First Primate Clones Produced Using the “Dolly” Method
Meet Zhong Zhong and Hua Hua—healthy newborn monkeys and the first primate clones produced via the same method that made Dolly the sheep two decades ago.
The advance at a lab in China edges scientists closer to a future in which they could create large numbers of genetically identical monkeys to serve as models for human diseases and other conditions. This could help researchers unravel complex questions, including how environmental factors may fuel common human cancers.
Primate research ethics could, however, limit such research. “It’s a cost-benefit analysis,” says Kevin Sinclair, a developmental biologist at the University of Nottingham who was not involved with the latest cloning work. “If you have a population of nonhuman primates that are genetically identical, that’s a really, really powerful model to study human disease, underlying mechanisms and potential cures. But it has to be done on a case-by-case basis to justify doing that.” Many countries, including the U.S., have strict guidelines on primate research due to ethical concerns about experimenting on our close genetic relatives. For example, U.S. government biomedical research on chimpanzees is effectively over, and all lab chimps are being slowly retired.
Scientists at the Chinese Academy of Sciences’ Institute of Neuroscience, in Shanghai, published a report on their two primate successes Wednesday in Cell. The cloning technique they used, called somatic cell nuclear transfer (SCNT), involves swapping the nucleus of a donor cell into a fertilized egg that has been purged of its own chromosomes. The egg will then contain an exact copy of the donor’s genome, and if it is implanted into a surrogate mother, the eventual offspring will be a clone. More than 20 other species, including pigs and dogs, had already been successfully cloned using SCNT. And numerous studies of animals produced by this method indicate they are as healthy as their noncloned cousins.
Making this process work in primates has been tough. When researchers previously tried using the “Dolly” approach on monkeys it produced fetuses—but no pregnancy that lasted beyond 80 days. The main obstacle, the Institute of Neuroscience researchers wrote, was likely that transferred nuclei were not properly programmed to support embryonic development. So this time the Chinese team deployed two critical enzymes that removed genes’ epigenetic memory of being somatic cells (cells that make up tissues and organs). This extra step allowed development to proceed, says stem cell expert Alan Trounson, an emeritus professor at the Hudson Institute of Medical Research in Australia who was not involved in the new research. The success rate was still extremely low. But as scientists adjust their methods they could create dozens of clones in the near future, he notes.
Researchers have managed to clone nonhuman primates in the past couple of decades using other techniques, including a similar nuclear transfer method that relies on embryonic stem cells instead of somatic cells. But using SCNT is a major advance because it would likely be easier to use and reproduce in large numbers. It could also be more successfully coupled with CRISPR gene-editing techniques for future research on specific diseases or genetic mutations, the Institute scientists wrote in their paper.
This approach to cloning could eventually help save endangered primates, Sinclair says. In situations where habitat destruction has left only a small number of primates, he adds, researchers could obtain somatic cells from body tissue and freeze it for storage in gene banks. But this would require further scientific progress, because the recent Chinese SCNT work was successful using fetal cells—not adult cells, which can be more difficult to reprogram.
Aspects of monkey SCNT will also need to be improved before the technology can be used to produce primates for research, experts caution. “From a scientific standpoint the advances here are significant. But from a practical, immediate utilization perspective there are still some technical issues that exist,” says Jon Hennebold, chief of the division of reproductive and developmental sciences at the Oregon National Primate Research Center who was not part of the work. “The pregnancy rate and the live birth rate were not at a level that would allow this to be done on some wide scale. You would also have to have expertise in assisted reproductive technologies, reproductive physiology—and a large cohort of donors. And all those things are limiting with this current technology.”