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5-Animals: News on transgene pigs for xenotransplantation



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Pigs Grown With Human Genes
By PAT EATON-ROBB Associated Press Writer

NEW HAVEN, Conn. (AP) - At a top-secret farm hidden in the Northeast, 
scientists are growing pigs whose DNA has been altered with human genes. 
It sounds like the stuff of science fiction, yet officials at Alexion 
Pharmaceuticals Inc. (Nasdaq:ALXN - news) say they are close to figuring 
out how these pigs can figure in the treatment of human organ failures, 
spinal cord injuries and illnesses such as Parkinson's disease. The idea 
of transplanting animal parts to humans, called xenotransplantation, 
isn't new. But, until recently, nobody knew how to keep the human body 
from rejecting the organs.
About 18,000 organ transplants are performed in the United States each 
year and more than 40,000 patients are waiting for donor organs, 
according to the United Network for Organ Sharing. About 10 Americans die 
each day waiting for transplants, network officials say.
Alexion's first altered pigs, created with the help of researchers at 
Virginia Tech in the early 1990s, contained a human gene called CD-59. 
Scientists hoped the grafted gene would trick the human body's immune 
system into believing that the pig parts were human.
While transplanted organs from those pigs were able to survive for a 
couple of days in their new host, the body eventually rejected the parts.
A major breakthrough came last year when the small biotechnology firm, 
working with scientists in Australia, figured out a way to alter a 
sugar-like molecule in pig cells so that human antibodies would not 
recognize it as foreign.
The molecule had been acting as a magnet for human antibodies, betraying 
the fact that the transplanted tissue was not human. Alexion quickly 
patented
the process.
''If you now take cells from those animals and challenge them with human 
serum, they are almost indestructible in the lab,'' said Stephen P. 
Squinto, the chief technology officer at Alexion.
Scientists at Alexion have already transplanted brain cells from their 
transgenic pigs into rodents with a syndrome similar to Parkinson's, a 
degenerative nerve condition that affects motor function.
The transplanted cells not only survived, they became neurotransmitters 
in the animals' brains and helped correct the tremors, Squinto said.
The same experiments are now being conducted in baboons. If those 
experiments work, Alexion hopes to begin human trials by the end of the 
year.  Researchers hope that within 15 years humans will be able to 
receive permanent organ transplants from swine.
The company also has seen remarkable results by transplanting cells from 
a pig's snout into the damaged spinal columns of rodents, Squinto said. 
The cells replace the damaged protective sheath around the spine and 
allow nerve cells to regenerate.
''Would we expect that we will be able to take a person who is a 
paraplegic and have them walking or running in the Olympics?'' Squinto 
said. ''No, I don't think that's the case. But restoring some function to 
that person is certainly a goal.''
Xenotransplantation faces stiff opposition from some in the medical 
community and from animal-rights activists. Alexion was unwilling to 
allow a reporter or photographer to visit their facilities, in part 
because they could be targeted by animal rights protesters.
Among the medical concerns: the fear that transplanted organs could bring 
with them new diseases caused by viruses now living only in pigs. A virus 
originally transmitted from chimpanzees to humans is believed to have 
caused AIDS.
Because a transplant patient's immune system is suppressed with drugs, 
xenotransplantation provides an ideal environment for pig viruses to 
mutate, said Dr. Thomas Murray, director of the Center for Biomedical 
Ethics at Case Western Reserve University.
''There are risks to third parties here,'' he said. ''If you get an organ 
from a cadaver, you decide whether to accept that risk for yourself. But 
if you get an organ from a pig, many more people are put at an unknown 
risk.''
The FDA had temporarily banned animal-to-human transplant experiments 
because of pig viruses, but dropped the ban late in 1997. Scientists now 
believe they have identified all the so-called retroviruses that are 
unique to pigs and can screen for them, Squinto said.
Dr. David Hull, director of the clinical transplant program at Hartford 
Hospital, is excited by the idea of farms filled with transplantable 
organs.
The technology could dramatically improve the lives of thousands of 
people, many of whom can no longer even get out of bed because their own 
hearts or livers are failing, he said.
''You'd be able to meet the needs of everybody,'' he said. ``You would 
save a tremendous amount of money and lives.''
But animal rights activists say they whole process is unnecessary. Rather 
than killing animals for organs, they suggest everyone be considered an 
organ donor unless they specifically request an exemption, the opposite 
of the current policy.
''That is the way to save a lot of money, and it would save a lot of 
suffering,'' said Sandra Larson, with the New England Anti-Vivisection 
Society.


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