First successful cloning of a mammal - Jul 05, 1996 - HISTORY.com First successful cloning of a mammal Share this: First successful cloning of a mammal Author First successful cloning of a mammal URL Publisher A+E Networks On this day in 1996, Dolly the sheep–the first mammal to have been successfully cloned from an adult cell–is born at the Roslin Institute in Scotland. Originally code-named “6LL3,” the cloned lamb was named after the buxom singer and actress Dolly Parton. The name was reportedly suggested by one of the stockmen who assisted with her birth, after he learned that the animal was cloned from a mammary cell. The cells had been taken from the udder of a six-year-old ewe and cultured in a lab using microscopic needles, in a method first used in human fertility treatments in the 1970s. After producing a number of normal eggs, scientists implanted them into surrogate ewes; 148 days later one of them gave birth to Dolly. Dolly’s birth was announced publicly in February 1997 to a storm of controversy.

On one hand, supporters argued that cloning technology can lead to crucial advances in medicine, citing the production of genetically modified animals to be organ donors for humans as well as “therapeutic” cloning, or the process of cloning embryos in order to collect stem cells for use in the development of treatments for degenerative nerve diseases such as Alzheimer’s and Parkinson’s. Some scientists also looked at animal cloning as a possible way to preserve endangered species. On the other hand, detractors saw the new cloning technology as potentially unsafe and unethical, especially when it was applied to what many saw as the logical next step: human cloning. Over the course of her short life, Dolly was mated to a male sheep named David and eventually gave birth to four lambs. In January 2002 she was found to have arthritis in her hind legs, a diagnosis that raised questions about genetic abnormalities that may have been caused in the cloning process. After suffering from a progressive lung disease, Dolly was put down on February 14, 2003, at the age of six. Her early death raised more questions about the safety of cloning, both animal and human.

Though Ian Wilmut, the lead scientist on the team that produced Dolly, has spoken out publicly against human cloning, its supporters are unlikely to be dissuaded. As for Dolly, the historic sheep was stuffed and is now on display at the National Museum of Scotland in Edinburgh. Related Videos Dolly, First Cloned Sheep What effect has the successful cloning of Dolly had on the general population?. About Dolly Dolly, a Finn Dorset sheep, was born on July 5th, 1996, at the Roslin Institute in Edinburgh, Scotland. Her birth, not revealed to the public until February 3rd, 1997, sparked controversy instantly, because Dolly was the world's first mammal to be cloned from an adult cell. Considered one of the most significant scientific breakthroughs ever, Dolly's birth and subsequent survival proved that adult cells can reprogram themselves into a new being.

The team that created her, led by Scotsman Ian Wilmut, hoped to create an animal whose cells were genetically young again, rather than prematurely adult; however, when Dolly was reported to have been euthanased on February 14th, 2003, nearly six years after her birth, concern was raised that her progressive lung disease was caused because her cells were already old; she also had premature arthritis. Sheep can normally live to 11 or 12 years of age, and lung disease is not common in younger sheep. There was some speculation as to whether she caught it or not from the other sheep that she was housed with, but that claim has been neither confirmed nor denied. Dolly, named after singer Dolly Parton, bred normally on two occasions, with a Welsh mountain ram named David, and over the course of her life gave birth to four lambs; proving thus that clones can reproduce. Francis Crick and James Watson are widely recognized as some of the first pioneers in cloning technology. Their discovery of the double-helix structure of DNA in 1953, and later, their work on moecular heredity, helped to propel the science of biotechnology into the public view.

This in turn led to an increase in scientific research that focused on learning the intricacies of the human genetic code and, subsequently, the discovery that cloning is possible and within reach of scientists today. Cloning as it exists today would probably not exist but for the research of these two men, who in 1962 received a Nobel prize for their work. Another important name in cloning history is John Gurdon, who in 1962 announced that he had used the nucleus of fully differentiated adult intestinal cells to clone South African frogs. Gurdon’s experiment was widely talked about, although it was never proven that the frogs were true clones. In 1984, Steen Willadsun cloned a sheep from embryo cells, which were the predecessor to Dolly’s method of cloning. His work was the first verified incidence of cloning using nuclear transfer, which was remarkable at the time considering that only a few months earlier it had been said that it was biologically impossible. The major debate over Dolly was the issue of subsequent human cloning. The ethics that need to be considered over this issue are enormous, and there is no one right answer.

