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They Were Made Without Eggs or Sperm. Are They Human?

The Atlantic

www.theatlantic.com › health › archive › 2024 › 10 › human-embryo-model-ethics › 680189

The little clump of cells looked almost like a human embryo. Created from stem cells, without eggs, sperm, or a womb, the embryo model had a yolk sac and a proto-placenta, resembling a state that real human embryos reach after approximately 14 days of development. It even secreted hormones that turned a drugstore pregnancy test positive.

To Jacob Hanna’s expert eye, the model wasn’t perfect—more like a rough sketch. It had no chance of developing into an actual baby. But in 2022, when two students burst into his office and dragged him to a microscope to show him the cluster of cells, he knew his team had unlocked a door to understanding a crucial stage of human development. Hanna, a professor at the Weizmann Institute of Science in Israel, also knew that the model would raise some profound ethical questions.

You might recall images of embryonic development from your high-school biology textbook: In a predictable progression, a fertilized egg morphs into a ball of cells, then a bean-shaped blob, and then, ultimately, something that looks like a baby. The truth is, though, that the earliest stages of human development are still very much a mystery. Early-stage embryos are simply too small to observe with ultrasound; at 14 days, they are just barely perceptible to the naked eye. Keeping them alive outside the body for that long is difficult. Whether anyone should is another matter—for decades, scientific policy and regulation has held 14 days as the limit for how long embryos can be cultured in a lab.  

Embryo models—that is, embryos created using stem cells—could provide a real alternative for studying some of the hardest problems in human development, unlocking crucial details about, say, what causes miscarriages and developmental disorders. In recent years, Hanna and other scientists have made remarkable progress in cultivating pluripotent stem cells to mimic the structure and function of a real, growing embryo. But as researchers solve technical problems, they are still left with moral ones. When is a copy so good that it’s equivalent to the real thing? And more to the point, when should the lab experiment be treated—legally and ethically—as human?  

Around the 14th day of embryonic development, a key stage in human growth called gastrulation kicks off. Cells begin to organize into layers that form the early buds of organs. The primitive streak—a developmental precursor of the spine—shows up. It is also at that point that an embryo can no longer become a twin. “You become an individual,” Jeremy Sugarman, a professor of bioethics and medicine at the Johns Hopkins Berman Institute of Bioethics, told me.

[Read: A woman gave birth from an embryo frozen for 24 years]

The primitive streak is the main rationale behind what is often referred to as the “14-day rule.” Many countries limit the amount of time that a human embryo can be kept alive in a petri dish to 14 days. When a U.K. committee recommended the 14-day limit in the 1980s, IVF, which requires keeping embryos alive until they are either transferred or frozen around day five or six, was still brand-new. The committee reasoned that 14 days was the last point at which an embryo could definitively be considered no more than a collection of cells, without potential individual identity or individual rights; because the central nervous system is formed after the 14-day milestone, they reasoned, there was no chance it could feel pain.

But the recent rise of advanced embryo models has led some groups to start questioning the sanctity of the two-week mark. In 2021, the International Society for Stem Cell Research relaxed its 14-day guideline, saying that research could continue past 14 days depending on ethical review and national regulations. (The organization declined to set a new limit.) In July, U.K. researchers put out a similar set of guidelines specifically for models. Australia’s Embryo Research Licensing Committee, however, recently decided to treat more realistic models like the real deal, prohibiting them from developing past 14 days. In the United States, federal funding of human-embryo research has been prohibited since 1996, but no federal laws govern experiments with either real or model embryos. “The preliminary question is, are they embryos at all?” Hank Greely, a law professor and the director of the Center for Law and the Biosciences at Stanford University, told me. Allow one to develop further, and “maybe it grows a second head. We don’t know.” (Having a second head is not necessarily a reason to disqualify someone from being human.) In the absence of an ethical consensus, Hanna is at work trying to cultivate his models to the equivalent of day 21, roughly the end of gastrulation. So far, he said, he’s managed to grow them to about day 18.

