Stem cell feat revives ethics debate on human cloning

Researchers successfully breed healthy living mice from non-embryonic stem cells, taking a step closer to human cloning. 'We have gone from science fiction to reality,' says one expert.

By Thomas H. Maugh II

News that Chinese researchers have succeeded in growing healthy living mice from mouse skin cells takes scientists a significant step closer to human cloning, experts say, and is thus likely to reopen debate about the ethics of such reproductive techniques.

The new feat -- in which animals were grown from cells that had been reverted back to their embryonic state -- is technically different from cloning. But the outcome is the same in both cases: a genetically identical copy of the donor animal.

"We are fast forwarding to the era of designer babies," said Dr. Robert Lanza, chief scientific officer at Advanced Cell Technology Inc. in Worcester, Mass., who was not involved in the studies. "We have gone from science fiction to reality."

Cloning, in which the nucleus is removed from a cell and implanted in a fertilized egg, has never been achieved in humans. Nor has the new technique -- using what is known as induced pluripotent stem, or iPS, cells -- been tested in them. Because that process works in mice, however, it should also work in humans, Lanza said.

"We now have the technology to create iPS cells from skin or hair follicles. Combine that with showing that they can actually create a living organism, and that's pretty scary," Lanza said. "All the pieces are here for serious abuse. The only way to find out if it works in humans is if someone does it."

And that could happen in a backroom in Tijuana as easily as in a major laboratory, he said in reaction to Thursday's announcement. "You can order the necessary genetic constructs, the protocols are published and have been reproduced. There are a dozen approaches that could be used. What's very troubling is that if you have a piece of skin from anybody -- Albert Einstein, Marilyn Monroe, Michael Jackson -- you could create a child."

But "that is an experiment that shouldn't be done," said biologist Kathrin Plath of UCLA's Broad Center of Regenerative Medicine and Stem Cell Research, who was not involved in the research. "If you look back at the mouse cloning experiments," she noted, many died shortly after birth or suffered from genetic abnormalities.

The scientists involved in the new research agreed.

"It would not be ethical to attempt to use iPS cells in human reproduction," Fanyi Zeng of Shanghai Jiao Tong University said in a telephone news conference. "It is important for science to have ethical boundaries." Her study, she added, was "in no way meant as a first step in that direction."

What her study, and that of a second group of researchers, does show is that the iPS technique can produce any type of tissue and thus create cells identical to embryonic stem cells.

But even as the finding revives the cloning issue, it should relieve much of the debate about the morality of using embryonic cells in research on curing diseases such as diabetes and Parkinson's because it provides a source of tissue that can be obtained without destroying fetuses.

Researchers first produced iPS cells two years ago, but there have been lingering doubts about whether the cells are truly identical to embryonic cells or instead are capable of producing only some types of body cells.

The new results, published online Thursday by the journals Nature and Cell Stem Cell(09)00335-X, appear to erase those doubts. The results also open the door to a variety of applications beyond producing stem cells for medicinal purposes, including the production of endangered species and the reproduction of prized farm and other animals.

The reports "show that iPS cells are identical to embryonic stem cells," Plath said. "It hadn't worked before, so it wasn't clear that it would ever work." The approach the teams used was "the gold standard because it is the only assay [test] that proves the cells are pluripotent."

The results are "comforting, because there has been a lingering concern that iPS cells had failed in this particular assay," added biologist Robert Blelloch of UC San Francisco's Broad Center for Regeneration Medicine and Stem Cell Research, who was not involved in the current work. But he cautioned that the teams were ultimately successful in only a few of many attempts. "What's missing, which will really be key, is whether there is anything about the cells that did pass the test that is different from those that didn't."

The technique that both teams used is called tetraploid complementation.

When researchers first started studying iPS cells, they would assess their properties by injecting them into a blastocyst, a very early embryo. What they found in those studies was that the iPS cells and the host embryo's cells would both contribute to the resulting animal, producing a chimera -- a mosaic of genetically different cells -- rather than a copy of the original animal.

More recently, researchers have fused the cells of the host blastocyst to one anotherso that each cell contains four sets of chromosomes, instead of the standard two sets, making them tetraploid. When that is done, the host cells can form only the placental tissues; all the animal's tissues must come from the injected iPS cells. Though researchers have been able to produce living animals from embryonic stem cells using this technique, they have never been able to produce them from iPS cells, creating doubts that the iPS cells were truly pluripotent, or able to become any type of cell.

In the new studies, "the method of producing iPS cells didn't change," Blelloch said. "They used the same methods and materials everybody else is using." He characterized their research as a "brute force effort" in which enough attempts finally yielded success.

The more successful of the studies, by Zeng and colleagues at the Chinese Academy of Sciences in Beijing, created 37 iPS cell lines that could be grown in the laboratory. Three of those lines produced 27 live offspring by tetraploid complementation. Some of the mice have successfully mated and have produced more than 100 healthy second- and 100 third-generation mice.

But Zeng cautioned that some of the first-generation living mice had abnormalities, although she did not say how many and what those abnormalities were. That, she said, will be the subject of a future paper.

The second team, from the National Institute of Biological Sciences in Beijing, achieved only four births, with only one mouse making it to adulthood.

thomas.maugh@latimes.com

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