Illustration: Charlotte Ager

Replotting the human: the thorny ethics of growing babies outside the womb

Science is getting nearer to producing babies outside the womb. The moral arguments will need to catch up fast
June 7, 2021

In its worthy pursuit of what the philosopher Francis Bacon called “the relief of man’s estate,” science has a habit of creating previously unknown moral dilemmas. That’s nowhere more apparent than in the sciences pertaining to the beginning of human lives.

When IVF took off after the birth of Louise Brown in 1978, fertility doctors were faced with the question of what to do with embryos produced “in vitro”—that is, outside the womb—which would not, either because of their unviability or sheer excess in number, be implanted for gestation. Many were donated for embryological research, which has made huge strides as a result. But this has also complicated the already impassioned arguments—still unresolved—about the moral status of the human embryo.

Similar wrangles loom over the recent report in Nature by a team of scientists based in Israel who say that they can gestate mouse embryos in glass jars for up to 12 days. That might not sound long, but it is half a mouse’s normal gestation period: the embryos can reach a stage where the internal organs are in place, the heart is beating, and the hind legs are developing.

By contrast, no human embryos have been grown outside the womb beyond 14 days (the legal limit in the UK, Israel, China and many other countries), which is of course still at a very early stage of the journey towards becoming a baby. But Jacob Hanna, who led the Israeli project at the Weizmann Institute of Science, told Technology Review that it “sets the stage for other species… I hope that it will allow scientists to grow human embryos until week five.”

At the same time, advances in biology are enabling the creation of entirely new types of embryo-like structures, which some call “simbryos,” by assembling “from scratch” the embryonic cells of humans and other animals. Because these entities are in some sense “artificial,” though made from ordinary living cells, researchers aren’t sure if they qualify as genuine embryos, and so whether they should fall under the 14-day legal constraint. Meanwhile, scientists in the US and China have recently reported making “chimeric” embryos that contain a mixture of human and monkey cells, which they could keep alive in vitro for up to 20 days.

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Illustration: Charlotte Ager

All these studies are motivated by biomedical questions and needs, from trying to understand the early stages of human development (and what can go wrong, for example, leading up to miscarriages) to trying to grow human organs for transplants within livestock animals. Yet they are also blurring boundaries: between natural and artificial, tissue culture and actual conception, humans and other species. We are, in the words of academic Susan Merrill Squier, “replotting the human”—and, so far, with no moral framework to guide us.

When the Warnock Committee, chaired by moral philosopher Mary Warnock, was established in 1982 to navigate the thicket opened up by IVF, it intentionally ducked the issue of the human embryo’s moral status. “A key strategy of the Warnock Committee,” says Sarah Franklin, director of the Reproductive Sociology Research Group at Cambridge, “was to eschew the moral debate, for the simple reason it can never be resolved.” The committee’s recommendation of the 14-day rule was pragmatic: this is roughly the point after which an embryo cannot split into twins, and so served as an otherwise entirely arbitrary kind of proxy for personhood. No more rigour was needed because there was not at that stage any practical possibility of going beyond that line.

But technological advances mean that governments and scientific bodies are reconsidering the 14-day rule—and thereby taking the lid back off the moral debate. Simbryos might simply sidestep it—but should they? These are dilemmas that science has created but cannot answer. The great danger is that, amid the murk, we will grab onto polarised ideologies in the hope of settling things. 

Eugenic hatcheries

Arguments about embryology have long been divisive, and come weighted down with heavy cultural baggage. Growing embryos and even babies “ex utero” was christened “ectogenesis” in the early 20th century; its possibility motivated the biologist JBS Haldane to write Daedalus, or Science and the Future in 1924. Haldane presented a fictionalised future in which ectogenesis was introduced in the 1950s to combat plummeting birth rates. His narrator explains that, by 2073, less than a third of children were still “born of woman.”

Haldane welcomed this prospect. First, he said, it would allow population increase to be rationally planned and controlled. Better still, it would be possible to control who reproduced. Like many of his progressive contemporaries, while he supported female emancipation, he worried that better educated, “well-bred” women would prefer their new opportunities over their traditional role as mothers, leading to a decline in the quality of the gene pool. Ectogenesis could facilitate the necessary corrective of eugenic engineering. An enthusiasm for eugenics was shared by Haldane’s friend Julian Huxley, who served as vice president and then president of the British Eugenics Society from 1937 to 1962. (No, eugenic advocacy was not killed off by the example of the Nazis.)

