On 24 January, a group of Chinese scientists announced their success of cloning two female macaques. This marks the first time that primates have ever been cloned through the somatic cell nuclear transfer (SCNT) technique – a breakthrough in the field of biomedical sciences.

The monkeys, Zhong Zhong and Hua Hua, were named after the word zhonghua, an adjective for Chinese people. Both monkeys – eight and six weeks old – are genetically identical, and are clones of the same donor culture of foetal monkey cells. The young monkeys are also reportedly healthy and are currently incubated.

"We're excited – extremely excited," expressed one of the co-authors of the paper, Professor Mu-ming Poo from the Chinese Academy of Sciences, further adding that “the barrier of cloning primate species is now overcome.”

The discovery will undoubtedly spark debate over cloning their fellow primate species: humans. However, it leads to a daring new world of biomedical research, full of potential.

The long, arduous journey to cloning primates

The SCNT method used in the Chinese paper is not new in the world of cloning. It is the same technique Scottish scientists used to clone Dolly the sheep back in 1996.

The technique utilises the DNA taken from the nuclei of foetal monkey cells and transferred into monkey eggs, which have had their respective DNA removed. The eggs were then stimulated to develop into embryos and then transplanted into surrogate monkeys for subsequent development.

Dolly the Sheep in a field at The Roslin Institute in Scotland. Photo credit: The Roslin Institute/The University of Edinburgh
Dolly the Sheep in a field at The Roslin Institute in Scotland. Photo credit: The Roslin Institute/The University of Edinburgh

There were many previous attempts to clone non-human primates using SCNT, but most failed as the authors note that they were "caused by inappropriate reprogramming of the somatic nucleus for supporting the development of transplanted embryos."

In this study, the scientists had modified and optimised the experimental protocols, proving that the cloning of a species that is genetically closer to humans is not at all impossible.

“It’s about time, because I thought it would never happen,” said Shoukhrat Mitalipov, the head of Oregon Health and Science University’s Centre for Embryonic Cell and Gene Therapy. He was not involved with the study, but has worked on previous monkey-cloning efforts.

“However, the reason we chose to break this barrier is to produce animal models that are useful for human medicine. There’s no intention to apply this method to humans,” assured Professor Poo.

The ultimate question that comes to mind: is the technique viable to produce animal models?

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Assessing the viability of cloning monkeys for research

The Chinese scientists' attempt to clone monkey is an expensive one. It was estimated that each successfully-cloned macaque monkey costed approximately USD50,000 – the figure was not inclusive of miscellaneous costs to maintain the precious animal.

The successful yield of the experiment was also dismal, given the technical difficulties that had to be overcome. Out of 79 embryos transferred into 21 surrogate female monkeys, pregnancy was confirmed in only six of the surrogates.

Eventually, only two live babies were obtained at full term through caesarean section. The new-born Zhong Zhong and Hua Hua were described as having a normal growth rate and exhibited no obvious abnormalities compared to monkeys born by natural fertilisation.



It is also worth noting that, when adult monkey cells – instead of foetal cells – were used in the cloning attempts, the success rate was significantly lower. Only two monkeys were obtained from 181 embryos and both died within 30 hours from respiratory failure.

“If there would be an efficient way to clone monkeys, that could actually reduce the number of monkeys needed to answer a certain research question,” noted Koen Van Rompay, a virologist at the California National Primate Research Centre.

A scientific breakthrough, or a complete waste of time?

Genetically identical monkeys are valuable research models as it may address the inherent variability in the experimental subjects. Environmental and physical variabilities are relatively easy to control, but subtle genetic differences within the same species have proven to be a challenge to overcome.

While this is achieved in rodent models through inbreeding, the approach is not practical in non-human primates that have a much longer generation time.

Professor Poo expressed his confidence in cloned animals that are evolutionarily closer to humans as a necessity in drug development. "I'm personally not confident that we can produce really good medical treatments without testing real animals," he said.

However, many scientists are quick to question the point of the exercise. In addition to the hefty price tag, the yield of such cloning experiment is simply far too low to make any meaningful impact in biomedical research.

Robin Lovell-Badge from the Francis Crick Institute commented that "…. the numbers are too low to make many conclusions, except that it remains a very inefficient and hazardous procedure."

Some scientists also pointed out that clones may not be identical to each other after all, as many epigenetic factors will subsequently influence the development of these clones.

Professor Mu-ming Poo, director of the Chinese Academy of Sciences Institute of Neuroscience, Shanghai, co-led the research of SCNT cloning non-human primates, which yielded two female macaques. Photo credit: AFP
Professor Mu-ming Poo, director of the Chinese Academy of Sciences Institute of Neuroscience, Shanghai, co-led the research of SCNT cloning non-human primates, which yielded two female macaques. Photo credit: AFP

As the debate goes on, experts such as Jeffrey Kahn, a bioethicist at Johns Hopkins University urged for a global discussion. “What should we do about it – the ‘we’ being societies, countries, oversight bodies, governments?” he questioned.

“What kind of governance do we think is necessary to prevent bad things from happening to humans, in the context of technology like this?”

The Chinese research team said they will continue to monitor the long-term health of Zhong Zhong and Hua Hua, especially the development of their brains. Through the governmental support from Shanghai, the team also hopes that the Chinese society will keep an open mind to conducting research on non-human primates.

“With all this improvement, along with the high standards of ethical concerns, I think that Chinese society will accept this,” said Professor Poo. “I hope that societies in Western countries will realised once we demonstrate the cloned monkeys’ usefulness in curing disease, they will gradually change their mind.” MIMS


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Sources:
http://www.cell.com/cell/fulltext/S0092-8674(18)30057-6
https://www.npr.org/sections/health-shots/2018/01/24/579925801/chinese-scientists-clone-monkeys-using-method-that-created-dolly-the-sheep
http://www.independent.co.uk/news/science/clone-monkey-human-zhong-hua-china-cloning-fears-macaque-replicant-a8176181.html
https://mashable.com/2018/01/24/chinese-laboratory-clones-monkeys/#cIKIBnceaOq6
https://www.theverge.com/2018/1/24/16927476/monkey-clones-somatic-cell-nuclear-transfer-dolly-china-medical-research-disease
http://www.sciencemag.org/news/1997/03/monkey-clones-get-mixed-reviews
https://www.washingtonpost.com/archive/politics/1997/03/02/monkeys-cloned-for-first-time/8563de78-9a7e-4ee4-8621-ba78070ded81/?utm_term=.88136973ab4a
https://news.nationalgeographic.com/2018/01/monkey-clones-dolly-sheep-china-medicine-science/