Scientists Create Designer Livestock

From the same people who produced Dolly the sheep come three lambs, complete with designer genes.

The three lambs are products of a process called gene targeting. With unprecedented precision, the method inserts new genes or alters specific parts of sheep DNA that are then carried by the clone.

It's the first time so-called gene targeting has been done in any mammal besides the mouse, and it promises healthier livestock. The technique could even lead to producing livestock that could be used as organ banks for humans.

'Holy Grail' For Livestock Future

"For some of us, this was sort of the Holy Grail, the ability to achieve this kind of modification," said Alan Colman, research director at PPL Therapeutics in Edinburgh, Scotland - the same laboratory that helped produce Dolly the cloned sheep in 1996.

Colman and his colleagues first altered DNA in sheep cells and then used the cells to create sheep by cloning. Three female sheep produced last year with genetic changes are still alive.

Two of the sheep carry a human gene that makes them produce milk with a certain human protein. The third animal's DNA contains a deliberate disruption in its natural DNA code.

Livestock clones with genetic changes have been created before by simply inserting human genes into a fertilized egg. But that approach gave scientists no control over where in the animal's body the inserted gene would turn on or how active it would be. The older technique also did not permit making specific changes in the animals' own genes.

The new approach largely solves those problems.

"We are clearly at the dawn of a new era in mammalian genetic technology," Milind Suraokar and Allan Bradley write in this week's journal Nature, where the study appeared. Suraokar and Bradley are molecular geneticists at Baylor College of Medicine in Houston.

Disease-Free And Better-Tasting

It is hoped that within a few years, the work will lead to healthier sheep that are stripped of weak genes, such as one that makes them vulnerable to scrapie, the disorder linked to "mad cow" disease.

The technique could also enhance animals and make their meat or milk tastier and more nutritious for eating.

This "is a significant advance," said Randall Prather, a professor of animal science at the University of Missouri at Columbia. "It's something that people have talked about and said, 'Yeah, we can do it.' But this is the first time it's been shown that it can be done."

PPL Therapeutics also hopes to use the new gene targeting process to create genetically altered pig clones that could provide organs for transplant into humans.

Gene targeting would be used on pigs to remove the chemical red flag that normally alerts the human immune system to react to foreign tissue. Eliminating that signal would reduce transplant patients' risk of suffering organ rejection.

Colman the method could also allow scientists to mimic human diseases in a wider range of animals to test new therapies. Mice are now widely used for such research, but human diseases often evolve differently in mice than in people because of physiological differences.

Method Not Yet Perfected

Still, the new process isn't without its problems.

Among the 80 genetically altered embryos that were implanted in ewes, only 14 survived to birth. And only three of the 14 lived past six months. Colman attributes the high death rate to factors in the cloning process, not the genetic manipulation.

An approach used since the mid-1980s to genetically alter mice hasn't worked in livestock. As Suraokar and Bradley explain, "The hope that livestock could be genetically manipulated like mice languished until a few years ago, when it was revived by the cloning of livestock species."

Borrowing from cloning technology, PPL's scientists created altered copies of a stretch of sheep DNA, then inserted them into sheep cells called fibroblasts. In some of those cells, the altered DNA pieces took the place of their natural counterparts.

From those cells, scientists removed the nucleus - the part that contains the DNA. They inserted each nucleus into a fertilized sheep egg stripped of its own nucleus. These eggs were then grown into embryos and implanted in ewes.

ABCNEWS Radio correspondent Linda Albin, ABCNEWS.com's Amanda Onion and The Associated Press contributed to this report.

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This article posted July 3, 2000.