Medical ethics experts are divided over an experiment in which Chinese scientists cloned gene-edited monkeys to induce mental illness in them.
The five cloned monkey embryos had been edited to remove the BMAL1 gene, leading the baby animals to display symptoms of conditions such as anxiety, depression and schizophrenia as a result of disruption to their circadian rhythms, according to a study published in National Science Review on Thursday.
The findings by researchers at the Chinese Academy of Sciences' Institute of Neuroscience could help develop treatments for a range of human medical conditions including sleep disorders, diabetes, cancer and neurodegenerative diseases, according to team member Chang Hung-Chun.
The study has drawn attention for its use of cloned animals, as well as the researchers' use of the gene editing tool CRISPR/Cas 9.
That tool was also used by He Jiankui, the Chinese scientist who recently created the world's first genetically edited human babies as part of a controversial and unauthorised experiment.
But unlike He's experiment, the cloned macaques study was authorised and funded by the Chinese Academy of Sciences and the Shanghai municipal government.
Andrew Knight, a professor of animal welfare and ethics at the University of Winchester in Britain, called it "disturbing news".
"Human mental illnesses are complex, and even harder to predict than purely physical diseases," he said. "The likely benefit from harming animals in this way is extremely small. However, there is no doubt that these animals will suffer - and probably, very significantly. Primates are highly intelligent and social animals. It is not ethical to deliberately harm them, and especially when the chance of tangible benefit for human patients is so small. Such research is very irresponsible."
China is the only country in the world that has the technology to clone primates bred in captivity, which are still widely used in scientific research globally due to their neurological similarities to humans over other common lab animals such as rodents. As such, primates can experience pain and psychological distress in similar ways to humans as a result of scientific experiments.
But there have been ethical concerns for decades over using a species with such remarkable similarities to humans when there have been significant advances in neural imaging and other digital brain modelling techniques.
Great apes such as orangutans, chimpanzees and gorillas are banned or highly restricted from research uses in Britain, the Netherlands, Sweden, Germany and New Zealand, while Austria prohibits the use of all primates in lab experiments.
The United States is the world's largest user of lab chimpanzees for scientific research, although hundreds have been retired in recent years after the National Institute of Health ended its chimpanzee biomedical research programme in 2015.
Chimpanzees are believed to share around 98 per cent of human DNA.
In Britain alone, around 3,000 monkeys such as macaques and marmosets are used in medical research annually, primarily for developing vaccines and studying the human nervous and reproduction systems, according to the Royal Society for the Prevention of Cruelty to Animals.
Alan Bates, a fellow at the Oxford Centre for Animal Ethics, said it was "especially controversial" to be conducting the research in the field of mental illness.
"There are substantial differences between human and non-human primate cognition that make any non-human model of a specifically human disease problematic," he said. "If monkeys' mental processes were sufficiently close to humans to provide a valid model, then it would certainly be unethical to experiment on them.
"Cloned animals are inherently unsuited for drug testing as they lack the genetic diversity sent in wild populations. Furthermore, it is difficult to see how laboratory-reared captive animals could fail to show symptoms akin to mental illness."
Other bioethics experts agreed there were ethical issues surrounding the use of animals similar to humans in nature, and that any animal experimentation must continue to be closely regulated.
"I think it's a very natural reaction to think that there is something rather perverse and horrible about intentionally inducing a disease in an animal for the purposes of studying it," said David Hunter, associate professor of medical ethics at Flinders University in Australia.
"On the whole, harm to animals might be reduced by this kind of research, however is that worth the cost to us of instrumentalising those animals who are having harm induced in this way?"
Arthur Caplan, professor of bioethics at New York University, said the low success rates of cloning carried an "ethical price" due to the risk of creating malformed animals. But he believed that the use of animals for disease models was ultimately justified as a replacement for experimenting on humans.
"I think if the scientists are competent, making disease models to study human diseases is ethical. You can try experimenting with drugs and gene editing to fix diseases that you could not ethically try first in humans," he said. "All such research must be done with close supervision of animal experimentation committees and with full transparency."
But Terry Kaan Sheung-hung, co-director of the University of Hong Kong's Centre for Medical Ethics and Law, said he had no objection to the experiment.
"Gene editing is not so different from the older gene knockout technique, which has been widely accepted in scientific circles for a long time. This new instance is a further development of the technique," he said, adding that the gene knockout technique was commonly used in lab mice.
"The report says that the scientists were careful in carrying out the experiment in accordance with animal welfare regulations, and the findings are open and subject to peer scrutiny."
For Alexandre Erler, assistant professor at the Chinese University of Hong Kong Centre for Bioethics, the findings represented a "positive development for biomedical research".
"Some use of animals, regrettable as this may be, is still unavoidable if such research is to make further progress, and monkeys provide optimal models for studying neurodegenerative diseases," Erler said.
"The use of cloning might actually help us reduce the total number of animals used in such research … and that's a goal we are ethically required to pursue."
This article was first published in South China Morning Post.