On Jan. 24 earlier this year, a paper published in the journal Cell described the successful cloning of two macaque monkeys at the Chinese Academy of Sciences Institute of Neuroscience in Shanghai.
Zhong Zhong and Hua Hua, the baby macaques, are the first primates cloned through a technique called somatic cell nuclear transfer (SCNT), famously used to clone Dolly the Sheep over 20 years ago.
SCNT involves removing the nucleus from an egg cell and replacing it with the nucleus of a non-reproductive, or somatic, cell. Alternatively the somatic cell can be fused with the enucleated egg cell.
The modified egg cell is then stimulated to divide, and it eventually becomes an early-stage embryo that can be transplanted into a surrogate female. The resultant animal, the clone, is genetically identical to the donor of the somatic cell.
Since Dolly, SCNT has been successfully used to clone 23 other mammals, from rats to cows. However, primates proved more difficult. Although a rhesus macaque named Tetra was created in 1999, the cloning technique used was an entirely different one known as embryo splitting. This method is simpler than SCNT and more limited, in terms of the potential number of clones able to be created.
The researchers in Shanghai, led by Qiang Sun, used somatic cells taken from both fetal and adult monkeys. 127 egg cells transplanted with fetal cells resulted in 79 embryos, transferred to 21 surrogates.
Zhong Zhong and Hua Hua were the only live births, born at full term by caesarean section, and are currently around two months old. While there were also two live births from embryos created with adult cells, neither infant survived past 30 hours.
The researchers’ successful procedure involved treating egg cells with compounds that modified the transplanted DNA and facilitated embryonic development.
The cloning of the two macaques has raised concerns about the possibility of human cloning. Human embryos have already been cloned for the purpose of producing embryonic stem cells, and the recent development in Shanghai has sparked worry that it could be a first step towards human reproductive cloning.
In the near future, it is more likely that this technology will be adapted to create cloned animals for research. This application was anticipated even after the cloning of the rhesus monkey Tetra 18 years ago, when the BBC reported in 2000 that the researchers who created Tetra were motivated to produce cloned monkeys to study human diseases.
As a procedure to create animals for research, SCNT, used to clone Zhong Zhong and Hua Hua, would be an advancement over embryo splitting, used to clone Tetra. Mu-Ming Poo, who participated in the Shanghai study and is one of the paper’s co-authors, has been explicit about the intention to develop laboratory animals, telling reporters that the macaques can be widely used to study human disease and treatment options
“I do think it will be likely if the efficiency [of cloning primates] can be improved, since it would offer a research tool not otherwise available,” Jeffrey Kahn, Director of the Johns Hopkins Berman Institute of Bioethics, said, in an interview with The News-Letter.
Using genetically identical primate research subjects would be of great interest in Parkinson’s and Alzheimer’s research, among other fields. It would allow scientists to examine, in an animal closer to humans, the impact of drugs and treatments more effectively, without having to consider genetic differences.
In addition, using SCNT in conjunction with gene editing could also be used to produce research animals with specific genetic alterations.
Conducting research on cloned primates carries its own set of new ethical considerations.
“Cloning non-human primates hasn’t been a topic of consideration in bioethics prior to the announcement, and I think the community of bioethics scholars is waiting to understand the potential uses and applications of the technology,” Kahn said.
For the time being, the researchers in Shanghai have said that they abided by the U.S. National Institutes of Health’s international guidelines on animal research. They are anticipating the birth of more macaque clones in the next few months, in addition to continuing to monitor Zhong Zhong and Hua Hua, who appear to be developing normally.
