Good-bye dolly
Authors: Inder M. Verma
Journal: Molecular Therapy (2003)

Seldom do major newspapers and television networks flash pictures of, or devote editorials and commentaries to, a sheep. But this was no ordinary sheep: It was Dolly, the first mammal to be cloned from the cells of an adult. A team of scientists at the Roslin Institute in Edinburgh, led by Ian Wilmut, created Dolly from the frozen udder cells of a ewe that had been dead for six years. The scientists painstakingly transplanted nuclei from udder cells into unfertilized sheep eggs whose own nuclei had been removed. The procedure was repeated at least 276 times before Dolly was born on July 5, 1996, a healthy lamb of 14.5 pounds. Filing of the appropriate patent applications delayed the actual announcement of the birth until February 27, 1997, when the journal Nature published the landmark paper entitled, “Viable offspring derived from fetal and adult mammalian cells.”John Gurdon cloned frogs by nuclear transplantation in 1962, but little success had been achieved in other species until Dolly. Now we have cloned cows, pigs, rabbits, goats, mice, and even a calico kitten, but the process remains difficult, cumbersome, and highly inefficient. The best results have been obtained in mice—but it still requires nearly one hundred attempts to get a single cloned mouse. A surprising, but not totally unexpected, observation is that the cloned animals often have serious problems with various organ systems. Dolly was obese, severely arthritic, and was showing signs of premature aging. She was put to sleep on February 14, 2003, to end her suffering from a serious lung infection. However, the particular infection and Dolly's life span were not unusual for a sheep kept in an indoor pen. Dolly otherwise led a good life: She gave birth to six lambs by traditional mating with a ram—and continued to enjoy the celebrity spotlight.Dolly's remains will be given to the National Museum of Scotland and put on display. However, she leaves us with much more than her physical remains: Dolly leaves an important legacy and a continuing controversy. With her birth, the prospect of human cloning could no longer be dismissed as fiction or fantasy. Both the clergy and lawmakers were suddenly confronted with an ethical and political dilemma. Unfortunately, the distinction between therapeutic cloning and reproductive cloning has become confused in this debate. To nearly everyone, from scientists to religious and political leaders, reproductive cloning is unacceptable. Therapeutic cloning on the other hand will generate embryonic stem cells that might be used to generate replacement tissues and organs. Furthermore, deficient or malfunctioning genes might even be repaired by gene transfer approaches. Not surprisingly, given its conservative bent, the Bush administration has declared its complete opposition to all forms of cloning. Congress is deadlocked, with the House of Representatives having approved a bill to ban the use of embryos for either medical research or to make human clones. Critics of the bill hope that there are enough votes to block it in the Senate. With the impasse in Congress, individual states are filing their own bills banning cloning—some carrying penalties of up to ten years in prison and $1 million in fines.An important scientific triumph has become a political quagmire akin to the abortion debate. Clearly, research in the important area of regenerative medicine has already slowed in the U.S. With the present preoccupation with war in Iraq, the issue of therapeutic cloning will likely continue to languish in limbo. Dolly's birth created complex ethical and moral dilemmas that remain unresolved. The promise and prospect of improving human health by cloning technologies is exciting and worth pursuing. This should be the true lasting legacy of Dolly! Seldom do major newspapers and television networks flash pictures of, or devote editorials and commentaries to, a sheep. But this was no ordinary sheep: It was Dolly, the first mammal to be cloned from the cells of an adult. A team of scientists at the Roslin Institute in Edinburgh, led by Ian Wilmut, created Dolly from the frozen udder cells of a ewe that had been dead for six years. The scientists painstakingly transplanted nuclei from udder cells into unfertilized sheep eggs whose own nuclei had been removed. The procedure was repeated at least 276 times before Dolly was born on July 5, 1996, a healthy lamb of 14.5 pounds. Filing of the appropriate patent applications delayed the actual announcement of the birth until February 27, 1997, when the journal Nature published the landmark paper entitled, “Viable offspring derived from fetal and adult mammalian cells.” John Gurdon cloned frogs by nuclear transplantation in 1962, but little success had been achieved in other species until Dolly. Now we have cloned cows, pigs, rabbits, goats, mice, and even a calico kitten, but the process remains difficult, cumbersome, and highly inefficient. The best results have been obtained in mice—but it still requires nearly one hundred attempts to get a single cloned mouse. A surprising, but not totally unexpected, observation is that the cloned animals often have serious problems with various organ systems. Dolly was obese, severely arthritic, and was showing signs of premature aging. She was put to sleep on February 14, 2003, to end her suffering from a serious lung infection. However, the particular infection and Dolly's life span were not unusual for a sheep kept in an indoor pen. Dolly otherwise led a good life: She gave birth to six lambs by traditional mating with a ram—and continued to enjoy the celebrity spotlight. Dolly's remains will be given to the National Museum of Scotland and put on display. However, she leaves us with much more than her physical remains: Dolly leaves an important legacy and a continuing controversy. With her birth, the prospect of human cloning could no longer be dismissed as fiction or fantasy. Both the clergy and lawmakers were suddenly confronted with an ethical and political dilemma. Unfortunately, the distinction between therapeutic cloning and reproductive cloning has become confused in this debate. To nearly everyone, from scientists to religious and political leaders, reproductive cloning is unacceptable. Therapeutic cloning on the other hand will generate embryonic stem cells that might be used to generate replacement tissues and organs. Furthermore, deficient or malfunctioning genes might even be repaired by gene transfer approaches. Not surprisingly, given its conservative bent, the Bush administration has declared its complete opposition to all forms of cloning. Congress is deadlocked, with the House of Representatives having approved a bill to ban the use of embryos for either medical research or to make human clones. Critics of the bill hope that there are enough votes to block it in the Senate. With the impasse in Congress, individual states are filing their own bills banning cloning—some carrying penalties of up to ten years in prison and $1 million in fines. An important scientific triumph has become a political quagmire akin to the abortion debate. Clearly, research in the important area of regenerative medicine has already slowed in the U.S. With the present preoccupation with war in Iraq, the issue of therapeutic cloning will likely continue to languish in limbo. Dolly's birth created complex ethical and moral dilemmas that remain unresolved. The promise and prospect of improving human health by cloning technologies is exciting and worth pursuing. This should be the true lasting legacy of Dolly!