In the first week, a fertilized human egg develops into a hollow ball of 200 cells and then implants itself in the uterine wall. Over the course of the next three weeks, it distributes into the various tissues of a human body.
And those crucial few weeks remain a black box for the most part.
“We know the basics, but we just don’t know the very fine details,” said Jacob Hanna, a developmental biologist at the Weizmann Institute of Science in Israel.
Dr. Hanna and a number of other biologists are trying to uncover those details by creating models of human embryos in the lab. They trick stem cells into organizing themselves into groups that take on some of the crucial characteristics of real embryos.
This month, the team of Dr. Hanna in Israel, as well as groups in Britain, the United States and China, have all released reports of these experiments. Although the studies have not yet been published in scientific journals, they have sparked great interest from other scientists, who have hoped for years that such advances could finally shed light on some of the mysteries of early human development.
Ethicists have long warned that the advent of embryo models would further complicate the already complicated regulation of this research. But the scientists behind the new work were quick to stress that they hadn’t created actual embryos and their clusters of stem cells could never produce a human.
“Our goals have never focused on human reproduction,” said Tianqing Li, a developmental biologist at Kunming University of Science and Technology in China who led one of the new studies.
Instead, Dr. Li and his fellow scientists believe that embryo models will lead to new treatments for infertility and even diseases such as cancer.
“We’re in it to save life, not create it,” said Magdalena Zernicka-Goetz, a developmental biologist at the University of Cambridge and the California Institute of Technology, who led another effort.
For decades, the only human embryos that developmental biologists could study were samples collected from miscarriages or abortions. As a result, scientists were left with profound questions about the beginnings of human development. Thirty percent of pregnancies fail in the first week and another 30 percent fail during implantation. Researchers have no idea why a majority of embryos do not survive.
After the development of in vitro fertilization in the 1970s, scientists began studying embryos donated by fertility clinics. Some countries have banned the investigation, while others have allowed it to continue, usually with a 14-day limit. By this time, the human embryo begins to take on some of its most important characteristics. For example, a structure called the primitive streak organizes the head-to-toe arrangement the body will take.
For years, the 14-day rule was a moot point because no one could keep embryos alive more than a few days after fertilization. Things got more complicated in 2016, when Dr. Zernicka-Goetz and another team managed to keep embryos alive near the 14-day mark. The embryos no longer survived because the scientists destroyed them.
The achievement has led scientists to debate the possibility of growing embryos beyond 14 days. But even if those experiments became legal, they would still be difficult to perform because the supply of donated embryos is scarce.
In recent years, researchers have been looking for an easier way to study embryos: by making models of them in the lab. The scientists took advantage of the fact that stem cells, given the right environmental conditions, can transform into new types of tissues.
Adults have stem cells in only a few parts of the body. In the skin, for example, stem cells produce all kinds of new cells that heal wounds. In contrast, in early embryos, all cells have the potential to turn into a wide variety of tissues.
Last year, the team of Dr. Zernicka-Goetz and the team of Dr. Hanna mouse embryonic stem cells to create models of embryos. Since then, she and other scientists have been trying to do the same with human embryonic stem cells.
Each team used a different method, but they all benefit from the same underlying biology. By the time a human embryo implants in the uterus, the cells begin to diverge into different types. One type of cell will go on to produce the cells of the body. The other types produce tissues that surround the embryo during development, such as the placenta. These cell types send each other molecular signals that are essential for their development.
The researchers coaxed stem cells to mimic some of these cell types and then mixed them together. The cells swarmed together and spontaneously organized into clusters. The cells destined to become the embryo huddled in the middle, while the other types migrated outward.
As the cells communicated with each other, they divided and formed new structures that resembled parts of embryos. Dr. For example, Mo Ebrahimkhani, a developmental biologist at the University of Pittsburgh, and his colleagues observed the formation of a yolk sac in their experiment. From the yolk sac, they even observed the development of blood cell precursors.
Dr. Zernicka-Goetz and her colleagues also looked at the development of cells that resembled the precursors of eggs and sperm.
“This was absolutely thrilling,” said Dr. Zernicka Goetz. “It’s sometimes hard to believe that these stem cells are growing in these structures.”
If scientists can create accurate, reliable models of embryos, they can conduct large-scale experiments to test possible causes of pregnancy failures, such as viral infections and genetic mutations.
The models could also lead to other medical advances, noted Insoo Hyun, a member of the Harvard Medical School Center for Bioethics who was not involved in the new studies.
“Once you have the embryo models in place and you can rely on them, that could be an interesting way to screen drugs that women take when they are pregnant,” he said. “That would be a huge advantage.”
Dr. Hannah and Dr. Ebrahimkhani also saw an opportunity to use embryo models as a new form of stem cell treatment for diseases such as cancer.
In conventional stem cell transplants, doctors remove blood stem cells from the bone marrow before killing cancer cells with radiation or chemotherapy. They then return the healthy cells to the body.
Unfortunately, this method does not have a high success rate. Some researchers have suggested that earlier forms of stem cells might be more likely to cure patients.
Embryo models enable doctors to turn back time. Researchers would take skin cells from a patient and douse them with chemicals to put them in a stem cell-like state. With other chemical baths, those stem cells could then be converted into an embryo model, which could in turn develop into the early blood cells the patient needs after a transplant.
Alysson Muotri, a developmental biologist at the University of California San Diego who was not involved in the new studies, cautioned that the new studies showed only a preliminary step. First, while the techniques sometimes resulted in embryonic clusters, they often failed.
“The work is at a very early stage and current methods are far from reliable,” said Dr. Muotri.