A new crop of biotech startups want to revolutionize human reproduction.
n 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, most 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.”
For now, Krisiloff is the only person at Conception who concentrates on the business side of things. He works alongside thirty-five scientists, many of them in their first jobs outside of academia; none are the kind of big-name principal investigators who tend to spin off private companies based on research in their own labs. “There’s some suspicion about the company aspect versus the academic approaches,” Krisiloff admitted. “Four or five years ago, it was, like, What are you kids doing here?” But, he added, “it became obvious early on that having teams of very specialized people working on different parts of this in parallel rather than having to think about their individual first-author publications would be quite helpful.”
Still, in this era of disgraced tech-company wunderkinds and hubristic billionaires, Krisiloff seemed intent on avoiding the impression that he was another maverick tech entrepreneur—Mark Zuckerberg’s motto, “Move fast and break things,” does not inspire confidence when the desired outcome is a baby. Some observers have said that human biology is too complex for I.V.G. ever to become a viable method of reproduction, and I asked Krisiloff what would happen if they couldn’t make it work. “If we’re getting negative data in terms of in-vitro experiments or animal-safety testing, we’re not just going to try and brute-force it through,” he said. “We need to be cognizant that we’re trying to develop a technology that, if it does come to fruition, the impact is new human life.”
When I met Conception’s founders in January, the three kept up an easygoing banter. Krisiloff tends to defer to his co-founders for technical explanations. Seres, dark-haired and earnest, is analytic and adept at metaphor. Hurtado González, who is six feet five and has a thin mustache, speaks English with the sharp consonants of his native Spain and has had to become something of a scientist Jack-of-all-trades, managing the delivery of lab equipment between studying the latest published papers. He stood up at a certain point in the conversation to coördinate the burrito order for the company’s Friday lunch.
They clicked through slides depicting cells that had been stained to reveal their internal structures in bright magenta, blue, and green. Human egg cells begin their formation inside fetal ovaries in utero but start maturing individually only in adolescence, at the onset of menstruation. Conception’s researchers, who are trying to grow such cells through I.V.G., began by reprogramming blood cells, donated with consent for embryonic research, into stem cells, which can become any type of cell in the body. The stem cells are then programmed into primordial germ cells, the precursors to eggs. These germ cells are placed in dishes with lab-grown helper cells, which re-create the ovarian environment and are known collectively as ovarian organoids. The hope is that these helper cells will send out the necessary signals to coax the germ cells along in their development into mature eggs capable of being fertilized. The researchers use a variety of techniques, such as RNA sequencing, to insure that the lab-made cells are expressing the same genes that they would at a similar stage in the womb, and that they’re forming what are called follicles, the structures in the ovary in which immature egg cells develop.
On a cellular level, “the body” can become an abstract concept: as Krisiloff put it to me, “You don’t really need a heart to produce an egg.” You may not need the twelve or thirteen years that pass before an egg cell starts maturing in the body, either. If the germ cells are given the right signals, they will move on to the phase of development they would normally reach after puberty.
Conception has re-created many stages of egg development, but it had not yet put them all together into a single process that would culminate in a primary follicle, the phase that indicates an egg is ready to begin the final stages of maturation. “The prime focus right now is getting this follicle-formation step to occur,” Krisiloff said. “We think once we have this figured out, which we also think we’re relatively close to, then everything else we kind of have model systems for.”
Other researchers in the field are using the same techniques of stem-cell biology for different strategies. Some are trying to grow human eggs and sperm to test the toxicological effects of chemicals on gametes, or to develop contraceptive methods. Others are experimenting with how I.V.G. might result in cells that can be transplanted back into the body, such as spermatogonial stem cells (the precursors of sperm) for an infertile male.
Gameto, a New York-based biotech startup founded in 2020, is exploring in-vitro maturation: how to mature eggs that have been extracted from the body rather than made in a dish. It was co-founded by Martin Varsavsky, the owner of a chain of fertility clinics, and Dina Radenkovic, a physician turned entrepreneur. Unlike sperm cells, which most men produce in the hundreds of billions in the course of their lives, a woman is born with all the eggs she will ever have. These eggs mature slowly, normally just one per menstrual cycle. During I.V.F., women are given hormone injections that stimulate their ovaries to mature multiple eggs, but the process is onerous, and patients typically undergo anesthesia to retrieve the eggs.
