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Three Genetically Cloned Calves Contain Extra Gene

By Rick Weiss
The Washington Post
WASHINGTON

Scientists for the first time have cloned genetically engineered calves, a feat they said would help them create herds of identical cows that make medicines in their milk.

The three calves, born last week at a research farm in Texas, represent the latest in a string of rapid advances in animal cloning since researchers in Scotland announced one year ago they had cloned an adult sheep named Dolly.

The calves were created with a technique somewhat more efficient than the one used to make Dolly. Dolly was the result of 277 attempts; each of the three calves - and a fourth that died within a week after birth - was the result of about 50 tries.

And unlike Dolly, the cloned calves (the first two were named Charlie and George; the third, born Friday, has not yet been named) were genetically altered in advance so that all of their cells contain an extra gene.

That gene is just a "marker" gene that has no significant physiological effect. But the successful integration of that gene into each calf provides important proof that it is possible to manipulate the genetic makeup of cattle in the process of cloning them.

"This moves cloning technology a major step forward toward making it practical and useful in a very important commercial species," said James Robl, a developmental and reproductive biologist at the University of Massachusetts in Amherst, who led the work with Steven Stice, chief scientific officer at Advanced Cell Technology, a biotechnology company in Amherst.

Stice and Robl described their work Tuesday at a meeting of the International Embryo Transfer Society in Boston.

Dolly is still the only clone made from a cell taken from an adult mammal. The newborn calves and other cloned mammals born in recent months all were cloned from cells taken from fetuses, which is easier to accomplish.

The U.S. beef and dairy industries combined have annual revenues of about $60 billion, and that value could be enhanced with genetic engineering, said Robl, who is a consultant and co-founder of ACT. Eventually, Robl said, the company hopes to use similar techniques to grow engineered animals containing cells and organs suitable for transplantation into people.

Robl said the team has already advanced the work by creating several cow clone embryos containing the gene for a protein called human serum albumin. Those calves, which would be the first cloned calves engineered to contain a medically useful human gene, are developing inside the wombs of surrogate mother cows.

In those clones, the gene was placed under the control of a molecular switch that should limit the protein's production to the calves' udders. Robl declined to say when they were due to be born.

Human serum albumin is infused into many hospital patients suffering from burns or other injuries whose treatment requires an increase in blood volume. Robl said the team hopes to extract the albumin from the cows' milk, purify it, and sell it as a substitute for existing human serum albumin products, which are obtained from human blood donors and carry a small risk of contamination with infectious agents.

ACT is under contract to produce the albumin for Genzyme Transgenics of Framingham, Mass., a company that has been producing human drugs in the milk of genetically engineered, non-cloned goats.

George and Charlie are not the first farm animal clones to be genetically engineered. Last month, Ian Wilmut and his colleagues at the Roslin Institute and PPL Therapeutics in Scotland described in a scientific journal their creation of Polly and Molly, two cloned sheep carrying extra copies of gene called Factor IX.

That gene should allow the two sheep to make in their milk a blood-clotting factor needed by some hemophiliacs. But scientists won't know if they were successful until this spring, when the lambs become old enough to lactate.

Still, it is unclear how complicated or expensive it may be to extract the Factor IX or other drugs from the milk of cows or sheep. And although the clones are, by definition, genetically identical, no one knows whether all the members of a cloned herd or flock will produce their products with sufficient uniformity and quality to satisfy regulators such as the Food and Drug Administration, which require pharmaceutical production methods to meet a minimum requirement known as Good Manufacturing Practice.