Chinese scientists have announced the successful creation of two cloned monkeys, representing a major advance in cloning practice and potentially opening the way for a revolution in animal-model lab research.
The monkeys, long-tailed macaques called Zhong Zhong and Hua Hua, are described in the journal Cell by a team led by Qiang Sun, director of the Nonhuman Primate Research Facility at the Chinese Academy of Sciences Institute of Neuroscience.
The animals were cloned using a technique called somatic cell nuclear transfer (SCNT). This was the method used to create Dolly the sheep, the first successfully lab-cloned mammal, in 1996.
Since then, it has been successfully used to clone other species, including mice and cows, but primates have remained stubbornly resistant.
SCNT involves removing the nucleus from an egg cell and replacing it with another derived from differentiated body cells. The implant then determines the animal that develops. Because it is theoretically possible to implant the same genetic information infinite number of times, it is therefore possible to produce (again, theoretically) an infinite number of identical animals – providing a perfect standardised cohort for medical research.
There have been several previous attempts to clone primates using SCNT, but all failed. Zhong Zhong and Hua Hua were created using fibroblasts, cells normally found in connective tissue. The key achievement of Sun’s team, however, was discovering how to introduce epigenetic modulators into the nucleus – effectively allowing the scientists to switch on and off the genes that control, or inhibit, embryo development.
The fibroblasts used to make the monkeys was obtained from macaque foetal tissue. The team also tried the same technique using adult cells, in which the resulting embryos were carried to term, but died only hours after birth.
“We tried several different methods, but only one worked,” says Sun. “There was much failure before we found a way to successfully clone a monkey.”
Success in part was improved through practice. As well as the complex business of enabling the fusion of egg and nucleic matter, and the introduction of the epigenetic tools, the whole procedure turned out to be heavily dependent on the speed and dexterity of the scientists.
“The SCNT procedure is rather delicate, so the faster you do it, the less damage to the egg you have,” says co-author Mu-ming Poo.
“It takes a lot of practice. Not everybody can do the enucleation and cell fusion process quickly and precisely, and it is likely that the optimisation of transfer procedure greatly helped us to achieve this success.”
Strictly speaking, Zhong Zhong and Hua Hua, are not the first cloned monkeys in history. In 1999, a rhesus monkey called Tetra was made by a team from Oregon in the US. However, the technique used was a far simpler one, called embryo splitting, which often happens naturally, creating twins, and is inherently restricted to only one reproduction.
With SCNT, the number of genetically identical Zhong Zhongs and Hua Huas is potentially unlimited.