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Scientists Produce Monkeys With DNA From Two Mothers

By Rob Stein
Washington Post Staff Writer
Thursday, August 27, 2009; A04

Scientists have produced monkeys with genetic material from two mothers, an advance that could help women with some inherited diseases have healthy children but that would raise a host of safety, legal, ethical and social questions if attempted in people.

Using cloning-related techniques, the researchers developed a way to replace most of the genes in the eggs of one rhesus macaque monkey with genes from another monkey. They then fertilized the eggs with sperm, transferred the resulting embryos into animals' wombs and produced four apparently healthy offspring.

The technique was developed for women who have disorders caused by defects in a form of DNA passed only from females to their children, and the researchers said they hope the work will eventually translate into therapies for people.

"We believe this technique can be applied pretty quickly to humans and believe it will work," said Shoukhrat Mitalipov of the Oregon Health & Science University in Portland, who led the work, published online Wednesday by the journal Nature.

Many scientists hailed the research as a technically impressive feat that could help many families rid themselves of a variety of terrible disorders caused by defects in genetic material known as mitochondrial DNA.

"This is of great importance. This approach will be beneficial to many families," said Jan Smeitink, a professor of mitochondrial medicine at Radboud University Nijmegen in the Netherlands.

But the work could also raise thorny ethical and legal issues, including questions surrounding the creation of offspring with DNA from two mothers and a father.

"With this you have potentially three genetic parents," said David Magnus, director of Stanford University's Center for Biomedical Ethics. "This will create the potential for legal and social conflicts."

If applied to people, the work would permanently alter genes for their future generations, violating a long-standing taboo against tinkering with the "germline" because of the chance of unforeseen consequences. Some experts worry, too, that germline genetic manipulation would give rise to a market in expensive elective genetic enhancements.

The researchers acknowledged that the work might raise ethical questions but said those must be balanced against the potential benefits.

"We realize this is not just a simple form of gene therapy. This type of gene therapy involves replacing genes in the germline which of course will be transmitted to next generations, which is a concern," Mitalipov said. "However, we're talking about patients and birth defects that cause terrible diseases due to these gene mutations. So the only way to prevent these birth defects is to replace these genes."

Mitochondrial DNA is found inside structures in cells called mitochondria, which are often referred to as the "power plants" for cells because they provide energy for growth and other functions. But defects in mitochondrial DNA can cause a variety of disorders that may occur in about one of every 5,000 people and that can cause a wide spectrum of health problems, including stunted growth, muscle weakness, blindness, deafness, mental retardation, diabetes, seizures and dementia. Defects in this DNA may also sometimes be involved in more common disorders including Alzheimer's, Parkinson's and Huntington's diseases.

For their experiments, Mitalipov and his colleagues extracted DNA from the nucleus of monkey eggs; the nucleus contains the genes for most of a creature's traits. The researchers then transplanted that DNA into eggs from other females that had healthy mitochondrial DNA but from which the nuclear DNA had been removed.

They then fertilized the eggs in the laboratory and transferred 15 of the resulting embryos into the wombs of nine females. Two twins were born -- named Mito and Tracker -- along with two other offspring, Spindler and Spindy. So far, all the offspring appear to be healthy.

Several experts said the work should be tried in people only after much more research has been done to test its safety.

"The number one concern I would have is safety," said Mark Rothstein, a bioethicist at the University of Louisville. "There's always a concern that a facility might jump the gun and try to put it into use before safety has been established."

Even if further animal studies show that the approach is safe, attempts in humans might still lead to defective embryos, others noted.

"When it is attempted in humans, some abnormal embryos are bound to result. If they are discarded, this will raise major ethical concerns for those who view human embryos as nascent human beings, and by some who do not," said Cynthia B. Cohen, a Georgetown University bioethicist. "Many in our society are reluctant to see abnormal embryos created and then discarded."

If it works, said Lori B. Andrews, who studies ethical and legal issues raised by new reproductive technologies at the Chicago-Kent College of Law, women who donated the mitochondrial DNA could seek visitation rights.

"If the mitochondria donor (who is probably a young woman) is later infertile, she might seek visitation to the child," Andrews wrote in an e-mail. "After all, people didn't think surrogate mothers, who are not the nucleic DNA donors, would want access to the couples' genetic child, but some have gone to the courts for such access."

Others worried about opening the door to other genetic manipulation. "Unfortunately, we're likely to hear some people saying, 'Okay, we've done this, so why can't we alter the DNA in the nucleus to, say, prevent a predisposition to breast cancer? And if you do it for breast cancer, why can't we do it to weed out a predisposition to baldness?' " said Marcy Darnovsky of the Center for Genetics and Society.

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