Limitations of Mammalian Cloning Revealed in Long-Term Study

A groundbreaking study conducted by researchers at the University of Yamanashi in Japan has revealed significant limitations in the cloning of mammals, specifically mice. Over a span of 20 years, the team cloned a female mouse and subsequently recloned its descendants for 58 generations. The results indicated that while initial generations appeared healthy, by the 58th generation, all clones died shortly after birth, raising concerns about the viability of long-term cloning practices.

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The study, published in *Nature Communications*, found that the clones accumulated mutations at a rate three times higher than those born through natural reproduction. This accumulation of genetic defects led to severe health issues, including reduced fertility and increased mortality rates. By the 27th generation, the clones began to show significant problems, with less than one percent surviving by the 57th generation. Ultimately, all clones in the 58th generation died within a day of birth, despite no visible physical abnormalities.

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Teruhiko Wakayama, the study's senior author, noted, “We had believed that we could create an infinite number of clones. That is why these results are so disappointing.” The findings suggest that mammals require genetic diversity to maintain healthy populations, as the cloning process perpetuates defective genes alongside healthy ones.

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The study's researchers sequenced the genomes of clones from various generations, revealing an average of over 70 mutations per generation. The mutations were particularly pronounced in the later generations, with some clones losing entire copies of their X chromosomes. The researchers hypothesized that the adult body cells used for cloning may inherently possess more mutations than sperm or egg cells, which are better protected against genetic defects during natural reproduction.

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Wakayama speculated that the nuclear transfer process itself could contribute to the mutation rate, stating, “I believe that if we could develop a gentler method of nuclear transfer, we might be able to reduce the mutation rate in cloned embryos.” However, he acknowledged that no solutions have been identified to date.

New Scientist

While the findings highlight the risks associated with cloning, some experts, such as Shoukhrat Mitalipov from Oregon Health & Science University, argue that the observed mutation rates may reflect the genomic state of the donor cells rather than the cloning process itself. Mitalipov emphasized the importance of careful selection and screening of donor cells to mitigate potential risks in cloning applications, particularly in medical contexts.

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The implications of this study extend beyond laboratory settings, affecting industries involved in livestock cloning and conservation efforts aimed at de-extinction or preserving endangered species. The findings suggest that the pursuit of cloning for these purposes may need to be reevaluated due to the inherent genetic limitations identified in the study.

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• “We had believed that we could create an infinite number of clones. That is why these results are so disappointing,” — Teruhiko Wakayama, Senior Author

Futurism

• “In cloning, all genes are passed on to the next generation, meaning that all defective genes are also passed on,” — Teruhiko Wakayama, Senior Author

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• “Unfortunately, however, while clones were once thought to be identical to the original, it has become clear that this is not the case, suggesting that there may be issues with their use,” — Teruhiko Wakayama, Senior Author

New Scientist

The study underscores the complexities of cloning technology and the necessity for further research to address the challenges posed by genetic mutations in cloned mammals.

New Scientist