Press "Enter" to skip to content

Scientists have cloned monkeys and it could help treat cancer

Zhong Zhong and Hua Hua, first cloned monkeys

Zhong Zhong and Hua Hua, not one of a kind

Qiang Sun and Mu-ming Poo, Chinese Academy of Sciences

MEET Zhong Zhong and Hua Hua, the world’s first monkeys cloned using the technique that gave us Dolly the sheep.

The female long-tailed macaques represent a technical milestone. It should make it possible to create customisable and genetically uniform populations of monkeys, which could speed up treatments for diseases such as Parkinson’s, Alzheimer’s and cancer. But the breakthrough will inevitably raise fears that human cloning is closer than ever.

The monkeys hold such huge potential because they all inherit exactly the same genetic material, says the Chinese team that cloned them.

Advertisement

This would enable scientists to tweak 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. It could accelerate the hunt for genes and processes that go wrong in these diseases, and ways to correct them, the team says.

Although 23 species of mammal have been cloned since Dolly – including pigs, cats, dogs, rats and cattle – monkeys have, until now, proved resistant to the technique (see “A brief history of mammal cloning”).

Hua-Hua-CREDIT-Qiang-Sun-and-Mu-ming-Poo,-Chinese-Academy-of-Sciences-(2)

Qiang Sun and Mu-ming Poo, Chinese Academy of Sciences

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, Qiang Sun at the Chinese Academy of Sciences Institute of Neuroscience in Shanghai and his colleagues 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.

“This could accelerate the hunt for genes that go wrong in disease, and ways to correct them”

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 (see diagram).

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 – 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.

Zhong-Zhong-CREDIT-Qiang-Sun-and-Mu-ming-Poo,-Chinese-Academy-of-Sciences

Qiang Sun and Mu-ming Poo, Chinese Academy of Sciences

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. The pair were the only live births from six pregnancies (Cell, DOI: 10.1016/j.cell.2018.01.020). Dolly was the only success from 277 implanted embryos.

Monkey_clone270118lato

Human clones

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. “That appears to be the case here as well,” he says.

This technical hurdle may put to rest fears often expressed after cloning successes: that it could lead to a Never Let Me Go scenario – the science fiction novel in which human clones are created for spare organs.

Post-Dolly, the Raëlian movement in California claimed it had cloned human babies. It set up a firm called Clonaid but its efforts were dismissed as a hoax.

“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.

Andrews says this concept has merit, especially given the long-standing difficulties of trying to mimic complex diseases like Alzheimer’s and Parkinson’s in mice.

To date, all therapies that have treated Alzheimer’s-like symptoms in mice have failed when trialled in humans. One potential reason for the repeated failure is that the Alzheimer’s mouse model is not a close enough replica of the human version of the disease.

“It may put to rest fears that it could lead to a Never Let Me Go scenario of creating human clones for organs”

Now 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.”

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. It is also reviewing its policies on other related animals.

In contrast, China plans to accelerate medical therapies by studying cloned and genetically engineered monkeys.

At a conference in May 2016, Mu-ming Poo of the Institute of Neuroscience in Shanghai 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.

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.

A brief history of mammal cloning

1996 Dolly the sheep is born using a technique called somatic cell nuclear transfer, in which the DNA from one animal is placed into an empty donor egg. The two components are stimulated with an electric current and given nutrients that stimulate them to grow into an embryo.

2000 First monkey cloned, but not using the Dolly technique. Instead, a monkey embryo is split to create more embryos. This method can only be used to create a maximum of four clones.

2001 The first attempt at using cloning to boost an endangered species fails after a cloned bison called Noah dies soon after birth.

2001 The first cloned cat arrives, called “Cc”, short for “carbon copy”.

2004 The first cloned monkey embryos are created using the Dolly technique, but none survive long enough to be implanted.

2004 South Korean scientist, Woo Suk Hwang, claims to have obtained embryonic stem cells from cloned human embryos.

2005 Snuppy, the world’s first cloned dog is unveiled, also by Woo Suk Hwang.

2006 Woo Suk Hwang’s claims of cloning human embryos are found to have been fraudulent.

2013 Embryonic stem cells are extracted from cloned human embryos by Shoukhrat Mitalipov at the Oregon Regional Primate Research Center.

2016 Mu-ming Poo at the Institute of Neuroscience in Shanghai, China, unveils the world’s first genetically engineered monkey with a version of Parkinson’s disease.

2018 The world’s first cloned monkeys using the Dolly technique are unveiled in China. They are called Zhong Zhong and Hua Hua.

This article appeared in print under the headline “Say hello to cloned monkeys”

Leader: “What does China’s monkey breakthrough mean for human cloning?

More on these topics:

Read More

Be First to Comment

Leave a Reply

Your email address will not be published. Required fields are marked *

%d bloggers like this: