A two-decade study into cloning has revealed a fundamental flaw in the technology, demonstrating that repeated duplication leads to an accumulation of fatal genetic mutations. Researchers in Japan generated 1,206 cloned laboratory mice from a single female donor between 2005 and 2025.
Initially, no outward signs of trouble were observed across the first 25 generations. However, genetic mutations subsequently began to pile up, ultimately proving fatal. The 58th generation of clones, despite appearing physically normal, died within days of birth due to these accumulated genetic mutations.
This extensive research directly contradicts the long-held notion that clones are identical copies of their original donor and disproves the idea that current cloning technology could be sustained indefinitely without adverse effects. Developmental biologist Teruhiko Wakayama of the University of Yamanashi, senior author of the research published earlier this year in the journal Nature Communications, said: 'No one has ever continued re-cloning for this long before. As a result, this is the first time we've discovered that repeated re-cloning eventually reaches its limits.'
'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. 'Because all these mutations continue to accumulate, mammals cannot sustain their species through cloning. This study has revealed one of the reasons why mammals, unlike plants and lower animals, cannot maintain their species through cloning.'
The researchers sequenced the genomes of 10 clones from various generations and found that serial cloning produced an effect akin to duplicating a picture using a copying machine. With each copy, quality deteriorates. The study results pointed to the importance of sexual reproduction in countering deleterious genetic mutations in mammals. The researchers gauged the fertility of the clones by mating them with ordinary male mice. Up to the 20th generation, they gave birth to about 10 babies per litter, but eventually the clones began having smaller litters, reflecting the effects of accumulating mutations.
'We had believed that we could create an infinite number of clones. That is why these results are so disappointing. 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,' Wakayama said.
