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Last year, at that time, the first primates cloned using a core transfer technique made headlines around the world. Now, Chinese researchers have pushed the envelope further – by breaking a regulatory gene in macaques before cloning them.
According to the researchers, the cloning of genetically modified primates has obvious advantages for medical tests. But as a result of the controversy surrounding gene editing in humans, progress in this controversial area could go beyond ethics.
After the new experiment, five macaques born at the Institute of Neuroscience of the Shanghai Academy of Sciences all share the same genes, derived from a fibroblast taken from the skin of a donor monkey .
More importantly, they all carry a copy of a specific gene – a version of BMAL1 modified in the donor with the help of CRISPR / Cas9 gene editing technology.
This gene normally produces a regulatory protein that plays a role in the management of certain biological rhythms in mammals. But in the modified version, this protein is not produced, which causes animals to exhibit symptoms of circadian disorders, such as decreased sleep and greater movements at night.
They also show signs of anxiety and depression, as well as behaviors similar to those of schizophrenia.
"Circadian rhythm disorders could lead to many human diseases, including sleep disorders, diabetes mellitus, cancer and neurodegenerative diseases," says neuroscientist Hung-Chun Chang.
"Our BMAL1 knockout monkeys could thus be used to study the pathogenesis of the disease as well as for therapeutic treatments."
Using genetically modified animals to study the disease is now almost equal in medical research. Scientists regularly activate and deactivate genes in mice, flies and fish to study their physiological effects.
At the same time, the creation of clones of transgenic models makes it possible to limit the experimental variables. Each animal is identical to the last, which makes it easier to notice subtle effects that might otherwise be missed.
Cloning of transgenic primates has not been possible so far, largely because of the way their genes block epigenetically when the fertilized cells are under stress.
Last year, the Chinese Institute of Neuroscience announced the successful reproduction of two long-tailed macaques using somatic cell nuclear transfer, a process identical to that which gave birth to the famous Dolly the Sheep in 1995.
For some, however, these scientific achievements have an unacceptable cost.
"A monkey after a monkey lived in distress and died a few days later," wrote British journalist Chas Newkey-Burden. L & # 39; Independent last January.
"PR people do not tell us the names of these babies."
This time, the team transferred 325 cloned embryos to 65 surrogate mothers, resulting in 16 pregnancies and five live births.
The question of whether the loss of life and the potential for suffering and distress in surviving animals is outweighed by the possibility of treating debilitating psychological disorders in humans is a complex issue for ethicists.
Animal models do not necessarily translate into human biology as easily as might be expected, raising fears that the results may not be worth the potential harm.
Yet researchers argue that genetic engineering could actually be a solution to a more serious problem.
"This line of research will help reduce the amount of macaque monkeys currently used in biomedical research around the world," said neuroscientist Mu-ming Poo, who has contributed to both the Macaque's edition and its cloning.
"Without the interference of genetic background, a much smaller number of cloned monkeys carrying pathological phenotypes might be sufficient for preclinical tests of treatment efficacy."
Everyone is not in agreement. Deborah Cao of Griffith University in Australia is an expert in animal welfare, ethics and law. It highlights the lack of international guidelines for this type of research.
"The best way to reduce the number of monkeys used in such experiments is to stop such experiments on animals," Cao said. Newsweek reporter, Hannah Osborne.
"Instead of developing nonhuman primate disease models in humans, they should develop human disease models for humans."
At present, China is proving to be a controversial testing ground on the ethical limits of genetic engineering technology. At the end of last year, Chinese scientist He Jiankui sensibly announced the announcement of the first genetically modified babies in the world, following the CRISPR edition.
He has since been accused of forging an ethical approval. Rumors later revealed that he had been arrested by the authorities.
Time will tell if these five cloned macaques herald a new era for transgenic animal models, or represent an ethical line that few people will want to cross again.
This research was published in National Science Journal, here and here.
