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New cloned monkey species highlights limits of cloning
Meet Retro, a cloned rhesus monkey born on July 16, 2020.
He is now more than 3 years old and is “doing well and growing strong,” according to Falong Lu, one of the authors of a study published in the journal Nature Communications Tuesday that describes how Retro came to be.
Retro is only the second species of primate that scientists have been able to clone successfully. The same team of researchers announced in 2018 that they had made two identical cloned cynomolgus monkeys (a type of macaque), which are still alive today.
“We have achieved the first live and healthy cloned rhesus monkey, which is a big step forward that has turned impossible to possible, although the efficiency is very low compared to normal fertilized embryos,” said Lu, an investigator at the State Key Laboratory of Molecular Developmental Biology and Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences. “Currently, we haven’t had the second live birth yet.”
The first mammal to be cloned — Dolly the sheep — was created in 1996 using a technique called somatic cell nuclear transfer, or SCNT, where scientists essentially reconstruct an unfertilized egg by fusing a somatic cell nucleus (not from a sperm or egg) with an egg in which the nucleus has been removed.
Since then, scientists have cloned many mammalian species, including pigs, cows, horses and dogs, but the process has been hit or miss, with typically only a tiny percentage of the embryos that are transferred into surrogates resulting in viable offspring.
“In a way we have made much progress in that, after Dolly, many mammalian species were cloned, but the truth is that inefficiency remains a major roadblock,” said Miguel Esteban, principal investigator with the Guangzhou Institute of Biomedicine and Health at the Chinese Academy of Sciences. He was not involved in the latest research but has collaborated with some members of the research team on other primate studies.
Cloning a rhesus monkey
The Chinese team, based in Shanghai and Beijing, used a modified version of SCNT in their work on cynomolgus monkeys (Macaca fascicularis) and tweaked the technique further to clone the rhesus monkey (Macaca mulatta).
During hundreds of failed cloning attempts, they realized that, in the early cloned embryos, the outer membrane that forms the placenta did not develop properly. To address this problem, they performed a process called inner cell mass transplantation, which involved putting cloned inner cells into a non-cloned embryo, and that allowed the clone to develop normally, Esteban explained.
The team then tested the new technique using 113 reconstructed embryos, 11 of which were transferred to seven surrogates, resulting in only one live birth, according to the study.
“We think that there might be additional…. abnormalities to be fixed. Strategies to further enhance the success rate of SCNT in primates remains …our main focus in the future,” Lu said
The first two cloned monkeys, Zhong Zhong and Hua Hua, are now more than 6 years old and live a “happy and healthy life” with others of the same species. Lu said thus far the researchers have not identified any potential limits on the cloned monkeys’ lifespan.
Zhong Zhong and Hua Hua are usually described as the first cloned monkeys. However, a rhesus monkey was cloned in 1999 using what researchers consider a simpler cloning method. In that case, scientists split the embryos, much like what happens naturally when identical twins develop, rather than using an adult cell like with the SCNT technique.
The implications of cloning monkeys
The researchers said that being able to successfully clone monkeys might help accelerate biomedical research given that there are limitations on what scientists can learn from lab mice. Research on nonhuman primates, which are closer to humans, has been pivotal to lifesaving medical advances, including the creation of vaccines against Covid-19, according to a report by a panel of the National Academies of Sciences, Engineering and Medicine released in May.
The use of monkeys in scientific research is a contentious issue because of ethical concerns about animal welfare. The team said it followed Chinese laws and guidelines governing the use of nonhuman primates in scientific research.
The UK’s Royal Society for Prevention of Cruelty to Animals said it has “serious ethical and welfare concerns around the application of cloning technology to animals. Cloning animals requires procedures that can cause pain and distress, and there can be high failure and mortality rates.”
Being able to produce genetically identical monkeys could be useful, Esteban said.
“This research is proof of principle that cloning can be done in different non-human primate species and opens the door to new ways of enhancing the efficiency. Cloned monkeys can be genetically engineered in complex ways that wild-type monkeys cannot; this has many implications for disease modeling. There is also a species conservation perspective,” he added.
Dr Lluís Montoliu, research scientist at the National Center for Biotechnology (CNB-CSIC) in Spain who wasn’t involved in the research, said that cloning both species of monkey demonstrated two things.
“First, it is possible to clone primates. And second, no less important, it is extremely difficult to succeed with these experiments, with such low efficiencies,” he said in a statement.
He added that the low success rate of the process showed that “not only was human cloning unnecessary and debatable, but if attempted, it would be extraordinarily difficult and ethically unjustifiable.”
“Reproductive cloning a human being is completely unacceptable,” Lu said.
