Cloned Pig Organs Easier to Transplant

By CHRIS KAHN
.c The Associated Press

 
BLACKSBURG, Va. (AP) - A research firm said Wednesday it has cloned pigs that
have been genetically altered to remove one of the paired genes that cause
the human immune system to powerfully reject transplanted pig organs.

``This is the first step in overcoming the rejection of pig organs in
humans,'' said David L. Ayares, vice president of research for PPL
Therapeutics Inc. ``We still need to make some modifications to create the
ultimate pig.''

He said both copies of the paired genes will have to be removed from a strain
of pigs before the animal organs would be accepted by the human immune
system.

Ayares said all the cloned pigs are female, but that male pigs with the
altered genes are expected to be born later this year. The animals then would
be bred in hopes of producing offspring that are true ``knockouts'' - animals
with both of the target genes knocked out of their gene structure.

PPL is a subsidiary of PPL Therapeutics in Scotland that helped clone Dolly
the sheep with the Roslin Institute in 1997.

The target gene that PPL scientists want removed puts a sugar on the surface
of pig cells. In humans, this sugar triggers a powerful rejection reaction
when swine tissue is transplanted. The hope is to remove both genes so the
swine tissue would not be rejected.

``This has been a major hurdle,'' Dr. Jay Fishman, director of
transplantation and infectious disease at Massachusetts General Hospital,
said of the PPL announcement. But he cautioned that more research is needed
before organs from genetically altered pigs would be ready for human
transplantation.

At least six labs have been searching for a way to manipulate pigs so their
organs could be used to replace ailing human hearts, lungs and livers.

The major problem has been finding a way to cause the recipient's immune
system to regard the transplanted organ as its own and not as foreign tissue
that must be destroyed.

Ayares said PPL will take several years to figure out how to deal with
adverse immune reactions and conduct trials with primates. If successful, PPL
could begin human clinical trials using harvested pig hearts, kidneys,
pancreases, livers, skin, and blood cells by late 2005.

According to the United Network for Organ Sharing, which manages the national
transplant waiting list, about 77,000 Americans were in line for transplants
in 2000, while 23,000 received them.

That same year, 5,742 people on the U.S. transplant waiting list died
awaiting transplants, according to the network.

Pigs have long been considered good candidates as a source for replacement
parts because their organs closely match the size of those in humans. But
organs from ordinary pigs would be rejected by humans because the surface of
pig cells have a sugar known as alpha-1-galactose.

The human immune system recognizes this sugar as foreign and reacts strongly,
causing a hyperacute rejection action that kills transplanted organs within
hours.

For this rejection action to be neutralized, both copies of the
alpha-1-galactose gene must be removed from the pig genome.

PPL's five piglets, born on Christmas Day, were engineered to lack one copy
of the gene responsible for alpha-1-galactose.

``People might wonder, who wants pig organs? I tell you, the people on the
waiting list,'' Ayares said.

The five newborns - named Joy, Angel, Mary, Star and Noel - huddled in the
corner of their pen of artificial turf at PPL's news conference Wednesday,
each with a number written above their tail.

At full size, these pigs will grow to several hundred pounds.

On the Net:

http://www.ppl-therapeutics.com