Scientists have created a human-chicken hybrid in a lab by transplanting human embryonic cells onto chicken embryos.
The researchers at the Rockefeller University in New York City have created the hybrid to give insight into fetal development.
Ethical guidelines and laws prohibit scientists from experimenting with human embryos more than 14 days old. The researchers were able to bypass the 14-day rule by growing embryo-like structures from human embryonic stem cells. The cells were cultured on squares just 22 millimeters across. They were able to force the cells to organize into structures instead of spreading horizontally. The cells were also treated with a series of growth factors that stimulated them to form various cell layers as are seen in early embryos.
Tests revealed that the embryo-like structures included a cluster of cells that expressed genes seen in other species’ organizer cells.
Organizer cells were discovered in 1924 with research on salamanders in Germany. A pair of developmental biologists transplanted the cells from the back of one salamander embryo to the front of another. The cells then grew into a second, conjoined salamander. This suggested that there are certain cells on the embryo’s back that could organize the neighboring cells into the complex array of structures that make up an animal, or specific parts of an animal.
Since then, researchers have identified organizer cells in the embryos of many other species, but not in humans. This is thought to be due to the 14-day rule.
“No one knew what happens after the ball of cells attaches itself to the uterus,” says Ali Brivanlou, a developmental biologist at the Rockefeller University in New York City and lead author of the latest study.
In 2016, Brivanlou’s team were the first to grow human embryos in a dish to the 14-day mark, around the time they’d expect to find organizer cells, but the cells were not found before the experiment ended.
Human-Chicken hybrid results
Brivanlou and his colleagues transplanted their embryo-like clusters of human cells onto 12-hour-old chicken embryos, which is the rough equivalent of a 14-day-old human embryo.
The researchers found that the as the modified embryos grew, human organizer cells developed and directed the chicken cells to differentiate and form a second chicken nervous system. That result mimics the findings of the 1924 salamander experiment, Brivaloud says.
The hybrid embryos did not live long enough to hatch.
What does it mean?
The technique may avoid ethical (and legal) issues associated with studying human embryos in the lab.
“It’s a real advance — it’s beautiful this can be shown without the need of using embryos,” says Martin Blum, a developmental biologist at the University of Hohenheim in Stuttgart, Germany. “At the moment I could not think of a case where an early human embryo would be needed to answer basic questions.”
Brivanlou disagrees. “There is no substitute for studying the real embryo,” he says. “Everything else we do when we try to model kind of oversimplifies it.”
The next step, he says, is to determine how exactly the human organizer cells influence their neighbors. “Human embryonic stem cells and eggs have all the information,” Brivanlou says. “Everything else is pushing the first domino.”
Future research with human-chicken hybrids could have a big impact on disease research and treatment.
For now, the scientists will pursue research on the human-chicken hybrid embryos to research Huntington’s disease, a deadly neurological disorder. Huntington’s disease is caused by mutant genes that are already at work in the early stages of embryonic development but the symptoms develop many decades later in life.
To study Huntington’s disease the researchers are planning to insert the mutant gene into hybrid embryos to see how their development differs from that of hybrid embryos that lack the gene. Ultimately they hope that it will be possible to identify drugs that might counteract the abnormal developmental process and enable humans with the gene to develop normally.
“It would be a good idea to start attacking the problem sooner,” Brivanlou says. “In my opinion, this could change reproductive medicine. If we’re able to find out what goes wrong early on, maybe we have a better chance of curing it.”
The scientists also hope to use the hybrid embryos to find cures for other complex diseases, caused in part by mutant genes, including Lou Gehrig’s disease and Alzheimer’s.