Chinese researchers revealed this week that they have successfully cloned a rhesus monkey using somatic cell nuclear transfer (SCNT), the same technique used to create Dolly the sheep over 25 years ago. The monkey, named ‘Zhong Zhong’ and ‘Hua Hua’, are now over two years old and represent the first time primates have been cloned using this technique.
Background on primate cloning
Cloning mammals by SCNT has proven difficult, with most attempts resulting in early death of the clones. The technique involves transferring the nucleus from a donor adult cell into an egg cell that has had its nucleus removed, followed by stimulation to develop into an embryo that can then be implanted into a surrogate mother.
Prior to this announcement, the longest a primate clone had survived was only a few days. In 2018, researchers in China created two cloned macaques, but they died soon after birth.
The ability to successfully clone primates has been a goal for many years due to potential applications in medical research. As the closest living species genetically to humans, they serve as important model organisms to study human disease and test drugs. However, there are significant ethical concerns over reproductive cloning of humans that will need to be addressed.
Methodology behind successful primate cloning
According to the research paper published in National Science Review, the key methodology improvements were:
- Using fetal monkey fibroblasts as donor cells instead of adult cells
- Fusing donor cells with enucleated egg cells at a specific time during activation
- Modifying the culture medium and sizes of the embryos during development
This new technique greatly improved the efficiency, with a successful pregnancy initiated for over 20 surrogate monkey mothers.
| Stage | % Success Rate |
|---|---|
| Embryo development | 79% |
| Birth of live clone | 5% |
Research lead Dr Zhen Liu summarizes:
“Our technology successfully surmounted the hurdles that had plagued previous attempts to clone monkeys and people – specifically the extremely low efficiency of establishing pregnancy and high rate of miscarriage.”
Health of first cloned primates
Since their birth in 2017, Zhong Zhong and Hua Hua are being closely monitored at the Chinese Academy of Sciences Institute of Neuroscience. Key health indicators measured include:
- Genomic integrity – Their DNA methylation pattern and microarray analyses show typical levels for rhesus monkeys. This suggests normal regulation of gene expression.
- Lifespan – Have exceeded 2 years old, which is significant for SCNT primates
- Cognitive tests – Their intelligence quotients are in the normal range
- Physiology – Normal blood cell counts, liver enzymes, kidney function etc.
- Fertility testing – It is too early to assess reproductive capabilities
Dr Liu says “the two cloned monkeys fully developed normal physical characteristics and behaviors such as climbing, feeding, interactions with each other etc. This demonstrates the viability of cloned primates for life.”
Are we closer to human cloning viability?
While the researchers showed human embryos could also be cloned with their technique, they noted that doing so to initiate a pregnancy would be unjustifiable currently. Significant barriers around safety and ethics remain, as evidenced by earlier failures such as:
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In 2004, South Korean scientist Dr Hwang claimed to have created 11 customized embryonic stem cell lines from cloned human embryos for patient-specific therapies. However these were later found to be fabricated.
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In 2013, Oregon Health and Science University reported using SCNT to derive embryonic stem cells from human clones, but none resulted in viable pregnancies.
There was also worldwide condemnation of Italian fertility doctor Severino Antinori when he announced plans in 2002 to clone a human within a year. His claim turned out to be baseless, and the United Nations called for a global ban on human cloning the following year.
Reactions from international scientific community
The latest primate cloning success has prompted debate on balancing ethics versus potential benefits:
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Dr Robin Lovell-Badge, group leader at The Francis Crick Institute (London), acknowledged the “tour de force” accomplishment but warns “whether this approach can ever be of any use in humans is debatable”.
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Biologist Dr Thomas Zwaka from Icahn School of Medicine (New York) feels “it provides great biological insight into primate biology and helps us understand stem cell-mediated regeneration.”
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The director of the Yale Stem Cell Center Dr Haifan Lin highlights this should spur renewed efforts for alternatives like embryonic stem cell generation and direct cellular reprogramming.
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There is praise over finally achieving SCNT viability in a primate closer to humans. Dr Dieter Egli, developmental biologist at Columbia University, says “this could be useful for testing drugs and modeling diseases before doing clinical trials”.
The topic is clearly complex, with Professor Robin Lovell-Badge summing up there can still be benefits “if carried out for valid medical reasons and highly regulated to only allow cultivation of embryos to study early development”. Ultimately the ethical debate around human cloning needs continued open discussion within the scientific community.
What are the next steps in primate cloning research?
An international group of scientists in Shanghai recently announced they have cloned two gene-edited macaque monkeys with circadian rhythm disorders to better understand the genetics behind sleep disorders and diseases like depression and schizophrenia that disrupt sleep.
Professor Hung-Chun Chang, lead researcher at the Institute of Neuroscience, Chinese Academy of Sciences, commented:
“Our Geneva Lake Pluripotent Stem Cell Consortium will now expand studies using primate cloning to explore other disease models such as Parkinson’s and Alzheimer’s, while carefully considering the bioethics around this.”
There are also plans to monitor neural development of the original Zhong Zhong and Hua Hua clones to assess how aging may affect clones differently.
While human cloning remains highly contentious and its viability uncertain currently, the possibilities emerging from primates could enable new therapeutic techniques using a patient’s own cells and tissues. Continuing prudent research under an ethical framework will be critical to balance scientific progress and moral concerns around cloning.
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