Dolly (sheep)

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Dolly
Dolly face closeup.jpg
Dolly (taxidermy)
Other name(s)6LLS (code name)
Species Domestic sheep (Finn-Dorset)
SexFemale
Born(1996-07-05)5 July 1996
Roslin Institute, Midlothian, Scotland
Died14 February 2003(2003-02-14) (aged 6)
Roslin Institute, Midlothian, Scotland
Cause of death Euthanasia
Resting place National Museum of Scotland (remains on display)
Nation fromUnited Kingdom (Scotland)
Known forFirst mammal cloned from an adult somatic cell
Offspring6 lambs (Bonnie; twins Sally and Rosie; triplets Lucy, Darcy and Cotton)
Named after Dolly Parton [1]

Dolly (5 July 1996 – 14 February 2003) was a female Finn-Dorset sheep and the first mammal that was cloned from an adult somatic cell. She was cloned by associates of the Roslin Institute in Scotland, using the process of nuclear transfer from a cell taken from a mammary gland. Her cloning proved that a cloned organism could be produced from a mature cell from a specific body part. [2] Contrary to popular belief, she was not the first animal to be cloned. [3]

Contents

The employment of adult somatic cells in lieu of embryonic stem cells for cloning emerged from the foundational work of John Gurdon, who cloned African clawed frogs in 1958 with this approach. The successful cloning of Dolly led to widespread advancements within stem cell research, including the discovery of induced pluripotent stem cells. [4]

Dolly lived at the Roslin Institute throughout her life and produced several lambs. [5] She was euthanized at the age of six years due to a progressive lung disease. No cause which linked the disease to her cloning was found. [6]

Dolly's body was preserved and donated by the Roslin Institute in Scotland to the National Museum of Scotland, where it has been regularly exhibited since 2003.

Genesis

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. [7] She was born on 5 July 1996. [5] She has been called "the world's most famous sheep" by sources including BBC News and Scientific American . [8] [9]

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]

Birth

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. [10] 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. [11] Dolly was the first clone produced from a cell taken from an adult mammal. [12] [13] 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. [2]

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. [7] 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. [14]

Life

The cloning process that produced Dolly Dolly clone.svg
The cloning process that produced Dolly

Dolly lived her entire life at the Roslin Institute in Midlothian. [15] 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. [5] The next year, Dolly produced twin lambs Sally and Rosie; further, she gave birth to triplets Lucy, Darcy and Cotton in 2000. [16] In late 2001, at the age of four, Dolly developed arthritis and began to walk stiffly. This was treated with anti-inflammatory drugs. [17]

Death

On 14 February 2003, Dolly was euthanised because she had a progressive lung disease and severe arthritis. [6] 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, [18] which is a fairly common disease of sheep and is caused by the retrovirus JSRV. [19] 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. [6] Such lung diseases are a particular danger for sheep kept indoors, and Dolly had to sleep inside for security reasons. [20]

Some in the press speculated that a contributing factor to Dolly's death was that she could have been born with a genetic age of six years, the same age as the sheep from which she was cloned. [21] One basis for this idea was the finding that Dolly's telomeres were short, which is typically a result of the aging process. [22] [23] The Roslin Institute stated that intensive health screening did not reveal any abnormalities in Dolly that could have come from advanced aging. [21]

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." [24] [25]

After her death Dolly's body was preserved via taxidermy and is currently on display at the National Museum of Scotland in Edinburgh. [26]

Legacy

After cloning was successfully demonstrated through the production of Dolly, many other large mammals were cloned, including pigs, [27] [28] deer, [29] horses [30] and bulls. [31] 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. [32] The reprogramming process that cells need to go through during cloning is not perfect and embryos produced by nuclear transfer often show abnormal development. [33] [34] 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, [28] and in 2016, a Korean company, Sooam Biotech, was producing 500 cloned embryos a day. [35] 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. [36]

