Two monkeys have followed in the footsteps of Dolly the Sheep by becoming the world’s first primates to be cloned from transferred DNA.
Identical long-tailed macaques Zhong Zhong and Hua Hua were born eight and six weeks ago respectively at a laboratory in China.
The success marks a watershed in cloning research and raises major ethical questions.
The scientists hope to pave the way for populations of genetically uniform monkeys that can be customised for ground-breaking research into human diseases.
But the cloning of monkeys will be seen by some as a step toward the creation of human clones.
Two monkeys have followed in the footsteps of Dolly the Sheep by becoming the world’s first primates to be cloned from transferred DNA. Identical long-tailed macaques Zhong Zhong (pictured) and Hua Hua were born eight and six weeks ago respectively at a laboratory in China
Zhong Zhong and Hua Hua are not the first primate cloned. Tetra, a rhesus monkey, was born in 1999 through a simpler method called embryo splitting.
They are, however, the first primates to be cloned using something known as the same single cell nuclear transfer (SCNT) technique.
This was the same technique used on Dolly, who made history 20 years ago after being cloned at the Roslin Institute in Edinburgh.
It was the first time scientists had managed to clone a mammal from an adult cell, taken from the udder of a Finn Dorset sheep.
Since then many other mammals have been cloned using the same single cell nuclear transfer (SCNT) technique, which involves transferring cell nucleus DNA to a donated egg cell that is then prompted to develop into an embryo.
They include sheep, cattle, pigs, dogs, cats, mice and rats – but until now, there has never been an SCNT-cloned monkey.
The Chinese team led by Dr Qiang Sun, director of the Non-Human Primate Research Facility at the Chinese Academy of Sciences Institute of Neuroscience, Shanghai, made the breakthrough using DNA from foetal connective tissue cells.
After the DNA was transferred to donated eggs, genetic reprogramming was used to switch on or off genes that would otherwise have suppressed embryo development.
The scientists hope to pave the way for populations of genetically uniform monkeys that can be customised for ground-breaking research into human diseases. Pictured is Hua Hua, one of two clones produced in a groundbreaking new study
WHAT IS CLONING AND COULD WE ONE DAY CLONE HUMANS?
What is cloning?
Cloning describes several different processes that can be used to produce genetically identical copies of a plant or animal.
In its most basic form, cloning works by taking an organism’s DNA and copying it to another place.
There are three different types of artificial cloning: Gene cloning, reproductive cloning and therapeutic cloning.
Gene cloning creates copies of genes or parts of DNA. Reproductive cloning creates copies of whole animals.
Therapeutic cloning produces embryonic stem cells for tests aimed at creating tissues to replace injured or diseased tissues.
To create somatic cell nuclear transfer (SCNT) clones, scientists take DNA (red circle) from tissue and insert it into egg cells (yellow) with their DNA (green) removed. The scientists then switch on or off certain genes to help the cells replicate (right)
Dolly the Sheep was cloned in 1996 using a reproductive cloning process known as somatic cell nuclear transfer (SCNT).
This takes a somatic cell, such as a skin cell, and moves its DNA to an egg cell with its nucleus removed.
Another more recent method of cloning uses Induced pluripotent stem cells (iPSC).
iPSCs are skin or blood cells that have been reprogrammed back into an embryonic-like state.
This allows scientists to design them into any type of cell needed.
Could we ever clone a human?
Currently there is no scientific evidence that human embryos can be cloned.
In 1998, South Korean scientists claimed to have successfully cloned a human embryo, but said the experiment was interrupted when the clone was just a group of four cells.
In 2002, Clonaid, part of a religious group that believes humans were created by extraterrestrials, held a news conference to announce the birth of what it claimed to be the first cloned human, a girl named Eve.
This was widely dismissed as a publicity stunt.
In 2004, a group led by Woo-Suk Hwang of Seoul National University in South Korea published a paper in the journal Science in which it claimed to have created a cloned human embryo in a test tube.
Gene cloning creates copies of genes or parts of DNA. Reproductive cloning creates copies of whole animals (stock image)
In 2006 that paper was retracted.
According to the National Human Genome Research Institute, from a technical perspective cloning humans is extremley difficult.
‘One reason is that two proteins essential to cell division, known as spindle proteins, are located very close to the chromosomes in primate eggs,’ it writes.
‘Consequently, removal of the egg’s nucleus to make room for the donor nucleus also removes the spindle proteins, interfering with cell division.’
The group explains that in other mammals, such as cats, rabbits and mice, the two spindle proteins are spread throughout the egg.
Zhong Zhong and Hua Hua were the result of 79 nuclear transfer attempts.
