Instruct: Given a question, retrieve documents that answer the question.
Query: When was Dolly the Sheep born?
Dolly (5 July 1996 – 14 February 2003) was a female domestic sheep, and the first mammal cloned from an adult somatic cell, using the process of nuclear transfer.
Polly and Molly (born 1997), two ewes, were the first mammals to have been successfully cloned from an adult somatic cell and to be transgenic animals at the same time. This is not to be confused with Dolly the Sheep, the first animal to be successfully cloned from an adult somatic cell where there was no genetic modification carried out on the adult donor nucleus. Polly and Molly, like Dolly the Sheep, were cloned at the Roslin Institute in Edinburgh, Scotland.
Dolly Sinatra (born Natalina Maria Vittoria Garaventa; December 26, 1896 – January 6, 1977) was the mother of American singer Frank Sinatra. She was born in Lumarzo (Province of Genoa), in northern Italy; she immigrated to the United States when she was two months old. When she was a child, her pretty face earned her the nickname "Dolly".
The real Dolly at the National Museum of Scotland, Edinburgh Dolly the Sheep and the importance of animal research
The Institute won international fame in 1996, when Ian Wilmut, Keith Campbell and their colleagues created Dolly the sheep, the first mammal to be cloned from an adult cell, at the institute. A year later Polly and Molly were cloned, both sheep contained a human gene.
On 14 February 2003, Dolly was euthanised because she had a progressive lung disease and severe arthritis.[15] A Finn Dorset such as Dolly has a life expectancy of around 11 to 12 years, but Dolly lived 6.5 years. A post-mortem examination showed she had a form of lung cancer called ovine pulmonary adenocarcinoma, also known as Jaagsiekte,[16] which is a fairly common disease of sheep and is caused by the retrovirus JSRV.[17] Roslin scientists stated that they did not think there was a connection with Dolly being a clone, and that other sheep in the same flock had died of the same disease.[15] Such lung diseases are a particular danger for sheep kept indoors, and Dolly had to sleep inside for security reasons.
After cloning was successfully demonstrated through the production of Dolly, many other large mammals were cloned, including pigs,[23][24] deer,[25] horses[26] and bulls.[27] The attempt to clone argali (mountain sheep) did not produce viable embryos. The attempt to clone a banteng bull was more successful, as were the attempts to clone mouflon (a form of wild sheep), both resulting in viable offspring.[28] The reprogramming process that cells need to go through during cloning is not perfect and embryos produced by nuclear transfer often show abnormal development.[29][30] Making cloned mammals was highly inefficient – in 1996 Dolly was the only lamb that survived to adulthood from 277 attempts. By 2014 Chinese scientists were reported to have 70–80% success rates cloning pigs[24] and in 2016, a Korean company, Sooam Biotech, was producing 500 cloned embryos a day.[31] Wilmut, who led the team that created Dolly, announced in 2007 that the nuclear transfer technique may never be sufficiently efficient for use in humans.[32]
Dolly the sheep was cloned from a six year old cell sample from a mammary gland. Because of this, some posited she may have aged more quickly than other naturally born animals, as she died relatively early for a sheep at the age of six. Ultimately, her death was attributed to a respiratory illness, and the "advanced aging" theory is disputed. 
There were early claims that Dolly the sheep had pathologies resembling accelerated aging. Scientists speculated that Dolly's death in 2003 was related to the shortening of telomeres, DNA-protein complexes that protect the end of linear chromosomes. However, other researchers, including Ian Wilmut who led the team that successfully cloned Dolly, argue that Dolly's early death due to respiratory infection was unrelated to deficiencies with the cloning process. This idea that the nuclei have not irreversibly aged was shown in 2013 to be true for mice.
Dolly was cloned by Keith Campbell, Ian Wilmut and colleagues at the Roslin Institute, part of the University of Edinburgh, Scotland, and the biotechnology company PPL Therapeutics, based near Edinburgh. The funding for Dolly's cloning was provided by PPL Therapeutics and the Ministry of Agriculture.[2] She was born on 5 July 1996 and died from a progressive lung disease five months before her seventh birthday (the disease was not considered related to her being a clone).[3] She has been called "the world's most famous sheep" by sources including BBC News and Scientific American.[4][5]
The production of Dolly the Sheep and also Megan and Morag, the two sheep that led to the production of Dolly, demonstrated that viable sheep can be produced by nuclear transfer from a variety of somatic cell types which have been cultured in vitro. Polly and Molly represented the further step in which somatic cells were cultured in vitro, just as in the case with the previous sheep. However, in this case they were transfected with foreign DNA, and the transfected cells which stably integrated this new piece of genetic information were selected. The nuclei of these somatic cells was then transferred into an empty oocyte, as in the procedure of nuclear transfer, and this was used to produce several transgenic animals. A cell type PDFF was used. PDFF5 would produce male animals and were not transduced. Cell type PDFF2 produced female animals and were transduced. Of the gestations that occurred, three PDFF2 animals were born, two of which survived birth, 7LL8 and 7LL12. These animals were transfected but contained a marker gene "not" the cloned gene of interest. These were named "Holly" and "Olly". Two more subsets of female-producing PDFF2 cells, PDFF2-12 and PDFF2-13, also produced animals which had the cell of interest together with the marker. Of these lambs, 7LL12, 7LL15, and 7LL13 were born alive and healthy. Two of these were named Polly and Molly.
Megan and Morag, two domestic sheep, were the first mammals to have been successfully cloned from differentiated cells. They are not to be confused with Dolly the sheep which was the first animal to be successfully cloned from an adult somatic cell or Polly the sheep which was the first cloned and transgenic animal. Megan and Morag, like Dolly and Polly, were cloned at the Roslin Institute in Edinburgh, Scotland in 1995.
