SUPERFISH: COMING SOON TO A LAKE NEAR YOU?

Walleye, chinook,bluegill—to anglers, these names conjure up images of fishing trips past. Gamefishing in the 1990s may call to mind a more unusual image, like that of a100-pound chinook that has been injected with cattle growth hormone genes.Spurred by global research in aquaculture, U.S. biologists are manipulatinggenes and chromosomes in hopes of creating "superfish" for the tableand the den wall.

"Geneticmanipulation is one of the first ideas that come to mind when people want toincrease the yield of some source of food," says Anne Kapuscinski, anassistant professor of fisheries at the University of Minnesota. "Some ofthis research is now spilling over into game-fish enhancement."

Kapuscinski,along with three Minnesota colleagues, molecular geneticists Kevin Guise, PerryHackett and Anthony Faras, is working under the auspices of the Minnesota SeaGrant College Program to engineer a superwalleye by inserting an extra growthhormone gene into the egg. The researchers hope to produce some of these"transgenic" walleyes by the summer of 1989. They dream of economical"cradle-to-grave" nurseries supplying the nation with walleye, laketrout and other traditionally slow-growing game fish of the upper Midwest. TheMinnesota legislature, the project's major funder, hopes the superfish willsomeday spark a tourist bonanza.

Before that canhappen, the products of genetic tinkering must be safe to release into theenvironment. Says Guise, "We are looking closely at being able to controlthe growth hormone gene so that we can turn it on while it's in the hatcheryand turn it off when it's released into the environment. That way the fish willgrow and act like a normal fish in the wild, but the DNR [Department of NaturalResources] will still see an increase in its hatchery efficiency—getting morefish for the buck."

Variations on the"designer fish" concept are already common in sport fisheries.Experimental crossbreeds, from tiger trout (a female brown trout-male brooktrout crossbreed) and splake (female lake trout and male brook trout) to theultra-aggressive result of the cross of a bluegill and a sunfish, are alreadythriving in the wild. To create the next generation of chimeras, experts incryo-preservation are trying to freeze fish sperm and eggs so species thatspawn in the spring can be crossed with species that spawn in the fall.

Other researchersare focusing on the production of sterilized leviathans. The states of Michiganand Wisconsin, for example, are stocking Lake Michigan with potentially giantchinooks, which have been sterilized either by steroids or triploidy (theinducement of an extra set of chromosomes). Sterilized chinooks never receivethe brain signals that tell normal chinooks to spawn and die. As a result, theychannel into growth all the energy that otherwise would go into reproduction.While Guise doubts Great Lakes fishermen will ever "go harpooning" forchinooks, those that can elude capture long enough could grow to be huge.Indeed, one computer model at the University of Wisconsin projects a chinook of100 pounds—four times its normal size.

Of all thebrave-new-world fish research going on, none is more fascinating—anddisturbing—than gene transfer. Scientists soon hope to splice into a fish's DNAcode the ability to resist disease, to grow faster on less food and perhapseven to perform special functions. "There are genes, for instance, thathave been isolated from bacteria that will degrade dioxin," says Guise."It might be possible one day to create a vacuum-cleaner type offish. Takea bottom feeder and put in the right genes...I wouldn't want to eat that fish,but you may be able to engineer biological systems to clean up a damagedenvironment. We're looking at all sorts of things, but you have to becautious."

The transgenicresearch at Minnesota parallels work being done in the People's Republic ofChina, where aquaculture is a 4,000-year-old tradition. Working with carp andloach, two valuable food species in Asia, Professor Zuo-Yan Zhu of theInstitute of Hydrobiology in Wuhan Hubei Province has succeeded intransplanting growth genes that were then passed on naturally to successivegenerations. While many loach grew 1½ times faster than normal loach, some withthe extra gene grew two to 4½ times faster. The Minnesota team hopes to achievesimilar results with walleyes. That effort may get a boost when Zhu travels toMinnesota this spring on a four-month scientific exchange.

From mainlandChina to the labs of Purina Mills, a U.S.-based subsidiary of BritishPetroleum, researchers share Guise's exhilaration over ichthyological eugenics.But many of them stress his note of caution—especially when it comes toreleasing genetically engineered fish into the wild. "As a scientist with astrong interest in conservation," says Kapuscinski, "I am disturbedthat people think we can circumvent nature by just doing fantastic geneticmanipulations. We don't really know that much yet about the performance ofthese kinds of animals in nature, and I think great caution has to beexercised."

