Tale of Dolly – The Cloned Sheep

Cloning is a technique of creating organisms that are exactly the same as their parent or the original one from which they are created. Since the beginning of the cloning phenomenon that was first carried out by Hans Spemann in 1938 when he split salamander embryonic cells using baby hair and found that each cell grown into a new salamander. From that day till today many organisms have been cloned so far. Among animals, mice, frogs and even horses have been cloned but the most famous mammal ever created by cloning was the Dolly sheep; born on 5th of July 1996, this sheep was the most renowned sheep ever. Dolly was born in 1996 but her existence was revealed in 1997 after the publishing of papers by the scientists regarding this work in ‘Nature Journal’.

Dolly was the outcome of a unique scientific method known as Somatic Cell Nuclear Transfer (SCNT).This method for creating cloned mammals was carried out in Roslin Institute (University of Edinburgh), Scotland for the first time by Sir Ian Wilmut, Dr Keith Campbell, William Ritchie and Jim McWhir in 1995. Sir Ian Wilmut, by using his skills in developmental biology, obtained zygotes from sheep, genetically engineered them and produced a sheep named Tracy during 1980’s. The purpose of this experimentation was to make such animals that produce engineered proteins in their milk against various diseases like cystic fibrosis and emphysema; the procedure is commonly known as ‘Pharming’. In 1991, in order to quench his thirst of studying nuclear transfer techniques in mammals for solving out problems in ‘Pharming’, Sir Ian Wilmut hired an English Biologist named Dr Keith Campbell. Work on cloning of mammals started in 1993 in Roslin Institute.

Ian Wilmut and his team were actually not interested in cloning; they only wanted to find out a solution for problems of pharming. They considered cloning to be unethical and they also knew the dangers of cloning which include embryo death before implantation, premature fetus death and susceptibility of clones to various fatal diseases. They were also against human cloning.

In 1995, Sir Ian Wilmut and his team created two Welsh Mountain sheep by cloning and named them as Megan and Morag using embryonic cells as nucleus donors. They removed the nucleus from sheep egg cell and replaced it with the embryonic nucleus. They also removed the nucleus from cow cells and replaced it with another embryonic cell’s nucleus, by doing so they also came across identifying a cell cycle protein named as Maturation Promoting Factor (MPF). Lower MPF meant that egg cell can receive a nucleus without DNA damage. Megan and Morag were created from 9 days old cultured embryonic cells. A similar method of cloning was again used and this time a different breed of sheep ‘Poll Dorset’ was used to create four clones named as Cecil, Cedric, Tuppence and Cyril in the winter of 1995-96. In the 2nd experiment, they used fibroblast cells from fetuses and produced two more clones named as Taffy and Tweed. In the third and most famous experiment Wilmut, Keith, Ritchie, and McWhir used the technique of ‘SCNT’, they isolated udder cells from a 6-years old White Finn Dorset sheep, these cells being the somatic cells were used as nucleus donors and their nucleus was transferred into the enucleated egg cells of another breed of sheep Scottish Blackface ewe. They made 277 embryos and cultured them in the laboratory to observe the cell division in embryos, the embryos that showed cell division were implanted into 13 Blackface surrogate mother sheep and only one of the surrogates got pregnant and this surrogate gave birth to a sheep that was named Dolly, born on July 5th, 1996. It was not completely white as was its original parent from whom the somatic cells were taken because only the nucleus was taken from White Finn Dorset ewe; mitochondria in Dolly’s cells were those of Scottish Blackface ewe. Dolly got more famous due to its creation from somatic cells as it was the first ever mammal to be created by the somatic cells nuclear transfer (SCNT) method. Dolly was born healthy, in order to let Dolly live a normal life, Dolly was allowed to breed, small welsh mountain ram was selected for her mating and she gave birth to a young one in 1998, and after that twins were born and triplets were born the next year, in this way Dolly gave birth to total 6 lambs successfully. In 1997 another clone was created named Polly from fetal fibroblasts of a Poll Dorset sheep. Polly was engineered to produce a blood clotting protein called ‘Factor IX’ against ‘Hemophilia B’. This entire cloning program was to produce mammals that could express proteins in their milk encoded by the genes engineered in their nucleus.

Dolly was created from a 6-year old ewe and normally sheep live up to 12 years, it is believed that Dolly was aging prematurely which means that she was already 6 years old at the time of her birth and it also proved right as the length of her chromosomal telomeres was shorter as compared to other cloned sheep. In 2001, Dolly suffered from arthritis in her hind leg, arthritis is mostly common in older sheep, and therefore, it also supported the fact of Dolly’s premature aging. In 2000, a male cloned sheep Cedric died from a viral disease called Pulmonary adenomatosis; this disease is common in sheep and causes the growth of tumors in the lungs, it is incurable disease and spreads from sheep to sheep, only prevention is the separation of the healthy animal from the affected ones. Dolly was separated, but another cloned sheep Morag died in the March of 2000 due to same viral disease. In September of same year 2nd young one of Dolly died of the same disease so now it was sure that Dolly also got that disease. On 10th February 2003, Dolly was coughing as observed by one of the workers, she was subjected to blood tests and CT scan, the scan showed tumors in her chest, now Dolly’s fate was only death, therefore, she was given anesthetic for CT scan which was necessary for scanning, so it was decided to give Dolly an overdose of anesthetic and as a result, she never regained her consciousness again.

Such cloning program may help young researchers to study the cloning process more deeply and to overcome the limitations or errors they may have encountered. Sir Ian Wilmut and his team not only created first cloned mammal but also paved the way for young researchers to study and re-think about several important steps for a precise outcome of their results. By this outstanding work on ‘Pharming’ for the production of important drugs in milk or meat of animals, cloning of such Genetically Modified mammals was a necessary step in order to keep on the continuation of drug production from them and also to keep the record of the loss of the inserted gene for drug production and secretion in milk of Dolly sheep, this technique of cloning process may be useful for prospective scientists who might work on ‘Pharming’ in future.

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