By Amanda Schaffer
Not too long ago, baby-in-a-box technology seemed imminent. In the late 1990s, scientists in Japan startled the world with a freestanding artificial womb: an acrylic, fluid-filled incubator. The scientists used it to gestate goats that had been removed prematurely from their mothers' uteruses. Again in the early 2000s, a group of IVF researchers in Manhattan made headlines with custom wombs: They grew endometrial tissue, molded it into a curved shape, and tried to bring human and mouse embryos to term. Neither project made it to fruition. But there was every reason to feel excited by the promises of high-tech womb substitutes, in which human babies might someday come to term. Since then, though, the scientific quest for artificial uteruses has sputtered. Why has it gone thoroughly out of fashion?
In the last five years, scientists have come to believe that the environment of the mother's womb is more, not less, complex and crucial. Across several different fields, research has taken off on the intertwining of mother and embryo, or fertilized egg, that occurs from the very beginning. Psychologists are finding that maternal cues may influence the personality of the developing fetus. Cellular cross-talk between mother and fetus seems to shape normal development and susceptibility to disease. And some IVF scientists have tried to reduce chromosomal abnormalities by incubating fertilized eggs within the mother's body, minimizing the time in a Petri dish. All of this adds up to a sea change in how scientists view the uterus, and makes the idea of bypassing the maternal womb seem nearly impossible. At the beginning of our lives, we apparently need mothers even more than we ever thought.
It's worth revisiting how close scientists thought they were to a brave new no-uterus world to see how clearly scientific attitudes have shifted. The group led by Yosinori Kuwabara in late-'90s Japan managed to keep goat fetuses alive for up to three weeks in a fluid-filled incubator, with an artificial placenta that supplied oxygen and nutrients and removed wastes. Remarkably, several fetuses made it to term (21 weeks for a goat). But they had lung disorders and other abnormalities. Also, they weren't popped into the incubator until a late gestational age. As one expert on preemies told me, if you translate goat time to human time, the fetuses "were practically teenagers" by the time they reached the artificial womb.
The IVF researchers also, fleetingly, boasted seeming success. Concentrating on the beginning of gestation rather than the end, they created tissue-engineered wombs in which fertilized eggs might develop. Led by researcher Hung-Ching Liu at the Center for Reproductive Medicine and Infertility in Manhattan, the group managed to grow human embryos for up to 10 days. Starting in 2002, Liu's team also created artificial mouse uteruses in which they incubated numerous mice. At least one survived almost to term. But ultimately, it died along with the others, some of which had striking physical abnormalities. Blood vessels linking the fetus to the artificial womb had failed to develop normally, Liu said at the time. Since then, she has stopped speaking publicly on the topic. A spokesperson would only confirm that the research "has not been ongoing for several years." (Never mind that in 2005, Liu confidently told a reporter that she expected to have a viable mouse womb in five to 10 years and a human one in "10 years, maybe, or a little more.")
Instead, the last five years of science have been a mother-appreciation fest. Recent work on the immune system is a case in point. Some of this research grows out of older studies; recently, the field has taken off. Growing evidence shows that during pregnancy, maternal cells slip across the placenta and integrate into the fetus' body. A paper published in Science in December, for instance, found that maternal immune cells that take up residence in the fetus help train it to distinguish between itself and others. This is crucial for normal immune development. Other research suggests that the open current between the maternal and fetal immune systems might later in life either protect from, or predispose to, disorders like lupus, type one diabetes, or rheumatoid arthritis.
Though major questions are still unanswered, gestation now seems like a kind of cellular apprenticeship, with mother and fetus even more deeply enmeshed than scientists used to think. "Fundamentally, we are individuals at conception," but in the course of gestation, we become "composite creatures," as William Burlingham, an immunologist at the University of Wisconsin, put it. How on earth could an artificial system ever capture those mom-specific contributions?
The shift toward mothers is also apparent in some of the most avant-garde research by IVF researchers, designed to improve fertility treatments. Carlos Simon, an IVF expert in Spain, and his colleagues are testing a new technology that would reduce the time that fertilized eggs spend outside a woman's body before being transferred to her uterus. They are working with a permeable silicone capsule that can house fertilized eggs; it will be placed temporarily in a woman's womb, in order to allow "optimal exchange" between her body and the early fertilized cells (even if it's not known what substances, exactly, would flow from mother to capsule). In March, a pilot study of the technology-developed by a company called Anecova, which funded the research-suggested the potential benefits of getting the fertilized eggs into the mother sooner. The study found that cells cultured inside the uterine capsule on the first to third days after fertilization appeared to have fewer chromosomal abnormalities than those maintained for the same time in vitro. The approach reflects a sort of nascent, technical homage to mothers, whether or not it ultimately pans out.
The latest research on fetal psychological and neural development also ups the ante on what we would need or want an artificial womb to do. The uterus is not a quiet, still place. The fetus hears and responds to the sounds of its mother's voice, her heartbeat, her digestive gurglings, and these cues surely shape its brain and nervous system in fundamental ways, says Janet DiPietro of Johns Hopkins, a pioneer of this work.
In 2006, DiPietro found that when middle-class women are mildly to moderately stressed, anxious, or depressed during pregnancy, they tend-counterintuitively-to have babies who by age two are more developmentally advanced, with better motor development, a greater number of words, and a greater facility for puzzles. The psychological influence of the mother after birth doesn't account for the difference. Other research suggests, less surprisingly, that more severe maternal depression, anxiety, or stress may increase the risk of behavioral problems or mental illness in the child down the road. An artificial womb, DiPietro says, "could never be truly human-like in its complexity."
If the uterus has been revealed as too hard to replicate, then the science can put to rest the once-raging feminist debate about whether trying to build an artificial womb was a good idea in the first place. In the early 1970s, the formidable Shulamith Firestone argued that such technology might liberate women from their traditional reproductive roles. On the other hand, as The New Republic argued in 2003 (subscription required), an artificial womb could "redefine the abortion debate," by undermining the logic of the Supreme Court rulings that protect a woman's right to terminate a pregnancy at least until a fetus becomes viable. If fertilized eggs could develop entirely outside a woman's body, the question of viability might become moot. So might a woman's prerogative to abort. One could also worry that artificial wombs would allow men to "eliminate women from the planet and still perpetuate our species." (Of course, in an alternate sci-fi scenario, women could do the same to men-perhaps more easily since sperm are easier to freeze than eggs.)
Now, it looks like our species needs women and their wombs to stick around. It's another kind of creature that might be better off with less mother-time. In Australia, scientists are trying to use artificial uteruses to save a population of gray nurse sharks: In nature, 20 of the sharks share a mother's womb, but one eats the other 19 in the course of gestation. And so Shulamith Firestone's dream survives only in this wild corner of the animal kingdom, riddled with shark tartar.