Monkey Embryos Cloned for Stem Cells
Thursday, November 15, 2007; Page A01
Researchers in Oregon reported yesterday that they had created the world's first fully formed, cloned monkey embryos and harvested batches of stem cells from them -- a feat that, if replicated in people, could allow production of replacement tissues or organs with no risk of rejection.
Successful creation of the cloned embryos, each from a single monkey skin cell, effectively settles a long-standing scientific debate about whether primates -- the taxonomic grouping that includes monkeys and people -- are biologically incapable of being cloned, as some had come to believe after years of failures.
That fact alone could reinvigorate a stalled congressional battle over whether restrictions on human embryo cloning should be tightened or loosened. Currently, such work is legal with private funds but off-limits to federally funded scientists.
The Oregon researchers did not transfer the embryos to female monkeys' wombs to grow into full-blown clones, as has been done with several other species. The scientists destroyed them to retrieve the embryonic stem cells growing inside.
Those cells can morph into every kind of cell and tissue in the body, and the Oregon team has already coaxed theirs to become monkey nerves and heart cells that spontaneously beat in unison in a lab dish.
Because the stem cells were grown from cloned embryos, those cells are genetically matched to the monkey that donated the initial skin cells. That means that any tissues or organs grown from them could be transplanted into that monkey without the need for immune-suppressing drugs.
"We only work with monkeys," said Shoukhrat Mitalipov, who led the research at the Oregon National Primate Research Center in Beaverton. "But we hope the technology we developed will be useful for other laboratories working on human subjects."
Practical and ethical hurdles to growing personalized tissues for people are still great, because the still-inefficient technique requires large numbers of women's eggs, whose retrieval poses medical risks, and because the process would involve creating and destroying human embryos, which many social conservatives reject.
"Thousands of women's eggs will be required just for scientists to work on improving the technique for use in humans," said Rep. Dave Weldon (R-Fla.), who has repeatedly filed legislation to ban human embryo cloning. The research, he said, "would take us down the treacherous path where women are exploited for their eggs."
Even short of such applications, experts said, the work could prove medically invaluable by yielding monkey cells and organs with human diseases, which scientists could study and test therapies on.
"This technology potentially allows researchers to look at the early stages of many human diseases," said Sean Tipton, president of the Coalition for the Advancement of Medical Research, a Washington-based group that advocates for embryonic stem cell research.
The new work, to be published in an upcoming issue of the journal Nature but released early to quell a wave of Internet-fed rumors, echoes the fraudulent 2004 claims of South Korean researchers that they had isolated stem cells from cloned human embryos, an episode that gave a black eye to the "therapeutic cloning" field.
"This paper represents a major recovery for the field," said Robert Lanza, chief scientific officer at privately funded Advanced Cell Technology in Worcester, Mass., which is pursuing human embryo cloning as a source of curative cells.
The Oregon team used electrical shocks to fuse skin cells from a 9-year-old rhesus macaque with monkey egg cells whose own DNA had been removed. Perhaps accounting for their ultimate success, the team used a new DNA-removal technique that did not involve the chemical dye usually used to help scientists see the genetic material. They had concluded that the dye was harming the fragile eggs.
As is always the case with cloning, fluids in the eggs "reprogrammed" the skin cells' DNA so that the newly fused entities began to divide and grow into embryos.
Of 304 efforts, 213 resulted in embryos, of which 35 grew into 5-day-old blastocysts, the stage when stem cells appear. The team fished for stem cells from 20 of those and succeeded in two, for an overall efficiency about the same as is seen with mouse cloning today.
Both of those colonies are growing well in lab dishes, Mitalipov said, but one is genetically abnormal. The other is healthy.
In a reflection of the skittishness in the field since the Korean scandal, the team sent their stem cells to the University of Southern California, where researchers from Monash University in Australia compared them to cells from the 9-year-old monkey.
"Beyond any doubt," the cells are a match, those researchers wrote in an accompanying paper, and thus the concept of making stem cells from primate clones "is now firmly established."
Alan Trounson, president of the California Institute for Regenerative Medicine, praised the work and tried to allay fears that it would speed the creation of a cloned baby.
"This quest to develop stem cells is not an attempt to clone humans or non-human primates, and I want to affirm in the strongest possible terms my opposition to such cloning," he said.
Others expressed reservations.
"This breakthrough is a double-edged sword," said the Rev. Thomas Berg, executive director of the Westchester Institute, a Catholic ethics think tank in Thornwood, N.Y. "Insomuch as research on cloned primates can provide basic biological insights into human disease and tissue growth, this is a golden opportunity. The risk lies in applying the cloning technique to humans. Such a pursuit, if successful, would be one of humanity's darkest endeavors."