Growth-geneimplantation is not new to microbiologists, who have been using the techniqueon laboratory mice for years. With an extra growth gene, mice can grow to abouttwice their normal size, but no larger. Researchers hope for more dramaticresults with fish, many species of which exhibit so-called indeterminate growththat is limited only by food supply, longevity and the amount of energydirected toward reproduction. Some of Zhu's engineered carp, for instance, growat rates 4½ times faster than normal.

Researchers atfisheries typically use growth hormone genes extracted from cattle becausethese genes are easy to obtain. That they work in fish is an example ofconservative evolution—nature's tendency to reuse effective biochemical systemsup and down the evolutionary ladder. "Cow and sheep growth hormones, aswell as those from other fish, all work in a fish to produce larger fish,"says Guise. Blue shark growth hormone, for example, spurs growth in carp.Frightening as this may sound to the post-Jaws generation, shark hormone worksno more or less effectively than that from catfish.

Still, saysKapuscinski, there may be advantages to using species-specific genes. "Itmight be better regulated inside the fish," she says, "but we don'tknow at this point." To this end the team is hoping to clone walleye growthhormone genes for future experiments.

Of the manychallenges facing the Minnesota team, one of the most nettle-some is the masstransfer of the genes. Walleyes produce 20 to 30 thousand eggs during eachyearly breeding season, and it's extremely time-consuming to microinject eachone individually. Today, a technician working alone can treat only about 250eggs per hour. This must be done after fertilization but before cell divisionbegins; otherwise the transplanted gene will appear in a mosaic pattern in thetissues of the adult fish.

The Minnesotateam is working on a promising alternative—a process known as electroporationin which an electrical pulse creates tiny, temporary pores in the egg membranethereby creating a means of introducing the DNA into the fertilized egg.Ascertaining whether the gene transfer was successful used to mean waiting forthe fingerlings to grow up—a major slowdown to research. To expedite theprocess, Guise now attaches to the growth hormone gene a second gene thatprovides resistance to a specific poison. The hatchlings that survive thepoison are presumed to have also accepted the growth gene.

The ethicalramifications of their work are not lost on either Guise or Kapuscinski. Unliketriploid and crossbred fish, which occur naturally on occasion, transgenic fishare engineered mutants. "A giant carp with an extra growth hormone gene isfairly new," says Guise. "You have to look closely at what you're doingand figure out what the rules are for the next step."

Although visionsof boat-eating walleyes may tantalize some anglers, Guise points out thatbigger game fish may not necessarily mean better game fish. "Superwalleyesmay be sluggish," he says, "and they may not strike as hard. At thispoint, it's impossible to predict."

"I amconcerned about raising unrealistic expectations in anglers," saysKapuscinski.

A bigger worry isthe possibility of a decimated forage base or other hard-to-anticipate forms ofecological havoc. To guard against such developments, the team plans to studythe fish's behavior extensively—first in laboratory tanks and later inprotected research lakes—before even considering limited release. Says Guise,"We will study sterilized adult fish in lakes such as those found onsecured government facilities. There, you're very unlikely to get fishermenclimbing over barbed wire to get to the lake."

Sterilization, ofcourse, is an effective damage-control strategy only as long as it's foolproof."Unfortunately," says Michael Hansen, a fisheries biologist in chargeof the sterilized chinook program in Wisconsin, "the way to be sure to getabsolute sterilization is to surgically remove the gonads. And that's notcost-effective."

Given theFrankensteinian overtones, Kapuscinski, a committed environmentalist, says herdecision to do genetic engineering of fish was not an easy one. "After alot of soul-searching," she says, "I decided I had better be involvedin this research, because if I wasn't, the remainder of the team would be allmolecular geneticists. I felt I had a responsibility as a fisheries scientistto be in the middle of it and try to provide wise counsel on the political,economic and ecological issues.

"I realizefull well that I may end up in some uncomfortable situations, in which my inputwill not count as much as that of the politicians, but that's the risk I haveto take."

In the 1800s,says Guise, carp were introduced into the Midwest with the best of intentions.States fought over the limited supply of carp eggs. Before long, though, thecarp had taken over many of the waters in which they had been planted,displacing such valuable game fish as bass. "The DNR is not too happy aboutit right now," says Guise.

Does he everworry that the zeal to produce game fish for the 1990s might lead to a rerun ofthe carp fad of the 1800s? "Sure," says Guise. "That's why we'restudying as many aspects of this thing as possible."

James Thornton, who lives in St. Paul, writes often onscience and technology.

PHOTO

PATRICIA BARRY LEVY

Guise's experiments with gene transplants may lead to 100-pound chinooks.

PHOTO

MITCH KEZAR

A Minnesota researcher injects fish eggs with growth genes.