Meet Zhong Zhong and Hua Hua, the first primates cloned by reprogramming adult cells.
Two decades after Dolly the Sheep was successfully cloned (SN: 3/1/97, p. 132), Chinese researchers have used the same technique — somatic cell nuclear transfer — to clone two healthy baby macaque monkeys. The results, reported January 24 in Cell, could lead to more efficient cloning and a better way to study genetic diseases in primates.
“This could be it — the next step in cloning,” says Jose Cibelli, a geneticist at Michigan State University in East Lansing not involved with the study.
Over 20 species of mammals have been cloned via somatic cell nuclear transfer — including cats, dogs, rats and even a camel (SN: 3/23/02, p. 189). This cloning technology has improved since Dolly’s birth in 1996. Back then, she was the only sheep born from 277 attempts. By 2014, the cloning technique had an 80 percent success rate in pigs. Despite these gradual advances (SN: 3/8/14, p. 7), cloning of nonhuman primates has long eluded researchers.
A rhesus monkey “clone” was created through embryo splitting, a technique that divides a single embryo into genetically identical embryos, in 1999. But this type of cloning has little in common with somatic cell nuclear transfer.
In somatic cell nuclear transfer, a nucleus from a mature body cell is transplanted into an egg cell without a nucleus. The egg cell must then reprogram the nucleus’s DNA, basically stripping the body cell of its identity and returning it to an embryonic state. With no set identity, it can become any kind of cell in the body.
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TWICE THE FUN Zhong Zhong and Hua Hua, the first primates successfully cloned via somatic cell nuclear transfer, are healthy, playful and, so far, completely normal for baby macaques. The sisters will spend the next few months in an incubator together.
Previous failures in reprogramming primate cells probably happened because the egg ran into roadblocks — portions of the body cell’s DNA known as reprogramming-resistant regions, say study coauthor Mu-ming Poo, director of the Institute of Neuroscience at the Chinese Academy of Sciences in Shanghai, and his colleagues. In these regions, DNA is so tightly wrapped around proteins called histones that the egg can’t reprogram those bits. So the researchers added two molecules aimed at loosening the DNA’s packaging.
The team tried this method with two types of body cells: ovarian cells from an adult and connective tissue cells from a fetus. Although 22 out of 42 monkeys became pregnant with embryos cloned from ovarian cells, only two babies were born and neither survived long past birth. Efforts with embryos made with the fetal cells resulted in six pregnancies among 21 surrogate monkey moms and two healthy babies.
“After 20 years of trying from the most talented groups, and nothing working, finally this works,” Cibelli says. “This research is going to help cloning of all species.”
Cloned primates could help researchers better understand diseases in humans. Macaques are close genetic relatives to humans, making the monkeys better analogs than other lab animals. And clones make it easier to weed out the complications of different genetics when studying diseases or testing drugs.
The sisters are just a few weeks old, but they hold a lifetime of promise for researchers. Poo says the scientists will watch for any abnormalities as Zhong Zhong and Hua Hua grow and play.
“The monkeys are in good health and very active,” he says. “There are no signs they are unhealthy.”