Since Dolly, human cloning advocates have lobbied to legalize cloning; but so far this has not happened. Some people are of the opinion that cloning is essentially "playing God" and is abominable to say the least; they cite cloning experiments that have gone awry, with such results as deformed fetuses with oversized organs, and birthed animals that were twice the normal size and died soon after. Overall, the Dolly debate still continues internationally, and has never really died away. Whatever the future of cloning may be, Dolly existed, and that in itself is a momentous event in human history. The History of Cloning The History of Cloning The History of Cloning Lost in the midst of all the buzz about cloning is the fact that cloning is nothing new: its rich scientific history spans more than 100 years. The landmark examples below will take you on a journey through time, where you can learn more about the history of cloning. 1885 - First-ever demonstration of artificial embryo twinning Sea urchin Hans Adolf Edward Dreisch The sea urchin is a relatively simple organism that is useful for studying development.

Dreisch showed that by merely shaking two-celled sea urchin embryos, it was possible to separate the cells. Once separated, each cell grew into a complete sea urchin. This experiment showed that each cell in the early embryo has its own complete set of genetic instructions and can grow into a full organism. 1902 - Artificial embryo twinning in a vertebrate Salamander Hans Spemann Spemann’s first challenge was to figure out how to split the two cells of an embryo much stickier than sea urchin cells. Spemann fashioned a tiny noose from a strand of baby hair and tightened it between two cells of a salamander embryo until they separated. Each cell grew into an adult salamander. Spemann also tried to divide more advanced salamander embryos using this method, but he found that cells from these embryos weren’t as successful at developing into adult salamanders. This experiment showed that embryos from a more-complex animal can also be “twinned” to form multiple identical organisms—but only up to a certain stage in development.

1928 - The cell nucleus controls embryonic development Salamander Hans Spemann Again using a strand of baby hair tied into a noose, Spemann temporarily squeezed a fertilized salamander egg to push the nucleus to one side of the cytoplasm. The egg divided into cells—but only on the side with the nucleus. After four cell divisions, which made 16 cells, Spemann loosened the noose, letting the nucleus from one of the cells slide back into the non-dividing side of the egg. He used the noose to separate this “new” cell from the rest of the embryo. The single cell grew into a new salamander embryo, as did the remaining cells that were separated. Essentially the first instance of nuclear transfer, this experiment showed that the nucleus from an early embryonic cell directs the complete growth of a salamander, effectively substituting for the nucleus in a fertilized egg. 1952 - First successful nuclear transfer Frog Robert Briggs and Thomas King Briggs and King transferred the nucleus from an early tadpole embryo into an enucleated frog egg (a frog egg from which the nucleus had been removed). The resulting cell developed into a tadpole.

The scientists created many normal tadpole clones using nuclei from early embryos. But just like Spemann’s salamander experiments, cloning was less successful with donor nuclei from more advanced embryos: the few tadpole clones that did survive grew abnormally. Most importantly, this experiment showed that nuclear transfer was a viable cloning technique. It also reinforced two earlier observations. First, the nucleus directs cell growth and, ultimately, an organism’s development. Second, embryonic cells early in development are better for cloning than cells at later stages. 1958 - Nuclear transfer from a differentiated cell Frog John Gurdon Gurdon transplanted the nucleus of a tadpole intestinal cell into an enucleated frog egg. In this way, he created tadpoles that were genetically identical to the one from which the intestinal cell was taken. This experiment showed that, despite previous failures, nuclei from somatic cells in a fully developed animal could be used for cloning. Importantly, it suggested that cells retain all of their genetic material even as they divide and differentiate (although some wondered if the donor DNA came from a stem cell, which can differentiate into multiple types of cells). 1975 - First mammalian embryo created by nuclear transfer Rabbit J.