Cloning may have uses in preserving endangered species, and may become a viable tool for reviving extinct species. [37] In January 2009, scientists from the Centre of Food Technology and Research of Aragon in northern Spain announced the cloning of the Pyrenean ibex, a form of wild mountain goat, which was officially declared extinct in 2000. Although the newborn ibex died shortly after birth due to physical defects in its lungs, it is the first time an extinct animal has been cloned, and may open doors for saving endangered and newly extinct species by resurrecting them from frozen tissue. [38] [39]

In July 2016, four identical clones of Dolly (Daisy, Debbie, Dianna, and Denise) were alive and healthy at nine years old. [40] [41]

Scientific American concluded in 2016 that the main legacy of Dolly has not been cloning of animals but in advances into stem cell research. [42] Gene targeting was added in 2000, when researchers cloned female lamb Diana from sheep DNA altered to contain the human gene for alpha 1-antitrypsin. The human gene was specifically activated in the ewe’s mammary gland, so Diana produced milk containing human alpha 1-antitrypsin. [43] After Dolly, researchers realised that ordinary cells could be reprogrammed to induced pluripotent stem cells, which can be grown into any tissue. [44]

The first successful cloning of a primate species was reported in January 2018, using the same method which produced Dolly. Two identical clones of a macaque monkey, Zhong Zhong and Hua Hua, were created by researchers in China and were born in late 2017. [45] [46] [47] [48]

In January 2019, scientists in China reported the creation of five identical cloned gene-edited monkeys, again using this method, and the 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. [49] [50]

See also

Related Research Articles

<span class="mw-page-title-main">Cloning</span> Process of producing individual organisms with identical genomes

Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without a mate is known as parthenogenesis. In the field of biotechnology, cloning is the process of creating cloned organisms of cells and of DNA fragments.

<span class="mw-page-title-main">Human cloning</span> Creation of a genetically identical copy of a human

Human cloning is the creation of a genetically identical copy of a human. The term is generally used to refer to artificial human cloning, which is the reproduction of human cells and tissue. It does not refer to the natural conception and delivery of identical twins. The possibilities of human cloning have raised controversies. These ethical concerns have prompted several nations to pass laws regarding human cloning.

<span class="mw-page-title-main">Somatic cell nuclear transfer</span> Method of creating a cloned embryo by replacing the egg nucleus with a body cell nucleus

In genetics and developmental biology, somatic cell nuclear transfer (SCNT) is a laboratory strategy for creating a viable embryo from a body cell and an egg cell. The technique consists of taking a denucleated oocyte and implanting a donor nucleus from a somatic (body) cell. It is used in both therapeutic and reproductive cloning. In 1996, Dolly the sheep became famous for being the first successful case of the reproductive cloning of a mammal. In January 2018, a team of scientists in Shanghai announced the successful cloning of two female crab-eating macaques from foetal nuclei.

In cellular biology, a somatic cell, or vegetal cell, is any biological cell forming the body of a multicellular organism other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Somatic cells compose the body of an organism and divide through mitosis.

<span class="mw-page-title-main">Embryonic stem cell</span> Type of pluripotent blastocystic stem cell

Embryonic stem cells (ESCs) are pluripotent stem cells derived from the inner cell mass of a blastocyst, an early-stage pre-implantation embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. Isolating the inner cell mass (embryoblast) using immunosurgery results in destruction of the blastocyst, a process which raises ethical issues, including whether or not embryos at the pre-implantation stage have the same moral considerations as embryos in the post-implantation stage of development.

Commercial animal cloning is the cloning of animals for commercial purposes, including animal husbandry, medical research, competition camels and horses, pet cloning, and restoring populations of endangered and extinct animals. The practice was first demonstrated in 1996 with Dolly the sheep.

<span class="mw-page-title-main">Ian Wilmut</span> British embryologist (1944–2023)

Sir Ian Wilmut was a British embryologist and the chair of the Scottish Centre for Regenerative Medicine at the University of Edinburgh. He is best known as the leader of the research group that in 1996 first cloned a mammal from an adult somatic cell, a Finnish Dorset lamb named Dolly.

