In sci-fi films, cloned humans often appear and suffer identity confusion, or the same individual is repeatedly produced. But real mammals cannot be cloned endlessly like in the movies.
A research team led by Wakayama Teruhiko, a professor at Yamanashi University in Japan, said that after repeatedly cloning mice for 20 years, lethal deoxyribonucleic acid (DNA) mutations accumulated with each generation, making normal births more difficult. The study was published on the 25th in the international journal Nature Communications.
Cloning technology has been used in animal research and for preserving superior traits, but its success rate is low and its long-term stability has not been clear. In earlier work, the team confirmed that cloning mice up to the 25th generation did not cause major health problems in the offspring, but it remained unknown whether cloning beyond that was possible.
The researchers cloned a single mouse and then continued a serial cloning experiment by cloning that clone again. The early cloned mice were relatively healthy and had no major differences in lifespan.
Cloning continued up to the 57th generation. However, after the 27th generation, birth rates began to fall, and DNA mutations accumulated increasingly toward the later generations. In particular, after the 40th generation the birth rate dropped sharply, and in the 57th generation, the individuals born did not survive after birth.
DNA is like a blueprint for living organisms, and if errors repeatedly accumulate in it, normal development becomes difficult. Our bodies correct some of these errors when cells divide, but repeated cloning can allow damage to accumulate without being fully repaired.
In fact, such large-scale mutations were observed more often in later-generation cloned mice and appeared to be related to the drop in birth rates. Abnormal changes in placental structure during cloning were also confirmed across all age groups. Because the placenta supplies nutrients and oxygen to the fetus, structural abnormalities can have a major effect on development and survival.
However, the researchers also found an important clue in this experiment. In the next generation and the grand-offspring produced by later-generation cloned mice mating naturally, placental formation became closer to normal and reproductive capacity improved. This suggests that natural reproduction can help alleviate or resolve genetic problems accumulated during cloning.
The researchers said, "The natural reproduction process plays an important role in reducing or correcting large-scale genetic abnormalities," and noted, "In mammals, it is difficult to maintain healthy individuals indefinitely by repeating cloning alone as in asexual reproduction, and natural reproduction is necessary to preserve genetic stability."
References
Nature Communications (2026), DOI: https://doi.org/10.1038/s41467-026-69765-7