Derek Bromhall Mammalian egg cells are much smaller than those of frogs or salamanders, so they are harder to manipulate. Using a glass pipette as a tiny straw, Bromhall transferred the nucleus from a rabbit embryo cell into an enucleated rabbit egg cell. He considered the procedure a success when a morula, or advanced embryo, developed after a couple of days. This experiment showed that mammalian embryos could be created by nuclear transfer. To show that the embryos could continue developing, Bromhall would have had to place them into a mother rabbit's womb. He never did this experiment. 1984 - First mammal created by nuclear transfer Sheep Steen Willadsen Willadsen used a chemical process to separated one cell from an 8-cell lamb embryo. The he used a small electrical shock to fuse it to an enucleated egg cell. As luck would have it, the new cell started dividing. By this time, in vitro fertilization techniques had been developed, and they had been used successfully to help couples have babies. So after a few days, Willadsen placed the lamb embryos into the womb of surrogate mother sheep. The result was the birth of three live lambs.

This experiment showed that it was possible to clone a mammal by nuclear transfer—and that the clone could fully develop. Even though the donor nuclei came from early embryonic cells, the experiment was considered a great success. 1987 - Nuclear transfer from embryonic cell Cow Neal First, Randal Prather, and Willard Eyestone Using methods very similar to those used by Willadsen on sheep, First, Prather, and Eyestone produced two cloned calves. Their names were Fusion and Copy. This experiment added cows to the list of mammals that could be cloned by nuclear transfer. Still, mammalian cloning was limited to using embryonic cells as nuclear donors. Cloning using nuclei from differentiated adult somatic cells still wasn’t thought possible. 1996 - Nuclear transfer from laboratory cells Sheep Ian Wilmut and Keith Campbell All previous cloning experiments used donor nuclei from cells in early embryos. In this experiment, the donor nuclei came from a slightly different source: cultured sheep cells, which were kept alive in the laboratory. Wilmut and Campbell transferred the nuclei from cultured cells into enucleated sheep egg cells. The lambs born from this procedure were named Megan and Morag. This experiment showed that cultured cells can supply donor nuclei for cloning by nuclear transfer.

Because scientists had already learned how to transfer genes into cultured cells, this experiment showed that it might be possible to use such modified cells to create transgenic animals—such as cows that could make insulin for diabetics in their milk. 1996 - Dolly: First mammal created by somatic cell nuclear transfer Sheep Ian Wilmut and Keith Campbell In this landmark experiment, Wilmut and Campbell created a lamb by transferring the nucleus from an adult sheep's udder cell into an enucleated egg. Never before had a mammal been cloned from an adult somatic cell. What was the big deal? Every cell’s nucleus contains a complete set of genetic information. However, while embryonic cells are ready to activate any gene, differentiated adult cells have shut down the genes that they don't need for their specific functions. When an adult cell nucleus is used as a donor, its genetic information must be reset to an embryonic state. Often the resetting process is incomplete, and the embryos fail to develop. Of 277 attempts, only one produced an embryo that was carried to term in a surrogate mother. This famous lamb, named Dolly, brought cloning into the limelight.

Her arrival started conversations about the implications of cloning, bringing controversies over human cloning and stem cell research into the public eye. 1997 - First primate created by embryonic cell nuclear transfer Rhesus monkey Li Meng, John Ely, Richard Stouffer, and Don Wolf Primates are good models for studying human disorders. Cloning identical primates would decrease the genetic variation of research animals, and therefore the number of animals need in research studies. Similar to previous cloning experiments, Wolf’s team of scientists fused early-stage embryonic cells with enucleated monkey egg cells using a small electrical shock. The resulting embryos were then implanted into surrogate mothers. Out of 29 cloned embryos, two monkeys were born. One was a female named Neti, and the other was a male named Ditto. This experiment showed that primates, humans’ closest relatives, can be cloned. 1997 - Nuclear transfer from genetically engineered laboratory cells Sheep Angelika Schnieke, Keith Campbell, Ian Wilmut This experiment was an exciting combination of findings from earlier work. Campbell and Wilmut had already created a clone using the nucleus of a cultured cell.

