The Future of Fertility

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In 2016, two Japanese reproductive biologists, Katsuhiko Hayashi and Mitinori Saitou, made an announcement in the journal Nature that read like a science-fiction novel. The researchers had taken skin cells from the tip of a mouse's tail, reprogrammed them into stem cells, and then turned those stem cells into egg cells. The eggs, once fertilized, were transferred to the uteruses of female mice, who gave birth to ten pups; some of the pups went on to have babies of their own. Gametes are the cells, such as eggs and sperm, that are essential for sexual reproduction. With their experiment, Hayashi and Saitou provided the first proof that what's known as in-vitro gametogenesis, or I.V.G.—the production of gametes outside the body, beginning with nonreproductive cells—was possible in mammals. The mice that had descended from the lab-made egg cells were described as "grossly normal."

The Japanese experiment may change the science of human reproduction. The first successful in-vitro fertilization, in 1978, made it possible to conceive an embryo outside the body. Today, approximately two per cent of all babies in the United States are conceived in a lab, through I.V.F.—last year, analysts valued the global I.V.F. market at more than twenty-three billion dollars. Egg cells have become commodities that are harvested, bought, donated, and preserved. But egg cells, some of the most complex cells in the body, and large enough to be visible to the naked eye, are difficult to obtain; as a woman ages, their number and quality decline. "If ripe human eggs could be derived from a person's skin cells, it would avoid most of the cost, almost all of the discomfort, and all of the risk of IVF," the Stanford bioethicist Henry Greely wrote in his 2016 book, "The End of Sex and the Future of Human Reproduction," addressing new techniques to make stem cells which had won the Nobel Prize in 2012. He predicted that in the next twenty to forty years sex will no longer be the method by which most people make babies ("among humans with good health coverage," he qualified).

A hundred years ago, many Americans died in their mid-fifties. Today, we can expect to live into our seventies and eighties. In the U.S., as in many other countries, women give birth for the first time at older ages than they did several decades ago, but the age at which women lose their fertility has not budged: by forty-five, a person's chances of having a pregnancy without assisted reproductive technology are exceedingly low.

Biologists have theories, none of them conclusive, about why women have such a sharp decline in fertility at midlife, and why ovaries age at least twice as fast as the other organs in the body. Deena Emera, an evolutionary geneticist and the author of a forthcoming book about evolution and the female body, told me that the vast majority of female mammals, including chimpanzees, maintain the ability to get pregnant for most of their lives. Elephants, which can live up to seventy years, can conceive and give birth into their sixth decade. Human females share their long post-reproductive life span with only a few other mammals, mostly species of toothed whales. We are connected in this strange and frustrating reality with narwhals, belugas, and orcas. There's much debate, if not a definitive answer, about why.

In the U.S., according to census data, the number of births to women under the age of twenty-five has dropped significantly since 1990; an increase in births to women over thirty-five has not compensated for the decline. The United Nations has estimated that in 2019 nearly half the global population lived in countries with below-replacement fertility rates, which the U.N. defines as fewer than 2.1 births per woman. (In our country, population growth is also driven by immigration.) While the over-all growth in human population is not anticipated to plateau until the mid-twenty-eighties, economists say that aging populations in countries with fewer children can affect, among other things, the continued growth of economies, the provision of health care, and the funding of pension systems. Although there are also social and environmental benefits to a decrease in the global population, many countries are recognizing that they can no longer take a passive approach to fertility issues.

In recent years, the science of extending female reproductive longevity has seen a new flurry of interest, and biotech companies are attempting to begin clinical trials of a number of therapies, including new I.V.F. techniques and pharmaceuticals. (The research has earned philanthropic attention as well—Hayashi's and Saitou's labs are funded in part by Open Philanthropy, a foundation set up by the Facebook co-founder Dustin Moskovitz and his wife, the former journalist Cari Tuna.) But the ability to make egg cells without human ovaries would apply not only to people who are designated female at birth. This March, Hayashi, who is not currently trying to make a human egg, had another announcement: his lab had repeated the I.V.G. process in mice, but this time it had produced fertilized embryos whose egg cells had been developed using stem cells from male mice—"mice with two dads," as the headline in Nature put it. Futurists have speculated about broader possibilities, such as an embryo formed with the DNA of four people instead of two, or even a so-called "unibaby," the result of a person reproducing with herself. In a less hypothetical realm, in-vitro gametogenesis may have applications in livestock breeding, and might one day play a role in preserving endangered species—a group of scientists, including Hayashi, have been attempting to use the method to generate eggs from the northern white rhinoceros, a species of which only two females remain.