Researchers generally agree that today’s models show little risk of one day becoming walking, talking human beings. Combining sperm and eggs the old-fashioned way is already no guarantee of creating new life; even women in their 20s have only about a 25 percent chance of getting pregnant each month. Making embryos in a lab, sans the usual source material, is considerably harder. Right now, only about 1 percent of embryo models actually become anything that resembles an embryo, according to Hanna. And because scientists don’t have a great idea of what a nine-day-old embryo looks like inside the body, Greely said, they don’t actually know for certain whether the models are developing similarly.

[Read: The most mysterious cells in our bodies don’t belong to us]

And yet, in the past few years, scientists have already accomplished what seemed impossible not so long ago. Both Hanna and Magdalena Żernicka-Goetz, a developmental and stem-cell biologist at the California Institute for Technology and the University of Cambridge, have created models for mice with brains and beating hearts. Scientists and ethicists would be wise to consider what qualifies as human before human embryo models have beating hearts, too. The most important question, some ethicists argue, is not whether researchers can achieve a heartbeat in a petri dish, but whether they can achieve one with a model embryo implanted in a human womb. “It's no longer so much about how embryos are made or where they come from, but more what they can possibly do,” Insoo Hyun, a bioethicist and the director of life sciences at Boston’s Museum of Science told me. In an experiment published last year, seven-day-old model monkey embryos were successfully implanted in the uterus of three female monkeys. Signs of pregnancy disappeared about a week afterward, but the paper still raised the specter—or perhaps the promise—of a human version of the experiment.

Building more realistic embryo models could have enormous benefits—starting with basic understanding of how embryos grow. A century ago, scientists collected thousands of embryo samples, which were then organized into 23 phases covering the first eight weeks of development. Those snapshots of development, known as the Carnegie stages, still form much of the basis for how early life is described in scientific texts. The problem is, “we don’t know what happens in between,” Hanna said. “To study development, you need the living material. You have to watch it grow.Until recently, scientists had rarely sustained embryos in the lab past day seven or so, leaving manifold questions about development beyond the first week. Most developmental defects happen in the first trimester of pregnancy; for example, cleft palate, a potentially debilitating birth defect, occurs sometime before week nine for reasons that scientists don’t yet understand. It’s a mystery that more developmental research performed on embryo models could solve, Greely said.

Better understanding the earliest stages of life could yield insights far beyond developmental disorders. It could help reveal why some women frequently miscarry, or have trouble getting pregnant at all. Żernicka-Goetz has grown models to study the amniotic cavity—when it forms improperly, she suspects, pregnancies may fail. Embryo models could also help explain how and why prenatal development is affected by viruses and alcohol—and, crucially, medications. Pregnant people are generally excluded from drug trials because of potential risks to the fetus, which leaves them without access to treatments for new and chronic health conditions. Hanna has started a company that aims, among other things, to test drug safety on embryo models. Hanna told me he also envisions an even more sci-fi future: treating infertility by growing embryo models to day 60, harvesting their ovaries, and then using the eggs for IVF. Because stem cells can be grown from skin cells, such a system could solve the problem of infertility caused by older eggs without the more invasive aspects of IVF, which requires revving the ovaries up with hormones and surgery to retrieve the resulting eggs.

[Read: Christian parents have a blueprint for IVF]

Answering at least some of these questions may not require hyperrealistic models of an embryo. Aryeh Warmflash, a biosciences professor at Rice University, is studying gastrulation, but the cells that form the placenta aren’t relevant to his research questions, so his models leave them out, he told me. “In some sense, the better your model goes, the more you have to worry,” he said. Hyun told me he cautions scientists against making extremely complex models in order to avoid triggering debate, especially in a country already divided by ideas about when life begins. But given all the medical advances that could be achieved by studying realistic models—all the unknowns that are beginning to seem knowable—it’s hard to imagine that everyone will follow his advice.

