Cross-species cloning attempted

By Marilynn Marchione Milwaukee Journal Sentinel Published:

MILWAUKEE - Researchers have taken cloning technology one step further by getting eggs from a cow to accept genes from other species _ sheep, pigs, rats and even primates, one level away from man. Using the same technology that created Dolly the sheep, the world's first adult mammal clone, University of Wisconsin-Madison researchers took cow eggs, stripped them of their genetic material, and got them to grow and start functioning with new DNA from other species. They created 70 such inter-species embryos and grew them to a 60-to-120-cell stage that is considered viable for implantation. The researchers have made six or seven attempts at pregnancy so far, but none has succeeded. But the findings suggest many potential uses. Among them: creating animal organs for human transplantation, getting animals to produce antibiotics or other useful substances, preserving endangered species, and propagating commercially valuable animals such as racehorses or prized cows. The work was to be reported Monday in Boston at a meeting of the International Embryo Transfer Society. It was done in the lab of noted genetics researcher Neal First, a UW professor of animal science, at the suggestion of UW staff scientist Tanja Dominko. UW's work "is a starting point" to creating cross-species cloned animals, said Jorge Piedrahita, an embryologist and sheep cloning researcher at Texas A&M University, adding, "It's going to be quite a bit of work to get it from where it's at (now) to a viable pregnancy." "The potential is there," First said. "If we had offspring, it would have been a reality." John Van Blerkom, a professor of molecular biology at the University of Colorado, said the work revealed "a fundamentally important biological finding." "The egg doesn't care what kind of nucleus it is" that is inserted, he said. Once its own DNA has been removed, it will grow and take instructions from whatever new DNA has been added, he said. This is akin to taking an entire factory of workers who have been making one product a certain way, giving them a new boss and telling them to make something entirely different. In biological terms, getting the egg of one species to be ruled by another species' DNA is like teaching a fish to fly. Piedrahita said the work was scientifically important for the same reason Dolly was _ researchers were able to remove the genetic material of one animal, and insert the genetic material of another adult animal they wanted to clone. Currently, except in the case of Dolly and similar pioneering experiments, it's possible to add genetic material, but not to remove it. "Right now we don't do genetic engineering, we do mechanics," Piedrahita said. If animal eggs could be modified to carry and reproduce only the genetic material desired, "there's no limit to the possibilities these animals can give us," he said. The UW work suggests the possibility of using one species' eggs as a "universal recipient" for genes from other species, researchers said. Cow eggs are cheap and available from slaughterhouses _ the source for those in the UW experiments. With endangered species or animals that have been difficult to breed in captivity, scientists could take cells from any source _ skin, blood, whatever _ fuse them individually to cow eggs, grow embryos and then implant them in a surrogate animal that would give birth to them. The universal recipient of cow eggs also could benefit humans. Because of ethical and financial restrictions, human eggs aren't used for such purposes now. President Clinton has declared that no federal money will be used for human cloning, and he's proposed a five-year ban on such research. At a nearly science-fiction level, the specter of trans-species cloning could make obsolete the quintessential expression of impossibility: "when pigs fly." However, researchers don't believe freaks of nature or pigs with feathers will be the result of cross-species cloning. In these experiments, one species' unfertilized eggs essentially are robbed of their own genes and "fertilized" by a complete set of genes from a different species. The resulting embryo would be of the new species, not a jumble of both. The work was startling enough that when the UW researchers sent a short description of what they intended to present, the conference planners returned it, asking for more documentation and information. And a British journalist called First to ask if it were potentially feasible that a cow could give birth to a human baby. The UW researchers obtained the cow eggs from a slaughterhouse and removed their nuclei, which contained the cow DNA. They then inserted genes obtained from skin cells from adult sheep, pigs, rats and rhesus monkeys. The new genes took up residence and started reprogramming the cow eggs to accept the new species. An important aspect is that the researchers used adult cells from the other species _ cells that were already differentiated _ as did the researchers that created Dolly. Cloning from undifferentiated embryo cells has been done for some time.

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