By Sean Henahan, Access Excellence
England- (24 July 1997)- Move over Dolly, and make room for Polly,
the first sheep cloned by nuclear transfer technology bearing a human gene.
Investors hope the lamb will make them a mint, but more importantly, the
arrival of Polly could be good news for hemophiliacs and others who rely
on expensive protein therapy of their diseases.
Polly was created by the same team at the Roslin Institute that gained
fame earlier this year with the birth of Dolly, the first sheep cloned
using adult animal cells. In Polly's case, the researchers did not use
adult cells. Rather, they used fibroblast cells obtained from a sheep fetus.
This is considered a somewhat less tricky procedure. However, Polly is
the first sheep to receive genetically altered fetal cells, in this case
modified with a human gene. The human gene was introduced into the nucleus
of the lamb fibroblast which was then inserted in an enucleated donor ovum.
current technique represents a significant advance over techniques currently
used to produce transgenic animals. The current technology involves placing
target genes from one species into the fertilized egg of another, and then
waiting to see if the gene is expressed. This laborious process produces
results about ten percent of the time at best. Since fertilized eggs are
in short supply, the ability to use the more common fibroblast cells could
increase the success and efficiency of cloning transgenic animals.
Graphic: Cloning Dolly.
Polly also contains a human gene.
Five lambs were produced by the new technique. The scientists have so
far found marker-genes in two of five lambs. These marker genes confirm
that that the human gene was expressed in the sheep. While the researchers
report that the gene inserted in the sheep is of "therapeutic value" they
have yet to reveal what gene it is. The researchers took the controversial
step of announcing their findings in a press release rather than in a peer-reviewed
The Edinburgh company that sponsors the research, PPL, already produces
transgenic sheep that produce alpha-1-antitrypsin, a protein used to treat
the symptoms of cystic fibrosis. Transgenic sheep have also been
genetically engineered to produce proteins used by patients with clotting
disorders such as hemophilia, including fibrinogen, factor VII and factor
The new cloning technology will allow scientists to create large numbers
of identical, milk-producing ewes. Using genetic engineering, the sheep
can be modified to produce therapeutic proteins in their milk. These expensive
proteins can then be removed from the milk and used therapeutically.
"This is a realization of our vision to produce instant flocks or herds
which express high concentrations of valuable therapeutic proteins very
quickly," Alan Colman, PPL's research director, told the media. He estimated
the company could be selling therapeutic proteins from cloned sheep in
about two years.
It is more than likely that rather than produce expensive herds of cloned
sheep, the researchers would create a small number and then let nature
takes its course, allowing the animals to breed naturally. Finding out
how well the target genes carry from generation to generation is of great
interest to the investigators.
They won't be selling anything produced by the first batch of transgenic
sheep. This is because of concerns about scrapie infection, a sheep disease
believed to be related to BSE, or mad-cow disease. The five experimental
lambs did not come from a a scrapie-free herd. This problem highlights
the downside of transgenic animal cloning, since there is some concern
that humans could become infected with viruses or prions from the animals.
On a more positive note, the new research may open the way for scientists
not only to add desired genes, but to remove undesired genes. This would
be essential for removing antigens pig organs that might some day be used
as replacement parts in humans.
Related information on the Internet
Generation and In Utero Surgery
Article in NATURE
Wilmut Nature Article on Nuclear Cloning
Activity: Cracking the Code, Cloning Paper Plasmid