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Transgenic pioneer transplanting to Pitt

Team successfully inserted jellyfish gene in a monkey

Thursday, May 10, 2001

By Byron Spice, Science Editor, Post-Gazette

The biologist who took a gene from a jellyfish and inserted it into a rhesus monkey egg, creating the world's first transgenic primate, now is plucking his research team out of the Oregon Health Sciences University and transplanting it to Oakland.

 
    On the net

Gerald Schatten's research page

Oregon Regional Primate Research Center

 
 

Gerald Schatten, 51, will join the obstetrics, gynecology and reproductive sciences faculty of the University of Pittsburgh School of Medicine in July. His laboratory will become part of the Magee-Womens Research Institute, where he will head a newly established Pittsburgh Development Center.

The recruitment of Schatten is being touted as a coup both inside and outside the medical school.

"This is a huge breakthrough," said Dr. James Roberts, director of Magee's institute, a research arm of Magee-Womens Hospital. The outside research funding that Schatten will bring with him will immediately boost the institute's funding from $52 million to $65 million.

Much of Schatten's research in Pittsburgh will continue to focus on how to transfer foreign genes into monkeys, a technology that might allow scientists to design monkeys that mimic human disease. These genetically engineered monkeys promise to be particularly effective animal models of disease, and could speed research on such health problems as Alzheimer's disease, diabetes and Parkinson's disease.

Schatten's research group also will pursue such hot topics as embryonic stem cells, the biology of fertilization and early development, and attempts to clone nonhuman primates.

Schatten almost joined Pitt four years ago, but decided he needed to gain more experience in primate reproduction. He left a post at the University of Wisconsin-Madison to join the Oregon Health Sciences University in Portland and its renowned primate center. But he kept talking with Dr. Ronald Herberman, director of the University of Pittsburgh Cancer Institute, and eventually was persuaded to move to Pittsburgh.

"We love Oregon, but more importantly we love our science," Schatten said. In Pittsburgh, his research group can take advantage not only of a strong medical school, but of the expertise of nearby Carnegie Mellon University and a bustling private biotechnology sector.

"I know that the Pittsburgh area is booming with biotechnology, particularly in the area of tissue engineering," Schatten said. "My head is swimming just thinking of the possibilities. We're very excited."

About a third of his research team, which no consists of about two dozen scientists will move with Schatten this summer; the rest will remain in Oregon until the Magee research tower on Craft Avenue can be expanded to accommodate them.

Pitt officials anticipate that Schatten's lab could double in size yet again in the next couple of years and will generate between $4 million and $8 million in additional research grants over the next five years.

Like Schatten's other research animals, the transgenic monkey, named ANDi, will remain in Oregon, at least for now.

"ANDi is great," Schatten reported, noting that he is healthy at 7 months of age and growing normally.

ANDi -- a backwards acronym for "inserted DNA" -- carries a jellyfish gene that produces a protein that glows green. The gene is active in ANDi, though he does not glow. He may yet produce enough protein to glow, but researchers haven't bothered to check lately.

"He's busy being a monkey," Schatten explained.

Creating a glowing green monkey was never the point anyway.

"We took a very small step with ANDi," Schatten said. By using a modified virus to insert a foreign gene in a primate, Schatten's team duplicated a step accomplished in mice a quarter of a century ago.

Now, the challenge is to develop a technique to put a gene in precisely the right place within a monkey's chromosomes. If that is possible, it might be possible to create new models of human diseases.

As the closest genetic cousin to humans, monkeys might mimic human diseases much better than conventional lab animals, such as mice. When the genetic mutation that causes cystic fibrosis in humans is added to a mouse, for instance, the mouse does not develop the disease.

Monkeys might make excellent models for cystic fibrosis, but that doesn't mean they should be used that way, he said.

"Many of us would have serious concern about a colony of monkeys that was suffering from that kind of disease," he noted.

It might be possible, however, to model some diseases, such as Alzheimer's disease, in a way that is meaningful to researchers without causing debilitating symptoms in the monkeys, he added.

He also envisions using transgenic techniques to label monkey cells in such a way that they can be imaged with an MRI scanner. This technique would not cause any ill effects in monkeys, but would allow researchers to monitor the very earliest events in fetal development.

Some scientists suspect that the failure of genes to turn on or off at appropriate times during development may underlie certain conditions, such as autism, Schatten noted.

Schatten has a particular expertise in the mechanics of fertilization and for how the embryo rearranges itself.

"In scientific circles, he's probably better known for that than the more recent applied work with primates," said Ted Golos, a reproductive biologist at the Wisconsin Regional Primate Research Center in Madison.

Last year, he published a paper in the journal Nature that raised questions about the safety of intercytoplasmic sperm injection, or ICSI, a widely used technique for treating male infertility. The technique involves injecting sperm -- or sometimes just immature sperm, called spermatids -- directly into the egg.

Schatten's research suggests the injection may damage proteins in the eggs as well as disrupt the egg's normal removal of proteins from sperm. These seemingly subtle changes could have long-term effects on the physical or behavioral health of the child, he suggested.

Schatten also is using primates to study the potential of embryonic stem cells. Researchers hope they might be used to regenerate tissue in damaged hearts, to restore insulin-producing cells in the pancreases of diabetics or to replace brain cells damaged by Parkinson's disease.

But much of what is known about embryonic stem cells has come from studies of lab mice, inbred animals far different from humans, so the potential benefits and side effects are poorly understood.

Schatten plans to study the potential of these cells by creating "artificial twins" of a monkey. He would use a low-tech technique called embryo splitting to divide a monkey embryo in two; one embryo would be implanted in a womb and allowed to develop normally, while the other embryo would be used as a source of stem cells that could be tested in the genetic twin.



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