In a report that was requested by the FDA to better arm itself for the upcoming animal biotechnology regulatory decisions it will surely face, the National Academies' National Research Council said the gravest concern associated with the merging of biotechnology and animals is environmental.

The report, released publicly Tuesday, examined how the genetic engineering of animals might affect humans and the planet. Although its findings have drawn criticism from some, it identifies areas of concern and at the very least provides a basis for further probing.

"We examined three main areas: food safety, environmental safety and animal-welfare issues," said John Vandenbergh, chair of the council and a professor of zoology at North Carolina State University in Raleigh. "We found that environmental safety is the most serious. We rated this our highest concern."

The council said its greatest fear is the ability of genetically engineered animals to escape confinement and infiltrate wild populations, thus affecting gene pools and food chains. In a scenario that would have Darwin rolling over in his grave, genetically altered species might better attract mates, reproduce and/or acquire food, therefore phasing out wild populations through normal survival-of-the-fittest principles. Vandenbergh gave the example of genetically engineered salmon already being produced in the U.S.

"Should those [salmon] be released into aquaculture enclosures, the potential for their escape exists," he told BioWorld Today. "These transgenic fish grow four or more times quickly than normal fish. They could out-compete [native populations] for food and perhaps for mates."

It's the mobile nature of fish and shellfish, coupled with their aquatic landscape, that make them a high risk for escaping confinement. Engineered insects pose a similar threat. It's more difficult to imagine a scenario in which genetically engineered cattle break loose from the corral and assimilate elsewhere.

Charles Margulis, genetic engineering specialist with Greenpeace, sees the same problems Vandenbergh does. Greenpeace said that in 2001 it protested at AF Protein Inc. in Waltham, Mass., to let the FDA know Greenepeace is against the approval of any application aimed at the commercial sale of genetically altered fish. AF Protein develops fish for the antifreeze protein found in the blood of species living in northern waters. The company focuses on using the proteins to control cold-induced damage, mainly in cosmetic and medical uses, including cryosurgery.

"We've taken a stand on fish because of the obvious implications," Margulis told BioWorld Today. "For example, in a lot of the meat industry, it's a very different risk for the environment - fish routinely escape into the environment. You can't say the same thing for broiler hens.

"In fish, it's clear this is a disaster waiting to happen," he added.

Margulis said the genetic altering of animals such as salmon would be easier to swallow if there were a guarantee of confinement. But that's a promise that simply can't be made, he said.

"We wouldn't be inherently opposed to any genetic engineering," he said. "We have no problem with [genetic engineering] in a strict laboratory environment, even a strict greenhouse environment." But, he said, there is no way to sufficiently contain fish.

"That's absolutely clear," he said. "They will have to rear them in aquatic facilities. And then a facility that is guaranteed to never break, breaks. You can't stop these kinds of accidents. These are sometimes caused by major weather events."

Vandenbergh, although he believes measures could be taken to limit the scope of damage done in such a scenario - one option is engineering sterile fish - agrees that "should [transgenic salmon] be released into aquaculture enclosures, the potential for escape exists."

Beyond Environmental Safety Issues

The other areas examined by the council - food safety and animal welfare - had issues of their own, but the associated risks were deemed moderate or low. Unknown allergens in food from gene-altered animals pose a moderate risk, Vandenbergh said, explaining that the probability of there being an allergen present is very low, but any occurrence could bring serious effects, thus earning an overall "moderate risk" designation.

The council voiced concerns for the welfare of genetically engineered fauna, saying, "Ultra sterilization and ultra isolation can have an effect on the animals." And the council expressed concern that animals designed for biomedical and biotechnology uses could accidentally enter the food supply. What harm that would cause is unknown, but the idea is unsettling.

"We are not sure what would happen," Vandenbergh said. "But the compounds [being produced in animals] are relatively unusual. The part of the milk that is not being used as a therapeutic should not be used for human consumption."

The council found that eating animals cloned from embryos or consuming cloned cow milk seems to present no concerns, Vandenbergh said, although the FDA should be receiving more data on the subject in the next few months. Greenpeace's Margulis agreed that while the report does not identify problems with consuming embryonic clones or their products, somatic cell clones are different.

"To say food from these clones is safe is incredibly risky," he said.

The report backs up Margulis. It says: "The cloning of animals from somatic cells is more recent. Limited sample size, health and production data, and rapidly changing cloning protocols make it difficult to draw conclusions regarding safety of milk, meat and other products from individuals that are themselves somatic cell cloned individuals."

BIO Says Report Leaves Out Benefits

Lisa Dry, communications director at the Biotechnology Industry Organization in Washington, said the report has a hole.

"What is missing is the benefits," she told BioWorld Today. "This is a new application of the technology. You really need to discuss the importance of why biotech and animals are coming together. It's because of human health, animal health and food safety."

Dry pointed to Hematech LLC, of Sioux Falls, S.D., a company cloning calves whose milk produces proteins that can fight anthrax, immune deficiency and cancer, as an example of what the science can do. Also, goats are being used to produce a spider silk that is used to make bullet-proof vests more impervious than Kevlar vests. There are companies working on blood-clotting agents extracted from genetically engineered milk to fight hemophilia. Just last week, PPL Therapeutics plc, of London, said it produced the first double gene knockout piglets, making further inroads in xenotransplantation.

"There were a whole range of benefits that were outside the scope of this report," she said.

But the council wasn't instructed to examine benefits, Vandenbergh said. Nor was it formed to deal with public reactions to transgenic animals. The council did was it was designed to do.

"I hope the committee's report provides an information base upon which these decisions can be made by individuals," he said. "We certainly did not come out with any statements, but we came out with a list of concerns.

"You'll find that 90 percent of [similar studies] say, We need more research,'" he added. "That's what scientists say and there's some legitimacy to that. We are facing the same kind of thing. We have data on some areas and it's in the report. But there are areas we are concerned about because there was a paucity of data, and those we pointed out in the text."