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from Motherboard Website
Chinese
Academy of Sciences the Chinese Academy of Sciences used the same cloning method used to create Dolly the sheep to clone two long-tailed macaques for the first time.
These monkeys are the
first primates to be cloned using a technique called somatic cell
nuclear transfer (SCNT), the same method that was used to create
the first animal clone,
Dolly the sheep, over 20 years ago.
Primates have been notoriously resistant to cloning efforts over the past two decades due to the unique complexity of their cellular machinery.
The birth of these macaque clones is a proof of concept that could lead to the cloning of other primates, and perhaps, eventually, humans.
the second SCNT primate clone. Image: Qiang Sun, et al. Chinese Academy of Sciences
In 1996, Dolly the sheep became the first animal to successfully be cloned using this method.
In the past two decades, 23 other species have also been cloned using SCNT, including cows, horses, cats, and pigs.
The success of these experiments prompted fears that humanity was on the cusp of designer babies or the production of human clones for harvesting organs, which prompted President Clinton to issue a ban on the use of federal funds for human cloning research in 1997.
As it turned out, however, making the jump from cloning sheep to cloning primates proved far more difficult than anticipated.
The first primate clone was technically a rhesus monkey named Tetra born in 1999.
Tetra was produced by a process called embryo splitting, which is similar to how twins are born naturally. It involves dividing a two-cell embryo into two separate, identical embryos and allowing them to develop on their own.
While this process is well documented and relatively straight forward, it limits the number of genetically identical offspring that can be produced from an embryo to a maximum of four.
To get larger populations of clones, SCNT is necessary since it can use the nuclei from any number of adult cells of the animal to be cloned.
One of the main reasons why primates have been so resistant to SCNT cloning has to do with the way primate egg cells are structured. In unfertilized primate egg cells, proteins called mitotic spindles are clustered close to the cell's chromosomes, unlike most other mammalian embryos, where the spindles are spread around the cell.
These spindles are responsible for guiding chromosomes to the right place during the cell division process that eventually results in a live primate.
Over the past decade, however, researchers have found that when the nucleus - and hence all the chromosomes - of a primate egg cell is removed, this can also damage or rearrange the mitotic spindles.
This means that when a new nucleus is injected into the embryo, the spindles are unable to guide chromosomes to the correct place during cell division.
So while researchers were able to successfully create primate embryos on a number of occasions, errors during cellular division meant none of these embryos would last more than a few weeks in a primate's womb.
Zhong Zhong and Hua Hua. Image: Qiang Sun, et al. Chinese Academy of Sciences
As detailed today in Cell (Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer), Qiang Sun and his colleagues at the Chinese Academy of Sciences surmounted this difficulty by optimizing the nuclear transfer process to minimize damage to the primate egg cell and adding some human RNA into the clone egg cell.
This RNA essentially worked to turn on and off the genes that would otherwise inhibit the development of the primate embryo. It is, in Sun's words, "programming" the nucleus to express the genes that are required for embryo development.
Still, it took a while to get the programming right.
According to the researchers, they tried using the nucleus from adult cells for clones in 42 monkeys, 22 of which became pregnant. Of these pregnancies, only two yielded live births, but both of the babies died a few hours after birth.
The researchers had better luck when they used the nucleus from connective tissue cells derived from an aborted monkey fetus, however.
These clone cells were injected into 21 female macaques and resulted in four pregnancies. Of these, two pregnancies were aborted within two months, but the other two pregnancies resulted in the birth of two healthy, genetically identical long-tailed macaques.
According to the researchers, the babies are still in excellent health almost two months later.
According to Sun, the same method used to clone the macaques could be applied to humans, but he said it's highly unlikely that the government would allow its extension to human cells (besides the ethical controversy, the method also had a low success rates among the primate test subjects).
Still, the SCNT method is a promising candidate for producing large populations of genetically identical primates, which Sun and his colleagues anticipate will be used to study human diseases while "greatly reducing" the number of animal subjects required to perform the studies.
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