Since Dolly the sheep was cloned in 1996, researchers have been unable to keep re-cloning animals for more than three generations without genetic abnormalities building up to a point where the clonal line fails.
The Japanese scientists, led by Teruhiko Wakayama of the Riken Center for Developmental Biology, developed a new cloning technique that was so successful that they were able to produce 26 generations of clones from a single mouse over seven years- a total of 598 mice that are genetic copies of one original donor mouse.
Wakayama’s team used a technique called somatic cell nuclear transfer (SCNT), which is the standard method for cloning animals, and added chemicals including a histone deacetylase inhibitor to prevent genetic degradation over time.
In SCNT, a cell’s nucleus, which contains the genetic information of the donor animal, is transplanted into the egg of that has had its own nucleus removed. The fertilized egg is implanted into a surrogate animal, which gives birth to the clone animal. The cycle continues with the cloned animal, which becomes the donor for another cell nucleus.
In standard SCNT, genetic abnormalities build up over successive generations of clones to a point where a viable animal can no longer be created. The researchers found that adding a chemical inhibitor for the enzyme histone deacetylase, which helps tightly wrap DNA into coils and can alter gene expression, kept the DNA structure from degrading over successive reproductions.
Unlike cloned mice that result from successive generations of standard SCNT, the cloned mice in Wakayam’s study had normal biological features, like normal longevity and reproductive abilities. Genetic analysis showed minor abnormalities like an enlarged placenta, but those abnormalities did not increase or decrease over successive generations of re-cloning animals.
Wakayama’s technique allows successful animal cloning to occur for many generations, showing that “repeated iterative re-cloning” is possible.
“I want to say we should be able to continue this forever. We will continue our study until we see the end of it,” he said.
This is a breakthrough that could address the major concern of anti-cloning activists, which is that cloning animals makes them more likely to suffer than normally bred animals. It has obvious appeal to farmers who want to reproduce prize animals for high-quality meat, or wealthy people who want to keep genetic replicas of their favorite pets alive indefinitely.
“By applying our study, mass reproduction of prized animals should become possible even after the original animals die,” said Wakayama.
Repeated iterative re-cloning could also help sustain living specimens of endangered species, long after the original donor animal dies. Re-cloning animals could be useful for conservation, though it does nothing to promote genetic diversity- the long-term success of a species depends on a wide variety of genetic traits that can mix over generations, allowing the species to survive threats that could wipe out a homogenous population with a specific genetic vulnerability.
Are we any closer to cloning humans? Wakayama’s method deals with some of the technical risks of cloning animals, but it changes nothing about the ethical quandaries of “playing God” with normal reproduction. While a leading British scientist expects the widespread existence of cloning humans within 50 years, there is no way it will happen without enormous public controversy.
In the meantime, cloning animals is much easier than it used to be.