Two Cloned Lambs May Produce Drug For Use By Humans Inserted Gene Creates Milk With Blood-Clotting Protein

The Scottish scientists who cloned Dolly have now produced Molly and Polly, two lambs cloned with a human gene so their milk will contain a blood-clotting protein that can be extracted for use in treating human hemophilia.

Molly and Polly were born in July and Dr. Ian Wilmut of the Roslin Institute in Scotland said his team should know by spring if the lambs’ milk will contain useful quantifies of factor IX, a protein that helps blood to clot.

Wilmut and his team announced the cloning achievement in a report in the journal Science to be published Friday.

Experts say the creation of Molly and Polly is the logical next step following last year’s cloning of Dolly, the first mammal cloned from an adult cell. The new work could prove that cloning is an efficient way to create herds of cows or flocks of sheep that act as drug-making factories.

Wilmut said Molly and Polly were produced with the same technique, called nuclear transfer, used to make Dolly, but the original cell used to produce the lambs came from a sheep fetus instead of from an adult animal.

In nuclear transfer, scientists remove the nucleus from an egg and replace it with the nucleus from another cell. The egg is then placed into the uterus of a surrogate mother that gives birth to an offspring that has only the genes of the original cell.

In Dolly, the original cell came from an adult ewe’s udder.

For Molly and Polly, Wilmut said his team took the original cell from a 26-day-old sheep fetus. Into this cell, the researchers inserted a human gene for factor IX, linked to a sheep gene that increases milk production. They also put into the cell a marker, a gene that causes resistance to an antibiotic.

The manipulated cell was then nurtured so it replicated to thousands of cells.

Wilmut said the team then added an antibiotic to identify those cells that included the antibiotic-resistant gene. These cells were separated from the rest.

A total of 425 of these gene-modified cells were then placed into eggs that had had their nucleus removed. These eggs were cultured for five to six days, growing to an early embryo stage.

Wilmut said 62 embryos were then implanted into surrogate mother sheep.

From these, six lambs were born. Three contained both the human gene and the marker gene. One of these lambs died, leaving only Molly and Polly.

“The new lambs are identical to each other and identical to the original fetus except for the new gene that we introduced,” said Wilmut.

Wilmut said the lambs will be allowed to grow normally and then given shots in the spring to induce lactation. This will enable the researchers to test their milk for the human factor IX. He said the lambs will mature by October and will be mated so they will produce lambs in February of 1999.

“By then, we should have a good idea of the milk volume and the yield of the useful protein from these animals,” said Wilmut.

The selective breeding of Molly and Polly and their offspring could lead to a whole flock of sheep, all of which produce human factor IX in their milk, he said.

The lambs are the first animals cloned to produce human drugs in their milk, but other techniques have been used to create drug-making animals. Several companies are now testing cystic fibrosis and heart attack drugs that come from the milk of genetically engineered sheep or goats. These animals, however, were produced by injecting genes into a fertilized egg and then implanting the egg in a surrogate mother, a technique less efficient than the Roslin Institute’s cloning. Only about 2 percent of such eggs grow to live animals and only a small percentage of the survivors actually contain the target genes.