To see Zhong Zhong and Hua Hua crawl over a giant Hello Kitty stuffed animal and fall over each other, you’d think they were just normal macaques — and indeed, what’s special about them isn’t immediately visible. They’re clones created in China using the same technique that over 20 years ago gave the world Dolly, the first mammal cloned from an adult sheep. Their existence proves that animals as complex as monkeys can be cloned, too.
The two macaques were born less than 10 weeks ago, and they’re healthy, at least for now. The researchers hope that their technique, described today in the journal Cell, will be used in the future to create herds of genetically identical macaques for medical research. Whether that will happen, though, remains to be seen. In the US, conducting studies on monkeys is often controversial. The cloning technique is also expensive and not very efficient — over 70 embryos were implanted in 21 surrogate mothers. Only six pregnancies resulted, and just two macaques were born.Photo by Qiang Sun and Mu-ming Poo / Chinese Academy of Sciences
Non-human primates are very similar to us, so they are key for studying diseases and testing drugs. But genetic differences between monkeys can skew the results. Having a group of cloned monkeys would solve that problem. The cloning technique also allows researchers to genetically engineer monkeys to have genes linked to a particular disease, such as Parkinson’s, creating better animal models for the illness.
“Even if it’s expensive, it’s a very precious animal,” says Pablo Ross, a geneticist at the University of California, Davis, who did not take part in the study.
Animals like cows, horses, and even dogs are already cloned for anything from sports to medical research. And it all began with Dolly the sheep: she was cloned in 1996 using a method called somatic cell nuclear transfer. It works this way: you take a cell from an adult sheep. You take an egg from another sheep, and strip it of its DNA. Then you fuse the adult sheep cell with the denuded sheep egg. The egg is then developed into an embryo and transferred into the uterus of a surrogate mother. The newborn lamb will have the same DNA as that first adult sheep — a clone.Zhong Zhong. Photo by Qiang Sun and Mu-ming Poo / Chinese Academy of Sciences
A similar technique has been used before, in 1997, to clone two monkeys, named Ditto and Neti. But those monkeys were cloned from cells taken from early embryos. Zhong Zhong and Hua Hua, the long-tailed macaques described in today’s study, were cloned from connective tissue cells taken from monkey fetuses. Unlike embryonic cells, these cells can be grown in the lab — and that allows researchers to create many clones, as well as genetically engineer the cells in a petri dish more easily.
The Chinese researchers worked on Dolly’s technique for three years to make it work in monkeys. And though they were eventually successful, they experienced a lot of failure: two healthy monkeys from 79 embryos, according to study co-author Mu-ming Poo, director of the Institute of Neuroscience at the Chinese Academy of Sciences. When they tried to clone monkeys from adult cells, instead of cells from fetuses, only two monkeys were born out of 181 embryos — and they both died of respiratory failure within 30 hours. “It’s feasible so that’s a good thing,” Ross says. “But I don’t see it being practical.”Hua Hua. Photo by Qiang Sun and Mu-ming Poo / Chinese Academy of Sciences
Cloning requires specialized technicians, state of the art equipment, and many animals to work with. The researchers had to use dozens of surrogate mothers for this study. That’s pricey: each successfully-cloned macaque cost $50,000, but the price would be even higher in the US, according to Ross.
Still, the potential of using cloned monkeys in medical research is enticing, Ross says, especially if the clones’ DNA is tweaked to study the role of specific genes in diseases like Parkinson’s, Alzheimer’s, Huntington’s, or even autism. With gene editing tools like CRISPR, inserting and deleting genes is easier than ever today. CRISPR and somatic cell nuclear transfer, for instance, have been used together to create pigs whose organs are safer for human transplantation.
As Zhong Zhong and Hua Hua get older, the Chinese researchers will be monitoring their health and behavior. Hopefully that means lots more cute photos as they grow up.