When I spoke with Radenkovic, Gameto’s C.E.O., over video, she punctuated her points by holding up a follicle-stimulating injection pen of the kind used in I.V.F. “If you just had one man go through the brutal treatment of I.V.F., they would have sat down, they would have put some money in, and they would have solved it,” she said. If the process of freezing eggs becomes easier and more reliable, she continued, very few people would need to resort to I.V.G., which she sees as too risky a proposition for a business. “We’re really hopeful of allowing women to go through I.V.F. with much fewer side effects, less clinical time, and a lower cost—something that you could do in, like, egg-freezing kiosks. I see it almost like an extension of the beauty studio, where being proactive about your reproduction and longevity just seems like an act of self-care.”
Nearly everyone in the industry whom I spoke with, including Conception’s founders, told me that they regularly hear from people desperate to have biological children, volunteering to donate their genetic material or participate in clinical trials to test technologies that are likely years away. I spoke with someone who had contacted Conception, a forty-nine-year-old woman who lives in upstate New York. She told me her story—a childhood in England; a successful career as a lawyer; a long-distance partnership that began in her late thirties with a colleague who already had children and seemed reluctant to have more. She tried cycles of I.V.F., and all failed. “I grew up so ignorant about this—I was very focussed on my career, and I was a late developer romantically,” she said. When I asked why it was important to her to pass on her genes, she told me that after her parents died she wanted to have something of them to love in the world. “I have so much life and energy still to give,” she said. She would like to find a gestational carrier for her last frozen embryos. (Older maternal age at pregnancy is associated with a higher risk of complications.) “It’s a shame that it has to be this difficult.”
The morning after my visit to Conception, I was picked up at my hotel in San Francisco by Jennifer Garrison, a neuroscientist and an assistant professor at the Center for Reproductive Longevity and Equality. Garrison, who is blond and in her mid-forties, is one of the country’s foremost critics of the common narratives about female reproductive longevity. She is frequently quoted in the media and invited to lecture at conferences on the subject. She has been a consultant for companies exploring I.V.G., but she sees I.V.G. as only one piece in the much larger puzzle of female reproductive inequality. “If I had to sum up what we’re doing, I want aging in the female reproductive system to be synched up with aging in the rest of the body,” she told me, as we drove across a fog-wreathed Golden Gate Bridge. “If we can do that, then there are all these amazing, profound impacts on over-all health, not to mention fertility.” Menopause doesn’t just signal the end of fertility—it has negative impacts on bone health and on cardiovascular, cognitive, and immune function, and also causes weight gain, depression, insomnia, low libido, and other issues.
As we drove, Garrison apologized that the rainy weather was ruining the views. We were heading to the Buck Institute for Research on Aging, which sits atop a hill in a nature preserve in Novato, a small city in Marin County, overlooking San Francisco Bay; deer and wild turkeys roam the nearby fields. I. M. Pei, who designed the building, avoided right angles, on the theory that doing so would encourage creativity. The Center for Reproductive Longevity and Equality was started here in 2018, with a six-million-dollar donation from the foundation of the intellectual-property lawyer, entrepreneur, and investor Nicole Shanahan, who was then married to Sergey Brin, the co-founder of Google (they separated in 2021).
Shanahan was not yet thirty when she was told that she had polycystic ovary syndrome; at the time, she and Brin were trying to create an embryo through I.V.F. to bank. Informed that she was an impossible candidate, Shanahan walked away from the I.V.F. clinic believing that she was not going to be a mother. When, two years later, she conceived naturally, she didn’t take it as a lucky break; rather, she was infuriated about the guidance she’d been given and began to wonder why the subject was so poorly understood. Her experience became a cause. Shanahan has said that she sees extending reproductive longevity as “the natural and necessary progression of the women’s-rights movement.” In 2020, she funded a sister center in Singapore. (Many of the countries and regions with the lowest fertility rates in the world right now are in Asia.)
Much of the biology of female reproductive aging is still a black box: Garrison told me that we don’t know the timer or the cue that marks the beginning of reproductive decline, or why the age of menopause has so much individual variation. We have little sense of what aging in the ovaries means for aging in the rest of the body, even though early menopause is correlated with a shorter life span, not only for the woman experiencing it but for her brothers. There is currently no reliable biomarker that tells a woman how many eggs she has left.
