30 Years of Cloned Sheep Dolly: Research and Legacy

At first, no one suspected the wave of astonishment and horror the little lamb would unleash. It was only eight months later, in early 1997, that the publication in the journal Nature caused ripples around the world. The sheep with the number 6LL3 instantly became world-famous and is still regarded as a scientific milestone to this day.

Dolly was the result of 277 attempts, of which only this one succeeded. After 277 attempts and 13 implanted embryos, a viable lamb was finally born, genetically identical to the donor animal. The name "Dolly" was a playful tribute to the American country singer Dolly Parton.

"I remember it well," says Daniela Haluza, an environmental physician at the Medical University of Vienna. "At the time, I was a high school student at the Gymnasium and fascinated by the idea that science could make things possible that had previously seemed unthinkable."

Stem Cell Research as the True Legacy

"Dolly changed our understanding of life," says Haluza. Dolly showed that the nucleus of a skin cell can be returned to a state from which a complete organism can develop. The insight paved the way for further breakthroughs, the researcher adds.

However, Dolly's true legacy lies not in the mass production of identical sheep, but in stem cell research. The cloning success paved the way for Shinya Yamanaka, who in 2006 succeeded in producing so-called induced pluripotent stem cells (iPSCs). Yamanaka later received the Nobel Prize for this work. Haluza emphasizes: "So Dolly's real legacy is not cloning, but the realization of how remarkably flexible our cells are."

Human cloning has, according to the current state of knowledge, not proven to be a realistic scenario. Haluza puts it this way: "It is not human cloning that has changed our future, but the knowledge we gained through Dolly about our cells, and the way of thinking that emerged from it." Dolly herself noticed little of the stir surrounding her creation.

Ethics and Animal Suffering in Focus

Dolly had offspring: a female sheep named Bonnie in 1998, and triplets the following year. "Dolly" herself, however, aged prematurely, suffered from arthritis as well as a lung disease, and had to be euthanized in 2003 at the age of just six. Normally, sheep can live to be about 10 or up to a maximum of 20 years old. Her death gave rise to debates about premature aging in clones that have still not been conclusively resolved to this day.

"Many people still associate Dolly with the idea of human cloning," says animal ethicist Arianna Ferrari from the Austrian Institute of Technology. She warns that for a single healthy cloned dog, numerous "egg cell donors" and surrogates would have to undergo invasive procedures. "This ethical question accompanies every major biomedical innovation, from genome editing with genetic scissors to artificial intelligence – and it is precisely here that Dolly becomes remarkably relevant again."

From Clone to Digital Twin

When the cloned sheep "Dolly" was born, there were still no regulations governing the handling of cloned animals – neither in Scotland nor at the European level. In the meantime, EU Directive 2010/63/EU regulates the handling of laboratory animals, supplemented by national provisions in Germany and other EU states. However, the ethical questions about balancing benefit and animal suffering that "Dolly" raised 30 years ago remain.

Thomas Hildebrandt from the Leibniz Institute for Zoo and Wildlife Research and his team collect genetic material from all over the world, which is stored in cryotanks at -195 degrees Celsius. Such cryopreservation is intended to preserve endangered species for the future. Even more ambitious is the company Colossal Biosciences, which, with financial support and the CRISPR-Cas9 genetic scissors, wants to bring back the mammoth. Such projects exemplify a development in which the creation of copies – biological or digital – has become a central tool of science.

"Because the principle of copying now confronts us constantly," says Haluza. "We are currently working, for example, on a project that is developing a digital twin of the city of Vienna for climate modeling. Of course, that is not the same as biological cloning, but the basic idea is comparable: we create the most precise possible replicas of reality in order to understand it better, predict it, or improve it."