The newly cloned rhesus monkey highlights the limitations of cloning

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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,” says Falong Lu, one of the teachers. study A paper published Tuesday in the journal Nature Communications describes how Retro came to be.

Retro is only the second type of primate that scientists have successfully cloned. The same team of researchers announced in 2018 that they had developed Identically 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 that turned out to be impossible, although the efficiency is very low compared to normal embryos,” said Lu, a researcher at the State Key Laboratory. Institute of Molecular Developmental Biology and Genetics and Developmental Biology, Chinese Academy of Sciences. “Currently, we don't have a second live birth yet.”

First mammal to be cloned – Dolly Goat – Developed in 1996 using a technique called somatic cell nuclear transfer, or SCNT Scientists essentially reconstruct a fertilized egg by combining a somatic cell nucleus (not from a sperm or egg) with an embryonated egg.

Since then, scientists have cloned many mammalian species, including pigs, cows, horses, and dogs, but the process has been flawed or botched, and usually only a small percentage of embryos are transferred and produce viable offspring.

“Since Dolly, we've made a lot of progress in that many mammalian species have been cloned, but the reality is that inefficiency remains a major roadblock,” said principal investigator Miguel Esteban of China's Guangzhou Institute of Biomedicine and Health. Academy of Sciences. He was not involved in the latest research, but has collaborated with some members of the research team on other primary studies.

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A Chinese team based in Shanghai and Beijing used a modified version of SCNT in their work on cynomolgus monkeys (Macaca fascicularis) and further adapted the technique to clone the rhesus monkey (Macaca mulata).

During hundreds of failed cloning attempts, they realized that in early cloned embryos, the outer membrane that forms the placenta did not develop properly. To solve this problem, they performed an internal cell mass transplant, which involves placing cloned internal cells into a non-cloned embryo, and this 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 there may be additional … abnormalities that need to be corrected. Strategies to further improve the success rate of SCNT in primates … are our main focus in the future,” Lu said.

The first two cloned monkeys, Zhong Zhong and Hua Hua, are now over 6 years old and living “happy and healthy lives” with others of the same species. Lu said researchers have not yet identified potential limitations on the lifespan of cloned monkeys.

Zhong Zhong and Hua Hua are generally described as the first cloned monkeys. However, there was a rhesus monkey Cloned in 1999 Researchers use a simple cloning method. In that case, rather than using the adult cell as in the SCNT technique, the scientists separated the embryos, as happens naturally when identical twins are formed.

Successfully cloning monkeys could help accelerate biomedical research, as there are limits to what scientists can learn from lab mice, the researchers said. Research on nonhuman primates closely related to humans is critical to life-saving medical advances, including the development of vaccines against Covid-19. A statement by a panel of the National Academies of Sciences, Engineering and Medicine, published in May.

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The use of monkeys in scientific research is a controversial issue due to ethical concerns about animal welfare. The group said it follows Chinese laws and guidelines governing the use of nonhuman animals in scientific research.

England's Royal Society for the Prevention of Cruelty to Animals states, “There are serious ethical and welfare concerns in using cloning technology for animals. Cloning animals requires procedures that cause pain and suffering, and can have high failure and death rates.”

Creating genetically identical monkeys would be useful, Esteban said.

“This research provides evidence that cloning is possible in non-human species and opens the door to new ways to improve 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 said. He added.

Dr. Luis Mandoliu, a research scientist at the National Biotechnology Center (CNB-CSIC) in Spain, who was not involved in the research, said cloning the two species of monkeys showed two things.

“First, it is possible to clone animals. Second, less important, it is very difficult to succeed in these experiments with such low efficiency,” he said in a statement.

The low success rate of the process, he said, “makes human cloning not only unnecessary and debatable, but, if attempted, extraordinarily difficult and ethically unjustifiable.”

“Reproductive cloning of a human is completely unacceptable,” Lu said.

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