Molecular Medicine Israel

First Human–Monkey Chimeras Developed in China

The researchers aim to grow transplantable human organs from primate embryos.

An international team of researchers has created embryos containing both human and monkey cells, the Spanish newspaper El País reported July 31. The controversial project was conducted in China, rather than in the US where the project leader is based, “to avoid legal issues,” according to the newspaper, and ultimately aims to grow viable organs for transplantation into humans.
Juan Carlos Izpisúa Belmonte of the Salk Institute in San Diego is spearheading the project with scientists from his own lab and those from the Murcia Catholic University in Murcia, Spain. The team wants to develop chimeras—organisms composed of cells from two or more species—capable of growing human organs.
Similar experiments using pig or sheep embryos have faced technical challenges, likely because the animals are genetically distant from humans. Primates, being more closely related to people, may offer more promise. “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,” Pablo Ross, a veterinary researcher at the University of California, Davis, who previously researched pig-human chimeras at Salk, tells El País.
Ross adds that he doesn’t see the utility of growing human organs in monkeys. “I always made the case that it doesn’t make sense to use a primate for that. Typically they are very small, and they take too long to develop,” he says in an interview with MIT Technology Review.
The National Institutes of Health forbids the use of federal funds to create human-monkey embryos. China, where Izpisúa Belmonte’s experiments are taking place, has no such restriction. The crux of the controversy, according to The Guardian, is that it is difficult to restrict human cell growth to just one organ of interest. Should a human-animal hybrid develop a human-like nervous system capable of consciousness, or be brought to term and display human-like behaviors, the ethical consequences could be extreme.
See “Bioethicists Concerned over Japan’s Chimera Embryo Regulations”
So far, the human-primate embryos have only been allowed to develop for a few weeks at a time, before organs have formed, according to Estrella Núñez, a biologist and administrator at the Catholic University of Murcia whose institution partially funds the research. “In no case is the gestation brought to full term,” she says in an interview with El País.
“I don’t think it is particularly concerning in terms of the ethics, because you are not taking them far enough to have a nervous system or develop in any way—it’s just really a ball of cells,” says Robin Lovell-Badge, a developmental biologist from the Francis Crick Institute in London, in an interview with The Guardian. “[But] if you allow these animals to go all the way through and be born, if you have a big contribution to the central nervous system from the human cells, then that obviously becomes a concern.”
In July, Japanese researchers—including Hiromitsu Nakauchi of the University of Tokyo and Stanford University—first received permission from the government to create human-animal embryos to be transplanted into surrogates. Japan had previously banned animal embryos containing human cells from developing beyond 14 days, let alone implanting them in a surrogate uterus. Although legal now, it remains unlikely that any of these animals will soon be brought to term as the proportion of monkey-to-human cells in the chimeras still has to be perfected, according to The Guardian.
It doesn’t make sense to bring human–animal hybrid embryos to term using evolutionarily distant species such as pigs and sheep because the human cells will be eliminated from host embryos early on, says Jun Wu, who researches human–animal chimaeras at the University of Texas Southwestern Medical Center in Dallas, in an interview with Nature last week.
“The evolutionary distance between humans and monkeys spans 30 to 40 million years, so it is unclear if this is even possible,” says Alejandro De Los Angeles of the Yale University School of Medicine, in an interview with The Guardian.
Beyond organ production, the research could address questions of evolutionary distance between species and investigate basic mechanisms in molecular biology, Ross tells MIT Technology Review. The results could also be used to develop better animal models of human disease, says Los Angeles to The Guardian.
“The ultimate goal would be to create a human organ that could be transplanted but the path is almost more interesting for today’s scientists,” says Núñez in an interview with Vice. “What we want is to make progress for the sake of people who have a disease.”

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