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It Came From the Gene Lab

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Times Staff Writer

One newly bioengineered salmon, endowed with a gene from an eel-like fish, grows five times faster than its natural cousins. Another genetically modified salmon produces antifreeze in its blood so it can survive icy waters that swirl through oceanic fish farms.

A tropical zebra fish, infused with the green fluorescent gene of a jellyfish, glows in the dark -- a living novelty that promoters hope will be a must-have for the home aquarium.

These experimental superfish are more than laboratory curiosities. They are the progeny of genetic engineers whose skill at mixing and matching genes is outpacing laws and regulations meant to protect the food supply and the environment.

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None of these designer fish, being pushed by biotech entrepreneurs as potential lucrative ventures, have yet reached the market. But the U.S. Food and Drug Administration has initiated a review of the souped-up salmon, a process that could lead to the first approval of a “transgenic” animal -- one that has genetic material transplanted from another.

Although the human health implications of eating bioengineered animals remain unknown, a panel of scientists last August reported it had “a moderate level of concern” that new species could trigger allergic reactions. What might happen, the scientists asked, if a gene from a shellfish were implanted into a fish? Could it cause a reaction in consumers hypersensitive to shellfish?

The National Academy of Sciences panel, assembled at the FDA’s request, said its primary concern was the potential for ecological havoc should highly mobile, fast-breeding transgenic species escape into the wild.

“It is possible,” the panel reported, “that if transgenic salmon with genes engineered to accelerate growth were released into the natural environment, they could compete more successfully for food and mates than wild salmon.”

That means these “Frankenfish,” as critics have labeled them, could squeeze out their wild cousins, driving them to extinction through interbreeding or by eating them.

Alarmed by the potential risks, Washington, Oregon and Maryland have banned genetically enhanced fish to protect the native fish populations.

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California’s Fish and Game Commission, trying not to hinder scientific research or the state’s burgeoning biotech industry, plans to grant permits, based on its own reviews, for each new transgenic species as it emerges under new rules that take effect today.

“We could have put up a stop sign and said, ‘No,’ ” said Michael Flores, president of the Fish and Game Commission. “But then we would have crippled our university researchers and other research and development. We will look at every single species and make sure safeguards are in place.”

West Coast commercial fishermen are pushing California to ban genetically altered fish, arguing that the potential threat to wild salmon and other native species is too great.

“Once this genie escapes, can we put it back in the bottle?” asked Zeke Grader, executive director of the Pacific Coast Federation of Fishermen’s Assns. “I doubt it.

“So what happens when these fish get out in the wild? Will they spread disease? Will they be predators of our native fish or interbreed with them? How can we assure the public the fish we catch are safe if transgenic fish are mixed in?

“It’s all unknown,” Grader said.

It’s the FDA’s job to answer those questions. But “marine ecology is not historically an area of FDA scientific strength,” said Michael Taylor, a National Academy of Sciences panel member and senior fellow at the nonprofit Resources for the Future.

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Taylor and others also fault the agency for closing its reviews to the public to protect trade secrets.

Lester M. Crawford, deputy FDA commissioner, said the agency is reconsidering its secrecy policy when weighing the food safety and ecological impact of newly designed species.

“We certainly have a framework to deal with environmental risks,” Crawford said.

But new breeds of transgenic animals have prompted some internal soul-searching. “We are evaluating whether we need new regulations or new money or congressional authority to tweak the law,” Crawford said.

He said the agency may never approve a transgenic fish or any other kind of genetically modified animal for the marketplace. But the pressure is mounting to do so, with a menagerie of them expected to arrive at the FDA’s offices soon.

Researchers at biotech companies and universities have redesigned the genes of freshwater catfish and tilapia to make them grow faster, and those of shrimp and abalone to help them resist disease.

Scientists in Singapore are designing ornamental fish -- such as the zebra fish -- that glow green when spliced with a jellyfish gene or red when infused with the gene of a sea anemone.

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Those same researchers are devising a fish that changes color when it passes through different temperatures. Such gene-splicing is being extended to goldfish and koi, stirring excitement in the $1-billion annual home aquarium trade.

Genetic manipulations are becoming so routine that an artist in Chicago has put a pair of florescent green zebra fish on public display, along with assorted glow-in-the-dark rodents and other creatures he calls “transgenic art” in an exhibit called “The Eighth Day.”

