A team of Chinese scientists led by Zhen Liu and Qiang Sun has managed to clone a rhesus monkey, called 'ReTro', which survived more than two years. This is the second cloning of primates, after the one achieved in 2018 of a small group of crab-eating monkeys and which arrived almost 22 years after the famous case of Dolly the sheep.
The researchers suggest that the new achievement, for which a method was developed that provided the developing clonal embryo with a healthy placenta, advances the understanding of the mechanisms of cloning in primates and could help improve the efficiency of cloning in the future. process, which until now is extremely low. The details of the cloning of the rhesus monkey are published this Tuesday in Nature Communications, which specifies that it was achieved after more than 110 failed attempts
The famous Dolly the sheep was born on July 5, 1996 and was the first mammal cloned from adult cells thanks to a technique devised by Ian Wilmut and his colleagues at the Roslin Institute in Edinburgh. However, the world would not know of this feat until February 1997.
Its publication in Nature that year marked the starting point of the cloning of other mammals (cow, pig or dog), "a slow drip that demonstrated the intrinsic difficulties of each species, with different characteristics of its reproductive biology, necessary to adapt the original method developed to clone Dolly the sheep," says scientist Lluís Montoliu, who is not involved in the research.
The cloning method is actually called the "somatic cell nuclear transfer process" (SCNT) and consists of replacing the nucleus of an egg, which contains the DNA, with that of an adult somatic cell from another individual. .
The team of Liu and Sun, from the Chinese Academy of Sciences in Shanghai, adapted this technique to achieve the new cloning. Sun reminds - in an email - that monkeys are vital and commonly used in the field of cognitive and biomedical research. For example, transgenic monkey models such as Huntington's disease or genetically modified monkey models such as Parkinson's disease have been used.
However, Sun points out that it is very difficult to obtain genetically identical monkey models, especially for gene-edited monkeys. "SCNT is the technology for cloning genetically identical animals."
The new cloning was obtained by combining the treatment of the cloned embryos with the inhibitor Trichostatin A and with the enzyme Kdm4d, both already used in the previous one of the cynomolgus macaque and aimed at altering the epigenetic state of the embryos, explains Montoliu, from the National Center of Biotechnology (CNB-CSIC), to the Science Media Centre, a platform of scientific resources for journalists.
They do this with a sophisticated method of replacing the trophoblast, the cells that surround the internal cell mass in the blastocyst - an embryo about five days old - and that will later give rise to the placenta.
In the experiments, a total of 113 cloned rhesus embryos were activated and 11 transferred to 7 females, of which two became pregnant; Finally, a baby was born, they detail in their article.
The efficiency was similar to that of previous processes, even lower: a cloned animal that survived from 113 initial embryos (efficiency of less than 1%).
In the case of rhesus, only one study had managed to clone somatic cells, but the animal did not survive birth. Now the specimen, which the researchers called 'ReTro', managed to live two years.
For José Manuel Bautista, professor of Molecular Biology at the Complutense University of Madrid, this is an important advance in knowledge. The result, he emphasizes to EFE, shows that for normal and healthy embryonic development there are a good number of epigenetic elements from both the mother and the embryonic cell.
Epigenetic changes affect the functioning of genes and have to do with the environment where the cell lives. Unlike genetic changes, these are reversible and do not modify the DNA sequence, but they can change the way the organism reads that sequence. "I think this study will help investigate other more specific epigenetic elements related to assisted reproduction in both animals and humans, which need to be understood."
In this sense, Qiang Sun tells EFE that there may be epigenetic anomalies that need to be corrected. "In the future we will focus on strategies to improve the success rate of SCNT in primates."
Both the cloning of the crab-eating macaque ('Macaca fascicularis') and that of the rhesus ('Macaca mulatta') demonstrate two things, Montoliu points out: it is possible to clone primates and, no less important, it is extremely difficult to be successful with these experiments, with efficiencies so low, "again ruling out the cloning of human beings.
These experiments could not have been done in Europe. Legislation on animal experimentation prohibits the use of non-human primates unless the study is aimed at investigating a serious, fatal disease that affects humans or the primate species itself, which is not the case of this experiment.
For Bautista, the research also brings into debate the concept of the moral status of primates because on the one hand it is an excellent model of human disease, while its use in research can be controversial and ethically problematic, especially if it harms the animal. . The researcher emphasizes that controls already exist and agrees with Montoliu on the clarity of European laws.