Research into women’s health has historically been underfunded. Most of our contraceptives and fertility treatments were developed in the last century; there has been little innovation since the nineteen-eighties. Reproductive-health-care research has been further impeded by political controversies surrounding abortion, contraception, fetal tissue, and the “personhood” of embryos. Women were not required by law to be included in government-funded clinical research until 1993, and many drugs and dosages are still optimized for the male body. One 2021 study, “Gender Disparity in the Funding of Diseases by the U.S. National Institutes of Health,” which was published in the Journal of Women’s Health, found that, “in nearly three-quarters of the cases where a disease afflicts primarily one gender, the funding pattern favors males.”
Shanahan has advocated against supporting the I.V.F. industry and I.V.G. research, seeing them as circumventing much needed research into understanding the causes of infertility. Instead, she leads an investment firm, Planeta Ventures, and a foundation, Bia-Echo, which support the development of precision medicine, nutritional interventions, and diagnostic tools, which she hopes will give individuals a much better idea of when and for how long and why they can get pregnant, one that is not based on a population average. “I think that there has been a very big missing category of medical services,” she said. “Many of the I.V.F. clinics are financially incentivized to offer you egg freezing and I.V.F. and not incentivized to offer you other fertility services.”
Garrison concurred, going so far as to describe egg freezing as “barbaric.” She argued that the private for-profit I.V.F. industry masks as innovation what is in fact a symptom of neglect. “There’s been a huge amount of research funding, consumer dollars, and government subsidies that have gone into that industry in the last four decades, and not just in this country,” she said. “If even a tiny bit of that had gone into answering some of these basic questions that we’re talking about, we wouldn’t be having this conversation.”
After pausing to look at some nematode worms glowing under a microscope in Garrison’s lab, we examined a graph that showed average male fertility—a slope that barely wavers until the end of life—and average female fertility, with its steep decline beginning in one’s mid-thirties. “I hate this graph,” Garrison said. For one thing, she explained, it obscures the fact that many women have a much “noisier” trajectory, with fluctuating periods of fertility and infertility. It would be helpful, she suggested, if women had a better way to monitor intervals of fertility as they age. Instead, the graph is used as evidence of the inexorable.
She contemplated another approach. “What if we didn’t move the age of menopause, but right up until the age of menopause your eggs were healthy and there wasn’t this fifteen-year window where your risk of miscarriage, aneuploidy, birth defects, and infertility goes up?” she asked. “What if we could just X that out?”
The following weekend, I returned to the Buck Institute for a conference in which the organization’s grant recipients gathered to present their work. The future of reproductive technology, the presentations suggested, might include not just I.V.G. but a whole range of interventions: a scientist from Mexico gave a talk about the hyperproductive ovaries of ant queens, which can be fertile for as long as thirty years; another discussed a trial of the drug rapamycin to determine whether it prolongs fertility in rhesus macaques; another spoke about the role of gut microbiota in reproductive aging.
It was a lot to take in. The graph indicating the decline in female fertility relative to male was shown four or five times, as if we might forget. In the past few years, several of my male friends over the age of fifty have become fathers for the first time. Their reproductive freedom is their privilege and their right. One of these friends told me that going through psychoanalysis finally gave him the ability to have intimacy in his life. How luxurious to have that time. I am childless and turning forty-two this month. I have eleven oocytes—immature egg cells—in cryogenic storage in a facility somewhere in Manhattan. Right now, that’s pretty much all that science can offer a late bloomer with ovaries. The oocytes, should I ever attempt to have them fertilized and implanted, have a forty-per-cent chance of resulting in a successful pregnancy.
That night, the researchers gathered for dinner at a nearby winery. A professor of molecular biology from Princeton named Coleen T. Murphy told a story about how, twenty years ago, she pitched a fertility diagnostic blood test to an investor. She recalled him responding, “Can’t you just get that from a Pap schmear?” Everyone laughed. I asked the others at the table—they were all women—if they were also concerned about research showing that sperm counts have declined worldwide. Murphy looked at me blankly. “But there’s still so many of them,” she said. “And, let’s be honest, they don’t even do that much,” an ob-gyn and research scientist chimed in. “I call them ‘the postmen of cells.’ ”
Conception’s founders have tried to apply an engineering approach to making eggs, in which an experiment is conducted over and over with slight modifications. To keep its researchers supplied, Conception has developed methods to make tens of millions of primordial germ cells and hundreds of ovarian organoids. During my visit, I watched as scientists checked the progress of cells under microscopes and pipetted liquids into dishes laid out across biosafety hoods, tweaking variables such as culture medium and timing. Bianka Seres told me that they keep mouse embryos in incubators with the dishes of cells; if the embryos stop growing, they know that something is wrong in the environment. Cells are temperamental—they don’t like plastic, or the cold.