This time, the researchers introduced the human Factor IX (“factor nine”) gene into the genome of sheep skin cells grown in a laboratory dish. Factor IX codes for a protein that helps blood clot, and it's used to treat hemophilia, a genetic disorder where blood doesn't form proper clots. To create the transgenic sheep, the scientists performed nuclear transfer using donor DNA from the cultured transgenic cells. The result was Polly, a sheep that produced Factor IX protein in her milk. This experiment showed that sheep could be engineered to make therapeutic and other useful proteins in their milk, highlighting the potential medical and commercial uses for cloning. 1998-1999 - More mammals cloned by somatic cell nuclear transfer Mice, cows, and goats Multiple groups After the successes leading up to Dolly and Polly, other scientists wanted to see if similar techniques could be used to clone other mammalian species. Before long, several more animals had been successfully cloned. Among them were transgenic animals, clones made from fetal and adult cells, and a male mouse; all previous clones had been female.

2001 - Endangered animals cloned by somatic cell nuclear transfer Gaur and Mouflon Multiple groups As the list of successfully cloned animals grew, scientists began to explore cloning as a way to create animals belonging to endangered or extinct species. A challenge to cloning endangered and extinct species is finding closely related animals to serve as egg donors and surrogates. The gaur and mouflon were chosen in part because they are close relatives of domestic cattle and sheep, respectively. In 2009, using goast as egg donors and surrogates, another group of researchers cloned the first extinct animal, a Spanish mountain goat called the bucardo. Sadly, the one kid that survived gestation died soon after birth due to a lung defect. 2007 - Primate embryonic stem cells created by somatic cell nuclear transfer Rhesus monkey Shoukhrat Mitalipov and colleagues Researchers took a cell from an adult monkey and fused it with an enucleated egg cell. The embryo was allowed to develop for a time, then its cells were grown in a culture dish. These cells, because they can differentiate to form any cell type, are called embryonic stem cells.

This experiment showed that nuclear transfer in a primate, which researchers had tried for years without success, was possible. It opened the door to the possibility of human therapeutic cloning: creating individual-specific stem cells that could be used to treat or study diseases. 2013 - Human embryonic stem cells created by somatic cell nuclear transfer Human Shoukhrat Mitalipov and colleagues Overcoming decades of technical challenges, Mitalipov and colleagues were the first to use somatic cell nuclear transfer to create a human embryo that could be used as a source of embryonic stem cells. The resulting stem cell lines were specific to the patient they came from, a baby with a rare genetic disorder. In this experiment, researchers took a skin cell from the patient and fused it with a donated egg cell. Key to the success of the experiment were modifications to the culture liquid in which the procedure was done and to the series of electrical pulses used to stimulate the egg to begin dividing. Following the cloning controversy of 2004–2005, in which South Korean scientists falsely claimed to have used somatic cell nuclear transfer to create embryonic stem cell lines, the scientific community demanded much stronger evidence that the procedure had actually been successful.

BBC ON THIS DAY | 22 | 1997: Dolly the sheep is cloned 1997: Dolly the sheep is cloned Scientists in Scotland have announced the birth of the world's first successfully cloned mammal, Dolly the sheep. Dolly, who was created at the Roslin Institute in Edinburgh, was actually born on 5 July 1996 although her arrival has only just been revealed. Dolly is the first mammal to have been successfully cloned from an adult cell. Previous clonings have been from embryo cells. The sheep's birth has been heralded as one of the most significant scientific breakthroughs of the decade although it is likely to spark ethical controversy. Scientists in Scotland cloned a ewe by inserting DNA from a single sheep cell into an egg and implanted it in a surrogate mother. They now have a healthy seven-month-old sheep - Dolly - who is an exact genetic duplicate of the animal from which the single cell was taken. DNA tests have revealed that Dolly is identical to the ewe who donated the udder cell and is unrelated to the surrogate mother.

