SIGHTINGS


 
Organ Rejection Breakthrough
Using Pigs With Human Genes
By Pat Eaton-Robb
The Associated Press
2-22-99
 
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. 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 http://www.unos.org/frame_Default.asp 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 http://www.cwru.edu/med/bioethics/bioethics.html 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 http://www.neavs.org/ New England Anti-Vivisection Society.





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