New cloned monkey species highlight the limits of cloning

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Meet Retro, a cloned rhesus monkey born on July 16, 2020.

It is now more than 3 years old and is doing well and growing strongly, 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 successfully cloned. The same team of researchers announced in 2018 that they had cloned two identical cynomolgus monkeys (a type of macaque), which are still alive today.

“We have achieved the first live and healthy cloned rhesus monkey, a great step forward that is impossible to achieve, although the efficiency is very low compared to normal fertilized embryos,” said Lu, an investigator at the State Key Laboratory . Molecular Developmental Biology and the Institute of Genetics and Developmental Biology at the Chinese Academy of Sciences. “Right now, we haven’t had a 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 recreate an unfertilized egg using the nucleus of a somatic cell (not from a sperm or egg ) is fused with an egg in which the nucleus has been removed.

Since then, scientists have cloned many species of mammals, including pigs, cows, horses and dogs, but the process has been hit or miss, and typically only a small percentage of the embryos are transferred to centers. centers resulting in viable offspring.

“In a way we have made great progress in that, after Dolly, many species of mammals have been cloned, but the truth is that inefficiency is still a major roadblock,” said Miguel Esteban, principal -investigator with Guangzhou Institute of Biomedicine and Health at China. Academy of Sciences. He was not involved in the latest research but collaborated with several 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 further refined the technique 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 inserting cloned inner cells into a non-cloned embryo, and allowed the clone to develop normally, Esteban explained.

The team then tested the new technique using 113 reconstructed embryos, of which 11 were transferred to seven surrogates, resulting in only one live birth, according to the study.

“We think there could be more…. fixing abnormalities. Strategies to further improve the success rate of SCNT in principals remain… our main focus going forward,” said Lu

The first two cloned monkeys, Zhong Zhong and Hua Hua, are now more than 6 years old and are living a “happy and healthy life” with others of the same species. Lu said the researchers have not identified any potential limits to the lifespan of cloned monkeys.

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, similar to what happens naturally when identical twins develop, rather than using an adult cell like the SCNT technique.

The implications of cloning monkeys

The researchers said successfully cloning monkeys could help speed up biomedical research since there are limits to what scientists can learn from lab mice. Research on non-human primates, which are closer to humans, has been key to life-saving medical advances, including the creation of vaccines against Covid-19, according to a report released by a panel of the National Academies of Sciences, Engineering and Medicine in May.

The use of monkeys in scientific research is a controversial issue due to ethical concerns about animal welfare. The team said they followed Chinese laws and guidelines governing the use of non-human primates in scientific research.

The UK’s Royal Society for the Protection of Animals said it has “serious ethical and welfare concerns about the application of cloning technology to animals. Cloning animals requires procedures that can cause pain and distress, and can have high rates of failure and mortality.”

It could be useful to produce genetically identical monkeys, Esteban said.

“This research is a proof of principle that cloning is possible in different non-human primate 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 modelling. There is also a species conservation mentality,” he said.

Dr Lluís Montoliu, a research scientist at the National Center for Biotechnology (CNB-CSIC) in Spain who was not involved in the research, said that the cloning of the two monkey species showed two things.

“First, primates can be cloned. And secondly, which is no less important, it is extremely difficult for these experiments to succeed, 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 extremely difficult and ethically indefensible.”

“Human reproductive cloning is completely unacceptable,” Lu said.

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