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From cloning to gene-editing: the enduring legacy of Dolly the sheep

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The team at the Roslin Institute was overwhelmed with media requests about Dolly.Credit: Colin McPherson/Corbis/Getty

Taxidermied, locked behind plexiglass and spinning slowly on a wooden dais in the National Museum of Scotland in Edinburgh, UK, the world’s most famous ewe remains a public spectacle three decades after her birth.

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From that moment on 5 July 1996, Dolly the sheep — the first mammal cloned from an adult cell1 — was destined for celebrity, and her imprint on science is still evident in fields such as developmental biology and biotechnology. Dolly’s creation demonstrated that an adult cell can be reprogrammed to an embryonic state, which opened up the possibility of creating stem cells from adult cells. Ten years on, in 2006, details of the first such induced pluripotent stem cells were published2. The first therapies made from these cells were conditionally approved this year in Japan.

Reproductive cloning is now being used in agriculture to generate gene-edited cattle with no horns and pigs with organs that might be suitable for transplantation into humans. Moreover, an industry has sprung up to create copies of cherished pets, show animals and sport horses.

But in one important respect, Dolly’s legacy is not that anticipated in the frantic weeks after news of her birth became public in 1997. From the start, much of the world’s media portrayed Dolly as a step towards the imminent creation of cloned humans. No such development has materialized.

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First and foremost, myriad ethical questions would surround cloning a human, not to mention formidable technical obstacles. The nuclear transfer technique that made Dolly was difficult to perform successfully in primates; monkeys would not be cloned using this method until 20183. The success rate is too low to consider the method in humans, and the risk of abnormalities resulting from the process is too high.

However, other advances in reproductive technology have been arriving at breakneck speed. Stem-cell technology, spurred by Dolly’s birth, has led to the creation of models mimicking the human embryo, and of mouse eggs and sperm from stem cells. Researchers have also developed techniques to replace faulty mitochondria in human embryos, and are engineering increasingly sophisticated artificial wombs. Last month brought a fresh wave of excitement, and worry, about the potential use of advanced gene-editing methods on embryos to create heritable genetic changes4,5.

Past imperfect

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