But Huxley’s brother Aldous was less taken with Haldane’s vision of a bioengineered population grown in artificial wombs. That scenario supplied the inspiration for the dystopian Brave New World (1932), with its “hatcheries” in which foetuses are chemically manipulated for intelligence to create the hierarchical society of the World State.

At one time, both men and women sympathetic to the feminist cause welcomed ectogenesis. In Hymen, or The Future of Marriage (1927), Norman Haire suggested that animals might instead act as gestational surrogates: human babies born to chimp mothers, for example. The pioneering feminist Vera Brittain, however, conceded in Halcyon, or the Future of Monogamy (1929) that “natural methods of reproduction” might make a comeback after a period of ectogenesis because children born outside the womb could suffer psychological problems. The trailblazing feminist writer Shulamith Firestone was another fan of ectogenesis. Her 1970 book The Dialectic of Sex portrayed childbearing as a primary cause of gender inequality: “I submit,” she wrote, “that the first demand for any alternative system must be… the freeing of women from the tyranny of their reproductive biology by every means available.”

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Illustration: Charlotte Ager

In stark contrast, more recent feminists have warned that artificial wombs could remove from women a source of social power. Australian sociologist Robyn Rowland worries: “We [women] may find ourselves without a product of any kind with which to bargain… if that last power is taken and controlled by men, what role is envisaged for women in the new world? Will women become obsolete?” Another worry is expressed by bioethicist Rosemarie Tong, who fears “a commodification of the whole process of pregnancy [and] a view of the growing child as a ‘thing.’”

History shows, then, that while putative reproductive technologies like ectogenesis and artificial wombs have long been controversial, the terms of the debate have shifted with social perceptions and attitudes. We haven’t even decided what the important questions are, let alone how to answer them.

Towards artificial wombs

True ectogenesis is still a far cry from what the Israeli group has just achieved. Their mouse embryos do not really exist in an artificial womb as such; they float freely in a nutrient medium, including human blood serum taken from the umbilical cord, in rotating glass jars kept at a carefully controlled temperature and in levels of dissolved oxygen elevated above normal. Because they have no placenta to attach to or umbilical cord to supply blood, eventually they die through lack of oxygen.

The work is impressive, but growing small mammal embryos far into gestation in artificial cell-culture conditions is not completely new. For example, developmental biologist Lynne Selwood at the University of Melbourne has been able to culture embryos of the stripe-face dunnart—a mouse-like marsupial—to within a few hours of full term. (Their gestation period is 11 days, the shortest of any mammal, and marsupials are born “premature” relative to other mammals.) Selwood’s interest in the technique was its potential use for conservation: breeding and preserving the species from frozen embryos, for example.

“For all its humanitarian objectives, embryonic research remains ethically fraught”

Only in the past few years have researchers, such as Magdalena Zernicka-Goetz at Cambridge—one of Prospect’s World Top 50 Thinkers last year—managed to grow human embryos in vitro right up to that 14-day limit. The difficulties, both practical and ethical, of investigating human embryos inside the womb mean that plenty remains unknown about their genetics, cell biology and tissue and organ formation. Ex utero studies beyond two weeks could potentially help us to understand and avoid, for example, miscarriages and growth defects that might cause disability or even death for babies carried to full term.

For all its humanitarian objectives, though, such research remains ethically fraught. A five-week-old human embryo, say, is very different from the shapeless mass of cells and folded tissues at 14 days: it has a shrimp-like form, with a rudimentary head, a neural tube that eventually becomes the central nervous system and brain—as well as a beating heart. In other words, it is more recognisably “human.” (When the foetus can potentially feel pain is not clear—that has generally been deemed impossible before the brain’s cortex matures at around 24 weeks, but some argue that pain of a kind, if not an awareness of “suffering,” might be registered as early as 12 weeks.)

“You needn’t be a ‘pro-lifer’ to accept there is still an urgent need to think all the consequences through”

Of course, abortion of such embryos is permitted well into pregnancy in many countries—up to 24 weeks (and in exceptional cases later) in Great Britain. But technologies for gestation in “artificial wombs”—both for the early embryo as in the latest Israeli work, and life support for very premature babies—could seriously complicate the legal and ethical dilemmas. If these two methods, coming from opposite directions, meet in the middle so that the entire gestational period becomes technologically supportable, then genuine Huxlerian ectogenesis becomes an option. Women with potentially life-threatening pregnancies might then no longer be faced with termination as the only option—but the law doesn’t currently cover such a scenario. And how would abortion rights fare in the face of a putative “technological solution” that can preserve the life of the embryo or foetus? It’s far from inconceivable that a state with strong anti-abortion leanings could mandate continued ex utero gestation rather than termination.

