Here’s the cautionary tale you didn’t know you needed: cloning the same mouse in perpetuity will produce horrific affronts to mammalian biology.
A team of researchers in Japan discovered this firsthand. In a stunning experiment lasting two decades, they cloned a female mouse, and then cloned its clones, for 58 successive generations. But over 1,200 clones later, the experiment stopped, because by that last generation the mice kept dying immediately after being born, despite displaying no outward physical abnormalities.
The findings, published in a new study in the journal Nature Communications, suggest there’s a hard limit to duplicating mammals. And to scientists hoping for “infinite” cloning, this came as a major let down.
“We had believed that we could create an infinite number of clones. That is why these results are so disappointing,” study senior author Teruhiko Wakayama, of the University of Yamanashi, told Reuters.
“At this point, we have no ideas for overcoming this limitation. I believe we need to develop a new method that fundamentally improves nuclear transfer technology,” he added, referring to leading technique for animal cloning.
At first, there didn’t seem to be much of a catch to “recloning,” as the practice is known. Between 2005 to 2013, the researchers recloned the mice for 25 generations and found that the clones were largely healthy. At the time, Wakayama said, they concluded that recloning could likely continue “indefinitely.”
As the experiment continued, however, the clones began showing signs of trouble. Starting with the 27th generation, they became less fertile as they gave birth to smaller litters, and they also had larger placentas. All the while, more and more of them kept dying. By the 57th generation, less than one percent of the clones survived. By the 58th generation, all of the recloned mice died the day after being born, their precise cause of death unknown.
Perfect clones, it turns out, aren’t perfect clones. Sequencing their DNA throughout the generations revealed that they were accruing small mutations over time that snowballed into larger ones, even though the clones were superficially identical. In some cases, the clones even lost an entire copy of their X chromosome.
“It was once believed that clones were identical to the original, but it has become clear through this study that mutations occur at a rate three times higher than in offspring born through natural mating,” Wakayama said.
What does ruthlessly cloning the same mouse tell us about our biology? Many organisms like certain plants and bacteria reproduce by essentially cloning themselves. But us mammals, which reproduce sexually, apparently can’t pull this off without paying a price. It seems we need an injection of genetic diversity to keep the whole blood line from crumbling down.
“In cloning, all genes are passed on to the next generation, meaning that all defective genes are also passed on,” Wakayama said. “Because all these mutations continue to accumulate, mammals cannot sustain their species through cloning,” he added.
This apparent recloning limit could put a dent in a number of sci-fi sounding but already burgeoning ambitions. Livestock are being cloned to produce a perfect herd of farmable animals, such as cows that produce more milk. There’s an entire industry dedicated to boutique animal cloning, with celebrities paying top dollar to clone their dead pets.
The findings also don’t bode well for a number of “de-extinction” initiatives, which hope to resurrect long dead species in part by cloning, or bail out endangered ones through the same intervention.
More on biology: Scientists Bring Mouse Brains Back to Life After “Cryosleep” Deep Freeze
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