BioWorld International Correspondent
LONDON - Obituary: Dolly the Sheep, July, 5, 1996 - Feb. 14, 2003.
The world's most famous sheep, Dolly - the first clone to be created from an adult cell - died Friday at age 6 and a half. She was put down after vets at the Roslin Institute in Edinburgh, Scotland, where she was born and lived, found she was suffering from a progressive lung disease.
The Roslin Institute said that while sheep can live to 11 or 12 years old, lung infections are common in animals that, like Dolly, have lived indoors.
After a post-mortem, Dolly is to be stuffed and exhibited in the National Museum of Scotland in Edinburgh. There she will join her cloned predecessor Morag, born at Roslin a year earlier from an embryo-derived cell.
Simon Best, chairman of the BioIndustry Association in Scotland, said Dolly would continue to be an important scientific landmark. "While we are not certain why Dolly has sadly died, we can be sure her creation has opened up enormously important new areas of medicine and agriculture."
Dolly caused a storm of global controversy when her birth was announced in February 1997. Her creation, from an udder cell taken from a 6-year-old ewe, confirmed that adult cells contain all the genetic information needed to produce a complete organism and raised the specter that humans could be cloned. While Dolly was invited to appear on chat shows, a fierce debate raged on the ethics of cloning and how it should be regulated.
Dolly was apparently fit and healthy, and produced six healthy offspring through conventional pregnancies.
However, in 1999 it was reported that cells in Dolly's body had started to show wear more typical of an older animal. Then, just over a year ago, on Jan. 4, 2002, the Roslin Institute announced Dolly was suffering from arthritis in her left hind leg. That raised the question that because she was cloned from a cell taken from a 6-year-old animal, Dolly was prematurely aging. Ian Wilmut, head of the team that cloned Dolly, said it was not possible to know if the arthritis was in any way the result of her being a clone. She was treated with anti-inflammatory drugs.
PPL Therapeutics plc, of Edinburgh, which is using the cloning technology to generate transgenic animals that produce therapeutic proteins in their milk, said there were no commercial implications of Dolly's arthritis for its programs. While not wanting to breed animals with health problems, the company is not interested in the founder animals, but in using them to create offspring with the desired genetic profile.
PPL has gone on to use the cell nuclear replacement technology that produced Dolly to generate a number of other clones, including cattle and pigs. Last August it announced the birth of the first double-gene knockout piglets, as part its xenotransplantation program. The four piglets do not have a copy of the alpha 1,3 galatosyl transferase gene. That gene codes for a sugar that the human immune system recognizes as foreign, and would trigger the hyperacute rejection of transplanted organs or cells. The xenotransplant program is now up for sale and PPL recently announced it is in exclusive negotiations with U.S. investors to buy those assets.
Although other groups have used cell nuclear transfer, or variants thereof, to clone many other animals, the technology is far from robust. It took more than 250 nuclear transfer procedures to produce Dolly, and success rates remain low in all species. According to the Roslin Institute only about 1 percent of embryos lead to live births.
Commenting on Dolly's death, Carl Feldbaum, president of the Biotechnology Industry Organization in Washington, said, "The announcement in February 1997 of the birth of Dolly clearly captured the imagination of the world. While we cannot yet be sure why Dolly died, we can be sure that she opened up significant new areas of medical research and veterinary science that could be of great benefit in the future."