The heirs of Dolly the sheep are enjoying a healthy old age, proving cloned animals can live normal lives and offering reassurance to scientists hoping to use cloned cells in medicine.
Dolly, cloning’s poster child, was born in Scotland in 1996. She died prematurely in 2003, aged six, after developing osteoarthritis and a lung infection, raising concerns that cloned animals may age more quickly than normal offspring.
Now researchers have allayed those fears by reporting that 13 cloned sheep, including four genomic copies of Dolly, are still in good shape at between seven and nine years of age, or the equivalent of 60 to 70 in human years.
“Overall, the results are suggesting that these animals are remarkably healthy,” said Kevin Sinclair of the University of Nottingham, whose team reported their findings in the journal Nature Communications on Tuesday.
It is the first time experts have made such a detailed age-related health assessment of cloned animals, looking at factors such as blood pressure, diabetes risk and joint damage.
While no animals were lame, there were signs of mild osteoarthritis in some sheep and one had moderate disease, which scientists said was to be expected at their age.
Dolly was the first mammal to be cloned from an adult cell, using a process called somatic cell nuclear transfer (SCNT).
This involved taking a sheep egg, removing its DNA and replacing it with DNA from a frozen udder cell of a sheep that died years before. The egg was then zapped with electricity to make it grow like a fertilised embryo. No sperm were involved.
Dolly‘s creation triggered fears of human reproductive cloning, or producing genetic copies of living or dead people, but mainstream scientists have ruled this out as far too dangerous.
Instead, the hope is to develop “therapeutic cloning”, in which cloned cells could be used to regenerate faulty tissue.
Dolly‘s healthy heirs offer encouragement for regenerative medicine, although the SCNT process remains tricky and many would-be clones still fail to develop properly, despite technical advances since Dolly‘s birth.
“This shows cells can undergo complete reprogramming and it’s reassuring to know that cells can be perfectly normal,” Sinclair said. “The challenge going forward is to increase the proportion of cells that undergo this complete reprogamming or better select for that.”
The four sheep cloned using the same genetic material as for Dolly – called Debbie, Denise, Dianna and Daisy – have just had their ninth birthdays and, together with nine other clones, are part of a unique flock based in Nottingham.
Unlike Dolly, who was housed indoors for security reasons, today’s clones live mainly outside, which may be one factor behind their relative health, since sheep kept in barns can be susceptible to infections.
Cloning is already used in some US food production, although not in Europe. But the big hope is to produce human stem cells that could replace damaged tissue in devastating conditions like Parkinson’s disease or spinal cord injuries.
Work on stem-cell medicine has been hobbled in the past by technical challenges as well as ethical issues but it received a boost three years ago when biologists finally created human stem cells using the same process that produced Dolly.
Until then, the most natural source of human stem cells was human embryos left over from IVF treatment, whose use in research is controversial.
Another approach involves adding genes to adult cells to turn back their biological clocks, creating so-called induced pluripotent stem cells that behave like embryonic ones. The long-term safety of these cell has still to be established.