low-polluting oinker Enviropig, touting his invention, in effect, as a pig that protects fish.
In the end, the pig made little headway over public objections, while the salmon continues to swim upstream through the regulatory waters. Last December, the U.S. Food and Drug Administration released a draft environmental assessment of the GM salmon, which concluded that it would have no significant impact on the environment. This was followed by a public consultation phase that ended in April and is essentially the final step before the FDA decides whether to approve the salmon for sale to consumers. The agency already declared in 2010 that the fish was safe for human consumption.
If the FDA eventually rules that the GM salmon can be raised and sold as food in the United States (the outcome is still far from certain), the decision will open the floodgates to the commercial development of GM animals.
“It’s a technology that works, and half the world is waiting to see what the FDA will do,” says Dr. Fletcher, now a professor emeritus and head of the department of ocean sciences at Memorial. “If our salmon is approved, the regulatory path will be set and it will open the door for other academics and companies working on animals such as fish, chicken or pigs.”
The stakes are enormously high for proponents and opponents of GM animals raised for food. Here’s why the pig lost and the fish may yet win despite the formidable hurdles in gaining regulatory approval and social acceptance.
Both the pig and the fish were leading-edge scientific successes. With pinpoint precision, Dr. Forsberg and his Guelph colleagues tweaked the genetic makeup of a conventional pig so that its salivary glands produced a phytase enzyme that cut the amount of phosphorus in its manure by half. They accomplished this technological feat by injecting a transgene from an E. coli bacterium and a mouse into a normal pig embryo. Their groundbreaking paper, “Pigs expressing salivary phytase produce low-phosphorus manure,” was published in Nature Biotechnology in 2001.
The Guelph scientists showed the transgene could be passed on reliably, breeding 10 generations of Enviropigs with their enhanced digestive capabilities. The pigs were remarkably healthy, reaching market weight 10 days sooner than conventional hogs, and the technology promised to lower feed costs since the pigs wouldn’t need dietary phosphate or enzyme supplements to help break down phosphorus in the gut.
As for the fish, Drs. Fletcher and Hew started out by adding an antifreeze protein gene from a winter flounder to produce strains of Atlantic salmon for farming that could survive in frigid waters. The gene transfer worked, but the salmon didn’t make enough antifreeze. Inspired by an image of the first gigantic transgenic mouse featured on the cover of Nature, they got the idea to engineer instead a fast-growing salmon that would appeal to the aquaculture industry. “If they can do it in a mouse, why can’t we do it in a fish?” Dr. Fletcher said to Dr. Hew.
The two scientists created the super-salmon by injecting Atlantic salmon eggs with a newly constructed all-fish growth hormone gene, which caused the fish to make growth hormone throughout the year instead of only in summer. They did this by splicing the coding region of the growth hormone gene from a warm-water Chinook salmon with the promoter (on-switch) region of the antifreeze gene from ocean pout, an eel-like fish. “The growth we saw in the salmon was absolutely phenomenal. The faster you can produce the fish, the more money you can make,” says Dr. Fletcher. Their research findings also were first published in Nature Biotechnology, in 1992.
The fish scientists hooked up with a business-savvy, risk-ready commercial partner. With financial support from the Natural Sciences and Engineering Research Council, Drs. Fletcher and Hew licensed the technology in 1992 to Elliott Entis, an entrepreneurial American in the aquaculture industry who had the vision, business acumen and marketing flair needed to sell the idea to investors.
AquaBounty Technologies, a Boston-based company, was formed to commercialize the GM salmon in 1994 and filed an Investigational New Animal Drug application with the FDA the next year. In 2006, the company raised about US$37 million through an initial public offering on the London Stock Exchange. To date, AquaBounty has reportedly spent US$60-million in its 18-year struggle through the FDA regulatory process. The company was recently acquired by Intrexon, an American synthetic biology company run by biotech billionaire Randal Kirk.
The pig, by contrast, floundered in its quest to find a worldly industrial partner with the deep pockets and strong stomach to negotiate the regulatory and social hurdles. Dr. Forsberg and the University of Guelph received some R&D funding from the industry association Ontario Pork early on. Yet they never found a suitable international or domestic licen-see willing to make the investment required to develop the product, take it through the regulatory process and bring it to market.
