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Unfertilized Monkey Embryos Yield Stem Cells

Technology may be way around ethical objections to research

THURSDAY, Jan. 31, 2002 (HealthDayNews) -- In a kind of laboratory version of immaculate conception, scientists say they've created embryonic stem cells using monkey eggs that have never been fertilized.

The process, called parthenogenesis (the word derives in part from the Greek word for virgin), tricks unfertilized eggs into behaving as if they've encountered sperm. The cells then form non-viable embryos, known as "parthenotes," that can be mined for stem cells. Since the method achieves embryonic stem cell production without an actual embryo, the technology could sidestep the ethical and moral issues that cloud such research in humans.

In the latest work, which appears in tomorrow's issue of the journal Science, the researchers used parthenogenesis to create a line of monkey stem cells that yielded neurons able to produce dopamine. This molecule is an important player in healthy brain function, and when depleted can lead to Parkinson's disease.

The research was conducted by stem cell experts at Wake Forest University in Winston Salem, N.C., Memorial Sloan-Kettering Cancer Center in New York City, the Mayo Clinic and Advanced Cell Technology, a biotech firm in Worcester, Mass. Late last year, the company announced it had created early-stage human embryos, both through cloning and parthenogenesis.

This time, the scientists took 77 eggs from cynomolgus monkeys (a common species of lab primate) and "activated" them with a mixture that convinced the eggs they'd had a run-in with monkey sperm.

Most of the eggs died off quickly, but four reached an early embryo phase called the blastocyst stage. From these bundles of cells, the researchers successfully derived a single line of embryonic stem cells. They then coaxed some of the stem cells into becoming neurons; 25 percent of those began producing dopamine. Some cells also turned into beating heart cells, smooth muscle, fat and other tissues.

Kent E. Vrana, a Wake Forest physiologist and a co-author of the study, says tests so far of the stem cells, which are now 10 months old, prove them "exactly normal." They have the full complement of monkey chromosomes and they appear to be the right age, at least genetically. When transplanted into mice stripped of their immune systems they develop into benign, mixed-tissue tumors called teratomas -- suggesting they are indeed capable of becoming virtually every cell in the body.

Researchers have created parthenotes of mice, cows, humans and now monkeys, Vrana says. None has gone on to become a viable embryo. Why they self-destruct isn't known, but Vrana says their evanescence might have something to do with the absence of instructions from sperm.

Because parthenotes clearly can't become a fetus, it's possible that cell lines drawn from them will also sputter as they develop.

"The [embryonic stem] cells look good in culture, but that's not to say that something might not happen down the road," Vrana says.

In a sign of how rapidly the field of stem cell research is evolving, the Science paper claims no other group has generated dopamine-producing neurons from primate embryonic stem cells. However, in the back-and-forth with the journal, the authors were scooped by the publication last week of a paper from a Japanese group demonstrating just that feat.

"We're very excited by those findings because it shows that if you get a bunch of hard-working people on a problem, you're going to get it solved," Vrana says.

Dr. Lorenz Studer, a tumor biologist at Sloan-Kettering and a co-author of the paper, says it's possible the two techniques could be fused to increase the yield of dopamine neurons from the parthenote stem cell lines.

However, how to increase the efficiency of making parthenotes is another matter. The success ratio is far from remarkable.

"I'm pretty sure you can increase the efficiency, but we have to see," Studer says. "It's still like a magical step. Some divide, some don't, and there's not much we do to them" to influence their decision.

Despite the fact that parthenotes are neither fish nor foul, the National Institutes of Health considers them embryos when it comes to funding -- or, more precisely, its refusal to fund -- research on the cells.

And at least one expert says it's unlikely that even unfertilized embryos with no chance of becoming a human would get a pass from those, such as President Bush, opposed to embryo research on religious or ethical grounds.

"People opposed to embryo research are probably not going to embrace research with these embryos," says Thomas Murray, president and chief executive officer of the Hastings Center for Bioethics. "They're going to see them as more unnatural, but probably still embryos."

Murray says scientists "probably aren't going to [make] many successful end-runs around the creation of human embryos. Adult stem cells may take some of the heat off, but we don't know that yet," since these cells haven't proven themselves as versatile as embryonic stem cells.

What To Do

To learn more about stem cells, try the National Institutes of Health. You can also visit the Coalition for the Advancement of Medical Research.

SOURCES: Interviews with Kent E. Vrana, Ph.D., professor, physiology and pharmacology, Wake Forest University School of Medicine, Winston Salem, N.C., Lorenz Studer, M.D., head, laboratory for stem cell and tumor biology, Memorial Sloan-Kettering Cancer Center, New York City; Thomas Murray, Ph.D., president and chief executive officer, Hastings Center for Bioethics, Garrison, N.Y.; Feb. 1, 2002, Science
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