One recent morning, I spoke by video with Katsuhiko Hayashi, one of the Japanese scientists who helped prove that I.V.G. was possible in mammals. It was six o’clock in the morning in Los Angeles, and ten o’clock at night in Japan, and Hayashi, who wore glasses and a sweater with a collared shirt, had his screen background blurred. I asked what he thought of the prospect of developing I.V.G. for human reproduction. “I think it takes a long, long time,” he said. “And even if we can get human oocyte cells in culture we need to carefully evaluate the quality of the oocytes, because even in the mice most of the oocytes are, how can I say, not potent enough to develop to a baby.”
Other academics, including those trying to make human eggs, are skeptical that startups such as Conception will supplant traditional scientific-research pathways. “If the end goal is only about getting to the tech, then yes, a biotech company has the advantage,” Amander Clark, a professor of molecular, cell, and developmental biology at U.C.L.A. who works on I.V.G., told me. “However, without an academic pipeline, there is no specialized and informed workforce to populate the biotech companies.” Clark points out that the industry has a long way to go: humans and mice are very different, and researchers have yet to prove that lab-made human cells can undergo meiosis in vitro.
Azim Surani, a developmental biologist at Cambridge and a mentor to many researchers in the field, explained some of the concerns: cells that look healthy and functional may still have unknown errors in their epigenome, and the long period of acculturation in dishes might result in the wrong modifications. Using skin or blood cells as the source of the DNA for the egg cell also risks introducing any mutations those cells have acquired during a person’s life—should I.V.G. become a reality, the best approach might begin with cells stored at birth. Among the parameters that will need to be evaluated in offspring, across multiple generations, are longevity, behavior, and susceptibility to disease.
“It’s going to take a lot of work to figure out how safe it is, and we’ll never know perfectly,” Henry Greely, the author of “The End of Sex,” told me. “I worry a lot that desperate people will try desperate things, that our regulatory system will not be up to it.” Other scientists feel that I.V.G. for human reproductive purposes may be jumping the gun—that researchers are attempting to create a process outside the body without fully understanding what takes place inside one. “Think of it this way,” Clark put it to me in an e-mail. “In the absence of this foundational scientific knowledge, it is the equivalent of trying to drive a car without a GPS to a destination that you have never traveled to before.”
The regulatory environment faced by a biotech startup like Conception is another unknown. “The United States has a political debate about abortion that has spilled over into everything that has to do with embryos,” Alta Charo, a retired professor of law and bioethics at the University of Wisconsin-Madison, told me. Federal law already prevents the government from funding the creation of human embryos for research, which means that funding for I.V.G. for human reproductive purposes has to come entirely from individual states, the private sector, or foreign entities. Also, in vitro-derived gametes for human use are likely to be regulated by the F.D.A. as a biological product; the F.D.A. cannot approve requests for clinical trials that would involve making heritable genetic modifications to human embryos, which may apply to some I.V.G. approaches. Charo predicts that human clinical trials for I.V.G. are far more likely to be first attempted in the U.K., which has a less polarized political climate around abortion, and a government agency, the Human Fertilisation and Embryology Authority, that licenses and monitors fertility clinics and provides recommendations about policy to lawmakers.
In 2021, the International Society for Stem Cell Research recommended extending the standard time limit on research done with in-vitro embryos, which is fourteen days, on a case-by-case basis. But such a step would come with its own thorny ethical questions. “Imagine a world where you could be doing research on an embryo very far along in development, but people can’t make any decisions about fetuses in their own bodies,” Sonia Suter, a professor of law at the George Washington University who studies bioethics and issues of reproductive technology, told me. She also feared a return to the idea that genetic connection is essential for families after decades of efforts by same-sex parents to be granted legal recognition of their relationships with their nonbiological children. Suter said that the technology would probably exacerbate existing inequalities. Because I.V.G. has the potential to create many more embryos than I.V.F., it may result in more screening for desired genetic traits. It is unlikely to be covered by many insurance plans, and attempts to optimize for health and success may primarily benefit the wealthy.
“It’s going to be the same parents who send their kids to private schools and get their kids in piano and ballet,” Suter said. “Then we have the opposite problem, where we have people who can’t get access to contraception and can’t terminate a pregnancy when they’re struggling financially.” She added, “That divide already exists. After Dobbs, it’s just going to get worse as we have more advanced technology.”
