Mouse Created From All-Female DNA

April 21, 2004 -- Researchers have created a mouse born from all-female DNA, raising the question: If female mammals can reproduce on their own, will males become obsolete?

A few plants, insects and reptiles are capable of male-free reproduction in a process known as parthenogenesis, from the Greek meaning "virgin birth." Via parthenogenesis, a female's egg is able to grow into a new organism without any fertilization from the male.

But mammals generally require sexual reproduction that combines two sets of DNA — one copy from the mother and one from the father. Although male and female DNA are very similar, they have chemical signals that distinguish them and an embryo usually will not develop properly if it does not sense the presence of both.

Until now, that is. In order to create a mouse with all-female parentage, researchers at Japan's Tokyo University and South Korea's National University College of Medicine in Seoul, "tricked" the embryo into believing it contained both male and female DNA by knocking out the gene that marked one strand as "female." With the "female" gene removed, the embryo interpreted the second strand of female DNA as male DNA.

The mouse, named Kaguya, grew to healthy adulthood and now has offspring of her own conceived naturally with a male mouse. The findings were published in today's edition of the journal Nature

Men No Longer Needed?

So does all this mean males will go the way of the dinosaur? Not likely, experts say.

While it might be possible for two women to reproduce using these techniques, practical application would be extremely difficult.

"Sure, it's theoretically possible to get rid of men," quips David Magnus, an assistant professor of pediatrics and co-director of the Center of Bioethics at Stanford University in California. "With all the sperm saved up in sperm banks, we probably could get rid of them now."

But Magnus points out the technology to create a human Kaguya is a long way off and may not be possible at all.

"In reproductive technology, there is a big gap between animals and humans. For example, cloning a mouse is easy. But no one has yet cloned a primate or a human. We don't even know if it's possible."

However, experts do not rule out the possibility that a similar technique might be available to humans in the future. On major hurdle is to find a way to genetically alter a woman's egg without altering the woman herself.

"I can outline a protocol right now where it could work in theory," George Daley, an assistant professor of medicine and a leading stem cell researcher at Harvard University. "Are we there yet with the technology? No. But sure it could work."

So while the female-female DNA combination might appeal to lesbian couples seeking to have a child, the technology is not likely to be used for reproduction any time soon.

"I don't see this applicable to human assisted reproduction," says David Wininger, an assistant professor in the OB/GYN department and director of the Center for Reproductive Medicine at Wake Forest University in Winston-Salem, N.C. "We wouldn't even know which genes to take out."

Also, while Kaguya appears healthy now, trouble may lurk down the road. Kaguya was one of only two mice out of 457 eggs to survive.

Rudolf Jaenisch, one of the founders of transgenic science and professor of biology at MIT explains, "This mouse is almost certainly not normal. It is just less abnormal than the ones who did not make it."

"We don't know the long-term effects of this technique," says Magnus. "Reproductive technology has grown so fast without much in the way of safety data. The first IVF baby ["test tube baby"] is only in her 20s. Who's to say what long-term effects our interventions might have on later life?"

Redefining Personhood

Creating embryos without fertilization may offer a way around some of the ethical concerns about embryonic stem cell research. If not for the genetic manipulation performed by Kaguya's creators, mammalian embryos created without fertilization die after a few days. "These embryos do not have the potential to become offspring," explains Wininger.

Wininger, who is working on creating human "embryos" without fertilization, sees this technique as a powerful research tool. "We are in the process of trying to isolate stem cells from these embryos," he says, adding that he hopes these specially-created stem cells will not have the same ethical issues that surround embryonic stem cells harvested from fertilized embryos.

At the very least, Magnus claims, the technology forces us to reconsider the definition of personhood.

"These findings challenge key concepts about the definition of 'embryo.' Is every egg a potential person now? Does menstruation equal death?"

Currently, the government considers parthenogenesis to be a form of reproduction and therefore stem cells derived via this technique are subject to the same ban on federal funding as traditional stem cells. Institutions can only pursue research on stem cells derived from parthenogenesis using private funding.