A 20-Year Mouse Cloning Experiment Reached a Grim Breaking Point
- Japanese scientists conducted a 20-year mouse cloning experiment, resulting in disastrous consequences after 27 generations.
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Once in a blue moon, an animal cloning story appears in the headlines before disappearing back into the ether. Cloning is one of the most novel feats in biotech, so one wonders why these stories don’t seem to gain much traction. Unintentionally, Japanese scientists have discovered why: cloning from clones may lead to disastrous consequences.
Over twenty years ago, scientists from the University of Yamanashi cloned one female mouse
. From there, they kept cloning from that original clone. While the experiment initially showed some promise, each new generation came with unintended consequences. By the time they got to the 20th generation of clones and beyond, the mice suffered from increasingly dangerous—and ultimately deadly—health
effects.
Fatal Facsimiles
Researchers found that mice cloned from previous clones began to degenerate after 27 generations.
©Max Acronym/Shutterstock.com
The project, led by Teruhiko Wakayama and his team of researchers at the University of Yamanashi, began over 20 years ago. It started simply enough: they cloned a mouse. Then they cloned a clone from a clone, and so on. After 58 generations and around 1,200 mice, the team learned just how disastrous making copies of copies can be. With each successive generation, more mutations appeared in the mice’s DNA.
Everything was on the up and up until the 27th generation . Each subsequent generation developed significant structural issues and, eventually, lethal mutations in its DNA. The 58th and final generation of cloned clones died within 24 hours of being born. According to the researchers, the mice’s oocytes could be fertilized, but most embryos degenerated.
This suggests that mammals rely on two-parent reproduction, rather than self-reproduction, to eliminate genetic anomalies. It also indicates a problem with the epigenetic programming of a cell. When scientists clone a mouse or a sheep, they use adult cells and revert them to embryos. The problem, however, is that each cell’s specific set of instructions needs to be completely reset to revert to that embryonic state. The researchers at the University of Yamanashi believe the problems they encountered when cloning successive generations were not due to DNA degradation. Instead, the issues stemmed from the way they were reprogramming the cells intended for cloning.
Further Insights
Some of the cloned mice lived just fine. Others were even successfully mated with non-cloned mice. However, the process eventually broke down. While the researchers were not sure exactly what caused the epigenetic breakdown, they suspected it involved Trichostatin A, an organic compound that enhances nuclear reprogramming.
Creatures like velvet worms and aphids can reproduce through parthenogenesis, but it remains unclear whether a similar process could work for cloning mammals. At the very least, according to the researchers , this experiment reaffirms “the evolutionary inevitability that sexual reproduction is indispensable for the long-term survival of mammalian species.”
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