One year after the birth of the world鈥檚 first two cloned primates, a team in China has used CRISPR gene editing and cloning to create monkeys that show some symptoms of depression and schizophrenia. While some researchers have praised the work鈥檚 potential for helping us understand psychiatric disorders in humans, others have raised ethical concerns.
Lead scientist Hung-Chun Chang of the Institute of Neuroscience in Shanghai told 快猫短视频 about how he hopes the monkeys will help us better understand mental health and find new treatments.
How did you create these monkeys?
[We are working on] the BMAL1 gene, which affects how our body responds to the day-night cycle. Mutations in BMAL1 are associated with . We used CRISPR to knock out the BMAL1 gene in monkey embryos, and three monkeys were born. Then we took the DNA of a monkey with obvious symptoms and used this to make five cloned monkeys.
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What symptoms do these monkeys have?
The most direct result is that they are not getting enough sleep. Healthy monkeys usually sleep for 9 hours every night, but these monkeys can鈥檛 rest for longer than 6 hours. They are also afraid of people, which is very unusual for such a sociable animal, and they show no interest in new environments.
We also found they have persistently high cortisol levels in blood tests. Elevated cortisol has been linked to anxiety and depression in monkeys and humans in past research.
Previous studies have shown that people with schizophrenia are less able to detect and pay attention to new stimuli, including sounds. We found that these monkeys have lower levels of brain activity compared with healthy monkeys when unexpected sounds were played.
How can you know that these aren鈥檛 just symptoms of sleep deprivation?
It鈥檚 impossible to separate the effects of sleep deprivation on monkeys鈥� mental state from their genetic mutation. We know that BMAL1 knockout could lead to psychiatric disorders, and we also know a disrupted body clock has negative influence on mental health. So it鈥檚 very likely that their symptoms worsen their conditions.
What are you hoping to learn from this work?
We will use these monkeys for drug testing. We have three general goals. First, we are curious whether drugs for body clock regulation, such as sleeping pills, are helpful in alleviating depression. Second, we want to know how effective the medicines we use currently for mental health conditions are. Ultimately, we aim to create better treatments for people.
Couldn鈥檛 this research be done in mice or people?
Monkeys have an identical body clock to humans. In contrast, mice are nocturnal and sleep much longer than us. In terms of depression, the monkey brain is more similar to that of a human. Doing tests in monkeys can really speed up the process of finding the right drug type and dosage without patients having to try everything themselves.
Is it ethical to genetically engineer monkeys to be depressed?
Gene editing in cynomolgus monkeys, the species we used here, is permitted worldwide. These monkeys are also the most common primate model used in research. Every year, thousands of monkeys are subject to drug testing. And because of the genetic variations among individuals, we need to repeat the testing in many monkeys for meaningful results. That鈥檚 why we chose to do cloning: with completely identical monkeys, we can use fewer of them.
Moreover, we urgently need better models to study psychiatric disorders. We don鈥檛 understand these conditions well, and we don鈥檛 really have good treatments for them. If we rely solely on mice studies, we would have to wait for years until we figure out how to help humans. I鈥檝e talked to many psychiatrists who are very excited about our monkey model.
What else is your team working on?
We are trying to create an Alzheimer鈥檚 model. Because the disease is age-related and involves more-complex genetic mutations, it will probably take another two to three years until the monkeys show symptoms.
Journal reference:聽National Science Review, DOI:聽;听
