Wednesday, July 22, 1998

Associated Press
Dr. Teruhiko Wakayama displays two genetically identical
mice at a news conference today in New York.

Cloning breakthrough atUH

The scientists cloned
more than 50 mice in three
generations using the
'Honolulu technique'

By Helen Altonn


First came Dolly, a cloned sheep in Scotland. Now, Hawaii has Cumulina, the first mouse ever cloned from an adult cell.

Moreover, she's not alone like Dolly. She's one of three generations of clones produced from what is being acclaimed as "the Honolulu technique."

More than 50 identical cloned mice were developed from the pioneering technology, developed by a research group in the University of Hawaii's John A. Burns School of Medicine.

The international team, led by Ryuzo Yanagimachi, UH professor of anatomy and reproductive biology, includes Teruhiko Wakayama, Tony Perry, Maurizio Zuccotti and K.R. Johnson.

Their research is reported tomorrow's edition of Nature.

Yanagimachi and Perry, in a telephone interview from New York yesterday, said the reproduceable cloning of a mammal from adult cells has far-reaching implications for agriculture and medicine.

The technique may be useful in studying differences in cells involved in aging and diseases such as cancer, Yanagimachi said.

He suggested the possibility of redirecting cells to address some medical problems or regenerating organs.

"This technique also may help endangered species," Yanagimachi said. "It may be a way to increase individuals by cloning."

Thinking of the "potentials," he added, "It is just a fantasy today, but I think it can be done in the 21st century."

The investigators licensed the technology to ProBio America Inc., a Honolulu-based biotechnology company, to commercialize and test for expanded uses.

Cameron Reynolds, ProBio commercial director, said, "This is the dawn of a new age in the scientific world."

By Cindy Ellen Russell, Star-Bulletin
Ryuzo Yanagimachi, front, Tony Perry, left, and
Teruhiko Wakayama in their UH lab.

He said the company will extend the process to pigs, horses, cattle and other large commercial animals. Specialists around the world will transfer the technology to cloning of those animals, he said.

Perry said an old method was used to make Dolly, Gene and Polly -- "all of these notorious barnyard animals." Gene is a cloned calf; Polly a cloned lamb.

"The Honolulu technique is quite distinctive," he said, noting that the experiments were conceived and executed by Wakayama, a postdoctoral researcher in Yanagimachi's laboratory.

"That's an absolutely amazing achievement."

Said Wakayama: "We succeeded in using a new method and new cell type to clone mice from adult cells, and in repeating it to produce clones of clones of clones in essentially identical mice born a generation or more apart."

Perry said the cloned mice are still quite young. "We haven't had a chance to check if it's possible to make a cloned clone clone clone," or four generations.

"One of the cardinal features of this technique is it's highly reproduceable," he said, with a success rate of 3 percent that the researchers hope to build on.

The method involves removing the nucleus from an adult cell, then injecting it into an egg from which genetic information has been removed, the scientists said.

This gives researchers precise control over the cloning outcome, unlike the earlier procedure, used for Dolly, that involved fusing cells and mixing the contents, they said.

Cumulina, the first-born, was named for the cumulus cells surrounding the developing ovarian follicle in mice. Cumulus nuclei were injected into the eggs.

One series of experiments yielded 800 embryos, of which 17 developed fully. Of the implanted embryos, 10 healthy female mice survived and produced offspring.

Perry said, "One of the fantastic things, one of the reasons we in Honolulu should be really proud, is that Teru (Wakayama) and Professor Yanagimachi ... have solved some of the difficult biological problems, so we can really move things forward."

Gov. Ben Cayetano today said the work of Yanagimachi's team brings significant attention and prestige to the UH and the state. It will help to attract more biotechnology research and development companies, he said.

One of the earliest uses, Perry said, will be to rapidly reproduce replicas of special mice used in biomedical research.

Pharmaceutical companies use special mice to mimic human diseases for development of drugs, but such mice usually are difficult to mate and take a long time to multiply, he said.

Reynolds said many scientists have tried to create new mice from adult mouse cells and decided it was impossible. "What Teru (Wakayama) did was ignore the conventional wisdom of scientists who failed repeatedly."

"It was really quite a feat, especially in a small institute there in Hawaii staffed by a handful of people," he said.

Having made the breakthrough with the Honolulu cloning method, the researchers said they plan to continue developing it.

Perry said Yanagimachi "is a visionary scientist" who has worked 30 to 40 years to understand how egg and sperm cells meet to produce an offspring.

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