It will enable us to study genetic diseases for which there is presently no cure Dr Ian Wilmut, embryologist Embryologist Dr Ian Wilmut, from the Roslin Institute, said: "It will enable us to study genetic diseases for which there is presently no cure and track down the mechanisms that are involved." The research, published in Nature magazine, follows the Edinburgh team's success in cloning sheep embryos. Last year they produced two identical sheep, which were clones of an original embryo. The company which has bought the rights to the research, PPL Therapeutics, said Dolly would help to improve understanding of ageing and genetics and lead to the production of cheaper medicines. US President Bill Clinton has set up a special task force to investigate cloning in order to examine the legal and ethical implications. What is Cloning What is Cloning What is Cloning Clones are organisms that are exact genetic copies. Every single bit of their DNA is identical. Clones can happen naturally—identical twins are just one of many examples. Or they can be made in the lab. Below, find out how natural identical twins are similar to and different from clones made through modern cloning technologies. How Is Cloning Done?

Many people first heard of cloning when Dolly the Sheep showed up on the scene in 1997. Artificial cloning technologies have been around for much longer than Dolly, though. There are two ways to make an exact genetic copy of an organism in a lab: artificial embryo twinning and somatic cell nuclear transfer. 1. Artificial Embryo Twinning Artificial embryo twinning is a relatively low-tech way to make clones. As the name suggests, this technique mimics the natural process that creates identical twins. In nature, twins form very early in development when the embryo splits in two. Twinning happens in the first days after egg and sperm join, while the embryo is made of just a small number of unspecialized cells. Each half of the embryo continues dividing on its own, ultimately developing into separate, complete individuals. Since they developed from the same fertilized egg, the resulting individuals are genetically identical. Artificial embryo twinning uses the same approach, but it is carried out in a Petri dish instead of inside the mother. A very early embryo is separated into individual cells, which are allowed to divide and develop for a short time in the Petri dish. The embryos are then placed into a surrogate mother, where they finish developing.

Again, since all the embryos came from the same fertilized egg, they are genetically identical. 2. Somatic Cell Nuclear Transfer Somatic cell nuclear transfer (SCNT), also called nuclear transfer, uses a different approach than artificial embryo twinning, but it produces the same result: an exact genetic copy, or clone, of an individual. This was the method used to create Dolly the Sheep. What does SCNT mean? Let's take it apart: Somatic cell: A somatic cell is any cell in the body other than sperm and egg, the two types of reproductive cells. Reproductive cells are also called germ cells. In mammals, every somatic cell has two complete sets of chromosomes, whereas the germ cells have only one complete set. Nuclear: The nucleus is a compartment that holds the cell's DNA. The DNA is divided into packages called chromosomes, and it contains all the information needed to form an organism. It's small differences in our DNA that make each of us unique. Transfer: Moving an object from one place to another. To make Dolly, researchers isolated a somatic cell from an adult female sheep. Next they removed the nucleus and all of its DNA from an egg cell.

Then they transferred the nucleus from the somatic cell to the egg cell. After a couple of chemical tweaks, the egg cell, with its new nucleus, was behaving just like a freshly fertilized egg. It developed into an embryo, which was implanted into a surrogate mother and carried to term. (The transfer step is most often done using an electrical current to fuse the membranes of the egg and the somatic cell.) The lamb, Dolly, was an exact genetic replica of the adult female sheep that donated the somatic cell. She was the first-ever mammal to be cloned from an adult somatic cell. Watch these videos of enucleation and nuclear transfer. How does SCNT differ from the natural way of making an embryo? Natural fertilization, where egg and sperm join, and SCNT both make the same thing: a dividing ball of cells, called an embryo. So what exactly is the difference between the two? An embryo's cells all have two complete sets of chromosomes. The difference between fertilization and SCNT lies in where those two sets come from. In fertilization, the sperm and egg have one set of chromosomes each.

