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In Laboratory, Ordinary Cells Are Turned Into Eggs
By Rick Weiss
Washington Post Staff Writer
Friday, May 2, 2003; Page A01
Scientists in Pennsylvania yesterday said they had turned ordinary mouse embryo cells into egg cells in laboratory dishes -- an advance that opens the door to creating "designer" eggs from scratch and, if repeated with human cells, could blur the biological line between fathers and mothers.
The work undermines the standard model of parenthood because the scientists made egg cells not only from female cells, but also from male cells, indicating that even males have the biological capacity to make eggs.
If the science holds true in humans as in mice -- and several scientists said they suspect it will -- then a gay male couple might, before long, be able to produce children through sexual reproduction, with one man contributing sperm and the other fresh eggs bearing his own genes.
That scenario raises difficult questions, including whether the second man would be recognized as the child's biological mother.
"It's absolutely remarkable," said Lee Silver, a Princeton molecular biologist who specializes in reproductive ethics. "This breaks down all the classic barriers in terms of sexual reproduction, with none of the problems of cloning."
Cloning produces offspring from just one parent, raising genetic and ethical problems that are not raised by the laboratory cultivation of eggs and sperm -- although the new work, in which embryonic stem cells spontaneously transformed themselves into eggs, raises issues of its own.
"Some of the applications will be seen as straightforward boons to humankind, such as for women who can't make healthy eggs the usual way," said Thomas Murray, president of the Hastings Center, a bioethics think tank in Garrison, N.Y. "But as with just about any medical development, there will be other uses that will give people hiccups, if not fits."
Human applications aside, the ability to mass-produce egg cells in a lab could make it much easier to engineer traits into animals, and help conservationists rebuild populations of endangered species.
The work also offers researchers an unprecedented opportunity to watch how mammalian egg cells mature -- something that usually happens in the privacy of an ovary -- and to learn about "meiosis," the mysterious process by which an egg or sperm spits out half of its genes so it can mate with its counterpart of the opposite sex.
"The mind boggles with potential wild applications of this stuff," said John Eppig, a mouse geneticist at the Jackson Laboratory in Bar Harbor, Maine.
If the mouse work does translate into an ability to create batches of human eggs, the most immediate effect might be on Capitol Hill. The Senate is debating whether to restrict the creation of cloned human embryos as a source of medically promising stem cells.
Until now, one argument for banning the creation of cloned embryos has been that it would require a huge supply of human eggs to make all the embryos and therapeutic cells that patients might need. That market demand could lead to an "egg-donor underclass" of poor women who might submit to repeated, health-compromising egg donation procedures as a way of making money.
But if scientists can grow lots of human eggs in the laboratory, experts said, that market would not appear. "Commodification and safety issues would be avoided," said Judy Norsigian, executive director of the Boston Women's Health Book Collective, who has been a leader in the movement against what is known as therapeutic cloning because of the risks it might pose to poor women.
Norsigian and others said they remain wary of the new technology because of its potential to facilitate the genetic engineering of people. Scientists have already learned how to add and subtract specific genes in stem cells. Those genetic changes would appear in eggs grown from such cells, offering an easy means of making heritable changes in a family line and possibly giving rise to a new age of eugenics.
The prospect of wholesale production of human eggs from embryo cells also raises alarms for religious conservatives and others who are opposed to all research involving embryos.
"It sounds like this could be another big step towards opening what President Bush has called 'human embryo farms,' " said Douglas Johnson, legislative director of the National Right to Life Committee.
The new work builds on more than 20 years of research on mouse embryonic stem cells -- primordial cells found inside mouse embryos that, in laboratory dishes, can develop into almost every kind of mouse cell or tissue. (Human embryonic stem cells, which have the same potential, were discovered much more recently, in 1998.) Until now, the only cells that scientists could not grow from embryonic stem cells were sperm and eggs.
Hans Schoeler and Karin Huebner of the University of Pennsylvania's School of Veterinary Medicine in Kennett Square, along with colleagues in France and Philadelphia, overcame that barrier by gradually selecting from a mixed population of stem cells the ones that bore certain genetic hallmarks that suggested a potential to become eggs, then isolating those in laboratory dishes.
After a while, perhaps because the number of like-minded cells reached a "critical mass," the stem cells in those dishes started to morph into two kinds of cells. Some became follicular cells -- the kind of cells found in ovaries that help young egg cells mature -- and others became young egg cells.
The eggs appeared to mature normally, the researchers reported yesterday in the online edition of the journal Science. In fact, many spontaneously developed into early embryos in their dishes, something that cultured mouse eggs often do. That offers evidence that the eggs are relatively healthy. But Schoeler said his team is now trying to fertilize the eggs with mouse sperm to see if they give rise to healthy mature embryos -- the gold standard of egg normalcy.
Perhaps most astonishing, said Eppig of the Jackson Laboratory, the lab-reared egg and follicle cells apparently engaged in the complicated cross-talk required for normal development. Follicle cells surrounded each egg in a gentle embrace as they would in an ovary, for example, and even produced female hormones, which the eggs need to mature.
"I am flabbergasted that these darn things are making estrogen," Eppig said. "Imagine what's going to happen when you can do the same thing and make sperm."
The genetic program for making sperm is believed to be more complicated than for making eggs, but sperm farming may not be farfetched, Schoeler said. Success could raise interesting questions about the biological relevance of males.
If sperm can be made from stem cells, for example, then lesbians could make babies by sexual reproduction. Unlike gay men, they would not have to turn to the other sex to gestate those babies.
"It will take a nanosecond for people in same-sex relationships to figure out the potential implications of this research for them," said Murray, of the Hastings Center. "People can just fill in the blanks."
