Japanese Scientists Clone Mammals for 58 Generations Before Genetic Collapse
A decades-long experiment in Japan has demonstrated both the potential and the limits of cloning technology, as researchers successfully replicated a single mouse across 58 consecutive generations—only to see the lineage ultimately fail when the final generation could not survive beyond birth.
The study, conducted over 20 years and published this week in Nature Communications, was led by scientists at the University of Yamanashi. It marks the longest continuous cloning of a mammal ever achieved. However, the 58th generation revealed a critical breaking point, as none of the cloned offspring lived past their first day.
The project began in 2005 under the direction of Professors Sayaka Wakayama and Teruhiko Wakayama, using the same somatic cell nuclear transfer technique that was used to clone Dolly the sheep. In its early phases, the experiment progressed with remarkable success: cloned mice were born healthy and genetically identical to the original, and success rates even improved over time. To help maintain genetic stability, researchers introduced a chemical compound called trichostatin A, intended to reduce errors in genomic reprogramming.
But after roughly 25 generations, signs of decline began to emerge. Researchers observed an increasing loss of the X chromosome, along with a steady buildup of genetic mutations—both microscopic and structural—that nearly doubled with each successive generation. By the time the 58th generation was produced, the genetic material had degraded to the point where it could no longer sustain normal life.
The findings provide the first experimental confirmation of “Muller’s Ratchet,” a theory suggesting that organisms reproducing without genetic mixing gradually accumulate harmful mutations until eventual genetic failure. “Our results clearly align with the principle of Muller’s Ratchet,” the researchers wrote. “Without sexual reproduction, the accumulation of genetic errors is a finite mathematical process.”
At the same time, the researchers identified a crucial insight. In a parallel experiment, when cloned mice from later generations were bred with non-cloned mice, their offspring—and subsequent generations—were healthy and fertile, with the previously observed defects largely disappearing. In effect, natural reproduction was able to “reset” the genetic system.
The study carries significant implications for efforts to preserve endangered species through cloning. While scientists have hoped that cloning could sustain rare animal populations, the findings indicate that such methods cannot fully replace natural reproduction over the long term.
“The results confirm that natural reproduction is an inseparable component of the long-term survival of mammals,” the researchers concluded. “Cloning may support temporary genetic preservation, but it can never serve as a true substitute for natural reproduction.”
{Matzav.com}