Designer Genes To Clone Cattle

Using cloning techniques similar to those that created the sheep Dolly, researchers have produced six genetically identical calves in an important step toward building herds of "designer" cattle.

The research proves that it will be possible economically to produce cows that give human milk or make drugs, or even to create pigs that grow human organs, said Steve L. Stice, chief scientist at Advanced Cell Technology Inc. in Worcester, Mass.

A report on joint research by Stice and scientists at the University of Massachusetts in Amherst, is being published on Friday in the journal Science.

Stice said the technique demonstrates that a cell culture from cattle or other livestock can be manipulated to contain specific, desirable genes, and that these cells can then be used to clone endless herds of genetically identical offspring.

"From a particular genetic mating," said Stice, "we could make a limitless supply of these animals."

The important advance represented by the new technique, said Stice, is that the researchers can make specific and targeted genetic changes in the cloning cell line. This was not possible with Dolly, he said.

Dr. Neil First, a prominent animal gene researcher at the University of Wisconsin, said the new technique "is an important step beyond Dolly," the Scottish sheep that is the first mammal cloned from a mature cell.

"This new work has a lot of significance," said First. "It allows a lot of flexibility in genetic engineering," something that was not demonstrated in the technique used to make Dolly.

Stice said that cloning techniques used for Dolly and in his laboratory both start with cells that are somatic that is, mature and of a stable, established cell type.

In Dolly's case, researchers at the Roslin Institute in Scotland started with a cell taken from the udder of an adult ewe.

Stice and his colleagues used fully developed fibroblast cells from a 50-day-old cow fetus. Although the calf was unborn, the cells removed from the fetus were mature.

In both cases, the retrieved cells were placed into a cow's egg from which the nucleus had been removed. Fusing the cell and the egg created an embryo, which was placed into the womb of an unrelated maternal animal that gave birth after carrying the young to full term.

This process results in animals that carry only genes from the original cells. While Dolly's creators, in effect, genetically duplicated a living, adult sheep, Stice and his group created a genetic duplicate of an unborn calf.

Stice said the new technique is more economically useful because cells derived from a fetus lend themselves to genetic manipulation.

"The reason we use fetal fibroblast cells is that they are much more robust, and we can do more with them," he said. "With these cells, we can make the genetic modifications faster and more efficiently."
Stice said he and his colleagues are working to build a herd of cattle genetically modified to be immune to mad cow disease, a brain disorder with a strain that can infect humans who eat infected meat.

He said the new technique also is being used to make cows that give milk containing human serum albumin, a medically important product now available only by separation from human blood.

Also planned, he said, are cows genetically altered to produce milk that closely resembles human milk. He said his group is also experimenting with pigs and hopes to create a herd of swine with hearts, lungs, livers and kidneys that carry human genes. Such organs could be transplanted into humans with less chance of rejection, said Stice.

Such human application of the animal cloning technology is many years away, said Stice, but agricultural use of cloning "is here now."

He said researchers will soon be able to produce "designer" dairy and beef herds that will make food production more efficient.

"Dairy farmers would like to have all females for their herd. With our transgenic process, we could produce bulls who would father only female offspring," said Stice. "The reverse could be done in the beef industry, where male cattle are wanted."