Such questions remain hypothetical: creating true artificial wombs is challenging, and the field has advanced at a snail’s pace for decades. But the latest work by Jacob Hanna and colleagues is a reminder of the direction of travel.

Sustaining human embryos beyond 14 days would not, however, currently be done with reproduction in mind. The aim is basic research for understanding developmental biology. An alternative approach for doing that, which would evade the 14-day rule, is to build synthetic embryo-like structures from stem cells. In the right conditions, you don’t need to do much more than bring the right sorts of cells together—they will organise themselves spontaneously into a configuration more or less resembling an embryo. Two teams in the US and Australia have recently described the in vitro generation of human “blastoids”—structures similar to early-stage embryos—from stem cells either taken from actual embryos or “reprogrammed” from adult skin cells. These blastoids resemble the so-called blastocyst, the stage that a human embryo reaches around five to nine days after fertilisation, when it is ready to implant in the uterus wall. The blastoids contain not only the mass of stem cells that will become the foetus, but also the cell types that can develop into the tissues needed to sustain and contain it: the yolk sac and the placenta. The team in Texas showed that their blastoids could attach themselves to the culture dish to mimic uterine implantation, and then continue to develop.

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Illustration: Charlotte Ager

Blastoids are just one example of what some have dubbed “synthetic human entities with embryo-like features” (SHEEFs); though simbryos is a catchier name. As they are not made by fertilisation of an egg by sperm, their legal and ethical status is unclear, and there is no consensus on regulation. UK and EU patent law rules that a synthetic cellular entity can’t be considered a human embryo if “in the light of current scientific knowledge, it does not, in itself, have the inherent capacity of developing into a human being.” In the US an absence of federal laws might mean that the guidelines of the International Society for Stem Cell Research (ISSCR) are adopted. These were revised in May, and advise that such research be governed by case-by-case consideration—but that such entities should not be transferred to the uterus of either a human or another animal. Current simbryos almost certainly couldn’t develop into a foetus in any case—but as they become ever better mimics of natural embryos, we can’t be sure what potential they might have. “Whether they could become babies is a crucial question,” says bioethicist Hank Greely of Stanford University in California, “but can we resolve that ethically? We won’t know without trying it in humans—which we can’t do.”

The edge of human

This science is in a Catch-22 situation, Greely says. “We want to do research about humans that we can’t ethically do on humans, so we go to non-human models. Existing non-human models [such as animals] aren’t that good, so we make new, better models”—like simbryos. “But the dilemma is the better the models get—the more ‘human’ they are—the more we get back into the same ethical issues.” Biotechnologies like simbryos and chimeric embryos, suggest Greely and Bartha Maria Knoppers of McGill University in Montreal, are “nibbling” at the legal definition of what a human is.

The new ISSCR guidelines advise relaxation of the 14-day rule on human embryo research, to be replaced by a case-specific decision on what the limit should be. Changes to national legislation will be needed to enact this in many countries. But if that happens, some anticipate not only learning more about human embryo development but even harvesting nascent organs from such embryos, such as pancreases or kidneys, that might be grown further in vitro for transplantation. It might also be possible to use embryos grown for several weeks to test the safety of human gene editing, for example, to avoid some nasty genetic diseases.

“History suggests that our response to disruptive technology will be highly dependent on contingent cultural preoccupations”

Even with such potential medical benefits, you needn’t be a “pro-lifer” to accept there is an urgent need to think all the consequences through. Our ability to transform, manipulate and culture cells takes us into uncharted territory where the boundaries of “natural” and “artificial,” and even of the human and non-human, are blurred. No off-the-shelf moral framework can be expected to guide the “should and shouldn’t.” And history suggests that our response to disruptive technology will be highly dependent on contingent and perhaps ephemeral cultural preoccupations and prejudices. To track a responsible and humane path forward, we need—somehow—to try and look beyond them.

Scientists lack the training and often the desire to take on that role. But the stifling of stem cell and embryo research in the US by George W Bush’s 2001 Council on Bioethics shows what happens when religious conservatives are given the reins. As that panel showed, “bioethics” is a label that covers a multitude of sins and sometimes shows no inclination to examine its own assumptions. And heaven forbid that these issues be allowed to become fresh fuel for the culture wars. If we can reconstitute the collective and pragmatic wisdom of the Warnock Committee, it won’t be a moment too soon.