The cluster on the right is a colony of iPS cells. Each one of them could become a sperm or egg cell under the right conditions, which scientists are trying to uncover. (Courtesy of UCLA Broad Stem Cell Research Center)

Get Ready for Same-Sex Reproduction

When artificial sperm and eggs become a reality, the sex of your baby-making partner won’t matter.

Renata Moreira’s 1-year-old daughter is just beginning to talk. She calls Renata “Mommy,” her other mother, Lori, Renata’s ex-wife and co-parent, “Mama,” and the man who donated the sperm that gave her life, “Duncle,” short for donor uncle. The couple’s sperm donor is Renata’s younger brother.

“I frankly never contemplated having kids because I didn’t have any role models,” Moreira begins as she tells her daughter’s origin story. But when she met Lori at a bar in New York in 2013, the gay marriage movement was in full swing. When the couple decided to marry, they saw many of their friends starting families because of the new legal protections that marriage offered LGBTQ families, and they too began thinking about their options.

After months of research and thinking about the values that were most important to their family, they decided that a genetic connection to their kid was a high priority. “It wasn’t that we didn’t believe in adoption,” says Moreira, who is executive director of Our Family Coalition, a nonprofit that works to advance equity for LGBTQ families. “But the idea was that we wanted a child that was related to our ancestors and the genetic code that carries.”

Moreira is Brazilian, of indigenous and Portuguese ancestry, and Lori is Italian. Given that they both wanted to carry on their genetic heritage, they asked Renata’s brother to donate his sperm, to be matched with Lori’s eggs. The family’s fertility doctor used in-vitro fertilization to conceive an embryo in a dish and implanted it into Moreira’s uterus, making her into her daughter’s “gestational carrier.”

Even as the social stigma around gay parenting lessens — the Williams Institute at UCLA estimates that as many as six million Americans have a lesbian, gay, bisexual or transgender parent — LGBTQ families that want a biological connection to their children have a lot to think about. A same-sex couple who make a baby must work through an arduous puzzle of personal values, technologies, and intermediary fertility doctors, egg and sperm donors, or surrogates.

But that could change dramatically before long. A developing technology known as IVG, short for in-vitro gametogenesis, could make it possible for same-sex couples to conceive a baby out of their own genetic material and no one else’s. They’d do this by having cells in their own bodies turned into sperm or egg cells.

The science of IVG has been underway for the last 20 years. But it really took off with research that would later win a Nobel Prize for a Japanese scientist named Shinya Yamanaka. In 2006, he found a way to turn any cell in the human body, even easy-to-harvest ones like skin and blood cells, into cells known as induced pluripotent stem cells (iPS cells), which can be reprogrammed to become any cell in the body. Until that breakthrough, scientists working in regenerative medicine had to use more limited — and controversial — stem cells derived from frozen human embryos.

There is a small international group of scientists racing to reprogram human iPS cells into sperm and egg cells.

In 2016, researchers at Kyoto University in Japan announced that they had turned cells from a mouse’s tail into iPS cells and then made those into eggs that went on to gestate into pups. There are a lot of steps that still need to be perfected before this process of creating sex cells, also known as gametes, could work in humans.

If it does work, the first application likely would be in reversing infertility: men would have new sperm made and women would have new eggs made from other cells in their bodies. But a more mind-bending trick is also possible: that cells from a man could be turned into egg cells and cells from a woman could be turned into sperm cells. And that would be an even bigger leap in reproductive medicine than in-vitro fertilization. It would alter our concept of family in ways we are only beginning to imagine.

Today same-sex couples have to involve other people’s genetic material in making a baby. Artificial gametes could let them procreate with their own. (Illustration by Aart-Jan Venema)

Sex cells!

There is now a small international group of scientists racing to recreate the mouse formula and reprogram human iPS cells into sperm and egg cells.

One of the key players is Amander Clark, a stem cell biologist at UCLA. On a Friday afternoon, she walks me through her open lab area and introduces Di Chen, a postdoctoral fellow from China who’s working on creating artificial gametes. We enter a small room with a microscope, a refrigerator incubator, and a biosafety cabinet where students work with iPS cells. Chen invites me to peer down the microscope and shows off a colony of fresh iPS cells. They look like a large amoeba.

Getting cells like these to become viable eggs or sperm requires six major steps, Clark says. All of them have been accomplished in a mouse, but doing it in a human will be no easy feat. (In 2016, scientists reported that they had turned human skin cells into sperm cells, a development that Clark calls “interesting — but no one has repeated it yet.”) And no one has yet made an artificial human egg.

Clark’s group and other labs are essentially stuck on step three. After the steps in which a cell from the body is turned into an iPS cell, the third step is to coax it into an early precursor of a germ cell. For the work in mice, one Japanese researcher, Katsuhiko Hayashi, combined a precursor cell with cells from embryonic ovaries — ovaries at the very beginning of development — which were taken from a different mouse at day 12 in its gestation. This eventually formed an artificial ovary that produced a cell that underwent sex-specific differentiation (step four) and meiosis (step five), and became a gamete (step six).

