No womb, No Problem: Israeli scientists “create” synthetic embryos

“Our stem cell-derived human embryo model offers an ethical and accessible way of peering into this box. It closely mimics the development of a real human embryo, particularly the emergence of its exquisitely fine architecture,” said Hanna.

The research builds on Hanna’s prior experience in creating synthetic models of mouse embryos without using fertilized eggs or a womb. Instead, they began with pluripotent stem cells, which are capable of differentiating into various cell types. Some of these cells were derived from reprogrammed adult skin cells, while others came from long-cultured human stem cell lines.

Hanna’s team reprogrammed these pluripotent stem cells to revert to an earlier, “naïve” state, similar to day seven of natural human embryo development. The researchers divided these cells into three groups, targeting their differentiation towards the placenta, yolk sac, or the extraembryonic mesoderm membrane needed for the chorionic sac.

When mixed together under optimized conditions, the cells self-organized into complete embryo-like structures.

“An embryo is self-driven by definition; we don’t need to tell it what to do—we must only unleash its internally encoded potential,” Hanna explained. “It’s critical to mix in the right kinds of cells at the beginning, which can only be derived from naïve stem cells that have no developmental restrictions. Once you do that, the embryo-like model itself says, ‘Go!’”

These stem cell-based, embryo-like structures (termed SEMs) developed naturally outside the womb for eight days, equivalent to day 14 in human embryonic development. At this point, natural embryos acquire the internal structures necessary for progressing to the next stage of development, including the formation of body organs.

Remarkably, when compared to classical embryology atlases from the 1960s, the inner organization of the stem cell-derived embryo models exhibited an uncanny structural resemblance to natural human embryos at the corresponding stage. Each compartment, supporting structure and even the cells responsible for producing pregnancy hormones were accurately replicated, the researchers said.

“Our models can be used to reveal the biochemical and mechanical signals that ensure proper development at this early stage, and the ways in which that development can go wrong,” said Hanna.

One finding of particular significance is the potential to investigate early pregnancy failure. The researchers found that improper envelopment of the embryo by placenta-forming cells at a specific point in the development process led to the failure of internal structures like the yolk sac to develop correctly.

“An embryo is not static. It must have the right cells in the right organization, and it must be able to progress—it’s about being and becoming,” Hanna stressed. “Our complete embryo models will help researchers address the most basic questions about what determines its proper growth.”

The findings open new avenues of research, including identifying causes of birth defects and infertility, developing innovative technologies for growing transplant tissues and organs, and providing an alternative to experiments that cannot be conducted on live embryos, such as studying the effects of drug exposure on fetal development.

While the development has the potential to help scientists understand genetic diseases or the causes of miscarriages, it raises serious questions about this type of experimentation and challenges existing laws. Many countries, including the US, don’t have laws that completely govern the creation or treatment of synthetic embryos. Unlike human embryos arising from in vitro fertilization, where there is an established legal framework, there are currently no clear regulations governing stem cell-derived models of human embryos.

Researchers in the US are currently limited by the “14-day rule” which limits research on human embryos to a maximum period of 14 days after their creation or to the equivalent stage of development that is normally attributed to a 14‐day‐old embryo. It is illegal to implant an experimental human embryo in a womb. In biological terms, the 15th day of embryo development is the point when the primitive streak forms: that is, the beginning of gastrulation when three layers of germ cells differentiate. 

Research with stem cells from mice and monkeys has shown that even when scientists have attempted to implant them in animal wombs, they don’t survive. It is believed that researchers haven’t been able to fully replicate the conditions of pregnancy. The current research in the United States and the UK has demonstrated that it is possible to culture embryos to the equivalent of 13 days and potentially longer raising the possibility of extending the 14-day rule.

Rabbi Moshe Avraham Halperin of the Machon Mada’i Technology Al Pi Halacha (the Institute for Science and Technology According to Jewish Law), emphasized that 

“Scientists can rearrange but they cannot create something from nothing, as God did in Genesis,” Rabbi Halperin said. “Scientists are merely combining and manipulating existing material. We know that actual Creation is forbidden by the Bible. And the Bible states that in any case, it is impossible for men to create a new life as only God has that ability. Even the greatest atheists have been unable to refute this.”

The rabbi told a joke that illustrated the point:

A group of scientists approached God and said that mankind had no use for Him anymore as they had created life. God acknowledged that if this was true, then Man had truly become independent. But he requested a demonstration. The scientists mixed some mud with water and began to process it.

“Just a moment,” God said. “Bring your own mud and water. I made these.”

Rabbi Halperin pointed out that the research had additional theological issues. 

“What the scientists are doing is not creation,” Rabbi Halperin explained. “They are manipulating cells that God created.”

“Science is discovering wonderful cures and aids but not everything is permitted in every case,” the rabbi warned. “Certain combinations, mixing species, for example, are forbidden. Science is always exploring what Man is capable of accomplishing. The Torah shows us what is good and even worthy to do.”

“If scientists ever do develop the ability to create life, Torah law explicitly prohibits this,” he said. “But that would require creating a being that can think and speak. Life is not enough to classify a being as a Man.The rabbi explained that such a creature, alive but without independent thought or the ability to communicate, would be classified as a golem; an animated, anthropomorphic being in Jewish folklore, which is entirely created from inanimate matter, usually clay or mud.