By Vicki Brower

Special To BioWorld Today

From the people who brought you Dolly, PPL Therapeutics plc announced the birth of its first cloned calf at its U.S. subsidiary in Blacksburg, Va.

The 98-pound Holstein calf, called Mr. Jefferson after its birth date and place — Presidents Day, in Virginia — was produced by nuclear transfer of a fetal somatic fibroblast cell, unlike Dolly, who was produced from the nucleus of an adult mammary cell.

"The birth of Mr. Jefferson is significant even though he is not transgenic, because we have now demonstrated that the technique of nuclear transfer can be used not only in sheep, but also in cattle," said Julian Cooper, Ph.D., chief operating officer at PPL in Blacksburg.

The ability to produce cows via nuclear transfer offers PPL a faster, more efficient method of generating large-volume products in transgenic animals, added Ron James, managing director of PPL at the company's headquarters, in Roslin, Scotland.

"Mr. Jefferson represents an important step toward using transgenic cattle to produce large quantities of cost-effective therapeutics quickly; producing transgenic cattle will be the easy part," Cooper added. Transgenic animals are produced by inserting a desired gene into a donor cell's nucleus while it is in tissue culture.

Cloning will permit a wide range of precise genetic modifications to be made, increasing the range of pharmaceuticals that can be produced in cows, such as human nutraceuticals, Cooper said. The company currently is producing alpha 1 anti-trypsin in sheep's milk, which is in Phase II trials for cystic fibrosis.

PPL's first commercial application for cattle will be to produce human serum albumin in the milk of transgenic cows. Specifically, it plans next to knock out the cow gene for this and replace it with its human homologue — thereby avoiding the need to purify the cow protein from the milk. Knocking out animal genes has been successful in tissue culture, so the next step will be to do that in cattle, Cooper told BioWorld Today.

PPL Moving To Silence Dolly Controversy

PPL stressed that from its commercial standpoint, it is more important to produce clones of founder transgenic animals from genetically modified fetal cells than to dwell on "any academic and scientific discussions surrounding Dolly's origins."

The company acknowledged the current speculation over the origins of Dolly — whether she was in fact cloned from an adult somatic cell — and stated that it recently has undertaken further tests which support the earlier conclusions that Dolly was produced from an adult cell. "We believe this will fully resolve this issue; results will be published when they are complete," PPL said.

In January, three cloned transgenic calves were born in Texas as a result of work done by Advanced Cell Technologies (ACT), of Worcester, Mass.

The cloning technique ACT used differed in a number of significant ways from that used by PPL: ACT used dividing cells, whereas PPL used ones that were quiescent; ACT started developing the embryos later than PPL, which began dividing right after fusion; ACT used eggs collected from slaughterhouse cows that it matured, whereas PPL took eggs from superovulated animals; and ACT cultured its embryos in an incubator and did nonsurgical transfers into a surrogate cow, whereas PPL did surgical transfers.

ACT also plans to raise a herd of transgenic cows to produce human serum albumin. (See BioWorld Today, Oct. 9, 1997, p. 1.) — BioWorld correspondent Nuala Moran contributed to this report.

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