In some circles, I.V.G. is already seen as the future of reproductive science. Bianka Seres, a co-founder of a startup called Conception Biosciences, which is trying to make egg cells from stem cells, told me that I.V.G.—along with a related, though more far-fetched, prospect, artificial wombs—was a prominent theme at the American Society for Reproductive Medicine's annual conference in 2021, hinting at a time when gestation could happen outside the human body. "It wasn't 'Oh, maybe this will happen,' " she said. "It was very factual: when this happens, this is how we're going to use it." She and her colleagues believe that one day dozens of egg cells might be generated from a simple biopsy or blood sample, perhaps even one taken from someone who is biologically male. Conception might not be the company that figures out I.V.G., but the prevailing sense is that it's only a matter of time before someone does.

In late January, I visited the headquarters of Conception, in Berkeley. The company was founded in 2018, and has since raised almost forty million dollars in venture capital in pursuit of in-vitro gametogenesis. The staff was temporarily based in a single-story co-working space near Aquatic Park, and things had gotten crowded. Conception's C.E.O., a thirty-one-year-old entrepreneur named Matt Krisiloff, was working from an armchair wedged between two desks. Krisiloff first tweeted about his interest in I.V.G. in 2017. At the time, he was the director of a nonprofit wing of Y Combinator, the startup incubator, established to fund technological research "for the benefit of the world," as the company put it. Sam Altman, who was then running Y Combinator, told me that he and Krisiloff were both interested in what he called "hard-tech companies that invest a long time in developing a difficult technology first and then don't bring a first product to market for many, many years." Krisiloff had helped out in the early months of OpenAI, which went on to invent ChatGPT, Dall-E, and the transcription service Whisper, an experience he has cited as formative in learning how to set up a research-oriented company with an ambitious end goal.

Krisiloff has close-cropped hair and a gap-toothed smile, and on the day of my visit he was dressed in jeans, a black crew-neck sweatshirt, and sneakers made by the Swiss brand On. He does not have a degree in the hard sciences—as an undergraduate, he majored in Law, Letters, and Society at the University of Chicago—and was still in his twenties when he and two scientists founded Conception, which was initially known as Ovid Research. Krisiloff's interest in I.V.G. was partly personal: he is gay, and liked the thought of one day being able to have biological children with a male partner. (Krisiloff once dated Altman; he is now in a relationship with Lucas Harrington, the co-founder of Mammoth Biosciences, which is focussed on the gene-editing technology CRISPR.)

While visiting Hayashi's lab in Japan in 2018, Krisiloff met Pablo Hurtado González, a Spanish biochemist who was a visiting scholar there. Over dinner at a ramen restaurant in Fukuoka one evening, the mission of Conception began to take shape. Hurtado González, who is thirty-two, is also gay, and has a Ph.D. in reproductive health and a particular interest in male-male reproduction. (The bio on his Instagram profile reads "Trying to make genetic gaybies at Conception Bioscience.") After placing an ad in Nature, Krisiloff and Hurtado González hired their third co-founder, Seres, who was born in Romania and raised in Hungary. She had worked as an embryologist at a fertility clinic in England before completing her Ph.D. at Cambridge University under Melina Schuh, a German cell biologist who is an expert in meiosis, the type of cell division unique to reproductive cells, which leads to the production of eggs and sperm. "Coming from I.V.F., in-vitro gametogenesis was the single most important solution to not having enough eggs," Seres told me. Seres, who is thirty-six, has a daughter conceived without assisted reproductive technology, but her experience working at fertility clinics had made the issue personal to her: she had seen many patients with infertility issues for which no clear cause could be found.

Krisiloff had secured an initial million dollars from Hydrazine Capital, a fund, co-founded by Altman, in which he was an investor. (Conception's investors now include Jaan Tallinn, the founder of Skype, and Laura Deming, who has a fund devoted to technologies that target the aging process to treat disease.) At first, Conception's plan was more modest: to try to bring undeveloped eggs from a human to maturation in vitro. But a conversation with a surgeon convinced Krisiloff that immature eggs would be too difficult to extract. "One of our investors gave us really good advice, like, Hey, if in-vitro gametogenesis is the main thing you care about, you can probably go surprisingly far if you just choose to focus on that rather than defer it for later," Krisiloff said. "That changed our trajectory."