CLONING MILESTONES CLONING MILESTONES 1938: German embryologist Hans Spemann proposes an experiment to remove the nucleus from an unfertilized egg and replace it with the nucleus from a specialized cell such as skin or liver, a cloning technique proven years later. 1984: Danish embryologist Steen Willadsen clones a lamb from a developing sheep embryo cell. His experiment is repeated by other scientists who clone a variety of animals. 1996: Ian Wilmut and his team at the Roslin Institute in Scotland clone the world's first sheep from adult cells, using the mammary cells of a ewe. The lamb born on July 5 is named Dolly after curvaceous country singer Dolly Parton. 1998: Human embryonic stem cells are isolated and cultured by researchers at the University of Wisconsin. 2001: Scientists at Advanced Cell Technology in Massachusetts announce they have cloned human embryos for the first time, but the embryos die after a few cell divisions. 2001: President Bush limits federally funded research on human embryonic stem cells to lines, or colonies, of cells that have already been created. 2002: California becomes the first state to approve a law legalizing the cloning of embryos to produce stem cells for scientific and medical purposes. 2003: Dolly is euthanized in Scotland at age 6 after being diagnosed with lung disease. She had given birth to four lambs during her lifetime. 2004: Researchers at Seoul National University led by Hwang Woo Suk claim to be the first to clone a human embryo and generate cell lines from them. April 2005: The South Korean scientists clone a dog, who was named Snuppy. Dogs are considered particularly difficult to clone because of the complex reproductive biology. May 2005: Hwang's team announces the creation of 11 cloned embryonic stem cell lines. In the United Kingdom, a University of Newcastle upon Tyne team announces in the same month that it has also cloned a human embryo, but did not generate a stem cell line. December 2005: University investigators announce that Hwang's findings on human embryos and stem cells are fraudulent. His team really did clone the dog. June 2006: Hwang's trial for fraud, embezzlement and bioethics breaches begins in Seoul District Court. Sources: Information Please Database, 2006 Pearson Education Inc, all rights reserved.; News @ Nature.com; USA TODAY, Feb. 14, 2004; CNN.com Dolly was world's hello to cloning's possibilities Dolly the sheep, the first mammal cloned from an adult cell, was born 10 years ago Wednesday, a birth met with elation by scientists who see cloning as a potential cure for illnesses and alarm by those who are fearful of a future populated by less-than-human clones. But Ian Wilmut, the scientist whose team at Scotland's Roslin Institute cloned Dolly — born July 5, 1996, and euthanized in 2003 because of lung disease — says the most interesting thing about the past decade is what has not happened. Wilmut, who has been in North America speaking at scientific conferences and promoting his book After Dolly: The Uses and Misuses of Cloning, says scientists have not fully succeeded in cloning human embryos, and it could be decades before it happens. Though scientists have cloned 10 other mammals — cows, goats, pigs, rats, mice, rabbits, cats, dogs, horses and mules — Wilmut says there is a "striking absence of primates." The most accepted explanation is that the molecular machinery of primate eggs is prone to damage during cloning. If that is true, it could be a beacon for scientists, he says. "I see it as, if you like, almost an enlightening thing," he says. "It would indicate the problem that has to be solved." Before 1996, scientists created animal clones from embryonic cells, but Dolly was cloned using an adult cell, a difference that is key in the promise and much of the controversy of the technology. Wilmut's team implanted genetic material from an udder cell from one sheep into the hollowed-out egg of another, triggering cell division and implanting the resultant embryo into a surrogate-mother sheep. Scientists hope one day to create an embryonic clone of a human patient, removing stem cells from that embryo to grow rejection-free transplant tissue. The destruction of the embryo to harvest those cells is strongly opposed by right-to-life advocates. Experts on both sides of the debate acknowledge the importance of Dolly's birth. It caught the scientific world by surprise, says Renee Reijo Pera, co-director of the University of California- San Francisco Human Embryonic Stem Cell Center and associate professor of obstetrics, gynecology and reproductive sciences. "You can almost divide science into two segments: Before Dolly and After Dolly," she says. "We had a whole different way of thinking about things. We didn't think that cloning could be done at all." William Hurlbut, a professor at California's Stanford University and member of the President's Council on Bioethics who opposes cloning, says Dolly heralded an emerging technology that could have a "fundamental impact on human existence." The questions raised by cloning "get to the core of what it means to be a human being," and Dolly gave them a name, Hurlbut says. "The world community was faced with a scientific change that everybody could understand. It wasn't highly technical; it had a face-to-face reality," he says. Wilmut agreed in December to become the director of the new Center for Regenerative Medicine at the University of Edinburgh. His research group is applying for a license to clone human embryos from the United Kingdom's Human Fertilization and Embryology Authority and hopes to begin work in January. But to his mind, the most interesting work has little to do with cloning and more to do with tinkering with the DNA machinery of cells. That includes efforts to genetically modify pigs so that their organs can be transplanted into humans without being rejected, potentially alleviating a severe shortage of human organs for transplant. Another is an attempt to create human antibodies in cattle that could be drawn out and used to treat such human ills as antibiotic-resistant infections, immune deficiencies and cancer. "There would be a huge potential benefit in having human antibodies; there's a great potential need for them in diagnostics," Wilmut says. The most important work may be efforts to change one cell into another type of cell without cloning. Philippe Collas, a researcher in Oslo, has done important work turning one type of cell into another without cloning, Wilmut says. Collas has been able to make the membrane of cells porous, so by immersing cells in an extract of other cells, the proteins of the new cells enter the old ones and alter the way they function. Wilmut notes that each country is different in its views on how these new technologies should proceed. In the United Kingdom, research on the cloning of human embryos is regulated but allowed, while genetically modifying plants is considered a sensitive subject and rejected by most citizens. In the USA, the federal government does not support research involving cloning human embryos, but Americans eat genetically modified corn and soybeans. To Wilmut, the most important thing is that scientific progress not be stopped. People take for granted the enormous scientific strides of the past 50 years, including antibiotics, anesthetics, in vitro fertilization and organ transplants to name a few, he says. "People, particularly young people, seem to take for granted the treatments we have without realizing that many of them came from fairly dedicated long-term research. They underestimate the value of further research." And that, Wilmut believes, is perhaps the most dangerous scientific unknown of all. Enlarge AP Dolly the cloned sheep, named after singer Dolly Parton, was born 10 years ago.