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Genetically-engineered salmon makes best inventions list

By Kelly Foss

A genetically engineered salmon produced at Memorial University has been named one of the 50 best inventions of 2010 by Time magazine.

These controversial Atlantic salmon grow twice as fast as wild fish, and have been making headlines recently as the U.S. Food and Drug Administration gets closer to approving it as the first transgenic animal for human consumption.

However, research conducted in Canada, primarily at Memorial University, began as far back as the 1980s when Dr. Garth Fletcher, now director of the Ocean Sciences Centre and Choy Hew, formerly of the Biochemistry department, formulated the idea of using gene transfer to produce strains of Atlantic salmon for aquaculture that could better tolerate the harsh winter conditions that prevail in Newfoundland waters

Dr. Fletcher says at that time they were looking into adding an antifreeze protein gene to salmon that would allow farmed fish to be cultured in sea cages in locations where water temperatures declined to lethal levels. Such antifreeze genes are found in a number of Newfoundland fish and Peter Davies of Queen’s University, the third member of the research team, had already isolated the one found in winter flounder. Since this gene was expressed in the liver it could be used for gene transfer without modification.

“It took a couple of seasons to figure out how to transfer the genes,” Dr. Fletcher explained. “We started out with a handheld needle and syringe trying to implant the genes into fish eggs with no success. Eventually we used a more sophisticated microinjection system and targeted a location within the cell where the genes had a reasonable chance of integrating into the salmon DNA.”

By the mid-80s the Memorial research team was finally seeing the antifreeze gene showing up in the salmon DNA and being expressed and passed from generation to generation. However the genes were only making trace amounts of antifreeze that were insufficient to protect the salmon from freezing. On the positive side the team had established proof-of-concept: genes can be transferred and stably integrated into salmon chromosomes.

So it was back to the drawing board. It was decided to take what had been learned about antifreeze gene transfer, and see if it could be used to develop a fast-growing fish by transferring a growth hormone gene. The thinking was that rapidly growing salmon would have worldwide appeal to the aquaculture industry.

“The growth hormone gene is normally only expressed in the pituitary under the control of the central nervous system,” said Dr. Fletcher. “Therefore there was no point in us inserting an intact growth hormone gene, because it would just get expressed in the pituitary gland and be subject to the same feed back regulatory mechanisms as the endogenously produced growth hormone. We had to modify the gene so that it could be expressed in tissues other than the pituitary.”

The researchers knew that antifreeze protein genes were expressed in liver and other tissues. They took the promoter region from an ocean pout antifreeze gene and spliced it to the coding region of the Chinook salmon growth hormone gene. Promoters generally dictate where the gene is expressed. Those microinjections were carried out in 1989.

“Much to our delight, but mostly surprise, in the spring of 1990 we saw some big fish,” said Dr. Fletcher. “They were five and six gram fish versus the others which were only about a quarter of a gram.”

Drs. Fletcher and Choy Hew, who at this time was working at the Toronto Hospital for Sick Children in Ontario, jointly patented the research, and with the encouragement of NSERC they began looking for a private sector partner to take over licensing the technology and running the test fish farms. Enter Elliot Entis, an American businessman involved in the fish industry in the United States. Mr. Entis, who had already formed a start-up biotechnology company for the manufacture and sale of fish antifreeze proteins, realized the potential value of the gene transfer technology and signed a license agreement. With him, the researchers became founding members of the company that is now known as Aqua Bounty Technologies with laboratory and office locations in Canada and the U.S.

Then began the long, long process of getting the fish approved by the FDA. This was a whole new area for the agency Dr. Fletcher says, and it took them many years to conclude what the regulatory process should be.

In September 2010, the FDA declared that Aqua Bounty’s growth hormone transgenic salmon were safe to eat. This is the first genetically modified animal product to be considered safe by FDA. Aqua Bounty expects to receive approval for the sale of the product in United States in the near future.