Paths to making a profit are uncertain. The inventors of I.V.F. never attempted to patent the technology, though the hormones injected in the process, which cost thousands of dollars, were patented by pharmaceutical companies. Conception has filed for a patent for some of the cells it has engineered, but, as Nature recently pointed out, the United States has laws against patenting the human organism, as well as medical procedures such as heart surgery or dialysis. Matt Krisiloff told me that, should Conception get governmental approval, its business model would be based on offering clinical services, which in the earliest stages might cost as much as two hundred thousand dollars per client.
Piraye Yurttas Beim, the C.E.O. of a biotech company called Celmatix, which is focussed on developing therapies to slow ovarian aging, told me that the excitement around I.V.G. could be misleading. “It feels like: we can go to Mars, so why can’t we make eggs?” she said. “But I think making eggs that have transgenerational reproductive potential—I think it’s probably, like, one hundred times as complex to do that as to go to Mars.”
I asked what she thought the options might be twenty years from now, if I.V.G. is not available. She described the world that she pictured for her daughter, who is six, in which assessment of ovarian and hormonal health will begin in young adulthood. “It’s going to be a standard part of her ob-gyn experience, from a place of optimizing for her long-term reproductive potential,” she said. Her daughter’s generation will likely freeze their eggs early, have babies in their forties or fifties, and anticipate living into their nineties. “It will feel completely arcane and mind-boggling for her that any generation before just simply went into menopause like it was an unavoidable thing,” she concluded. “That is going to feel as foreign to a woman in twenty years in the developed world as the pre-C-section or pre-birth-control era.”
In the weeks after I first visited Conception, researchers working under George Church, the well-known geneticist at Harvard, announced new breakthroughs in the creation of a human ovarian organoid. The research for the technology had been sponsored by Gameto, the New York-based startup, which then licensed it for use. I asked one of the researchers who worked on the project, a Ph.D. student named Merrick Pierson Smela, if he thought growing a stem-cell-derived egg in a dish would ever be possible. “Definitely,” he said, without hesitation. He added that the first person to do it is unlikely to be the one who captures the entire field. “Ten or twenty years after the first proof of concept is when you’re going to see actual human babies from it,” he estimated. Conception has not published papers, which makes it hard to know how Harvard’s organoid compares with its own, but the main difference between their approaches is that Conception is trying to use its organoids to grow egg cells made from stem cells, whereas Gameto, using Harvard’s technology, is creating what it calls “a signaling environment,” basically mimicking the ovaries, in which immature egg cells taken from the body will be placed and given the cues to mature, a potentially more attainable goal.
At the end of March, I returned to Conception for an update. A few weeks before, the staff had moved into a new office, in a renovated warehouse. Seres took me on a tour of the gleaming lab: an area filled with biosafety cabinets, incubators, and microscopes was devoted purely to the production of millions of primordial germ cells. We paused before a single-cell analyzer, a glossy black box the shape and size of a bread machine. It cost around ninety thousand dollars. Conception’s scientists also had news to share: they had brought their oocytes to the primary-follicle stage. “To our knowledge, nobody has been able to do that with in-vitro-derived germ cells,” Hurtado González said. “For us, that was one of the biggest bottlenecks, and it worked.”
“It’s very exciting,” Seres said. I asked if they planned to share the process with the broader scientific community. Krisiloff said they were still figuring out a way to do so that wouldn’t compromise their intellectual property, but that “obviously it’s extremely important for us that there’s general buy-in that we’re actually doing something legitimate.”
Hurtado González suggested that they might reveal only the follicle. “The morphology is excellent, it’s beautiful,” he said. They are now doing molecular analysis on the cells, he said, “to make sure they are what we would expect.”
That evening, the staff had a party to celebrate the move to the new space. In a play area in a corner, a few children took turns going down a plastic slide, and drawing pictures on a whiteboard. A karaoke machine had been set up for later in the night, and a projection screen on one wall featured images of the cells that Conception is growing, their colors brilliant with immunofluorescent staining. The cells were either the future of human reproduction or just something that was worth trying.
“It is valuable to show the possibility of such a new, let’s say alternative, type of reproduction for the future,” Katsuhiko Hayashi had said to me when we spoke over video. “But of course such a technology should be evaluated by the society.” ♦