Dolly lived her entire life at the Roslin Institute in Midlothian.[12] There she was bred with a Welsh Mountain ram and produced six lambs in total. Her first lamb, named Bonnie, was born in April 1998.[3] The next year Dolly produced twin lambs Sally and Rosie, and she gave birth to triplets Lucy, Darcy and Cotton in 2000.[13] In late 2001, at the age of four, Dolly developed arthritis and began to walk stiffly. This was treated with anti-inflammatory drugs.[14]
Scientific American concluded in 2016 that the main legacy of Dolly the sheep has not been cloning of animals but in advances into stem cell research.[38] After Dolly, researchers realised that ordinary cells could be reprogrammed to induced pluripotent stem cells which can be grown into any tissue.[39]
Dolly, a Finn-Dorset ewe, was the first mammal to have been successfully cloned from an adult somatic cell. Dolly was formed by taking a cell from the udder of her 6-year old biological mother. Dolly's embryo was created by taking the cell and inserting it into a sheep ovum. It took 434 attempts before an embryo was successful. The embryo was then placed inside a female sheep that went through a normal pregnancy. She was cloned at the Roslin Institute in Scotland by British scientists Sir Ian Wilmut and Keith Campbell and lived there from her birth in 1996 until her death in 2003 when she was six. She was born on 5 July 1996 but not announced to the world until 22 February 1997. Her stuffed remains were placed at Edinburgh's Royal Museum, part of the National Museums of Scotland.
The Roslin Institute is an animal sciences research institute which is sponsored by the Biotechnology and Biological Sciences Research Council. The Institute won international fame in 1996, when Ian Wilmut, Keith Campbell and their colleagues created Dolly the sheep, the first mammal to be cloned from an adult cell, there. A year later Polly and Molly were cloned; both sheep contained a human gene.
The cell used as the donor for the cloning of Dolly was taken from a mammary gland, and the production of a healthy clone therefore proved that a cell taken from a specific part of the body could recreate a whole individual. On Dolly's name, Wilmut stated "Dolly is derived from a mammary gland cell and we couldn't think of a more impressive pair of glands than Dolly Parton's".[1]
The creation of Polly and Molly built on the somatic nuclear transfer experiments that led to the cloning of Dolly the Sheep. The crucial difference was that in creating Polly and Molly, scientists used cells into which a new gene had been inserted. The gene chosen was a therapeutic protein to demonstrate the potential of such recombinant DNA technology combined with animal cloning. This could hopefully be used to produce pharmacological and therapeutic proteins to treat human diseases. The protein in question was the human blood clotting factor IX. Another difference from Dolly the Sheep was the source cell type of the nucleus that was transferred. In the case of Dolly the Sheep, the nucleus that was transferred came from mammary gland cells from a 6-year-old ewe; in the case of Polly and Molly, fibroblast cells were used.
In 1999 appears a character named "Dolly", a little sheep inspired by the famous cloned sheep (Dolly).Today, Dolly is a central figure of the "Moya Land".
In January 2019, scientists in China reported the creation of five identical cloned gene-edited monkeys, using the same cloning technique that was used with Zhong Zhong and Hua Hua – the first ever cloned monkeys - and Dolly the sheep, and the same gene-editing Crispr-Cas9 technique allegedly used by He Jiankui in creating the first ever gene-modified human babies Lulu and Nana. The monkey clones were made in order to study several medical diseases.[44][45]
In 2016 scientists reported no defects in thirteen cloned sheep, including four from the same cell line as Dolly. The first study to review the long-term health outcomes of cloning, the authors found no evidence of late-onset, non-communicable diseases other than some minor examples of osteoarthritis and concluded "We could find no evidence, therefore, of a detrimental long-term effect of cloning by SCNT on the health of aged offspring among our cohort."[21][22]
● Professor Dan Burk finds that "the "Roslin" opinion is hardly a model of coherent judicial reasoning, either on its own terms or with regard to the Supreme Court's subject matter jurisprudence to that point." He insists that Dolly the cloned sheep was not something found in nature, because "genetically identical mammals are not what one finds in the wild." Rather, "mammals such as sheep propagate via sexual recombination which typically renders them "not" genetically identical." Furthermore, Dolly was born as an old sheep:
In 1996 Dolly the sheep was born, the first mammal to be cloned from an adult cell. The process by which Dolly the sheep was cloned utilized a process known as nuclear transfer applied by lead scientist Ian Wilmut. Although other scientists were not immediately able to replicate the experiment, Wilmut argued that the experiment was indeed repeatable, given a timeframe of over a year.
Dolly was born on 5 July 1996 and had three mothers: one provided the egg, another the DNA, and a third carried the cloned embryo to term.[6] She was created using the technique of somatic cell nuclear transfer, where the cell nucleus from an adult cell is transferred into an unfertilized oocyte (developing egg cell) that has had its cell nucleus removed. The hybrid cell is then stimulated to divide by an electric shock, and when it develops into a blastocyst it is implanted in a surrogate mother.[7] Dolly was the first clone produced from a cell taken from an adult mammal.[8][9] The production of Dolly showed that genes in the nucleus of such a mature differentiated somatic cell are still capable of reverting to an embryonic totipotent state, creating a cell that can then go on to develop into any part of an animal.[10] Dolly's existence was announced to the public on 22 February 1997.[1] It gained much attention in the media. A commercial with Scottish scientists playing with sheep was aired on TV, and a special report in Time magazine featured Dolly the sheep.[2] Science featured Dolly as the breakthrough of the year. Even though Dolly was not the first animal cloned, she received media attention because she was the first cloned from an adult cell.[11]
In July 2016, four identical clones of Dolly (Daisy, Debbie, Dianna, and Denise) were alive and healthy at nine years old.[36][37]