New cloned rhesus monkey highlights limits 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 “in good condition and growing strongly,” according to Falong Lu, one of the study’s authors. Stady Published in the journal Nature Communications on Tuesday describes how Retro came to be.

Retro is the second species of primate that scientists have been able to successfully clone. The same team of researchers announced in 2018 that they had done just that Two identical cloned monkeys (a type of macaque), which is still alive today.

“We have achieved the first live, healthy cloned rhesus monkey, which is a huge step forward that turned the impossible into the possible, although the efficiency is very low compared to natural fertilized embryos,” said Lu, a researcher at the State Key Laboratory. Molecular Developmental Biology and the Institute of Genetics and Developmental Biology of 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 – It was created in 1996 using a technique called somatic cell nuclear transfer, or SCNT, where Scientists essentially reconstruct an unfertilized egg by fusing the nucleus of a somatic cell (not from the sperm or egg) with the egg from 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, with usually only a small percentage of embryos being transferred to surrogates resulting in viable offspring.

“After Dolly, we have made great progress in cloning many mammalian species, but the reality is that inefficiency remains a major obstacle in the way,” said Miguel Esteban, a principal investigator at the Guangzhou Institute of Biomedicine and Health in China. Academy of Sciences. He was not involved in the latest research but has collaborated with some members of the research team on other major studies.

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

During hundreds of failed cloning attempts, they realized that in early cloned embryos, the outer membrane that forms the placenta had not developed properly. To address this problem, they performed a procedure called endogenous cell block transplantation, which involved placing cloned endogenous cells into a non-cloned embryo, allowing the cloned embryo 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 believe there may be more… abnormalities to be repaired. Strategies to enhance the success rate of SCNT technology in primates remain… 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 living “happy and healthy lives” with others of their kind. Lu said that researchers have not yet determined any possible limits to the lifespan of the cloned monkeys.

Zhong Zhong and Hua Hua are often described as the first cloned monkeys. However, it was a rhesus monkey It was cloned in 1999 Using what researchers consider a simpler cloning method. In this case, scientists split the embryos, as happens naturally when identical twins develop, rather than using an adult cell as in SCNT technology.

The researchers said that the ability to successfully clone monkeys may help speed up biomedical research, given that there are limitations to what scientists can learn from laboratory mice. Research on non-human primates, the closest relative to humans, has been pivotal to life-saving medical advances, including creating vaccines against COVID-19, according to a report By a panel of the National Academies of Sciences, Engineering, and Medicine issued in May.

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

The UK's Royal Society for the Prevention of Cruelty to Animals said it had “serious ethical concerns regarding the application of cloning technology to animals. Animal cloning requires procedures that can cause pain and distress, and there can be high failure and mortality rates.”

Esteban said the ability to produce genetically identical monkeys could be beneficial.

“This research is a proof of principle that cloning can be done in different species of non-human primates and opens the door to new ways to enhance efficiency. It is possible to genetically engineer cloned monkeys in complex ways that wild monkeys cannot do; this has many implications for disease modeling.” There is also a species conservation perspective, he added.

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

“First, it is possible to clone primates. Second, and equally important, it is extremely difficult to succeed in these experiments with such low efficiency.

He added that the low success rate of this process showed that “human cloning was not only unnecessary and controversial, but if attempted, it would be extremely difficult and morally unjustified.”

“Human cloning for reproductive purposes is absolutely unacceptable,” Lu said.