In Defense of Marital Secrets

The Atlantic

www.theatlantic.com › books › archive › 2024 › 10 › scaffolding-lauren-elkin-review-marriage-infidelity › 680139

Is bad behavior in marriage back? In fictional marriage, I mean. For years, heterosexual matrimony in American novels has seemed rather like it’s become a trap for the female protagonist: Unhappy or misunderstood by her spouse, she may act out or seek retribution; whatever her behavior, though, readers are meant to see that it’s attributable to her environment—in other words, that she’s not really in the wrong. For this plotline to work, the wife must be attuned, sometimes newly so, to herself, her unhappiness, her desires—a fictional extension of the powerful, if reductive, idea that women can protect themselves from harm by understanding their own wants and limits.

In daily life, of course, human desires and boundaries are changeable. The feminist philosopher Katherine Angel writes, “Self-knowledge is not a reliable feature of female sexuality, nor of sexuality in general; in fact, it is not a reliable feature of being a person. Insisting otherwise is fatal.” Self-awareness has certainly killed sex (and sexiness) in a lot of novels; it’s killed a lot of novels, in fact. A story without badness isn’t much of a story, and a story whose hero has perfect self-knowledge is a story utterly devoid of suspense.

Stories about marriage are no exception to this rule. There’s an unbearable flatness to any book whose protagonist is always justified in her actions—or, for that matter, always able to justify them to herself. After years of reading such dead tales, I found both delight and hope in the critic and memoirist Lauren Elkin’s debut novel, Scaffolding, a tale of two slippery adulterers who consider understanding oneself an impossible—or, at best, incompletely possible—task. Its protagonists, Anna and Florence, are psychoanalysts who live in the same Parisian apartment nearly five decades apart, in the 2010s and 1970s, respectively. Both women have crises of faith in language, in intellectualism, in their role as a therapist and as a wife. Neither wants to leave their marriage, but both launch intense, clandestine affairs.

Anna and Florence don’t totally understand their motivations for cheating. They act on impulse—in Anna’s case, for what seems like the first time in her life—and yet each seems to recognize that her affair is a voyage of discovery. Elkin writes these events as complicated adventures in wrong decisions—which, crucially, she neither justifies nor condemns. She lets her characters be bad yet ordinary, bad yet sympathy-inducing, bad yet worthy of a good life. In a sense, their badness improves their situation. Their lack of self-awareness, their tendency or ability to submit to their id, gets them closer to what they consciously want: some privacy within their marriage. Just as Scaffolding argues that we can’t know ourselves fully, it makes plain that we can never completely know one another—and that there’s nothing fundamentally wrong with that, even when it leads to bad behavior; even when it breaks our hearts.

Scaffolding is about feminism as much as it is about marriage. Florence, its ’70s protagonist, is a psychoanalysis student who spends her free time with consciousness-raising groups. She commits herself to flouting convention, even though her marriage is fairly traditional: She cooks and cleans, and is busy redecorating the apartment that she and her husband, Henry, inherited from her grandmother, who survived the Holocaust. Elkin swiftly makes apparent to readers that Florence’s feminist rebellion is also a rejection of the (largely Christian) “Franco-Français” society that deported her family—something Florence herself seems not to notice. She’s too busy thinking about the affair she’s having with one of her professors. Anna, in the 21st century, is less rebellious and much less happy. She’s suffering from depression after a miscarriage, spending hours immobile in bed, “as if a large sheet of cling film were pinning me in place.” Sexually, she’s shut down; her husband, David, is working in London, and she declines to go with him and struggles to engage in any intimacy when he visits her in Paris. Her only live connection—very live, it turns out—is with Clémentine, a feminist artist in her 20s who grows determined, and successfully so, to draw Anna out of herself and into the world.

[Read: How should feminists have sex now?]