Di Chen and Amander Clark in the lab. (Photo by Reed Hutchinson/UCLA Broad Stem Cell Research Center)

Other researchers, Azim Surani at Cambridge and Jacob Hanna at the Weizmann Institute of Science in Israel, have gotten to step three with both human embryonic stem cells and iPS cells, turning them into precursors that can give rise to either eggs or sperm. Surani’s former student Mitinori Saitou, now at Kyoto University, also accomplished this feat.

It’s an impressive achievement: they’ve made something that normally begins to develop around day 17 of gestation in a human embryo. But the next step, growing these precursor cells into mature eggs and sperm, is “a very, very huge challenge,” Surani says. It will require scientists to recreate a process that takes almost a year in natural human development. And in humans they can’t take the shortcut used in mice, taking embryonic ovary cells from a different mouse.

At UCLA, Clark refers to the next three steps needed to get to a human artificial gamete as “the maturation bottleneck.”

Those amoeba-like iPS cells that Chen showed me are sitting in a dish that he lifts off the microscope and carries to the biosafety cabinet. There he separates the cells into a new dish, and adds a liquid with proteins and other ingredients to help the cells grow. He puts the cells into an incubator for one day; then he’ll collect the cells again and add more ingredients. After around four days, the cells ideally will have grown into a ball that is around the size of a grain of sand, visible to the naked eye. This ball contains the precursors to a gamete. Clark’s lab and other international teams are studying it to understand its properties, with the hope that it will offer clues to getting all the way to step six — an artificial human gamete.

“I do think we’re less than 10 years away from making research-grade gametes,” she says. Commercializing the technology would take longer, and no one can really predict how much so — or what it would possibly cost.

Some of these iPS cells have been coaxed to become early precursors to a gamete. The next steps will be much harder. (Courtesy of UCLA Broad Stem Cell Research Center)

Even then, same-sex reproduction will face one more biological hurdle: scientists would need to somehow make a cell derived from a woman, who has two X chromosomes, into a sperm cell with one X and one Y chromosome, and do the reverse, turning an XY male cell into an XX female egg cell. Whether both steps are feasible has been debated for at least a decade. Ten years ago, the Hinxton Group, an international consortium on stem cells, ethics, and law, predicted that making sperm from female cells would be “difficult, or even impossible.” But gene editing and various cellular-engineering technologies might be increasing the likelihood of a workaround. In 2015, two British researchers reported that women could “in theory have offspring together” by injecting genetic material from one partner into an egg from the other. With this method, the children would all be girls, “as there would be no Y chromosomes involved.”

Yet another possibility: a single woman might even be able to reproduce by herself in a human version of parthenogenesis, which means “virgin birth.” It could be the feminist version of the goddess Athena springing from Zeus’s head.

The genderqueer nuclear family

The question remains whether society will want this technology — and how often LGBTQ families will choose to use it. Current advanced reproductive technologies are already diversifying the ways we reproduce and opening reproduction to groups who previously may not have had access to it. This is expanding the concept of family beyond the traditional Ozzie and Harriet hetero-nuclear family. Many people who are single parents by choice now include their gamete donors as members. Many LGBTQ families are collaborations of friends and relatives who become egg and sperm donors and help raise the kids.

So it’s understandable that social and legal observers are already thinking about the potential consequences of artificial gametes for the shape of families. If the technology means that lesbian couples wouldn’t need a sperm donor, and gay male couples wouldn’t need a donor egg, it could, among other things, make it “easier for the intended parents to preserve the integrity and privacy of the family unit,” Sonia Suter, a law professor at George Washington University, wrote in the Journal of Law and Biosciences.

A single woman might be able to reproduce by herself, the feminist version of Athena springing from Zeus’s head.

Ironically, however, the technology also could create something rather conventional — a biological nuclear family, albeit one that looks more like Ozzie and Ozzie. “Collaborative reproduction has paved the way for radical new definitions of family, which really helped to lead the movement for marriage equality,” says Radhika Rao, a law professor at UC Hastings law school. “Instead of challenging hetero-normative values, IVG could end up perpetuating them.”

That’s why Renata Moreira isn’t sure she would have chosen it. “It might take away from this great opportunity to challenge and expand the notion of what family looks like,” she says.

But new reproductive technologies are invented to expand our choices more than to limit them, as egg freezing and IVF allow women to pause and even extend their biological clocks. In the coming decades, IVG could let us bend biology to bring together the genetic codes, as Moreira puts it, of people who otherwise can’t. This would increase the freedom to shape our families to meet our personal values and desires, and push human evolution in an altogether new direction.

Rachel Lehmann-Haupt is the editor of The ART and Science of Family and author of In Her Own Sweet Time: Egg Freezing and the New Frontiers of Family.

This story was updated on March 1, 2018, to delete a reference to men not needing a surrogate. That would require additional technologies such as an artificial womb.