Five cloned monkeys have been born with a host of genetic mental health conditions in a controversial experiment in China.
The monkeys – all clones of one primate – have been specially bred to create a ‘diseased’ population of animals to use in laboratory tests.
All five have the same DNA altered, which has resulted in symptoms similar to the human conditions of anxiety, depression and schizophrenia.
The quintet were born at the Institute of Neuroscience (ION) of the Chinese Academy of Sciences (CAS) in Shanghai. Researchers used the same technique as was used last year to produce Zhong Zhong and Hua Hua – the first ever two cloned monkeys – and Dolly the sheep, famously cloned in the late 90s in Scotland.
The animals will be destined for a life in a laboratory and the scientists claim the gene-edited primates will be used to test groundbreaking new treatments for diseases ranging from brain disorders to cancers.
But this latest move will inevitably raise ethical questions about the future of human cloning – and how close modern science is moving towards gene-edited clones.
China has also been rocked by controversy after scientist He Jiankui claimed to have created the world’s first genetically edited babies. State officials say he acted illegally in pursuit of fame and fortune.
Five monkey clones have been born with genetic conditions from a gene-edited animal. The animals are genetically identical to one another, as well as the donor monkey that was cloned (pictured)
Scientists hope that by repeating this process they can create one animal that exhibits the right symptoms and then use this as the future blueprint for all clones.
Cells from a donor monkey were used to create the clones.
A process known as somatic cell nuclear transfer (SCNT) was used to create the animals and it is the same procedure used to generate Zhong Zhong and Hua Hua, the first two cloned monkeys, and Dolly the sheep back in 1996.
Chinese scientists say the advance, reported online by the journal National Science Review, said the cloned quintet showed signs of a wide-range of symptoms associated with the loss of BMAL1.
The donor animals had this section of DNA deactivated via the famed gene-editing technique Crispr-Cas9.
This powerful tool allows scientists to manipulate genetic material and the changes are permanent and passed on down the generations.
It is also the technique allegedly used by Dr He Jiankui in China to create the first genetically modified human babies.
A pair of twins were created to be resistant to HIV by the now ostracised and disgraced academic.
He received huge backlash from his work due to the heinous ethical violations.
All five monkeys suffer the same issues relating to the absence of BMAL1 – a region of DNA involved in producing certain proteins, Animals can survive with this deactivated but suffer from circadian disorder characteristics such as lack of sleep, anxiety, depression and schizophrenia-like behaviour
Crispr and cloning is, however, permitted under international guidelines for animals.
Study senior author and investigator Dr Hung-Chun Chang said: ‘Disorder of circadian rhythm could lead to many human diseases, including sleep disorders, diabetic mellitus, cancer, and neurodegenerative diseases.
‘Our monkeys thus could be used to study the disease pathogenesis as well as therapeutic treatments.’
To create the monkey clones, Chinese researchers removed the nucleus from a monkey egg cell.
This was then replace with the nucleus from another cell in its body – from a fibroblast, a cell that creates collagen.
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.
To create the monkey clones, Chinese researchers removed the nucleus from a monkey egg cell. This was then replace with the nucleus from another cell in its body – from a fibroblast, a cell that creates collagen
A fibroblast is a somatic cell, meaning it comes from the body not the reproductive organs, and this provided the egg with the full compliment of chromosomes.
Egg and sperm cells undergo a process called meiosis where they half their chromosomes and rely on fertilisation to occur for the full set to be completed.
Once the fibroblast nucleus was implanted in the egg cell, the embryo was cultivated and differentiates until it forms a complete organism.
This is an identical copy of the original animal, flaws and all.
The embryo is implanted into the womb of a surrogate monkey that eventually give birth to the clones.
Zhong Zhong and Hua Hua hit headlines last year when they were born using the same method with cells from an aborted foetus.
WHAT ARE THE CRITICISMS OF CLONING?
The vast majority of animals cloning procedures end in failure with as little as 1 per cent resulting in living, apparently healthy offspring.
Dolly, who was cloned at the Roslin Institute in 1996, has developed arthritis earlier than might have been expected.
Scientists believe she may have aged prematurely because she was cloned from a six-year-old adult.
A study by professor Ian Wilmut, leader of the team that cloned Dolly the Sheep, highlighted unpredictable defects suffered by cloned animals.
He found a calf cloned in France did well for several weeks but died suddenly at 51 days after its ability to produce white blood cells failed.
Scientists at Roslin had to put down a 12- day- old cloned lamb because the muscles around its lungs had grown so thick that it had great difficulty breathing.
Dr Julia Baines, Science Policy Adviser at PETA UK, said: ‘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.’
Yesterday scientists revealed they had cloned two monkeys, potentially paving the way to ‘copying’ humans.
‘The work in this paper is not a stepping-stone to establishing methods for obtaining live born human clones’, said Professor Robin Lovell-Badge, Group Leader of The Francis Crick Institute.
‘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.’
Dr Qiang Sun, director of ION’s Non-human Primate Research Facility, said: ‘Our approach is to perform gene-editing in fertilised embryos to first generate a group of gene-edited monkeys, and then select one monkey that exhibits correct gene editing and most severe disease phenotypes as the donor monkey for cloning.
‘We believe that this approach of cloning gene-edited monkeys could be used to generate a variety of monkey models for gene-based diseases, including many brain diseases, as well as immune and metabolic disorders and cancer.’
The researchers plan to continue improving the technique to increase the efficiency of cloning.
They are expecting more macaque clones carrying disease-causing gene mutations to be generated in the coming years.
But they said the Institute of Neuroscience follows strict international guidelines for animal research.
Co-author Professor Mu-ming Poo, who directs the Institute of Neuroscience and helped to supervise the project, said: ‘This work required coordinated efforts of many laboratories, and serves as a clear example of the efficient team work that is highly emphasised by CAS.
‘This line of research will help to reduce the amount of macaque monkeys currently used in biomedical research around the world.’
He added: ‘Without the interference of genetic background, a much smaller number of cloned monkeys carrying disease phenotypes may be sufficient for pre-clinical tests of the efficacy of therapeutics.’
Since Dolly was cloned in Scotland back in 1996, more than 20 species of mammals have been cloned around the world – including cattle, cats, dogs, horses and rats
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.