In the spring of 2012, Ontario Pork halted funding after having spent $1.3-million. The pigs were euthanized and frozen samples of their DNA preserved in long-term storage. “We underestimated the size of the challenge and didn’t anticipate the investment required,” says Rich Moccia, associate vice-president of research at the University of Guelph.
The Guelph researchers bet the farm on marketing the GM pig on the strength of its proclaimed environmental, rather than economic, benefits. Dr. Forsberg argued in a 2003 journal article that an Ipsos-Reid survey showed an environmentally friendly message could help win over consumers. “Respondents were more receptive to the future consumption of GM pork once they were aware that it would come from pigs that produced less-polluting manure,” he wrote.
But critics maintained the Enviropig was simply a ploy to allow factory farms to raise many more hogs on the same amount of land while still meeting environmental restrictions. This commercial benefit, which Guelph chose not to highlight, was thus painted by critics as a nefarious hidden agenda.
Then, 11 GM piglets that had died were accidentally sent to a rendering plant and turned into animal feed instead of being destroyed as biological waste, contaminating 675 tons of poultry feed. The incident in 2002 highlighted the issue of potential escape and further undermined the GM pig’s image as an environmental champion.
The fish people handled the environmental issues more adroitly. Addressing concerns from environmentalists that if GM salmon escaped their pens they would out-compete wild Atlantic salmon for food and interbreed with them, AquaBounty decided to breed only sterile female GM salmon in landlocked tanks. (The fish eggs are produced in Prince Edward Island, while the fish are being raised in pens in Panama.)
A study by Ian Fleming and colleagues at Memorial published last spring in the journal Proceedings of the Royal Society B showed that GM salmon cross-bred with wild brown trout had hybrid offspring that grew faster than the GM salmon and out-competed other fish for food, potentially posing a risk to wild fish species. “Our study provides vital information on what may happen to the transgene if it enters nature. Aqua-Bounty is being proactive around regulatory issues by going with sterile fish in a land-based system,” says Dr. Fleming, noting that this research highlights the need for stringent containment safeguards.
The social stigma attached to the GM pig, meanwhile, was too much for the University of Guelph and the Ontario pork industry to handle. “The social and environmental movement demonstrated how strong it can be. Market reception is important, and the pork industry didn’t want to be tainted by the lack of social acceptance,” says Mart Gross, a professor in biodiversity science at the University of Toronto. Angry complaints from Guelph alumni about the Enviropig also weakened the university’s resolve. “We became the lightning rod for protests,” says Guelph’s associate vp Dr. Moccia.
Differences in how people perceive a pig and a fish also may have influenced the outcome of the race. “The regulators see the fish and the pig in the same way. But most people in the industrialized countries view fish as lower evolutionary creatures with less inherent rights than a pig. People feel a pig is closer to a human being. They will have a different philosophy on what’s okay to do with a fish versus a pig,” suggests Dr. Moccia.
While the fish faces social hurdles, too, society is generally more squeamish about a GM pig. “There is a threshold of social acceptability. A pig is an animal and we’re animals too. Modifying the genetic makeup of a pig seems a step too far for many people.” says Grace Skogstad, professor of political science at the University of Toronto and an expert in regulatory policy and GM foods. She adds, “The salmon will be a very interesting test of the consumer’s willingness to accept genetically modified animals as food.”
Whether the GM fish gets the green light from the FDA and how consumers will respond if the salmon is approved are unanswered questions. Dr. Skogstad argues that regulators should require that the salmon be labeled as a GM product as a condition of approval. “Consumers have a right to know and should be able to make a choice,” she says.
Nobody knows when the FDA decision will be made, but U of T’s Dr. Gross does think the fish will succeed. “AquaBounty is the trailblazer and the FDA hasn’t shut them down. It’s not an easy decision, but I believe the GM salmon will eventually be approved. There is a need to produce more food and this is the future,” he says.
One sure bet is that if regulators do approve – and enough consumers buy – GM salmon, then many other types of fish and eventually pigs, cows and other animals will inevitably follow. “You’ve got science versus politics. This technology can be used to improve food production and quality for a growing global population. Other companies are cautiously waiting for a decision,” says Memorial’s pioneering Dr. Fletcher.
Mark Witten is a science and medical writer based in Toronto. This is his first article for University Affairs.