Two other monkeys were initially cloned from a different type of adult cell, but died shortly after they were born.
Dr Sun said: ‘We tried several different methods, but only one worked. There was much failure before we found a way to successfully clone a monkey.’
Until now, there has never been a single cell nuclear transfer (SCNT)-cloned primate. The cloning of monkeys will be seen by some as a step toward the creation of human clones. Pictured are the two new clones
The Chinese team made the breakthrough using DNA from foetal connective tissue cells. After the DNA was transferred to donated eggs, genetic reprogramming was used to switch on or off genes that would otherwise have suppressed embryo development
The research is reported in the latest edition of the journal Cell.
Cloned monkeys would allow scientists to study ‘a lot of questions’ about primate biology, Dr Sun stressed.
He added: ‘You can produce cloned monkeys with the same genetic background except the gene you manipulated.
Zhong Zhong and Hua Hua were the result of 79 nuclear transfer attempts. Two other monkeys were initially cloned from a different type of adult cell, but died shortly after they were born
HOW WAS DOLLY THE SHEEP CREATED?
Dolly was the only surviving lamb from 277 cloning attempts and was created from a mammary cell taken from a six-year-old Finn Dorset sheep.
She was created in 1996 at a laboratory in Edinburgh using a technique called somatic cell nuclear transfer (SCNT).
The pioneering technique involved transferring the nucleus of an adult cell into an unfertilised egg cell whose own nucleus had been removed.
Dolly the sheep made history 20 years ago after being cloned at the Roslin Institute in Edinburgh. Pictured is Dolly in 2002
An electric shock stimulated the hybrid cell to begin dividing and generate an embryo, which was then implanted into the womb of a surrogate mother.
Dolly was the first successfully produced clone from a cell taken from an adult mammal.
Dolly’s creation showed that genes in the nucleus of a mature cell are still able to revert back to an embryonic totipotent state – meaning the cell can divide to produce all of the difference cells in an animal.
‘This will generate real models not just for genetically based brain diseases, but also cancer, immune or metabolic disorders and allow us to test the efficacy of the drugs for these conditions before clinical use.’
Professor Darren Griffin, a geneticist at the University of Kent who was not involved in the study, said: ‘The first report of cloning of a non-human primate will undoubtedly raise a series of ethical concerns, with critics evoking the slippery slope argument of this being one step closer to human cloning.
‘The benefits of this approach however are clear. A primate model that can be generated with a known and uniform genetic background would undoubtedly be very useful in the study, understanding and ultimately treatment, of human diseases, especially those with a genetic element.
Cloned monkeys would allow scientists to study ‘a lot of questions’ about primate biology, the researchers said. The scientists insisted they followed strict international guidelines for animal research, set by the US National Institutes of Health
‘Careful consideration now needs to be given to the ethical framework under which such experiments can, and should, operate.’
The scientists insisted they followed strict international guidelines for animal research, set by the US National Institutes of Health.
Co-author Dr Muming Poo, another member of the Chinese Academy of Sciences team, said: ‘We are very aware that future research using non-human primates anywhere in the world depends on scientists following very strict ethical standards.’
British cloning expert Professor Robin Lovell-Badge, from The Francis Crick Institute, London, said he did not believe successfully cloning monkeys has increased the chances of humans being cloned
British cloning expert Professor Robin Lovell-Badge, from The Francis Crick Institute, London, said he did not believe the research increased the chances of humans being cloned.
He said: ‘The work in this paper is not a stepping-stone to establishing methods for obtaining live-born human clones.
‘This clearly remains a very foolish thing to attempt. It would be far too inefficient, far too unsafe, and it is also pointless. Clones may be genetically identical, but we are far from only being a product of our genes.’
Technically Zhong Zhong and Hua Hua are not the first primate clones. That title goes to Tetra, a rhesus monkey born in 1999 through the much simpler method of embryo splitting that does not employ DNA transfer.
Technically Zhong Zhong and Hua Hua (pictured) are not the first primate clones. That title goes to Tetra, a rhesus monkey born in 1999 through the much simpler method of embryo splitting that does not employ DNA transfer
It is the same process that leads to the birth of natural twins, but can only generate up to four offspring at a time.
On the new experiment, Dr Julia Baines, Science Policy Adviser at PETA UK, said: Experimenters constantly receive funds to perform monstrous experiments on animals, and cloning monkeys is the latest Frankenscience that PETA condemns.
‘Cloning is a horror show: A waste of lives, time, and money – and the suffering that such experiments cause is unimaginable.
‘Because cloning has a failure rate of at least 90 per cent, these two monkeys represent misery and death on an enormous scale.’