A team of researchers working in China have announced that they have successfully created human-monkey chimeras, in the form of monkey embryos that grow human cells as part of their biological structure. This experiment aims to develop a new method of growing tailor-made organs that could be transplanted into waiting patients, although such a controversial procedure faces a major ethical challenge: exactly how “human” should we allow these lab-grown creatures to become?
Working at a laboratory in China, researchers from the Salk Institute in the United States and the Murcia Catholic University (UCAM) in Spain have produced genetically-modified monkey embryos that are designed to grow human organs, intended for transplantation into human recipients. The embryos were terminated at 14 days of gestation, a “red line” maximum gestation period set by the scientific community that doesn’t allow the embryo enough time to develop a central nervous system, at least in the case of humans.
The monkey embryos had their genes responsible for forming organs “deactivated”; then they were injected with human stem cells—special cells that have the unique ability to develop into one of the more familiar specialized cells that make up our bodies, like skin or muscle cells—producing a monkey embryo infused with human cells.
“From UCAM and the Salk Institute we are now trying not only to move forward and continue experimenting with human cells and rodent and pig cells, but also with non-human primates,” explains lead study author Juan Carlos Izpisúa.
The team’s intent is to lay the groundwork for the development of potential host animals that can be used to grow human organs, using stem cells taken from a human recipient to make the organs compatible for that individual. This process would alleviate both the problem of organ donor shortages and the issue of organ compatibility: since the organs would be made from the recipient’s own cells, they would, at least theoretically, not be rejected by the recipient’s body.
Izpisúa’s team had attempted to blend human cells into pig embryos in 2017, but the experiment wasn’t successful. “The human cells did not take hold. We saw that they contributed very little [to the development of the embryo]: one human cell for every 100,000 pig cells,” explains veterinarian Pablo Ross, a researcher from the University of California at Davis, a participant in that experiment. Later experiments using rats and mice—species more closely related to one another than pigs and humans are—were more successful, resulting in rat-mouse chimera embryos.
But this recent experiment was conducted in China due to heavy restrictions placed on such research in Spain, research that is typically limited to investigating deadly diseases. “We are doing the experiments with monkeys in China because, in principle, they cannot be done here because of lack of infrastructure,” explains Estrella Núñez, vice chancellor of research at UCAM. “What we want is to make progress for the sake of people who have a disease.” Núñez also points out that the Spanish ethical committees approved the 2017 human-pig chimera experiments conducted in Murcia.
A similar experiment has recently been given approval to proceed in Japan, using rat and mouse embryos as hosts for human cells, embryos that could then be transplanted to a surrogate animal to be brought to term. In March, Japan’s education and science ministry issued new guidelines that would allow for such experiments, guidelines that previously followed the 14-day rule.
Ethicists are concerned that stem cells being used in experiments such as these could leak into the developing brain of the host embryo, and take root there, and affect the creature’s cognition. “What happens if the stem cells escape and form human neurons in the brain of the animal? Would it have consciousness? And what happens if these stem cells turn into sperm cells?” asks Doctor Ángel Raya, director of the Barcelona Regenerative Medicine Center. Núñez says that the stem cells involved in their experiment had a built-in “self-destruct” mechanism that would activate if they were to enter the brain, should the organ manage to develop in the embryos in the first place.
As for the importance of such a controversial experiment? “The ultimate goal would be to create a human organ that could be transplanted, but the path itself is almost more interesting for today’s scientists,” says Núñez, regarding their team’s research in China. “I am essentially aware that I will not see it happen [the development of human organs in animals] but to arrive at that point, it’s necessary to pass through this one.”