Scientists report cloning monkey embryos
By MALCOLM RITTER, AP Science Writer 24 minutes ago
NEW YORK - American scientists reported Wednesday that they had cloned embryos from a 9-year-old male monkey and derived stem cells from them, reaching a long-sought goal that may pay off someday in new treatments for people.
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The work was published online by the journal Nature, which took the unusual step of asking another team of researchers to verify the work before publication. That reflects the legacy of a spectacular fraud in stem cell research from South Korea several years ago.
The new work is important because someday researchers hope to use such a process in humans to make transplant tissue that's genetically matched to patients, thus avoiding the risk of rejection.
Scientists had tried for years to produce stem cells through cloning in monkeys, because the animals are so closely related to humans and so provide a good way to study the process. But until now, it hasn't worked.
The advance is reported by Shoukhrat Mitalipov of the
Oregon National Primate Research Center in Portland with colleagues there and elsewhere. Some media outlets, including The Associated Press, had reported their success earlier, based on a presentation at a scientific meeting.
The scientists combined DNA from skin cells of the monkey, a rhesus macaque, with unfertilized monkey eggs that had their own DNA removed. The eggs were grown into early embryos, from which stem cells were removed.
The researchers cautioned that even if their procedure could be used to produce human stem cells, it's far too inefficient to be used in medicine. Human unfertilized eggs are in short supply and are cumbersome to obtain. The monkey work required 304 eggs from 14 female macaques to produce just two batches of stem cells, they wrote.
Still, Dr. George Daley of the Harvard Stem Cell Institute, who was familiar with the work, told the AP it was a "a very important demonstration" that the process is feasible in primates, the group that includes monkeys and humans.
Nature also published a verification of the results by an Australian team. In an e-mail to the AP, the journal said one reason was the highly publicized 2004 fraud that came out of South Korea, where researchers claimed to have produced stem cells from a cloned human embryo.
The journal emphasized that its request didn't indicate mistrust of scientists in the cloning field. Instead, the statement said, because of "questions will likely be raised about the veracity of the (American) experiments, given recent history in the cloning field, we view this as a relatively straightforward way of putting these questions to rest."
The Australian study, by David Cram and others at the Monash University, used DNA analysis of the male macaque, the two monkeys that donated eggs for creating the embryos, and the stem cells. The result "demonstrates beyond any doubt" that the stem cells came from cloned embryos, the Australians wrote in their Nature paper.
Oregon lab makes cloning breakthrough
Stem cells - A team says it has duplicated monkey embryos, a big medical advance
Wednesday, November 14, 2007
ANDY DWORKIN and RICHARD L. HILL
The Oregonian
Oregon researchers have made a breakthrough in the ability to reliably clone embryonic stem cells -- those with DNA identical to an adult monkey's -- a first step that could eventually lead to new medical treatments for humans.
The innovations, some as simple as marinating cells in a caffeine solution, have created dozens of multicelled blastocysts, the precursor to embryos in development. Blastocysts are a prime source of embryonic stem cells.
Shoukhrat Mitalipov, an Oregon National Primate Research Center researcher, told an Australian conference in June that his lab had crafted two stem cell lines whose genetic code came from skin cells off monkeys' ears, according to news reports from the conference.
"We were able to produce cloned embryos that grew to the blastocyst stage. That was a great breakthrough for us," said Don P. Wolf, a professor emeritus at Oregon Health & Science University who has long worked on cloning and reproduction at the primate center.
The work did not try to create pregnancies or babies from the cloned embryos. That would be technically difficult, Wolf said, because cloned embryos "aren't exactly normal" and don't lead to healthy successful pregnancies like normal embryos, even if they may yield stem cells.
The Oregon scientists are expected to announce further breakthroughs in the journal Nature in the coming weeks. Mitalipov, Wolf and officials with OHSU, which operates the primate center, declined to comment on that research Tuesday, saying Nature has placed an embargo on the information.
Scientists worldwide have spent years trying to create embryonic stem cells from primates -- cells that could grow and turn into any kind of cell in the body. Advocates say research could turn such cells into powerful tools to treat devastating diseases, including Parkinson's and multiple sclerosis, and spinal cord injuries. But to work well as treatments, the cells should be identical to the patient's: in other words, cloned to match a patient's DNA.
In August, Wolf and Mitalipov said they had used somatic cell nuclear transfer -- also called "therapeutic cloning" -- to produce embryos with DNA identical to that of adult rhesus macaques. The procedure involves removing the DNA from an egg and replacing it with DNA from another animal's adult cell.
That "cloned" cell must then be made to grow -- a challenge plagued with problems the Oregon lab has done much to solve.
Cells cloned from adult monkeys have grown poorly because the two cells involved -- the adult donor and the egg cell -- are at different life stages. When the two cells join, they essentially have different ideas about when to grow and divide. It's like two people trying to dance together, with one starting at a tune's first beat and the other starting in the middle of the song.
The Oregon lab realized that chemicals in the cell can send powerful signals to reprogram the donated adult DNA, telling it to divide like a fertilized egg. But those signals were being clouded by the steps used in therapeutic cloning.
The lab found better ways. For instance, a staining process used to see a spindle that pulls chromosomes apart harmed the hybrid cell's chances to grow normally. The Oregon scientists used polarized light to see that spindle instead. They also found that special chemical environments -- including small doses of caffeine -- can help give the proper signals for forming blastocysts.
The group made many cloned blastocysts from a variety of cells, including skin cells from adults, according to its August paper in the journal Human Reproduction.
Some blastocysts cloned from male adult monkeys had male sex chromosomes. That proved the DNA came from the male donors, not the female monkeys that produced the eggs. No one had previously given convincing evidence of cloning embryos from adult primates, Wolf said.
The research received renewed attention this week after a London newspaper, The Independent, reported on the work. The paper quoted Wolf as saying that "we could now produce cloned blastocysts (embryos) in the monkey at a reasonable frequency, at least a frequency that would allow us . . . to study the cloned blastocyst."
Finding a reliable and efficient way to clone blastocysts from adult DNA should let scientists make large numbers of primate embryonic stem cells. While that is a big advance, many more problems must be solved before medical treatments result.
Those include learning more about monkey stem cells, figuring out how to turn them into adult cells needed for disease treatments, perfecting the same methods in humans and -- finally -- testing whether the theories work to cure diseases.
The work to make embryonic stem cells in monkeys was largely funded by federal grants. Research on making embryonic stem cells, especially from humans, is politically controversial. The Bush administration has limited making new embryonic stem cells with federal money, but several states including California have financed that work.
The primate center has received worldwide attention before, often for efforts in "reproductive cloning" or making living animals, a different thing from therapeutic cloning for stem cells.
In 1997, scientists at the Hillsboro facility announced the birth of two rhesus monkeys -- Neti and her brother Ditto -- with a cloning-like technique, a first in nonhuman primates. In 2000, another group of primate center researchers produced a female monkey named Tetra using a technique known as embryo splitting.
Andy Dworkin: 503-221-8564;
andydworkin@news.oregonian.com
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I just dig this stuff (and it's being done in my backyard, too!--well, not my LITERAL backyard, but in the city I live in)
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