Dolly the sheep's scientific and ethical legacy

The team of scientists responsible for the birth of Dolly the sheep believed their achievement would help transform the fight against disease. Opponents warned human cloning would inevitably follow, giving rise to an array of ethical and moral dilemmas. Have any of the prophecies come close to realisation? 

David Tod, Investment Manager, Rathbones

At the centre of the Science Zone in Edinburgh’s National Museum, mounted on a hay-strewn plinth and protected by a glass case, stand the preserved remains of the world’s most famous sheep. Dolly was a result of experiments to enhance methods for producing genetically modified livestock, but it is her potential impact on the human race that has generated countless headlines and fierce debate in the 20 years since she was first revealed to the public.

Scientists had been exploring the mysteries of cloning for almost a hundred years when Ian Wilmut and his team at the University of Edinburgh’s Roslin Institute made their breakthrough. As far back as 1885, by virtue of little more than shaking a sea-urchin embryo, biologist Hans Driesch had shown separate cells could develop into complete organisms. In 1902, as part of work that would ultimately win him a Nobel Prize, embryologist Hans Spemann had grown two salamanders from an embryo split with a noose fashioned from a strand of baby hair.

Yet these and subsequent triumphs went all but unrecognised by the non-scientific community. It was only post-Dolly that the sort of ideas once confined to the pages of pulp magazines suddenly entered the mainstream, bringing with them dreams of extraordinary advances, warnings of dire consequences and a morass of new moral, ethical and philosophical quandaries.

Dolly was the first mammal cloned from an adult cell. The significance of this feat was that it proved a cell taken from a specific part of the body — in this instance a mammary gland — could recreate a whole individual. When Wilmut and his colleagues announced their accomplishment in February 1997, seven months after Dolly was born, the future appeared to have arrived.

The ensuing flood of predictions mixed the optimistic with the ominous. Novel means of preventing disease would emerge. “Designer babies” and immortality alike would soon be within reach. The dead would be resurrected — or at least recreated. Humans would be cloned. Whether desirable or dystopian, favourable or Frankensteinian, the possibilities seemed boundless. As pioneering biologist Alan Trounson remarked in recalling the moment Wilmut told him about Dolly: “I was stunned. It changed everything.”

But did it? Today, two decades on, neither the hopes nor the fears that greeted Dolly’s unveiling have been fully realised. As Scientific American observed on the 20th anniversary of her birth: “Cloning has had a bigger impact on science than many expected... but a smaller one on human life.”

In considering the first part of this assessment it is important to remember that Dolly embodied an advance most experts had thought impossible. The method used, known as somatic cell nuclear transfer, had been employed several times previously but never with an adult cell. Dolly therefore undoubtedly represented — to use one of academia’s most well-known tropes — a paradigm shift.

In due course Wilmut and his team coined the phrase “therapeutic cloning” to describe a process in which a cloned embryo is created purely for the production of stem cells, which are then harvested and used to help better understand and treat diseases. As is practically inevitable in any field of research, this approach has since been largely superseded. Now it is easier to make what are called induced pluripotent stem (iPS) cells by “reprogramming” adult skin cells — a method untainted by the need to destroy human embryos during the harvesting phase.

Although one recent appraisal of Dolly’s legacy dismissed therapeutic cloning as “passé”, the further march of progress in no way diminishes Wilmut’s achievement. Every scientist accepts his own contribution is likely to serve only as a stepping-stone to something superior. Shinya Yamanaka, who won a Nobel Prize for his research into iPS cells, has credited Dolly as his principal motivation. As Newton once said: “If I have seen further it is by standing on the shoulders of giants.”

Meanwhile, the cloning of humans remains the stuff of sci-fi. This is in no small part due to the enduring inefficiency of nuclear transfer and the consequent risk of abnormalities. Given that there were 277 would-be Dollies and only one survived, the mere thought of trying to apply such unreliable techniques to humans is at best inadvisable and at worst unconscionable.

Several claims of success have surfaced, but all have conspicuously lacked credibility. US-based “reproductive specialist” Panayiotis Zavos has provided no meaningful evidence to support his repeated boasts of cloning human embryos and transferring them to wombs. South Korean biotechnologist Woo-Suk Hwang, formerly a professor at Seoul University, was found to have fabricated numerous supposedly groundbreaking experiments and now, having earned a suspended two-year jail sentence for embezzlement, oversees a company that clones pet dogs at $100,000 a time. The Raëlians, a quasi-religious movement founded on the belief that extraterrestrials were responsible for life on Earth, say that in 2002 they cloned a baby girl, Eve, from a 31-year-old American woman. She has yet to come forward to seize her place in history.

Wilmut, now an emeritus professor, never envisaged Dolly as a milestone on the road to human cloning, once rejecting the concept as “repugnant”. As the controversy surrounding their work intensified, he and his colleagues determinedly nudged the narrative away from the nightmarish realms of Mary Shelley and HG Wells and back towards what had always been their intention: improving animal welfare and human health. Now, as well as arguing for both a modern-day “ark” containing tissues from endangered species and a “library” of cells compatible with as many human immune systems as possible, he pleads not just for caution but for patience.

Interviewed in 2008, the year he received a knighthood for services to science, Wilmut was asked how the Dolly story had shaped his thinking. “Well,” he said, “I guess maybe it made the world seem a bit greyer. You would think there are merely positive benefits to come from something new like this, but you also see there are problems as well. And so there’s a sort of grey area in the middle, where things aren’t as rosy and as satisfactory as you might like.”

In this reply, with its combination of undue modesty and near-regret, we perhaps find the dilemma at the heart of so many great scientific breakthroughs. Einstein expressed a similar sentiment when, reflecting on his role in the development of the atomic bomb, he lamented: “The unleashed power of the atom has changed everything save our modes of thinking, and we thus drift toward unparalleled catastrophe.” Even when it comes to the most famous sheep in the world, nothing is ever truly black and white.

Getting to know ewe

Dolly the sheep was born on 5 July 1996. A Finn Dorset, she had three “mothers”: the first provided the egg, the second provided the DNA, and the third carried the cloned embryo.

Having been grown from a cell taken from a mammary gland, she was named in honour of famously large-chested country-and-western singer Dolly Parton. “It wasn’t meant to be disrespectful,” said project leader Ian Wilmut. “Science and its presentation can sometimes look terribly serious. It made us look human.”

She was created using a technique known as somatic cell nuclear transfer. The cell nucleus was taken from an adult cell and transferred into an unfertilised egg cell whose own nucleus had been removed. An electric shock was used to stimulate and divide the hybrid cell, which was then implanted into a surrogate mother.

Dolly spent her life at the University of Edinburgh’s Roslin Institute, where she was encouraged to breed and produced six lambs. She died on 14 February 2003 after suffering from lung disease and severe arthritis.

There were fears that the comparative brevity of her life — Finn Dorsets usually live twice as long — may have been a corollary of the cloning process. However, recent research into the long-term health effects of cloning found no grounds to support this suggestion.