Researchers in China cloned five monkeys from an individual that had been gene-edited to be susceptible to certain diseases. The scientists said having a population of uniform macaques with specific disease-causing gene mutations will help advance research into human disease, while also cutting the number of monkeys required for biomedical research.
In two studies published in China's National Science Review journal, the team shows how it created a population of macaque monkeys using specific gene-editing and cloning techniques. Footage released by the researchers, from the Institute of Neuroscience at the Chinese Academy of Sciences (CAS), Shanghai, shows the five cloned monkeys in an incubator.
Scientists used the CRISPR/Cas9 gene-editing technique on a group of monkeys to knock out BMAL1, which is involved in circadian regulation. Macaques with this modification show a range of disorders, such as sleeping less, increased night-time activities, anxiety and depression. They also displayed behaviors associated with schizophrenia. The gene editing took place at the embryo stage.
Next, they picked a donor monkey from which they would make the clones. They removed the nucleus from a monkey egg cell and replaced it with the nucleus from a cell taken from the donor monkey. This egg then went on to develop into an embryo, and this was then transplanted into a female macaque that later gave birth to the monkey clones.
"Our approach is to perform gene-editing in fertilized embryos to first generate a group of gene-edited monkeys, and then select one monkey that exhibits correct gene editing and most severe disease phenotypes as the donor monkey for cloning by somatic cell nuclear transfer," Qiang Sun, senior author of the paper, said in a statement.
"We believe that this approach of cloning gene-edited monkeys could be used to generate a variety of monkey models for gene-based diseases, including many brain diseases, as well as immune and metabolic disorders and cancer."
Monkeys that have been genetically edited to have problems with its circadian system can be used in biomedicine to investigate a number of human disorders, including diabetes, cancer and neurodegenerative diseases, study author Hung-Chun Chang said.
The scientists planned to improve the cloning technique to make it more efficient. They expected to have more monkey clones that carry genetic mutations over the coming years. Mu-ming Po, another study author, said the work would help reduce the number of macaques being used in medical research in the future. "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," he said.
China has been at the forefront of cloning technology for many years. In 2014, the BBC reported that it was cloning animals on "an industrial scale," producing around 500 cloned pigs per year for medical testing. In January last year, it announced the first successful primate clones—two macaque monkeys.
Deborah Cao, a professor at Australia's Griffith University whose work focuses on animal welfare, ethics and law, commented on the latest announcement. She told Newsweek that while the studies presented said the team followed "strict international guidelines for animal research" many aspects of the monkeys' welfare remain unclear.
"Even if CAS follow the research guidelines, such animal research poses potential and unknown risks," she said. "Such risks are not inconsequential simply because they are animals, not humans. And it is inherently cruel to the animals as they cannot give or withhold consent. It is very disturbing that more such gene edited monkey clones will be produced for the sole purpose of further experiments, even if they said this may reduce the number of monkeys used for future experiments.
"The best way to reduce the number of monkeys used in such experiments is to stop such animal experiments. Instead of developing nonhuman primate disease models for humans, they should develop human disease models for humans."
This story has been updated to include additional information about cloning in China.
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