But even as Anna begins recovering from her depression, its effect on her career is devastating. Formerly devoted to her analysis practice, she’s now stopped valuing her profession. “Why look in other people’s narratives for the metaphors, the gaps, the gaffes, the subtexts, that point you to what they themselves may or may not realise?” she asks herself. “Maybe the words merely point to themselves.” Readers see her apply this feeling to her own life, expending less and less effort on making sense of her behavior. Florence follows a similar trajectory, though as a result not of trauma but of going to Jacques Lacan’s lectures and having an affair with a Lacanian psychology professor. (Don’t worry: Although Lacan famously deconstructed language, which led, in his case, to highly abstruse writing, Scaffolding does not. Elkin’s prose is elegant and straightforward, with just enough experimentation to suit its ideas.) “We have to absorb what we’re learning without passing it through language,” she tells a friend—no easy job for a shrink. But both Florence and Anna learn to see conscious thought as a scaffold, with impulse and desire as the real, substantial building it encases and supports.

Florence tries and fails to explain the intensity of her feelings for the professor she’s having an affair with; she tells herself he’s a stand-in for something but has no idea what. At the same time, she’s mystified by the fact that the affair is a “big, big deal” to her when she’s out and about in the daytime, but the moment she returns to her “evening life” with Henry (a cheater himself, not incidentally), thoughts of her lover either vanish or fuel the sex life that is the core of her marriage. Secrecy and deception as aphrodisiac—this may not be moral, and yet, Florence decides, it’s “exactly how [marriage] should work, and exactly not how it is supposed to work.”

Anna, for her part, keeps more secrets from herself than from David. She nurtures an attraction to her neighbor Clémentine without permitting herself to notice, though the reader can’t miss it: Anna, otherwise cut off from her body, is so physically attuned to her friend’s presence that she describes her as “her own charged atmosphere.” It’s through Clémentine, in fact, that Anna reencounters an ex whom she desires so intensely, she sleeps with him almost instantly, even though doing so means betraying both David and Clémentine. Unlike Florence, Anna doesn’t attempt to explain her feelings or actions to herself. She knows her behavior is wrong, yet she also knows how alone she’s been, how solitary and isolated from her husband her depression has made her. Having an affair punctures her cling film. It might be bad, but it also returns her to her marriage and her life.

Scaffolding isn’t really suggesting that adultery and secrecy are good for a marriage. Rather, the novel treats these things as bad but normal and manageable—and preferable to a total loss of connection. When Clémentine cheats on her boyfriend, she tells Anna the cheating is a disruption that can be “absorbed back into the relationship.” Novels that leave wrongdoing out of their worlds imply that no transgression, marital or otherwise, could be that small, and that for a character to do something genuinely harmful would bring their whole life crashing down. Our broader cultural impulse toward hyperconsciousness is rooted in the same idea. It reflects an inability or unwillingness to tell the difference between big bad things and the small bad ones—and, by extension, to forgive the latter.

[Read: A grim view of marriage—and an exhortation to leave it]

Elkin puts some big badness in Scaffolding to draw out this distinction. Clémentine is part of a brigade of women who graffiti anti–domestic abuse messages on Paris’s walls. Their work presents a vision of feminism very different from the one in Florence’s consciousness-raising groups, which are all about knowing oneself: For Clémentine, protest is the only way women can resist misogyny. Anna’s first positive emotion in the novel is a response to the graffiti: “Aren’t they incredible?” she says, pointing one out to David on one of his visits from London. Florence, meanwhile, isn’t just involved in raising her own consciousness. She also keenly follows the Bobigny trial, France’s equivalent of Roe v. Wade. Both characters are highly aware of how dangerous life can be for women. Compared with unsafe clandestine abortions or spousal violence, some cheating means nothing; but compared with the flatness of Anna’s day-to-day life and the conventionality of Florence’s marriage, their affairs have immensely high stakes.

Scaffolding strikes this balance well. Elkin is deft but clear in reminding readers that there’s a distinction between badness and evil, or badness and hate. She writes Florence’s and Anna’s marriages as immensely loving ones, despite their holes and wobbles; in such relationships, the novel seems to argue, it is conceivable—though not guaranteed—that almost anything can be forgiven or absorbed.

