Fatherless Mice Muddy the Water

Fatherless Mice Muddy the Water

Fatherless Mice Muddy the Water

Last week, Japanese researchers created a fatherless mouse using only female eggs, and turned the reproduction world on its head. The word on the street was men's role in baby making might one day be obsolete.

Fatherless offspring were previously considered impossible for mammals. And while reproduction experts have something new to think about, so do stem cell scientists. The technology used to create the "virgin birth" might engender better techniques for obtaining stem cells.

But just because the Japanese mouse was created using a technique previously considered infeasible in mammals doesn't mean it escapes President Bush's stem cell policy. Researchers are not allowed to use federal funds to destroy or work with stem cells obtained through this method, called parthenogenesis, which is Greek for "virgin birth."

In parthenogenesis, reproduction is achieved by development of an unfertilized egg. The process was formerly seen only in insects and some reptiles. Parthenogenesis offers one more possible route to obtaining stem cells, which many researchers believe could lead to cures for many ills – from Alzheimer's to Parkinson's – because the cells can become almost any kind of cell in the human body. But the method comes with as much controversy as any other technique to obtain these potential cures.

Former U.S. Rep. Jay Dickey (R-Arkansas) introduced an amendment into the appropriations bill of the Department of Health and Human Services in 1996 prohibiting the use of federal funds for any kind of research with human embryos, said Jose Cibelli, a stem cell researcher working in parthenogenesis at the Michigan State University. "When (lawmakers) define a human embryo, they are very careful to make sure they include nuclear transfer parthenogenesis."

Jerry Hall, co-director of ViaGene Fertility, who uses parthenogenesis to get stem cells, was surprised that the government includes parthenotes (the products of parthenogenesis) in its definition of a human embryo.

"They can just make up anything they want to, can't they?" Hall said. "It's really aggravating that people, including government officials, just synthesize any definition they want to and then call it right."

In 1999, officials in the Clinton administration found a loophole in the Dickey amendment. The amendment didn't say anything about federal funds spent on stem cells that had already been derived. So they formulated a plan to allow the government to fund stem cell research. But the plan wasn't complete before President Bush took office, and on Aug. 9, 2001, he reaffirmed the Dickey amendment, with the caveat that federal funds could be spent only on stem cell lines derived before that date.

According to the President's Council on Bioethics (an advisory team Bush formed the same day) report "Monitoring Stem Cell Research" (PDF): "The current policy on federal government funding of human embryonic stem cell research, then, must be understood in terms of the constraints of the Dickey Amendment and in terms of the logic of the moral and political aims that underlie that amendment."

The President's Council on Bioethics declined to comment on this story.

The Dickey amendment has been attached to every HHS appropriations bill since 1996.

But the law doesn't make stem cell research illegal. It's only illegal to spend taxpayer money on it. So, although Cibelli says federal funds would accelerate his research, he's nevertheless excited about the virgin-birth mouse.

To make matters even more complicated, the mouse was not conceived using true parthenogenesis. The researchers at the Tokyo University of Agriculture put a very young mouse egg inside a mature one. In the young egg, the researchers deleted two genes associated with "imprinting" in mammals. Imprinting is the process that ensures offspring will receive exactly one copy of each gene from the mother and the father. When imprinting goes wrong, the embryo typically dies. By removing chunks of DNA responsible for imprinting, the researchers circumvented this process. To kick-start cell division, they also inserted some genetic material from another, unrelated and unmodified female mouse.

The procedure contains elements of parthenogenesis, cloning and genetic manipulation. Regardless, for all intents and purposes, most scientists are calling it parthenogenesis.

Mammals evolved over time to require an exchange of genes from a mother and father to create an embryo, Cibelli said. "It was put in place to force mammals to reproduce sexually. These guys just bypassed that."

Stem cells taken from parthenotes could have certain advantages over other stem cells. For example, researchers want to use cloning to create stem cells that would be an exact genetic match for patients. But that technique would require a custom-made treatment for each individual, which could be prohibitively expensive. Researchers believe stem cells from parthenotes might contain fewer proteins that instigate immune rejection, and therefore might be the basis for medicines that many people could use.

Plus, if custom-made treatments were one day viable, this procedure might be even better than cloning.

"Stem cells from parthenogenic eggs will be completely compatible with the mother because they don't contain foreign genes from males," Hall said.

That doesn't sound promising for male patients, but Hall said they wouldn't necessarily be left out in the cold.

"If we made the egg contain male genes instead of female genes, which is possible, then the genetic complement would match with a male," he said.

Also, creating parthenotes is much easier than creating clones, Hall said. It's difficult to get parthenotes to grow into embryos (as the Japanese researchers did) but to get them to the stage where they produce stem cells is relatively simple.

Arthur Caplan, director of the Center for Bioethics at the University of Pennsylvania, pointed out that science is way ahead of legislation in the United States.

"The way to handle this is not by having presidential orders come out every time a new technology emerges," Caplan said in a phone interview. "It's time to get more systematic and legislative."

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