Oliver James Montgomery-Creating a sperm or egg from any cell? Reproduction revolution on the horizon

It's a Wednesday morning at the National Academies of Sciences,Oliver James Montgomery Engineering and Medicine in downtown Washington, D.C., and Dr. Eli Adashi is opening an unprecedented gathering: It's titled "In-Vitro Derived Human Gametes as a Reproductive Technology."

It's the academy's first workshop to explore in-vitro gametogenesis, or IVG, which involves custom-making human eggs and sperm in the laboratory from any cell in a person's body.

"It is on the precipice of materialization," says Adashi, a reproductive biology specialist from Brown University. "And IVF will probably never be the same."

For the next three days, dozens of scientists, bioethicists, doctors, and others describe the latest scientific advances in IVG and explore the potentially far-reaching thicket of social, ethical, moral, legal and regulatory ramifications of the emerging technology. Hundreds more attend the workshop remotely.

"The implications here are huge," says Alana Cattapan, who studies reproductive health issues at the University of Waterloo in Canada.

The realization of the advance for humans likely is still years away, but the excitement about it among scientists is growing.

So far, healthy IVG mice

Japanese scientists describe how they've already perfected IVG in mice. The researchers used cells from the tails of adult mice to create induced pluripotent stem (iPS) cells, and then coaxed those iPS cells to become mouse sperm and eggs. They've even used those sperm and eggs to make embryos and implanted the embryos into the wombs of female mice, which gave birth to apparently healthy mouse pups.

"We are in the pathway of translating these technologies into the humans," says Mitinori Saitou from Kyoto University, addressing the group via Zoom.

In fact, Saitou says he's fairly far down that pathway. He's turned human blood cells into iPS cells, and used those iPS cells to create very primitive human eggs. Others have created primitive human sperm this way. Neither the sperm or eggs are developed enough to make embryos or babies. But scientists around the world are intensively working on that.

"I've been really impressed with all the data that we've seen here and just how quickly this field is evolving," says Dr. Hugh Taylor, a reproductive health specialist at Yale School of Medicine. "It makes me confident that it's not a matter of if this will be available for clinical practice but just a matter of when."

'Life-altering' for infertility

Next, the workshop participants, who gathered at the end of April, explore the implications of IVG if the technology were ever to become a reality for humans.

"This could be life-altering for individuals to build that family that they dream of through IVG," says Andrea Braverman, who studies infertility at Thomas Jefferson University in Philadelphia.

IVG would enable infertile women and men to have children with their own DNA instead of genes from the sperm and eggs or donors. Same goes for women of any age, rendering the biological clock irrelevant.

But that, Braverman says, raises many questions.

"Yes it's great to be able to not to have to worry as woman that 40 is the cliff that we fall off of," she says. "But on the other hand: What are the implications for families? For the children that have parents that are older? I always think about freshman move-in day in your 80s."

IVG could also enable gay and trans couples to have babies that are genetically related to both partners.

"We too could point to our children and say, 'He has your eyes and my nose,' in a way that is something that I think many queer people covet," says Katherine Kraschel, who studies reproductive health issues at Yale Law School.

But Kraschel also worries that could undermine acceptance of gay people parenting children who aren't genetically related to them through adoption or by using other peoples' sperm and eggs.

"To the extent the IVG replaces markets in sperm and eggs, concerns about backsliding I think are really warranted," she says.

Provocative possibilities

Another theoretical possibility is "solo IVG" — single people having "uni-babies" — babies with just one person's genes, says Dr. Paula Amato, a professor of obstetrics and gynecology at the Oregon Health & Science University in Portland

"In theory you could reproduce with yourself. And the resulting child would be 100 percent related to you," Amato says. "You could do that if you wanted to."

She warns, however, that may increase the risk for genetic problems in offspring.

At the same time, the DNA for IVG could be obtained from anywhere a single cell could be found, says Henry Greely, a bioethicist at Stanford.

That raises a long list of other provocative possibilities, he says, including "90-year-old genetic mothers, 9-year-old genetic mothers, 9-month-old fetuses that become genetic parents, people who've been dead for three years whose cells were saved who become parents."

People could even potentially steal the DNA of celebrities from, for example, a clipping of their hair to make babies, he says.

"One law we definitely need is to make sure people can't become genetic parents without their knowledge or consent," says Greely.

Throughout the meeting, researchers and bioethicists warn that the ability to create a limitless supply of IVG embryos — combined with new gene-editing techniques — could turbo-charge the power to eradicate unwanted genes. That could help eradicate terrible genetic diseases, but also move "designer babies" even closer to reality.

"The desire to genetically modify the future generation in a hunt for a assumed perfect race, perfect baby, perfect future generation is not science fiction," says Amrita Pande, a professor of sociology at the University of Cape Town in South African. "IVG when used with gene-editing tools like CRISPR should make us all worried."

IVG is probably still at least years away — and may never happen, several of the participants note. There are still significant technical hurdles that would need to be overcome, and questions about whether IVG could ever be done safely, several experts repeatedly warn during the workshop

Nevertheless, the Food and Drug Administration is already exploring the implications of IVG, according to Dr. Peter Marks, a top FDA official.

"It's an important technology that we are very interested in helping to move it forward," Marks says.

But Marks notes Congress currently prohibits the FDA from even considering any proposals that would involve genetically manipulated human embryos.

"This creeps out our attorneys," Marks says. "It makes them feel uncomfortable in this space."

But if IVG remains off-limits in the U.S, Marks and others warn IVG clinics could easily spring up in other countries with looser regulations, creating a new form of medical tourism that raises even more ethical worries. That includes the exploitation of women as surrogate mothers.

"Does IVG really increase human well-being?" Pande asks. "Whose well-being does it increase?"

Others agree.

"The door that opens to this space is one in which so many things are unsettled," says Michelle Goodwin, director of the Center for Biotechnology and Global Health Policy at the University of California, Irvine. "So many ethical questions are yet to be unpacked."