Neither Florence nor Anna knows why they cheat on their husband. Perhaps more important, neither of them knows why they love their husband. In a novel less invested in psychological mystery, this would signal crisis for the fictional marriage. In life, it’s the most normal thing there is. Complete self-awareness is both an unattainable standard and a false promise, as is complete transparency with someone else, no matter what your wedding vows say or suggest. Accepting this fact is terrifying. It turns commitment into suspense. In reality, many of us prefer not to acknowledge that, which is more than reasonable: Who goes into their marriage wanting deception and drama?

Novels, though, are built to let us test-drive uncertainty—to feel it without living it. Where marriage is concerned, this is an important option for many of us to have. Marriage stories whose protagonists never slip up don’t give readers this option; if anything, they flatten our views of intimacy rather than letting us expand them through imagination.

The Mistakes Israel Can’t Afford to Repeat

The Atlantic

www.theatlantic.com › international › archive › 2024 › 10 › mistakes-israel-afford-repeat › 680185

“They’re cheering us now,” I said to the soldier next to me in the jeep, as we drove through Beirut to applause and showers of rice. “But soon they’ll be shooting.” It was June 9, 1982, four days after Israel had invaded Lebanon. The war followed years of Palestinian rocket fire on northern Israel, but the proximate trigger was a Palestinian gunman’s attempt to assassinate the Israeli ambassador in London. The goal of Operation Peace for Galilee, as then–Israeli Prime Minister Menachem Begin called it, was to push the terrorists out of rocket range, but Defense Minister Ariel Sharon ordered the army to advance farther north and besiege Beirut. After evicting the terrorists and the Syrian troops occupying the country, Israel hoped to install a Christian, pro-Western government that was committed to peace.

I was serving in a reserve reconnaissance unit of the Israel Defense Forces at the time, but in civilian life, I was studying Middle East history. I’d learned that the Lebanese had often cheered invading armies but later turned on them. Previous efforts to pacify the country had uniformly failed. Sharon’s plan, I thought, was reckless. “We’ll never get out of here,” I said to the soldier as we drove, rice-pelted, through Beirut’s suburbs. “We’re stuck.”

Stuck we were, both militarily and diplomatically. President Ronald Reagan at first backed the operation, but then, appalled by the number of civilian casualties, forced Israel’s troops to fall back to southern Lebanon. The U.S. Marines who replaced us also abandoned Beirut after 243 of them were killed by a suicide bomber from a previously unknown Shiite group named Hezbollah. Those same Iranian-backed terrorists relentlessly attacked IDF positions in the south, until finally, a full 18 years after they’d invaded Lebanon, the last Israeli soldiers withdrew.

[Gal Beckerman: A naked desperation to be seen]

Though Israel succeeded in freeing Lebanon of Syrian troops and evicting many Palestinian terrorists, and a peaceful Christian government emerged, that progress proved fragile. The new president was soon assassinated, and the country gradually came to be dominated by Hezbollah. On July 12, 2006, Hezbollah terrorists ambushed an IDF patrol, killing eight soldiers and capturing two. Israel responded with the Second Lebanon War.

The conflict raged for 34 days, during which Hezbollah rockets pummeled Israeli cities and towns and IDF jets bombed strategic targets in Lebanon. President George W. Bush initially supported Israel’s right to self-defense, before recoiling from the high civilian casualty rate and demanding a cease-fire. A last-minute thrust by Israeli ground forces succeeded only in further antagonizing the Americans. Their response was United Nations Resolution 1701, which ended the fighting and instructed Hezbollah to withdraw to north of the Litani River, creating a buffer zone in the south of Lebanon.

In this second war, I served as an IDF spokesperson, rather than a combat soldier. But on its last night, I volunteered for battlefield duty. My assignment was to help transport the remains of fallen soldiers out of the combat zone and back over the border to Israel. Their comrades watched us as we worked, their faces grim with disappointment and fatigue. More than 100 soldiers had died, yet none of us could say exactly for what.

Although Israel managed to inflict a toll on Hezbollah—its leader, Hassan Nasrallah, publicly regretted ambushing that patrol—it gained little in the long term. In defiance of Resolution 1701, Hezbollah deployed along Israel’s northern border and burrowed multiple attack tunnels beneath it. Directly opposite the frontier fort where I served after 2006, Hezbollah erected a huge billboard on which a laughing terrorist hoisted an Israeli soldier’s severed head.

