FDA considering approval of AquAdvantage salmon
while Enviropigs wait
posted November 1, 2010
James D. Murray, PhD, thinks it is clear that genetic engineering of food animals could improve human and animal health and help to feed a growing world population.
A professor in the departments of Animal Science and Population Health and Reproduction at the University of California at Davis, Dr. Murray has conducted research involving transgenic animals since 1982. He expects that, were federal regulators to provide the approvals needed for a company to sell transgenic salmon in grocery stores, this action would encourage other companies to increase their investment in genetic engineering.
"It has been an incredibly long period of regulatory uncertainty, and regulatory uncertainty affects industries' willingness to invest in a technology," Dr. Murray said. "So it has had a stifling effect in the U.S., Canada, Australia, New Zealand, places like that."
Food and Drug Administration officials have recently begun considering whether genetically modifying salmon by inserting an rDNA construct that will cause them to grow to market weight in half the time of their conventional relatives is safe for humans, the environment, and the salmon (see JAVMA, Nov. 1, 2010, page 1005). The agency is considering AquaBounty Technologies' rDNA construct, which contains gene-coding sequences from ocean pout and Chinook salmon, as a new animal drug because it is intended to alter the structure or function of the salmon.
Ronald L. Stotish, PhD, CEO and president of AquaBounty, said the first AquAdvantage fish was produced in 1989, and the company first submitted an application to the FDA in 1995. The company has studied 10 generations of the salmon.
Dr. Stotish worries that if the company's application fails to gain approval, this could signal the end of the use of such technology in the U.S. He said it is difficult to gain investors when it is unclear whether regulatory approval will be granted and suggested that many other companies have already stopped work on such applications because of the current regulatory uncertainty. On the other hand, he believes that researchers in other countries, including Brazil, China, and Argentina, would continue to develop transgenic animals.
"What started as an American advance and an American technology, for a variety of reasons, may in a very real sense be lost to developing nations who take a more progressive view of production and have the economic and social incentives to adopt this technology," Dr. Stotish said. "So it wouldn't be hyperbole to say that this first application is very, very important here in the United States."
Dr. Stotish said the FDA has worked extensively with his company, but he was disappointed with the results of a recent public meeting held by the FDA Veterinary Medicine Advisory Committee, during which some committee members indicated they found flaws in AquaBounty's studies and data. However, Dr. Stotish attributes those statements to misunderstandings. For example, he said studies involving 30 salmon included 24 with hormone concentrations lower than the detection limit for the assay used in the studies, but committee members thought the studies included only six fish.
While Dr. Stotish was encouraged that some committee members indicated the salmon was safe, he said afterward that "we think that the process itself can be improved, and we hope that there's an opportunity to constructively address this before the next application goes before a similar process."
Dr. Paul C. Stromberg, a professor of veterinary pathology at The Ohio State University and a member of the VMAC, expects the rDNA construct will eventually receive FDA approval and set a precedent for approval of food from other genetically engineered animals. He said uncertainty and the overwhelming amount of information is contributing to public fears of genetically engineered food, particularly because when it comes to food safety, some people may have difficulty differentiating between absolute certainty and reasonable certainty.
Dr. Murray anticipates that the FDA will next consider approval of transgenic Yorkshire pigs developed at the University of Guelph.
The FDA is considering approval of AquaBounty Technologies' Atlantic salmon, and the approval process could affect other transgenic animals, like the University of Guelph's transgenic Yorkshire pigs.
Bringing home better bacon?
Researchers at the Ontario university have developed pigs that they say are healthier, slightly cheaper to produce, and potentially less harmful to the environment than conventional pigs.
Cecil W. Forsberg, PhD, professor emeritus in the Department of Molecular and Cellular Biology at the University of Guelph, is one of the researchers who developed the transgenic animals, known as Enviropigs. The animals contain a mouse parotid secretory protein promoter gene sequence and an Escherichia coli phytase gene, university information states.
"The social and ethical question is whether one additional gene and part of a promoter from another species really changes the pig—and in terms of the overall genome of the pig, that is very minimal," Dr. Forsberg said. "The other interesting thing is that, as far as the similarity of genes between mammals, they're all very similar. So in that sense, you're not introducing something that is very different from what's already there."
While conventional pigs require the addition of phytase to their rations to enhance digestion of phytic acid in cereal grains, the Enviropigs are modified to produce phytase in their saliva, Dr. Forsberg said.
"The Enviropig is able to metabolize the phytate, and, therefore, is able to satisfy its phosphorus requirement without the addition of phytase or supplemental phosphorus," he said.
The university began seeking approval from U.S. regulators in 2007 and Canadian regulators in spring 2009. While Dr. Forsberg said it seems the application has stalled in the U.S. during FDA deliberations regarding genetically engineered salmon, the university and Environment Canada have worked out conditions for production, and the university is seeking approvals from Health Canada and the Canadian Food Inspection Agency.
As a result, the university can produce the pigs but not sell them for human or animal consumption, and Dr. Forsberg said the pigs will not be moved from university facilities until they are approved for both.
University data indicate the pigs grow and reproduce without the supplements at least as efficiently as naturally occurring counterparts that receive the supplements, Dr. Forsberg said. While pork producers can save money on phytase and phosphorus, he thinks they will benefit even more by producing healthier pigs.
In addition, Dr. Forsberg said, the Enviropig name refers to the additional benefit of reduced phosphorus concentration in fecal material, which can leech into nearby bodies of water and promote algal growth. Weanling and growing pigs of up to 60 kilograms, or about 132 pounds, will produce manure with 50 to 60 percent less phosphorus, while older pigs will produce manure with about 30 percent less, he said.
Dr. Forsberg expects that consideration of AquaBounty's genetically engineered salmon is helping regulators determine which issues are important for consideration in genetically engineered foods, and he said it has been useful to read public comments during that process.
"And issues that the public has raised probably will spin into other analytical aspects that will be required, which may not have been apparent to the FDA scientists," Dr. Forsberg said.
The researchers are giving people an option, Dr. Forsberg said, noting that the pigs could be particularly useful in countries with large human and animal populations. He said the university has had numerous inquiries from Chinese swine production companies.
"I think the major determinants probably will be societal issues," Dr. Forsberg said of the Enviropigs. "That's all I see with the transgenic salmon from the science I have seen and the public response. It really is a societal determination."