<span class="mw-page-title-main">Nuclear transfer</span> Form of cloning

Nuclear transfer is a form of cloning. The step involves removing the DNA from an oocyte, and injecting the nucleus which contains the DNA to be cloned. In rare instances, the newly constructed cell will divide normally, replicating the new DNA while remaining in a pluripotent state. If the cloned cells are placed in the uterus of a female mammal, a cloned organism develops to term in rare instances. This is how Dolly the Sheep and many other species were cloned. Cows are commonly cloned to select those that have the best milk production. On 24 January 2018, two monkey clones were reported to have been created with the technique for the first time.

Tetra is a rhesus macaque that was created through a cloning technique called "embryo splitting". She is the first "cloned" primate by artificial twinning, and was created by a team led by Professor Gerald Schatten of the Oregon National Primate Research Center.

Polly and Molly, 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 wasn’t modification carried out on the adult donor nucleus. Polly and Molly, like Dolly the Sheep, were cloned at the Roslin Institute in Edinburgh, Scotland.

<span class="mw-page-title-main">Biologist</span> Scientist studying living organisms

A biologist is a scientist who conducts research in biology. Biologists are interested in studying life on Earth, whether it is an individual cell, a multicellular organism, or a community of interacting populations. They usually specialize in a particular branch of biology and have a specific research focus.

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.

<span class="mw-page-title-main">KDM4D</span> Protein-coding gene in the species Homo sapiens

Lysine-specific demethylase 4D is an enzyme that in humans is encoded by the KDM4D gene. KDM4D belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily.

Keith Henry Stockman Campbell was a British biologist who was a member of the team at Roslin Institute that in 1996 first cloned a mammal, a Finnish Dorset lamb named Dolly, from fully differentiated adult mammary cells. He was Professor of Animal Development at the University of Nottingham. In 2008, he received the Shaw Prize for Medicine and Life Sciences jointly with Ian Wilmut and Shinya Yamanaka for "their works on the cell differentiation in mammals".

<span class="mw-page-title-main">Roslin Institute</span> Scottish animal sciences research institute

The Roslin Institute is an animal sciences research institute at Easter Bush, Midlothian, Scotland, part of the University of Edinburgh, and is funded by the Biotechnology and Biological Sciences Research Council.

<i>In re Roslin Institute</i> (Edinburgh) 2014 decision of the United States Court of Appeals for the Federal Circuit

In re Roslin Institute (Edinburgh), 750 F.3d 1333 (Fed. Cir. 2014), is a 2014 decision of the United States Court of Appeals for the Federal Circuit rejecting a patent for a cloned sheep known as "Dolly the Sheep"— the first mammal ever cloned from an adult somatic cell.

<span class="mw-page-title-main">Zhong Zhong and Hua Hua</span> Worlds first cloned primates (born 2017)

Zhong Zhong and Hua Hua are a pair of identical crab-eating macaques that were created through somatic cell nuclear transfer (SCNT), the same cloning technique that produced Dolly the sheep in 1996. They are the first cloned primates produced by this technique. Unlike previous attempts to clone monkeys, the donated nuclei came from fetal cells, not embryonic cells. The primates were born from two independent surrogate pregnancies at the Institute of Neuroscience of the Chinese Academy of Sciences in Shanghai.

<span class="mw-page-title-main">Mu-ming Poo</span> Chinese-American neuroscientist

Mu-ming Poo is a Chinese neuroscientist. He is the Paul Licht Distinguished Professor Emeritus at the University of California, Berkeley and the Founding Director of the Shanghai-based Institute of Neuroscience (ION) of the Chinese Academy of Sciences. He was awarded the 2016 Gruber Prize in Neuroscience for his pioneering work on synaptic plasticity. At ION, Poo led a team of scientists that produced the world's first truly cloned primates, a pair of crab-eating macaques called Zhongzhong and Huahua in 2017, using somatic cell nuclear transfer (SCNT).

Grahame Bulfield, CBE, FRSE, Hon FRASE is an English geneticist, vice-principal and Emeritus Professor of Genetics at the University of Edinburgh. He is best known as the former director and chief executive of the Roslin Institute, Edinburgh, when in 1996 the research group led by Ian Wilmut first cloned a mammal from an adult somatic cell, a Finnish Dorset lamb named Dolly.

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