Friday, July 24, 1998



Isle firm joins
cloning venture

ProBio America Inc. will
join Roslin in cloning pigs
for organ transplants

From staff and wire reports

Tapa

WASHINGTON -- Researchers who created Dolly the sheep and 50 cloned mice have teamed up in a business deal to try to clone pigs whose organs could be used for transplants in people.

They want to use new cloning technology to try to make genetically engineered pigs whose organs could be used in animal-to-human il,14p,10p transplants known as xenografts.

The new business deal pairs two very controversial technologies -- cloning, and the use of animal organs in humans.

PPL Therapeutics Plc, the company set up to exploit technology developed by scientists at the Roslin Institute in Edinburgh, Scotland, announced the tie-up yesterday with ProBio America Inc. That Honolulu company is working with the team at the University of Hawaii headed by Dr. Ryuzo Yanagimachi which announced Wednesday that it had cloned mice.

"What we are now going to try and do is see if we can make their technique, the Honolulu technique, used with mice, work with pigs," Dr. Ron James, the managing director of PPL, said in a telephone interview.

James has said for a long time that he would like to try cloning to breed pigs for xenografts, but the cloning method used to make Dolly has not worked well on pigs. "It does seem that this new technique may be quite a bit more efficient," he said.

James noted that, like mice, pigs have litters rather than single offspring, so they can be bred more quickly than animals such as sheep and cows.

Douglas Vincent, University of Hawaii Animal Sciences Department chairman, said the proposed venture makes him a little nervous. "Even though I'm real impressed with the work Dr. Yanagimachi has done, I would say, 'Whoa. Let's slow down a bit.'"

There are are too many unanswered questions about possible viruses transmitted from pigs to humans, Vincent said. "I think there's great potential but we're still a long way off."

Dolly's cloners used electricity to fuse the nucleus from one sheep's cell to another sheep's egg, and then to reprogram that new egg so it started growing into a lamb embryo.

Yanagimachi and Teruhiko Wakayama and of the University of Hawaii developed a new technique which physically injects the new nucleus into the egg cell and uses chemicals to reprogram and activate the egg.

Scientists hope it will work on a wider range of animals than the Dolly technique. They note that sheep are easy to clone and mice are among the most difficult animals to clone, because of their biology.

Pig organs have been transplanted into people. They are favored for such use because pigs are about the same size as humans and are bred for food anyway. But there are problems -- the human immune system recognizes pig organs as foreign, and rejection can be fatal.

Pigs can be genetically engineered -- bred to carry human genes that will make their organs look like human organs to the immune system. That, however, is an expensive, hit-and-miss technique. Human genes only "take" in very few pigs.

Pigs also carry viruses that are integrated into their genes, known as porcine endogenous retroviruses.

Scientists do not know whether people can become infected with those viruses if they get pig organ transplants, and if so, whether the viruses would make them sick. They do not harm the pigs.

One of the big problems with primate-human transplants is they have been alleged to transmit HIV and some other viruses, Vincent pointed out.

"Some emerging viruses alleged to come from animals to humans are really a challenge, and I'm fearful if we move too fast on these things, there are some unknown things maybe in pigs that could do some serious damage to humans."

Dr. Richard Gill, senior vice president and general manager of BTG International, Pennsylvania-based technology transfer firm, said, "We are sensitive to concerns over using these powerful techniques inappropriately.

"We believe that, although human cloning is not something in which BTG has an interest, the use of gene therapy -- the cloning and implantation of genes to treat disease -- has great potential both medically and commercially."

BTG has a licensing relationship with PPL Therapeutics for synthetic production of a clotting factor for a rare form of hemophilia. PPL is working on a method to produce the protein in the milk of genetically altered sheep.

With cloning technology, genetic engineering becomes much more reliable. Not only can genes be put in, they can be taken out. So perhaps the Honolulu technique can be used to create pigs whose organs look human to the immune system, and do not contain the viruses.

Once a good pig model for human transplants is created, it could be cloned repeatedly to create a herd of pigs for "farming" for organs.

ProBio's Chief Executive Laith Reynolds says he hopes the Honolulu technique, which it has licensed, can be used to create many different kinds of animals for medical, agricultural and research uses. "There's an infinite number of uses for clones," said Reynolds, whose company is 25 percent-owned by Australian company ForBio.

Some analysts say the xenotransplant industry could be big business. More than 55,000 Americans are on the waiting list for an organ transplant but only about 20,000 transplants are done each year -- due mostly to a shortage of organs.

Experts have asked for a moratorium on animal-to-human transplants until scientific and ethical issues are explored.


Science center in
New Jersey gets the mice

By Helen Altonn
Star-Bulletin

Tapa

Hawaii's famed cloned mice -- seen around the world on television the past few days -- didn't return home this morning with the scientists who produced them.

They were donated to the Liberty Science Center in New Jersey where they will be exhibited to teach people about cloning. Dr. Betty Faber, staff scientist there, said the center is delighted to have the four mice.

They were happily playing around in a 10-gallon tank at the museum while University of Hawaii researchers Ryuzo Yanagimachi and Teruhiko Wakayama tried to get home on Delta Airlines from New York.

Vincent De Feo, chairman of the UH Anatomy and Reproductive Biology Department, planned to greet the men who succeeded in cloning the first mice from an adult cell at 9 p.m. But the plane had to return to San Francisco because of engine problems, he said.

The men had to change planes to go to Los Angeles and didn't arrive until 5 a.m. today, he said. Nonetheless, he said, Wakayama, credited with the technique leading to the successful cloning, was in his office when he arrived this morning, De Feo said.

He said the scientists didn't bring the four mice back that they took to New York for an announcement of their achievement because they might have been exposed to organisms. "The fear was if they brought them back, it would ruin the rest of the colony."

Cumulina, the original cloned mouse, wasn't among those taken to New York.

Aside from the potential medical and agriculture developments expected from the cloning process, De Feo said, "There could be books about this wonder mouse. "There's fascination with this little creature -- an alternative to the fictional Mickey Mouse, and it's for real."




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