China’s ReTro is the first successfully cloned rhesus monkey

The backstory: Cloning is a scientific technique for creating identical living organisms with the same genetic makeup. In 1996, scientists hit a cloning milestone with Dolly the sheep, the first mammal cloned from the cell of another animal, using something called somatic cell nuclear transfer (SCNT). Basically, this method combined a cell nucleus, the part that contains the most genetic information, from an adult sheep with an unfertilized egg that had its own nucleus removed. After Dolly, scientists tried cloning other animals, but it worked better with some than others.

Zhong Zhong and Hua Hua, the first monkeys cloned using the same method as Dolly, have been living for over six years now. While many consider these monkeys to be the first monkey clones, there was a rhesus monkey cloned in 1999 using a simpler, different method. The ambition behind cloning monkeys centers on how genetically similar primates are to humans, meaning they could help with research into human diseases. By using clones, hypothetically research would be more reliable since genetically identical subjects would produce like-for-like results.

The development: Now, Chinese scientists have achieved a big feat by cloning the first rhesus monkey, according to results published in a study in Nature Communications last week. ReTro, named after a method used in its creation (trophoblast replacement), is now 3 years old. Zhong Zhong and Hua Hua, cloned in 2018, are macaque monkeys. But rhesus monkeys are preferred for research because their genetics are closer to humans.

Many attempts to clone a rhesus have been made – and failed – and these researchers were able to figure out why. The placentas weren’t reprogrammed correctly in the process, so they never developed normally. To solve this, the team introduced a new method called inner cell mass transplantation. They put cloned inner cells into non-cloned embryos, which were then inserted into a surrogate. The team used this technique on 113 embryos. The result was two pregnancies and one live birth out of 11 embryos that had been transferred.

Scientists believe this cloning breakthrough could make experiments produce more reliable results from identical animals. But, worries about the well-being of cloned animals are raising ethical concerns among critics. Some also point out the amount of attempts it took, suggesting that the benefits don’t outweigh the challenges in the process. Other critics argue progress like this means we’re that much closer to cloning humans, which is a whole other ethical can of worms.

Key comments: 

“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 Falong 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 and one of the authors of a study published in the journal Nature Communications earlier this week. “Currently, we haven’t had the second live birth yet.” 

"All animal procedures in our research adhered to the guidelines set by the Animal Use and Care Committees at the Shanghai Institute of Biological Science, Chinese Academy of Sciences (CAS), and the Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology. The protocol has been approved by the Animal Use and Care Committee of the CAS Center for Excellence in Brain Science and Intelligence Technology,” said Lu to the BBC. 

“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.

"Having animals of the same genetic make-up will reduce a source of variation in experiments. But you have to ask if it is really worth it,” said Professor Robin Lovell-Badge, of the Francis Crick Institute in London, who supports animal research when the benefits to patients outweigh the suffering to animals. ''The number of attempts they had is enormous. They have had to use many embryos and implant them into many surrogate mothers to get one live born animal.''

''You cannot make any conclusions about the success rate of this technique when you have one birth. It's nonsense to ever propose you can. You need at least two, but preferably more,'' Lovell-Badge also said.