The small cluster of cells appeared
almost
similar to a human embryo. Developed using stem cells, devoid of eggs, sperm, or a uterus, the
embryo model
featured a yolk sac and what appeared to be an initial placental structure, similar to the stage at which actual human embryos develop around day 14. This entity also produced hormones strong enough to yield a positive result on a store-bought pregnancy test.
From Jacob Hanna’s seasoned perspective, the model was far from flawless—it resembled more of a crude outline than anything precise. There was little hope it could evolve into an authentic infant. However, in 2022, as two students rushed into his office and pulled him over to a microscope to display the group of cells before them, he realized that his team might have opened up new avenues for comprehending key phases of human growth. As a professor at the Weizmann Institute of Science in Israel, Hanna understood well that this breakthrough would inevitably spark significant moral debates.
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.
[
A woman had a baby born from an embryo that was frozen for 24 years.
]
The primary justification for what is frequently
referred
as “the 14-day guideline.” Numerous
countries
restrict the duration for which a human embryo can survive in a petri dish to 14 days. When a U.K. panel suggested this 14-day restriction.
in the 1980s
IVF, which involves maintaining embryos until they can be transplanted or cryopreserved typically between day five and six when they’re viable, had just emerged. The committee concluded that 14 days represented the latest stage where an embryo could strictly be viewed as nothing more than a group of cells—without recognizable personal identity or inherent rights. They argued that since the development of the central nervous system occurs past this 14-day mark, there would be no possibility for the entity to experience pain during earlier stages.
However, the emergence of sophisticated embryo models recently has prompted certain organizations to begin challenging the significance of the two-week threshold. In 2021, the International Society for Stem Cell Research
relaxed its 14-day guideline
,
saying
That research might extend beyond 14 days based on ethical reviews and national regulations. (The organization chose not to establish a different limitation.) In July, scientists from the U.K. released
a comparable series of guidelines
Specifically regarding models, Australia’s Embryo Research Licensing Committee recently ruled that highly accurate models should be treated akin to actual embryos, thus banning their development beyond 14 days. In contrast, the U.S. has banned federal funding for human-embryo research since 1996; however, there are currently no federal regulations governing experiments involving either genuine or simulated embryos. “The initial query is whether these entities qualify as embryos?” stated Hank Greedly, a law professor and the Director of the Center for Law and the Biosciences at Stanford University. He continued, “If allowed to progress further, perhaps it might sprout another head—something we have yet to determine.” (Presence of a second head does not automatically exclude something from being considered human). Without reaching an ethical agreement, Hanna continues working towards cultivating her models up until approximately day 21—the point when gastrulation concludes. As per his update, she shared that so far, they’ve successfully grown these models till around day 18.
Researchers generally agree that
today’s
The models indicate minimal risk of them ever evolving into sentient, humanoid entities. Fusing gametes through conventional means doesn’t ensure the inception of new life; even individuals in their twenties possess roughly a similar likelihood.
a 25 percent chance
Of becoming pregnant every month, the process is quite challenging. Creating embryos in a laboratory without typical components is significantly more difficult. Currently, merely around 1% of these embryo models develop into something resembling actual embryos, as stated by Hanna. Additionally, since scientists lack a clear understanding of how a nine-day-old embryo appears within the human body, Greely mentioned that they cannot be entirely sure if these models are progressing correctly.
[
The most enigmatic cells within our body aren’t ours.
]
Despite this, over the last several years, researchers have achieved what was once thought unattainable. Hanna alongside Magdalena Żernicka-Goetz, who specializes in developmental and stem cell biology at both the California Institute of Technology and the University of Cambridge, has
created
Models for mice possessing both brain function and functioning hearts highlight critical considerations. Before developing human embryo models that also exhibit heartbeats, scientists and ethicists should reflect upon criteria defining humanity. According to certain ethicists, the pivotal issue isn’t merely achieving a heartbeat in vitro but rather doing so when such models are implanted into human uteri. “The focus has shifted,” notes Insoo Hyun, a bioethicist and the director of life sciences at Boston’s Museum of Science, “from how embryos originate to their potential capabilities.” This shift is underscored in recent experimental work.
published last year
Seven-day-old model monkey embryos were successfully transplanted into the uteri of three female monkeys. However, signs of pregnancy vanished approximately one week later; nonetheless, the study was published.
raised the specter
— or maybe the promise — of a human iteration of the experiment.
Developing more lifelike embryo models might bring substantial advantages—beginning with a fundamental comprehension of embryonic growth. About a hundred years ago, researchers gathered
thousands
of embryo specimens, which were subsequently categorized into
23 phases
Covering the initial eight-week period of development, these developmental snapshots referred to as the Carnegie stages, continue to serve as a significant foundation for describing early life in scientific literature. However, according to Hanna, “We lack knowledge about what occurs during this time.” She explains that studying development requires observing the live specimen. It necessitates watching it progress over time.
”
Until
recently
, scientists had seldom managed to keep embryos alive in the laboratory for more than approximately seven days, raising numerous questions about growth during the period after the first week. The majority of developmental abnormalities occur during this phase.
first trimester
Of pregnancy; for instance, cleft palate, a possibly disabling congenital anomaly, happens at some point.
before week nine
For reasons that scientists haven’t yet figured out, this remains an enigma. According to Greely, additional developmental studies conducted using embryo models might help unravel this puzzle.
Enhanced comprehension of the initial phases of life might provide knowledge well beyond developmental abnormalities. This insight could assist in uncovering reasons behind frequent miscarriages in certain women or their difficulties in achieving pregnancy altogether. Żernicka-Goetz has cultivated models to investigate the formation of the amniotic cavity; when this process goes awry, pregnancies often do not succeed. These embryo models could further elucidate how and why viral infections and alcohol consumption impact fetal development during these early stages—an essential aspect being medication effects as well. Expectant individuals are typically barred from participating in clinical drug trials due to possible hazards posed to the developing baby, leaving them unable to obtain therapies for both acute and long-term medical issues. Hanna has initiated
company
That aims, in part, to assess drug safety using embryo models. Hanna mentioned that he imagines an even more futuristic scenario where they might treat infertility by cultivating embryo models until day 60, extracting their ovaries, and utilizing the eggs for in vitro fertilization (IVF). Since stem cells can be derived from skin cells, this approach could address fertility issues related to aging eggs without resorting to the more intrusive elements of traditional IVF procedures, which involve stimulating the ovaries with hormones and undergoing surgical egg retrieval.
[
Christian parents have a guideline for IVF.
]
Addressing some of these inquiries might not necessitate highly detailed models of an embryo. According to Aryeh Warmflash, a biosciences professor at Rice University who focuses on gastrulation, the cells forming the placenta are irrelevant for his specific research questions; thus, they do not feature in his models. “To some extent, the more accurate your model becomes, the greater concern arises,” he noted. Hyun advised caution regarding overly intricate modeling to prevent controversy, particularly considering America’s divisions over beliefs concerning the onset of life. However, with numerous potential medical advancements from researching precise models—many previously unanswerable mysteries now appearing within reach—it seems unlikely that everybody would heed this counsel.