“We’re adding one day to the seven days of creation,” said Eduardo Kac, a self-described “biotech artist” at the School of the Art Institute of Chicago.

“From the technical point of view, the technology is here and part of society. I’m saying, ‘What are we going to do with it?’ ”

Genetically enhanced fish are just the beginning.

A Canadian firm has spliced a spider gene into goats so their milk is laced with spider thread that can be extracted to make bulletproof vests or surgical sutures.

Other animals are being tailored to the demands of factory farms, from featherless fowl that don’t need to be plucked to low-emission pigs that excrete 75% less phosphorous, a key contaminant in agricultural runoff.

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Advances in genetically modified plants are much further along, both in government approval and public acceptance. Unlike Europeans, most Americans have readily digested the idea of genetically engineered corn, soybeans and cotton that have been modified to resist insects and tolerate herbicides.

The first animal candidate for FDA approval is an Atlantic salmon with the transplanted gene of an ocean pout, an ugly, bottom-dwelling fish that resembles an eel.

Elliot Entis, co-founder and president of the firm that wants to market the salmon, Aqua Bounty of Waltham, Mass., said the pout gene allows the salmon to produce growth hormones year-round, instead of during warmer months, so that it grows five times as fast as a normal farm-raised salmon.

Aqua Bounty’s salmon do not end up larger than their natural cousins. But they reach marketable size much faster, in 18 months -- and do so with 10% to 25% less food, Entis said.

“It’s like tuning up your car,” he said. “Instead of 10 miles per gallon, in the early stages it gets 40 miles per gallon.”

Raising salmon on less food is an important advance. It now takes about 2 1/2 pounds of wild fish ground into meal to produce one pound of farmed salmon.

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For that reason, feeding salmon on those proliferating farms contributes to the overfishing that is rapidly depleting the world’s oceans.

Entis said genetically enhanced fish are needed to feed a growing global population. He believes the risk of the fish escaping can be all but eliminated by containing them in inland tanks. He also proposes to make them sterile.

But scientists say fish tend to flop out of the most secure pens and that no sterility technique works 100% of the time.

The FDA has brought in a team of experts from the Environmental Protection Agency, National Marine Fisheries Service and U.S. Fish and Wildlife Service to help assess the potential ecological impact.

One of the few studies to look into the issue focused on the risk of extinction of native species by what researchers at Purdue University called the “Trojan gene” effect.

Genetics professor William Muir and biologist Richard Howard, studying mating and survival rates, found that transgenic fish are typically larger than their wild cousins.

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That gives them an advantage in attracting mates. If the genetic change reduces the offspring’s life expectancy, as it did in their laboratory experiments, a transgenic fish could wipe out a wild population in as few as 40 generations.

Worried about Northern California’s salmon runs, state Sen. Byron Sher (D-Stanford) has asked California officials to yank the new regulations on genetically enhanced fish, arguing that it is premature to legalize the “commercialization of transgenic fish” with so many unknowns and potential threats.

“The FDA has not yet decided whether farm-raised transgenic fish are safe to eat,” Sher wrote to California Fish and Game Director Bob Hight.

“Equally important, there are growing concerns that FDA’s regulatory process does not adequately consider the potential environmental risks to native fish species.”

Fish and Game officials defend the regulations, saying they are designed to protect native species rather than promote genetic tinkering.

State officials have no idea how many bioengineered fish may exist in California.

The new rules are designed to help them find out and impose state controls, such as requiring secure fish tanks to prevent escape as researchers, farmers or fish sellers obtain permits to possess, transport or raise animals with altered genes.

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Fish and Game officials expect to hear first from biomedical researchers at UCLA and UC San Francisco, who work with genetically altered zebra fish in research on human heart disease.

Zebra fish, a tropical freshwater species, are gaining popularity as a lab research tool. That’s partly because they reproduce quickly and are cheap to maintain, and partly because scientists are nearly done mapping the fish’s genome, which has significant similarities to that of humans.

“Once you get the genome completed, it begs for you to do some manipulation,” said Marc Aarens, UC’s director of academic legislative issues.

Researchers tinkering with zebra fish genes declined to be interviewed.

“It’s important work -- research dealing with heart disease -- and none of them want publicity,” Aarens said.

“We might get protesters who fear they are creating ‘Frankenfish’ and going to ruin the environment.”

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