Researchers have created a monkey with two different sets of DNA by injecting stem cells from one monkey embryo into another of the same species. This method has been used in rats and mice before—but the recent feat marks the first time ever that it has been successful in another animal, including primates. Scientists say the breakthrough could help with medical research in the future.
“This is a long-sought goal in the field,” Zhen Liu of the Chinese Academy of Sciences (CAS) says in a statement. “This work could help us to generate more precise monkey models for studying neurological diseases as well as for other biomedicine studies.”
However, the monkey had to be euthanized after ten days due to breathing issues and hypothermia, which some scientists say highlights ethical concerns in this type of research, reports Nature News’ Carissa Wong.
In reference to the mythological, fire-breathing chimera that has a lion’s head, a goat’s body and a serpent’s tail, individuals that contain two or more different sets of DNA in their bodies are referred to as “chimeric” by scientists. Chimerism can occur naturally, as when one embryo in a set of fraternal twins dies in the womb and the other absorbs its cells. This has been documented in several species of birds, reptiles and mammals, including humans.
But chimerism can also occur artificially with an organ or bone marrow transplant. In this case, the researchers transplanted stem cells, which can develop into any kind of cell.
To create the monkey chimera, Liu and his colleagues removed stem cells from seven-day-old embryos of long-tailed macaques (Macaca fascicularis). They labeled these with green fluorescent protein so that any tissue the cells created in a chimeric monkey could be visually identified later. They then injected these cells into four- to five-day-old embryos of the same species and implanted them into 40 female macaques.
Of these surrogate mother monkeys, 12 became pregnant, and 6 gave birth to live young. The team’s analysis showed that just one live-birth male and one miscarried male were substantially chimeric. In the live monkey, donor cells made up 67 percent of its tissues on average, but across the 26 different tissue types tested, that number ranged between 21 percent and 92 percent.
Scientists saw evidence of glowing green fluorescence—the mark of the donor cells—in the live monkey’s fingertips and around its eyes. Percentages of donor cells in the miscarried fetus were lower. The team published its research this month in the journal Cell.
“It is a very good and important paper,” Jacob Hanna, a stem cell biologist and embryologist at the Weizmann Institute of Science in Israel who was not involved with the study, tells CNN’s Katie Hunt. “This study may contribute to easier and better making of mutant monkeys, just like biologists have been doing for years with mice. … Of course, work with [nonhuman primates] is slower and much harder but is important.”
Researchers have been creating chimeric mice since the 1960s to learn more about critical developmental processes, including how stem cells grow into more specialized cells. They’ve also used the mice as models to study diseases. But trying to understand humans by looking at rodents has its limitations.
“Mice don’t reproduce many aspects of human disease for their physiology being too different from ours,” Liu tells CNN. “In contrast, human and monkey are close evolutionary, so human diseases can be more faithfully modeled in monkeys.”
In controversial research, scientists have previously created human-monkey chimeric embryos, though these only grew for 20 days before being destroyed—not long enough to develop a brain or nervous system. Some scientists hope these techniques could be used to grow human organs inside other animals for transplantation, per Nature News. But such efforts involving animals—especially once human cells are added—can quickly pose ethical quandaries.
“All animal research warrants careful consideration, but this is particularly important for all non-human primate research,” stem cell researcher Megan Munsie, of the University of Melbourne and Murdoch Children’s Research Institute, tells Peter de Kruijff of the Australian Broadcasting Corporation (ABC).
Munsie notes to the publication that, of all 74 chimeric monkey embryos transferred into surrogate mothers in the recent study, only one living macaque produced the desired results—and it had to be euthanized. Future efforts should focus on improving embryo viability to “avoid the high abortion rate and associated distress and waste,” she adds.
Additionally, long-tailed macaques, while commonly used as lab monkeys, were listed as endangered by the International Union for Conservation of Nature last year. Munsie suggests limiting research to animals that are not endangered, per the ABC. The authors, however, say this research could help with conservation efforts.
“Monkey chimeras also have potential enormous value for species conservation if they could be achieved between two types of nonhuman primate species, one of which is endangered,” co-author Miguel Esteban, of the Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, and a researcher with BGI-Research Hangzhou, tells CNN. “If there is contribution of the donor cells from the endangered species to the germ line, one could envisage that, through breeding, animals of these species could be produced.”