Two macaque babies are the first living primate clones using the 'Dolly method'

Cloned primates: For the first time, Chinese researchers have cloned monkeys using the 'Dolly method'. As with the famous cloned sheep, the two healthy young animals were created by the fusion of reprogrammed body cell nuclei with decored ova - a process that had previously failed with primates. The successful cloning of long-tailed macaques could now open up new possibilities for research - but it is also a methodological step towards ethically controversial human cloning.

The clone sheep 'Dolly' made the beginning: In 1996, its birth proved that cloning from already differentiated mammalian body cells is possible. For this so-called somatic nuclear transfer, the nucleus of a body cell is removed and transplanted into a decored egg cell. There, it is put back into the embryonic state by the environment, as well as slight surges of current or chemical additives - its genetic material is reprogrammed.

As a result of this manipulation, a normal embryo develops, which is genetically an identical copy of the cell nucleus donor - a clone. In this way, researchers have already cloned 23 species of mammals - including pigs, cattle, mice, cats and dogs.

Primates are difficult

However, this cloning method has so far been unsuccessful with monkeys - and thus with our next of kin. The reason for this is that in primates, cells that have already been differentiated cannot be returned to the embryonic state as easily as in other mammals. The only monkey clone so far - a rhesus monkey - was created by the division of embryos. In principle an artificially produced twin.

Now, however, Zhen Liu and his colleagues from the laboratory for primate neurobiology in Shanghai seem to have succeeded in overcoming the hurdles in the reprogramming of primate cells. They used special enzymes to remove blockages in the genes of the implanted cell nucleus. This enabled them to bring the genetic material back to its original embryonic state.

109 clone cells - two live monkey babies

However, with adult monkey cells this method was only successful to a limited extent - the monkey clones did not survive long. The researchers therefore used the connective tissue cells of a long-tailed macaque fetus as cell nucleus donors for their successful cloning experiment. They removed these fibroblasts from the cell nucleus, transplanted them into a previously decored egg cell and treated the whole thing with their enzyme cocktail.

Of the 109 cloned eggs produced in this way, 79 developed further. The researchers transferred them to 21 macaque females as surrogate mothers. A month later, check-ups showed that four of these female monkeys were pregnant - cloned monkey cubs developed in them. However, two of these unborn babies were miscarried after two months, the researchers report. The other two ape cubs were born by caesarean section.

'A methodical success'

The two monkey babies - baptized Zhong-Zhong and Hua-Hua - are the first living monkeys produced by the Dolly method. So far, they seem to develop quite normally despite their unusual origin:

Both babies are in good condition, Liu and his colleagues report. This proves that cloning of non-human primates through somatic nucleus transfer is feasible.

However, it is still too early to rule out late effects of cloning in animals.

Nevertheless, other scientists also regard this experiment as a success:

From a technical and methodological point of view, this work is clearly progress, comments Rüdiger Behr from the German Primate Center in Göttingen. Biologically, the new procedure is also a step towards human beings.

However, human cloning is still strictly forbidden in most countries for ethical reasons.

Useful but controversial

For medical research, however, cloned monkeys could certainly bring advantages: Since genetically identical animals can be produced using this method, researchers can investigate the malfunctions or functions of individual genes on such clone monkeys more specifically.

This enables us to create models for genetic brain diseases, cancer, immune or metabolic diseases in humans and to better test the efficacy of drugs, according to Liu and his colleagues.

However, the use of apes in research is anything but uncontroversial, as the researchers admit:

We are well aware that future research with non-human primates depends on the researchers adhering to very strict ethical standards, they emphasize.

Source: Cell, 2018; doi: 10.1016/j. cell. 2018.01.020