Israelis deluded ourselves by thinking that the war had deterred Hezbollah when, in fact, the war had deterred us. We remained largely passive while, over the next 17 years, Hezbollah expanded its rocket arsenal tenfold and grew to become one of the region’s most formidable military forces.

Israel’s indifference ended after October 7, 2023. We now know that 3,000 terrorists of Hezbollah’s elite Radwan unit had been planning to smash through the border and ravage Israel’s north much as Hamas had in the south. Timely bombing by the Israeli air force preempted that attack, but Hezbollah compensated by shelling the Galilee. Nearly 100,000 Israelis became refugees in their own country, their fields and houses scorched.

Historically, Israel has never done well with wars of attrition, yet Hezbollah was waging one that steadily crept south, toward the Sea of Galilee in the east and toward Haifa in the west. Israel’s return fire failed to deter Hezbollah and, by its very ineffectiveness, may have egged it on. Throughout, Hezbollah declared its readiness to agree to a cease-fire if Hamas did, but Hamas wanted a war in the north that would relieve the pressure it faced in Gaza. It was only a matter of time before Israel, assured that Hamas was sufficiently degraded, would turn its attention to Hezbollah. On September 19 of this year, after the pagers and walkie-talkies used by Hezbollah operatives simultaneously exploded, seriously wounding thousands of people and killing at least 37, the Third Lebanon War began.

Though also launched in response to terrorist attacks from Lebanon, the Third Lebanon War differs from its predecessors in several crucial ways. For Israel, Lebanon is now just one front in a year-long, multifaceted struggle with Iranian proxies throughout the region, as well as with Iran itself. Unlike the previous two wars, both of which were perceived by many Israelis as wars of choice, the current conflict is seen by almost all Israelis as fully justified. We know that Israel cannot lose the north and survive.

For that reason alone, Israelis need to consider how the Third Lebanon War can succeed where the first two failed.

Success will depend principally on setting clear and realistic objectives. Israel cannot, as it did in 1982, seek to remake Lebanon into a Middle Eastern Belgium or, as in 2006, merely retaliate for Hezbollah’s aggression. Rather, Israel’s limited goals must be to drive Hezbollah beyond the Litani and to end the rocket fire on the north. Israel must deny any intention of permanently occupying southern Lebanon and declare its openness to any diplomatic means of implementing and reliably enforcing Resolution 1701.

[Dara Horn: October 7 created a permission structure for anti-Semitism]

The United States must also avoid its former mistakes, committing instead to supporting Israel and allowing it to complete its military mission. Israel began this war with a series of brilliant strikes against Hezbollah’s leaders and military infrastructure, but the fighting ahead is likely to remain brutal. The U.S. must desist from imposing premature cease-fires or sponsoring UN resolutions that the terrorists can handily violate. But the United States should also insist that Israel honor its pledge not to occupy Lebanon, and that it engage earnestly with diplomatic envoys.

Although I recently volunteered for reserve duty guarding a Galilean kibbutz, I will not take part in this Lebanon war. For the young Israeli soldiers engaged in close combat, I can only offer one older veteran’s advice: You are fighting to restore security to your people, not to refashion Lebanon or to remain indefinitely on its soil. Your job is not to punish Hezbollah for any specific act of aggression, but to deter it and its Iranian sponsors from further attempts to destroy us. Your job is to fight with all the skills you’ve been taught, the superior gear you’ve been issued, and the values you learned at home, in order to complete your mission—and then to return to help lead Israel into the future.

The third time—so the colloquialism goes—is always a charm. The Third Lebanon War can yield positive and perhaps transformative results. Hezbollah and its Iranian patrons can be defeated, Israel can reinforce its security and revive its deterrence, and the United States can reaffirm its superpower status. But all of that will require a consistent effort to study the mistakes of Israel’s first two wars in Lebanon, and to avoid repeating them.