This time last year, the first primates cloned using nuclear transfer technology made headlines worldwide. Now, Chinese researchers have pushed the sheath further – breaking a regulatory gene into macaques before cloning them.
According to the researchers, cloning of genetically modified primates has clear advantages for medical testing. In the controversy over the editing of genes in humans, progress in this controversial area could outperform ethics.
According to the new experiment, five infant macaques born at the Department of Neuroscience of the Chinese Academy of Sciences in Shanghai share exactly the same genes that are derived from a fibroblast derived from the skin of a donor monkey.
More importantly, they all contain a copy of a specific gene ̵
This gene normally produces a regulatory protein that plays a role in the management of certain biological rhythms in mammals. In the modified version, however, this protein is not produced, so animals show symptoms of circadian disorders, such as decreased sleep and more exercise during the night.
They also show signs of anxiety and depression as well as schizophrenia-like behavior.
"Disruption of the circadian rhythm can lead to many human diseases, including sleep disorders, diabetic mellitus, cancer, and neurodegenerative diseases," says neuroscientist Hung-Chun Chang.
"Our BMAL1 knock-out monkeys could therefore be used to study the pathogenesis and treatment of therapies."
The use of genetically modified animals to research diseases is almost a matter of course in medical research today. Scientists regularly turn genes on in mice, flies and fish to examine their physiological effects.
The generation of clones of transgenic models helps to limit variables in experiments. Each animal is identical to the last, making it easier to notice subtle effects that might otherwise be overlooked.
Cloning of transgenic primates was not possible until recently, mainly thanks to the way their genes block epigenetically when fertilized cells face stress.
Last year, the Chinese Institute of Neuroscience reported on the successful reproduction of two long-tailed macaques with somatic cell nuclear transfer, the same process that in 1995 produced the world-famous Dolly the Sheep.
However, these scientific achievements are associated with unacceptable costs.
"Monkey after monkey was living in stressful conditions and then dying after a few days," wrote British journalist Chas Newkey-Burden in The Independent . last January.
"The 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.
Whether the loss of life and the potential for suffering and distress in animal survivors are counterbalanced by the ability to treat debilitating mental disorders in humans is a complex issue for ethicists.
This will inevitably translate as readily into human biology as we might expect and raises concerns that the results may not be worth potential harm.
The researchers disagree, however, that genetic engineering could actually provide a solution to a larger problem. This research line will help reduce the number of macaque monkeys currently used in biomedical research around the world, "said neuroscientist Mu-ming Poo, who contributed to both the processing of the original macaque and its cloning.  Due to the genetic background, a much smaller number of cloned monkeys bearing disease phenotypes may be sufficient for preclinical testing of the efficacy of therapeutics. "
Not always Somebody agrees. Deborah Cao from Griffith University in Australia is an expert in animal welfare, ethics and law. It points to 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 animal testing," said Cao Newsweek reporter Hannah Osborne.
"Instead of developing non-human primary disease models for humans, they should develop human disease models for humans."
At present, China proves to be a controversial test site for the ethical limits of genetic engineering. At the end of last year, the Chinese scientist He Jiankui announced in a sensational way, according to the CRISPR editors, the world's first genetically modified babies.
He was charged with faking ethical recognition, with rumors that he had been received by authorities.
Time will tell if these five cloned macaques are heralding a new age in transgenic animal models or an ethical line that few will soon cross.
This research was published in National Science Review . here and here.