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Dolly the sheep

2006-07-03 17:55

Dolly the sheep阅读提示:绵羊多利(1996年7月5日—2003年2月14日)是人类通过成年体细胞克隆成功的第一只哺乳动物。它是苏格兰罗斯林研究所培育的,7年里它一直生活在那里。最初科学家并没有宣布它出世的消息,直到1997年2月22日全世界才得知第一只克隆哺乳动物已经诞生。

Dolly (5 July 1996 – 14 February 2003), a ewe, was the first mammal to have been successfully cloned from an adult cell. She was cloned at the Roslin Institute in Scotland and lived there until her death when she was 6. Her birth was announced on 22 February 1997.

The sheep was originally code-named "6LL3". The name "Dolly" came from a suggestion by the stockmen who helped with her birth, in honor of Dolly Parton, because it was a mammary cell that was cloned[1]. The technique that was made famous by her birth is somatic cell nuclear transfer, in which a cell is placed in a de-nucleated ovum, the two cells fuse and then develop into an embryo. When Dolly was cloned in 1996 from a cell taken from a six-year-old ewe, she became the center of much controversy that still exists today.

On 9 April 2003 her stuffed remains were placed at Edinburgh's Royal Museum, part of the National Museums of Scotland.

Dolly

Dolly was created by a research team managed by Ian Wilmut at the Roslin Institute in Scotland. The goal of the research was the reliable reproduction of animals genetically modified to produce therapeutic proteins in their milk. Wilmut's team had already created 2 sheep clones from embryonic cells grown in culture called Megan and Morag; the work was published in Nature in 1996[2]. Dolly was a Finn Dorset lamb, created from fully differentiated adult mammary cells using a technique called somatic cell nuclear transfer; her creation was described in a Nature publication in 1997[3]. Dolly was the first mammalian clone produced from an adult cell.

Controversy over Credit

Ian Wilmut's fame rests on being the first author on the 1997 Nature paper describing the work of cloning Dolly the sheep, implying that he had actually done the work of cloning Dolly, but his role in the project has since been disputed and remains in doubt (see below).

In March 2006 it was revealed that the scientists involved are in major disagreement over who deserves credit for Dolly.

In 2006, while testifying at an Edinburgh court following accusations of racial harassment of his fellow Prim Singh, Ian Wilmut denied the accusations, but acknowledged that he was not the 'father' or "creator" of Dolly, that he has minimised the role of some of his fellows, and he gave most of the credit (66% ) to Keith Campbell, while playing a "supervisory" or managerial role himself. Wilmut's credit in cloning Dolly the sheep is in doubt, but is less than 1/3rd as other people, in addition to Keith Campbell, did some of the work [4].

Although it is not certain, it can be inferred from Wilmut's own testimony in court and from the statements of Mr Bill Ritichie, one of the two technicians who did the nuclear transfer experiments, and from an anonymous source, to the Guardian newspaper, that without the intellectual input of Keith Campbell the group would still be trying to clone a sheep. This is because Keith Campbell had the crucial idea of co-ordinating the stages of the "cell cycle" of the somatic cells and eggs which was required for successful cloning.

Premature Aging

In 1999 research was published in the journal Nature suggesting that Dolly may have been susceptible to premature aging, due to shortened telomeres in her cells[5]. It was speculated that these were passed on from her parent, who was six years old when the genetic material was taken from her, so that Dolly may have been genetically six years old at birth. This is because telomere length is reduced after each cell division, which requires DNA replication before mitosis occurs. The polymerase, part of the replication machinery, cannot reach the end of the chromosome being replicated and clips a little of the telomere at the end off every time replication occurs. However, Dr. Sean Lamb indicated that most cloned animals actually have telomeres of normal length and in serial clones the telomeres are actually getting longer in each successive generation. This is because the enzyme telomerase is active in those clones, which keeps the telomeres from shortening. However, telomerase, which is present in many bacteria, can be responsible for causing mutation through its enzymatic activity, which leads to cancer. In fact, in the course of carcinogenesis many human cancer cells produce telomerase, which is not normally present in adult human cells.

Possible signs of her condition were reported in January 2002, when Dolly was five years old. She had developed a potentially debilitating form of arthritis at an unusually early age. This supported the theory of premature senescence, although Dr. Dai Grove-White of the Faculty of Veterinary Science at Liverpool University was reported as saying, "Conceivably arthritis could be due to the cloning but equally it could not be. For all we know, she may have damaged her leg jumping over a gate and developed arthritis."

The arthritis further fueled worry among some that this form of cloning may not be appropriate for mammals, and there is now a consensus both in- and outside scientific community that at this point the risk of unforeseen effects of cloning on the clone makes experiments in human reproductive cloning premature and unethical.

Supporters of this method of cloning counter that the technique used to clone Dolly simply needs to be refined. However, others contend that with very limited understanding of the nascent field of applied genetics, scientists can not and should not attempt to control the action of so many genes at once. Many outside the scientific community have stated that this is vindication for their initial assertions that any form of cloning is ethically wrong and should be banned.

Death

On February 14, 2003 it was announced that Dolly had died from a progressive lung disease. A necropsy confirmed she had Ovine Pulmonary Adenocarcinoma (Jaagsiekte), a fairly common disease of sheep. Roslin scientists stated that they did not think there was a connection with Dolly being a clone, and that other sheep on the farm had similar ailments. Such lung diseases are especially a danger for sheep kept indoors, as Dolly had to be for security reasons.

Legacy

After the cloning was successfully demonstrated by Dolly's creators once, many other large mammals have been cloned, including horses and bulls. Cloning is now considered a promising tool for preserving endangered species, usually by those who do not work in species conservation. Most animal conservation professionals point out that cloning does not alleviate the problems of loss of genetic diversity (see inbreeding) and habitat, ergo must be considered an experimental technology for the time being, and all in all would only rarely be worth the cost, which on a per-individual basis far exceeds conventional techniques such as captive breeding or embryo transfer. The 2000-2001 attempt to clone a gaur failed, with the animal, "Noah", dying 2 days after birth, and the attempt to clone argali sheep did not produce viable embryos. The attempt to clone a banteng bull was more successful, as were the attempts to clone mouflon, both resulting in viable offspring. The banteng example is a case illustrating the circumstances under which the uncertainties of cloning attempts are outweighed by the benefits: the cell donator was an adult of a rare genotype combination which had been killed in a fight.

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