WHY THIS MATTERS IN BRIEF
So far monkeys have proven resistant to cloning, but now that barrier has been broken, and many suggest it leaves the way open for a day when we can see the first cloned humans.
Last week Zhong Zhong and Hua Hua, the world’s first monkeys cloned using the technique that gave us Dolly the sheep, were unveiled to the world, and the female long-tailed macaques represent what the researchers behind the unveiling called “a technical milestone,” one that should make it possible to create customisable and genetically uniform populations of monkeys, which could speed up treatments for diseases such as Alzheimer’s disease, cancer and Parkinson’s disease. But the breakthrough will also inevitably raise fears that human cloning has just edged another step closer to becoming a reality.
“The monkeys hold such huge potential because they all inherit exactly the same genetic material,” says Qiang Sun, the lead researcher at the Chinese Academy of Sciences Institute of Neuroscience (ION) in China, and this is a trait that would let scientists tweak the genes the monkeys have that are linked to human disease, and then monitor how this alters the animals’ biology, comparing it against animals that are genetically identical except for the alterations – something that could accelerate the hunt for genes and processes that go wrong in these diseases, and ways to correct them, the team says.
Meet The Monkeys
Although 23 species of mammal have been cloned since Dolly the sheep, including pigs, cats, dogs, rats and cattle, monkeys have, until now, proved resistant to the technique
In 2000, researchers cloned monkeys for the first time, but did so by splitting an embryo after it had been fertilised, essentially just producing a genetically identical twin. This method can only be used to create a maximum of four identical animals.
Now Sun and his team have tweaked the technique used to produce Dolly to create a theoretically limitless number of clones.
Called somatic cell nuclear transfer, the method involves removing the nucleus from a donor egg cell and replacing it with one taken out of a cell from another animal.
An electric current is used to trick the egg into thinking it has been fertilised, and it starts to develop into an early embryo. When implanted into the uterus of a surrogate mother, the embryo will grow into a carbon copy of the animal that donated the nucleus.
Previous attempts to do this in monkeys have never progressed beyond an early embryonic stage called a blastocyst.
Sun and his colleagues went further by introducing two new ingredients to the soup of nutrients and growth factors that help cloned embryos grow before being placed into the surrogate. The ingredients, which included messenger RNA and a compound called trichostatin A, awakened at least 2000 genes that are vital for various stages of embryonic development, enabling development to proceed.
The team also discovered that it is easier to clone macaques if you use cells from fetal macaques rather than adults. Zhong Zhong and Hua Hua were both created using cells destined to form connective tissue, extracted from an aborted female fetus.
Altogether, 79 embryos were implanted into 21 surrogates and the pair were the only live births from six pregnancies, meanwhile Dolly was the only success from 277 implanted embryos.
Although attempts to perform the technique using cells taken from adult macaques also produced two live animals, both died soon after birth, and one had abnormal body development.
“For many cell types, reprogramming is more difficult for adult cells than for fetal cells,” says Robert Lanza, chief scientist at the Astellas Institute for Regenerative Medicine in Massachusetts, whose team cloned human adult skin cells for the first time in 2014, “and that appears to be the case here as well,” he says.
This technical hurdle may put to rest fears often expressed after other cloning successes – the fear of human cloning, but then, that said, let’s face it we’re going to get there one day, and it’s a matter of when not if.
“It could be a step towards human cloning, but why would you do it?” says Peter Andrews at the University of Sheffield, UK, “in terms of human biology, it’s illegal to clone a human in Britain and many other countries, and I don’t think anyone would rationally want to do it.”
The Chinese team says its focus is to use the cloned monkeys to create better animal models of disease in order to accelerate medical therapies for humans, and Andrews says this concept has merit, especially given the long standing difficulties of trying to mimic complex diseases like Alzheimer’s and Parkinsons disease in mice.
To date, all therapies that have treated Alzheimer’s-like symptoms in mice have failed when trialled in humans, and one potential reason for the repeated failure is that the Alzheimer’s mouse model is not a close enough match to the human version of the disease.
Now though it might be possible to better model Alzheimer’s in cloned monkeys by knocking out genes that have a similar role in monkeys and humans, such as one that triggers the production of beta-amyloid plaques that clog up Alzheimer’s brains.
There are issues though, says Andrews.
“Not least the cost of keeping primates, and that you’d need to breed many of them for it to be useful. You would then run into ethical problems – you can see why people would object,” he says, for example, the most recent UK assessment on the ethics of primate research, published in 2006, found “a strong scientific case for the carefully regulated use of non-human primates where there are no other means to address clearly defined questions of particular importance”.
In 2013, the US announced plans to retire all but 50 of its 360 research chimpanzees and phase out the majority of research on these animals that it previously supported, and it is also reviewing its policies on other related animals. In contrast though China plans to accelerate medical therapies by studying cloned and genetically engineered monkeys.
At a conference in May 2016, Mu-Ming Pau of ION unveiled the world’s first genetically engineered monkey with a version of Parkinson’s disease and presented ambitious plans to expand the use of monkeys to study neurodegenerative disease, and he made the same case in New Scientist shortly after, arguing that because monkeys are so closely related to us and have advanced minds and complex social networks, they will tell us much more about diseases of the brain than mice ever could.
So for now at least it looks like animal research is sticking around, like it or not, but one bright spot for campaigners who are looking to get it banned is Humans on Chips, a an emerging technology that lets scientists model the biochemical and biological behaviours of the human body.