China's 5 Gene-Edited, Mentally Ill Monkey Clones Raise Ethical Concerns

They express "behaviors resembling anxiety, depression, and schizophrenia."

Five clones of a gene-edited long-tailed macaque with several symptoms of genetic disease have been successfully bred, announced a team of scientists in Shanghai this week. The original monkey had been altered with CRISPR/Cas9 gene editing technology to give its clones a disrupted circadian rhythm so that scientists can learn how to treat humans with related disorders. The psychological effects of the gene editing on the monkeys has, unsurprisingly, raised concerns among ethicists.

The researchers from the Institute of Neuroscience at the Chinese Academy of Sciences published their results in two separate papers on Thursday in the journal National Science Review. In the paper, they explain that the ability to produce gene-edited clones will help them study diseases related to disrupted circadian rhythm, including Alzheimer’s disease, depression, and other sleep problems.

“Disorder of circadian rhythm could lead to many human diseases, including sleep disorders, diabetic mellitus, cancer, and neurodegenerative diseases, our BMAL1-knock out monkeys thus could be used to study the disease pathogenesis as well as therapeutic treatments” says Hung-Chun Chang, senior author on both papers and a researcher at the Chinese Academy of Sciences Institute of Neuroscience, said in a statement.

The original monkey was altered as an embryo by knocking out its BMAL1 gene, which is associated with regulating sleep-wake patterns, and the five newborns produced with SCNT all have identical genomes that also lack the BMAL1 gene. The researchers used somatic cell nuclear transfer, the same technique used to clone Dolly the sheep more than two decades ago, to clone the monkey and produce five cloned offspring.

A) a diagram of the cloning procedure, B) the cloned embryos at different stages of development, and C) the five cloned monkeys.
A) a diagram of the cloning procedure using SCNT, B) the cloned embryos at different stages of development, and C) the five cloned monkeys.

Exactly one year ago, the same researchers announced that they’d successfully cloned two macaques, named Hua Hua and Zhong Zhong. As Amber Tong reported for Endpoints News at the time, the challenges of cloning primates made this achievement a momentous one. Adding on top of that the successful cloning of primates with CRISPR-mediated gene deletions, the researchers have gone to great lengths to study the biological mechanisms for genetic diseases.

Other scientists are, of course, skeptical. For one thing, the team used the cloned monkeys’ resulting psychiatric disorders — including “behaviors resembling anxiety, depression, and schizophrenia” — as signs that they had performed the experiment successfully. Bioethicist Carolyn Neuhaus from The Hastings Center told Gizmodo that the research raises a lot of questions, including the fundamental concern that this gene deletion might not actually produce the same effects in humans as it did in the monkeys. Whether or not that’s the case, the researchers have inflicted a fair amount of suffering on these animals just to find out.

“If I were on an ethics review committee, I would be very hesitant to approve [this research] because of the incredible amount of harm to the animals,” Neuhaus said. “I would expect the scientists who are proposing this research to have very good responses to very hard questions about their methods and the expected benefits of their research.”

Additionally, cloning the monkeys remains tricky, expensive, and labor-intensive. Out of over 300 embryos the researchers created, only five developed enough to implant them in a surrogate mother to mature.

“The efficiency is still very low. It remains a big problem for the cloning technology,” an anonymous Shanghai-based life scientist who was not involved in the story told South China Morning Post.

The researchers are undeterred, as the benefits of the cloned monkeys could be significant for drug research. After all, large groups of cloned animals would help eliminate some of the variation that occurs in animal trials, since all of the monkeys would be expected to respond to a drug in the exact same way. And in fact, Mu-ming Poo, Ph.D., a senior investigator at the Academy’s Institute of Neuroscience and one of the authors on the papers, says the research could actually result in a net decrease to monkey suffering in scientific labs.

“This line of research will help to reduce the amount of macaque monkeys currently used in biomedical research around the world,” he told The Independent. “Without the interference of genetic background, a much smaller number of cloned monkeys carrying disease phenotypes may be sufficient for pre-clinical tests of the efficacy of therapeutics.”

Media via National Science Review/ Liu et al, Chinese Academy of Sciences Institute of Neuroscience