Healthy cloned monkeys born in Shanghai

Thursday, January 25, 2018

In findings published Wednesday in the scientific journal Cell, a team of scientists from the Chinese Academy of Sciences in Shanghai, China have announced the first-ever cloning of a primate from post-embryonic cells, namely two macaque monkeys. They used somatic cell nuclear transfer, the same method that was used to create Dolly the sheep in 1996.

In somatic cell nuclear transfer, scientists remove the nucleus, which is the organelle that contains the chromosomes, from an unfertilized ovum, or egg cell, and implant the nucleus from a somatic cell, or non-reproductive cell, into that ovum. The ovum is then stimulated and develops in the normal way, growing into a whole organism that has the same nuclear DNA as the donor organism, though it will have all of the ovum's mitochondria and other cellular machinery. Clones like these have been described as identical twins to their donors, but younger.

The scientists implanted 21 ova into surrogate mother monkeys, resulting in six pregnancies, two of which produced living animals. The young clones were named "Zhong Zhong" and "Hua Hua," both derived from Zhōnghuá, the Chinese-language word for the Chinese people. They are both cynomolgus monkeys, or crab-eating macaques (Macaca fascicularis). The scientists also attempted to clone macaques using nuclei from adult donors. They implanted 42 surrogates, resulting in 22 pregnancies, but there were still only two infant macaques, and they died soon after birth. The Scotland-based team that created Dolly the sheep in 1996 required 277 attempts and produced only one lamb.

Generally, the older the donor organism, the more difficult it is to get the DNA from the harvested nucleus to reactivate the genes that allow the clone organism to grow. Previous efforts to clone rhesus monkeys (Macaca mulatta) using embryonic donor cells have been successful, but the current attempt used significantly older donors: fetal fibroblast cells, which are key cells in connective tissue, and adult monkey cumulus cells.

"We're excited — extremely excited," said study co-author Muming Poo. "This is really, I think, a breakthrough for biomedicine." He went on to say that the cloned monkeys could be used as test subjects for the study of neurological diseases such as Parkinson's and Huntington's. Primates are already a popular model organism for neurological studies. In the United States, for example, non-human primates are used in less than 0.3% of all animal experiments, most of them involving neuroscience, and macaques in particular are a well-established animal model of atherosclerosis, which causes heart disease.

"I think it's a very exciting landmark. It's a major advance," agreed reproductive biologist Dieter Egli of Columbia University. "It should be possible to make models of human disease in those monkeys and study those and then attempt to cure it."

About 90% of the laboratory animals used in the United States are rodents. Although the first cloned mouse was born in 1998, cloned mice are not currently common in laboratory settings. This may be because producing inbred mouse lines is still relatively effective.

Although the announcement raised enthusiasm from researchers, it also drew caution from bioethicists. "Cloning one individual in the image of another really sort of demeans the significance of us as individuals," says Harvard Medical School's Dr. George Daley, speaking specifically of cloning humans. "There's a certain sort of gut sense that it violates sort of natural norms." While Muming Poo concedes it is now theoretically possible to clone a human, he says his lab has no plans to do so.

Although somatic cell nuclear transfer was used successfully in amphibians as early as 1952, getting it to work in mammals took much longer. Dolly, the first cloned mammal, was born in 1996. Teams have been trying to clone monkeys for decades, but primate DNA is notoriously difficult to work with. "The trick is we choose the right chemicals to turn on these genes we transfer into the egg," Mu-ming Poo told the press. "So that's what we did different. I think that's the key." One of the agents used to treat the ova was messenger RNA from the human Kdm4d gene.

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Sources

Zhen Liu, Yijun Cai, Yan Wang, Yanhong Nie, Chenchen Zhang, Yuting Xu, Xiaotong Zhang, Yong Lu, Zhanyang Wang, Muming Poo, Qiang Sun. "Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer" — Cell (journal), January 24, 2018
Rob Stein. "Chinese Scientists Clone Monkeys Using Method That Created Dolly The Sheep" — National Public Radio, January 24, 2018
Kimberley A. Phillips, Karen L. Bales, John P. Capitanio, Alan Conley, Paul W. Czoty, Bert A. ‘t Hart, William D. Hopkins, Shiu-Lok Hu, Lisa A. Miller, Michael A. Nader, Peter W. Nathanielsz, Jeffrey Rogers, Carol A. Shively, and Mary Lou Voytko. "Why Primate Models Matter" — American Journal of Primatology, April 10, 2014
Genetic Science Learning Center. "The History of Cloning" — University of Utah, January 24, 2018 (date of access)

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