Researchers affiliated to China’s premier science academy have successfully cloned the first rhesus monkey to survive into adulthood.
Retro, now three years old, was born after the team added an extra step to the conventional cloning method.
Identical cloned monkeys such as these could be used to study diseases and drug efficacy without genetic difference interfering with the results, according to the team based in Beijing and Shanghai.
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The scientists also said that the extra step added to the cloning method could have future applications in human assisted reproduction.
Retro is the first of his species – and only the second primate species ever – to be successfully cloned.
He was just over two years old when the team – from the Chinese Academy of Sciences’ (CAS) neuroscience and genetics and developmental biology institutes – began writing a paper on their achievement. It was published in the peer-reviewed, open access journal Nature Communications on Tuesday.
A previous attempt to clone rhesus monkeys in 2020 using somatic cell nuclear transfer (SCNT), the conventional cloning method, did result in a live birth, but the monkey died within a day.
Rhesus monkeys are used in research to study human infections and immune response, due to their similar genetic make-up.
Cloning could allow researchers to produce “a large number of genetically uniform monkeys that can be used for drug efficacy tests”, Poo Mu-ming, director of the CAS Institute of Neuroscience (ION), told the journal.
This would allow researchers to examine the impact of drugs “without the interference of genetic background”, he said.
Poo was not an author on the paper, but some members of ION were.
SCNT involves transferring the DNA of an adult non-reproductive cell from the intended clone into an egg cell from a donor that has had its DNA removed.
The technology successfully helped to clone the first mammal from an adult cell in 1996, when Dolly the sheep was born at a Scottish facility.
Since then, other species like mice, rabbits and dogs have been cloned as well, the paper said.
But cloning primates presented a bigger challenge.
In 2018, Chinese scientists were able to clone cynomolgus monkeys – another primate species used in biomedical research. They were the first non-human primates to be cloned using SCNT, under a team led by Sun Qiang, director of the non-human primate facility at ION.
That attempt resulted in the birth of a pair of cynomolgus monkeys, called Zhong Zhong and Hua Hua.
However, previous efforts to clone rhesus monkeys with the same method had failed, the authors wrote.
The new feat with rhesus monkeys was also led by Sun.
The team carried out experiments comparing SCNT-derived rhesus embryos with control embryos made using in-vitro fertilisation. They found cloned embryos exhibited abnormal traits, including thicker, calcified placentas.
DNA methylation, an important process in development that impacts gene expression, was reduced in the cloned embryos. This caused the embryos to develop differently, Poo said.
There was also a loss of maternal gene imprinting, a critical step in development that determines the expression of certain genes.
The researchers found four genes with abnormal imprinting “which may play a critical role in the development of monkey SCNT embryos”, the paper said.
To improve the cloning method for rhesus monkeys, they added an extra step – called trophoblast replacement.
China’s monkey cloners’ success down to blood, sweat and tears
Trophoblasts are cells in the outer layer of an early embryo that will develop into the placenta. The researchers removed the trophoblasts of the SCNT embryos – which were causing the abnormalities – and replaced them with those from in-vitro fertilised embryos.
“Using this approach, we successfully achieved the live birth of a healthy SCNT rhesus monkey that has survived for over two years,” the team wrote.
The team created 113 active embryos, 11 of which were transplanted into surrogate monkeys.
These resulted in two pregnancies, of which one went to term and a “healthy” male was born, the paper said.
However, a scientist in Spain questioned the feat’s likely potential for human cloning.
Dolly’s birth had sparked fears about the possibility of human cloning, Lluis Montoliu, a researcher at the National Centre for Biotechnology in Madrid told Science Media Centre Spain, referring to the technology’s ethical implications.
However, the pace and efficiency of mammalian cloning had shown that “those fears were entirely unfounded”, Montoliu said.
At less than 1 per cent, the efficiency of the process that created Retro was “even lower” than the one for cloning cynomolgus monkeys in 2018, he added.
Montoliu or the Madrid centre were not involved in the research.
While the CAS team had demonstrated that cloning primates was possible, the low efficiency highlighted “the technical difficulties of the SCNT process”, Montoliu said.
Their success in 2018 had “confirmed the obvious: not only was human cloning unnecessary and debatable, but if attempted, it would be extraordinarily difficult and ethically unjustifiable”.
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Even with this new feat, using “a sophisticated method of trophoblast replacement”, Montoliu said that the low efficiency “once again” ruled out the potential of human cloning.
However, while the potential for human cloning may still be off the table, the Chinese researchers said that the trophoblast replacement technique could have applications in in-vitro fertilisation (IVF) for assisted human reproduction.
“We’re seeing the beginning of the use of these cloned monkeys [in researching diseases and drugs]”, Poo said, but there was still more work ahead as they had “not solved” the efficiency problem.
Montoliu said carrying out experiments on non-human primates would not be possible in Europe, where their use in the study of anything other than life-threatening diseases is prohibited.
More from South China Morning Post:
- China’s success in cloning monkeys was a victory for hard work, not new tech, team leader says
- Chinese scientists plan monkey reproduction experiment in space station
- Chinese scientists create gene-edited pigs with immunity to Aids-like virus
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