© 2003 The Washington Post Company
By Rick Weiss
Washington Post Staff Writer
Friday, May 2, 2003; Page A01
Scientists in Pennsylvania yesterday said they had turned ordinary mouse embryo cells into egg cells in laboratory dishes -- an advance that opens the door to creating "designer" eggs from scratch and, if repeated with human cells, could blur the biological line between fathers and mothers.
The work undermines the standard model of parenthood because the scientists made egg cells not only from female cells, but also from male cells, indicating that even males have the biological capacity to make eggs.
If the science holds true in humans as in mice -- and several scientists said they suspect it will -- then a gay male couple might, before long, be able to produce children through sexual reproduction, with one man contributing sperm and the other fresh eggs bearing his own genes.
That scenario raises difficult questions, including whether the second man would be recognized as the child's biological mother.
"It's absolutely remarkable," said Lee Silver, a Princeton molecular biologist who specializes in reproductive ethics. "This breaks down all the classic barriers in terms of sexual reproduction, with none of the problems of cloning."
Cloning produces offspring from just one parent, raising genetic and ethical problems that are not raised by the laboratory cultivation of eggs and sperm -- although the new work, in which embryonic stem cells spontaneously transformed themselves into eggs, raises issues of its own.
"Some of the applications will be seen as straightforward boons to humankind, such as for women who can't make healthy eggs the usual way," said Thomas Murray, president of the Hastings Center, a bioethics think tank in Garrison, N.Y. "But as with just about any medical development, there will be other uses that will give people hiccups, if not fits."
Human applications aside, the ability to mass-produce egg cells in a lab could make it much easier to engineer traits into animals, and help conservationists rebuild populations of endangered species.
The work also offers researchers an unprecedented opportunity to watch how mammalian egg cells mature -- something that usually happens in the privacy of an ovary -- and to learn about "meiosis," the mysterious process by which an egg or sperm spits out half of its genes so it can mate with its counterpart of the opposite sex.
"The mind boggles with potential wild applications of this stuff," said John Eppig, a mouse geneticist at the Jackson Laboratory in Bar Harbor, Maine.
If the mouse work does translate into an ability to create batches of human eggs, the most immediate effect might be on Capitol Hill. The Senate is debating whether to restrict the creation of cloned human embryos as a source of medically promising stem cells.
Until now, one argument for banning the creation of cloned embryos has been that it would require a huge supply of human eggs to make all the embryos and therapeutic cells that patients might need. That market demand could lead to an "egg-donor underclass" of poor women who might submit to repeated, health-compromising egg donation procedures as a way of making money.
But if scientists can grow lots of human eggs in the laboratory, experts said, that market would not appear. "Commodification and safety issues would be avoided," said Judy Norsigian, executive director of the Boston Women's Health Book Collective, who has been a leader in the movement against what is known as therapeutic cloning because of the risks it might pose to poor women.
Norsigian and others said they remain wary of the new technology because of its potential to facilitate the genetic engineering of people. Scientists have already learned how to add and subtract specific genes in stem cells. Those genetic changes would appear in eggs grown from such cells, offering an easy means of making heritable changes in a family line and possibly giving rise to a new age of eugenics.
The prospect of wholesale production of human eggs from embryo cells also raises alarms for religious conservatives and others who are opposed to all research involving embryos.
"It sounds like this could be another big step towards opening what President Bush has called 'human embryo farms,' " said Douglas Johnson, legislative director of the National Right to Life Committee.
The new work builds on more than 20 years of research on mouse embryonic stem cells -- primordial cells found inside mouse embryos that, in laboratory dishes, can develop into almost every kind of mouse cell or tissue. (Human embryonic stem cells, which have the same potential, were discovered much more recently, in 1998.) Until now, the only cells that scientists could not grow from embryonic stem cells were sperm and eggs.
Hans Schoeler and Karin Huebner of the University of Pennsylvania's School of Veterinary Medicine in Kennett Square, along with colleagues in France and Philadelphia, overcame that barrier by gradually selecting from a mixed population of stem cells the ones that bore certain genetic hallmarks that suggested a potential to become eggs, then isolating those in laboratory dishes.
After a while, perhaps because the number of like-minded cells reached a "critical mass," the stem cells in those dishes started to morph into two kinds of cells. Some became follicular cells -- the kind of cells found in ovaries that help young egg cells mature -- and others became young egg cells.
The eggs appeared to mature normally, the researchers reported yesterday in the online edition of the journal Science. In fact, many spontaneously developed into early embryos in their dishes, something that cultured mouse eggs often do. That offers evidence that the eggs are relatively healthy. But Schoeler said his team is now trying to fertilize the eggs with mouse sperm to see if they give rise to healthy mature embryos -- the gold standard of egg normalcy.
Perhaps most astonishing, said Eppig of the Jackson Laboratory, the lab-reared egg and follicle cells apparently engaged in the complicated cross-talk required for normal development. Follicle cells surrounded each egg in a gentle embrace as they would in an ovary, for example, and even produced female hormones, which the eggs need to mature.
"I am flabbergasted that these darn things are making estrogen," Eppig said. "Imagine what's going to happen when you can do the same thing and make sperm."
The genetic program for making sperm is believed to be more complicated than for making eggs, but sperm farming may not be farfetched, Schoeler said. Success could raise interesting questions about the biological relevance of males.
If sperm can be made from stem cells, for example, then lesbians could make babies by sexual reproduction. Unlike gay men, they would not have to turn to the other sex to gestate those babies.
"It will take a nanosecond for people in same-sex relationships to figure out the potential implications of this research for them," said Murray, of the Hastings Center. "People can just fill in the blanks."
© 2003 The Washington Post Company
So which of you 'Poly lads wants to be the first to have one of my babies?
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