注释：
cynomolgus: n
表示" [动]猕猴,食蟹猴"，如：Moreover, it is tolerated at higher doses in rats and cynomolgus monkeys than the same conjugate prepared by conventional approaches. 而且，与常规结合方法相比，这种药物在小鼠和猕猴中显示出更大的耐受性。
macaque: n
表示" 短尾猿；猕猴"，means "short-tailed monkey of rocky regions of Asia and Africa"，如：Inside this room sits a motionless macaque monkey. 这房间里坐着一个不动的猕猴。
fertilize: v
表示"[生]使受精；"，means "introduce semen into (a female"，如：I help my father fertilize the crops. 我帮助父亲给农作物施肥。
embryo: n
表示" 胚胎；萌芽"，means "the young of any creature in its state before it is born"，如：The embryo develops into a fetus. 胚胎发育成胎儿。
somatic: adj
表示" 身体的；肉体的；体壁的"，means "affecting or characteristic of the body as opposed to the mind or spirit;"，如：The computerists make no real distinction between behavioral learning and somatic learning. 计算机专家没有真正区别行为的学习和肉体的学习。
mammalian: n; adj
表示" 哺乳动物( 的） "，如：The large mammalian brain is the most complicated thing, for its size, known to us. 如我们所知，大型哺乳动物的脑组织，从体积上来说，是最为复杂的器官。
roadblock：n
表示" 路障；"，means "a barrier set up by police to stop traffic on a street or road in order to catch a fugitive or inspect traffic etc."，如：His car was swerved to avoid bumping against the roadblock. 为了避免撞上路障,他把车打了个急转弯。
tweak: v; n
表示" 拧；扭"，means "pinch or squeeze sharply"，如：She tweaked his ear playfully. 她拧他的耳朵玩儿。He gave the boy's ear a painful tweak. 他用力拧了一下那男孩的耳朵。
membrane: n
表示" 【C】薄膜"，means "a thin pliable sheet of material"，如：A vibrating membrane in the ear helps to convey sounds to the brain.耳膜的振动帮助声音传送到大脑。
pivotal: adj
表示" 重要的；关键的；轴的"，means "being of crucial importance"，如：It was a pivotal moment in her life. 那是她一生中重要的时刻。
contentious: adj
表示"有争议的"，means "involving or likely to cause controversy;"，如：There is a contentious clause in the treaty. 这条约中有一条有争议的条款。
debatable: adj
表示"成问题的"，means "open to doubt or debate"，如：It is also a very debatable argument. 这也是个争论很大的话题。
中文简要说明：
中国大陆科学家宣布成功复制一只名为「Retro」的恒河猴，这是科学界至今复制的第2种灵长类动物，如今Retro已经3岁、「状况良好、愈来愈壮」，不过科学家也指出，他们尝试了数百次才成功，坦言和一般受精胚胎相比，效率不高。
美国有线电视新闻网（CNN）报导，中国科学院遗传与发育生物学研究所等北京与上海学者，于2020年7月16日成功复制一只恒河猴「Retro」，团队发表的研究成果已于16日刊登于顶尖期刊《自然通讯》（Nature Communications）。
遗传与发育生物学研究所研究员陆发隆表示，Retro已经3岁多，「状况良好、愈来愈壮」。
Retro是科学家成功复制的第2种灵长类动物，陆发隆的团队2018年才宣布成功复制2只一模一样的食蟹猕猴（cynomolgus monkey）「中中」与「华华」，研究团队指出，目前中中与华华和其他食蟹猕猴一起生活，过着「开心、健康」的日子。
陆发隆表示，「我们实现第一只活体、健康的复制恒河猴，这是把不可能变成可能的一大步」，不过他也坦言，「和正常受精胚胎相比，效率非常低」，指出目前还没有复制出第2只恒河猴。
■研究团队历经数百次失败 坦言复制技术效率不高
人类首次成功复制哺乳类动物是1996年的桃莉羊，当时科学家使用称为体细胞核移植（SCNT）的技术，自此科学家复制了猪、牛、马、狗等不同哺乳类动物，但只有少数胚胎存活。
未参与研究的中国科学院广州生物医药与健康研究院首席研究员艾斯泰班（Miguel Esteban）表示，虽然在桃莉羊后，学界在复制哺乳类动物领域方面有很大进展，但效率差仍是主要障碍。
中科院的报告指出，团队使用了改良版的体细胞核移植技术来复制恒河猴，在尝试数百次都失败后，团队意识到早期的复制胚胎中，形成胎盘的外膜没有正常发育，团队随后使用称为内细胞团移植（inner cell mass transplantation）的技术解决问题，并且重建113个胚胎，当中11个胚胎植入7个代孕体内，最终只有1个胚胎存活。
陆发隆表示，团队认为可能还有其他异常状况，接下来将持续专注于加强体细胞核移植技术的成功率。
研究人员指出，成功复制猴子可能有助于促进生物医学研究，不过英国皇家爱护动物协会（Royal Society for the Prevention of Cruelty to Animals）指出，复制动物技术有严重的伦理、福祉问题，尤其复制动物的过程可能造成动物疼痛及痛苦，而且失败率及死亡率非常高。
未参与研究的西班牙国家生物技术中心（National Center for Biotechnology）科学家蒙托利乌（Lluís Montoliu）表示，这项研究证明2件事，第一，复制灵长类动物是有可能的，第二、也同样重要的是，这些实验要成功是极度困难，而且效率很低，他认为成功率低，代表复制人类不只没必要，而且争议很大，如果持续尝试，将会极度困难，道德上也无法接受。
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