When the sperm and egg join, they grow into an embryo with two sets—one from the father's sperm and one from the mother's egg. In SCNT, the egg cell's single set of chromosomes is removed. It is replaced by the nucleus from a somatic cell, which already contains two complete sets of chromosomes. So, in the resulting embryo, both sets of chromosomes come from the somatic cell. Is cloning an organism the same as cloning a gene? You may have heard about researchers cloning, or identifying, genes that are responsible for various medical conditions or traits. What's the difference? When scientists clone an organism, they are making an exact genetic copy of the whole organism, as described above. When scientists clone a gene, they isolate and make exact copies of just one of an organism's genes. Cloning a gene usually involves copying the DNA sequence of that gene into a smaller, more easily manipulated piece of DNA, such as a plasmid. This process makes it easier to study the function of the individual gene in the laboratory. cloning dolly the sheep Cloning Dolly the sheep Dolly the sheep, as the first mammal to be cloned from an adult cell, is by far the world's most famous clone.

However, cloning has existed in nature since the dawn of life. From asexual bacteria to ‘virgin births’ in aphids , clones are all around us and are fundamentally no different to other organisms. A clone has the same DNA sequence as its parent and so they are genetically identical. Several clones had been produced in the lab before Dolly, including frogs , mice , and cows, which had all been cloned from the DNA from embryos. Dolly was remarkable in being the first mammal to be cloned from an adult cell. This was a major scientific achievement as it demonstrated that the DNA from adult cells, despite having specialised as one particular type of cell, can be used to create an entire organism. How Dolly was cloned Animal cloning from an adult cell is much more difficult than from an embryonic cell. So when scientists working at the Roslin Institute in Scotland produced Dolly, the only lamb born from 277 attempts, it was a major news story around the world. To produce Dolly, scientists used an udder cell from a six-year-old Finn Dorset white sheep .

They had to find a way to 'reprogram' the udder cells - to keep them alive but stop them growing – which they achieved by altering the growth medium (the ‘soup’ in which the cells were kept alive). Then they injected the cell into an unfertilised egg cell which had had its nucleus removed, and made the cells fuse by using electrical pulses. The unfertilised egg cell came from a Scottish Blackface ewe. When the research team had managed to fuse the nucleus from the adult white sheep cell with the egg cell from the black-faced sheep, they needed to make sure that the resulting cell would develop into an embryo. They cultured it for six or seven days to see if it divided and developed normally, before implanting it into a surrogate mother, another Scottish Blackface ewe. Dolly had a white face. From 277 cell fusions, 29 early embryos developed and were implanted into 13 surrogate mothers. But only one pregnancy went to full term, and the 6.6 kg Finn Dorset lamb 6LLS (alias Dolly) was born after 148 days. What happened to Dolly? Dolly lived a pampered existence at the Roslin Institute.

She mated and produced normal offspring in the normal way, showing that such cloned animals can reproduce. Born on 5 July 1996, she was euthanased on 14 February 2003, aged six and a half. Sheep can live to age 11 or 12, but Dolly suffered from arthritis in a hind leg joint and from sheep pulmonary adenomatosis, a virus-induced lung tumour that is common among sheep which are raised indoors. The DNA in the nucleus is wrapped up into chromosomes, which shorten each time the cell replicates. This meant that Dolly’s chromosomes were a little shorter than those of other sheep her age and her early ageing may reflect that she was raised from the nucleus of a 6-year old sheep. Dolly was also not entirely identical to her genetic mother because the mitochondria, the power plants of the cell that are kept outside the nucleus, were inherited from Dolly’s egg donor mother. Why clone sheep? Dolly the sheep was produced at the Roslin Institute as part of research into producing medicines in the milk of farm animals.

Researchers have managed to transfer human genes that produce useful proteins into sheep and cows, so that they can produce, for instance, the blood clotting agent factor IX to treat haemophilia or alpha-1-antitrypsin to treat cystic fibrosis and other lung conditions. Inserting these genes into animals is a difficult and laborious process; cloning allows researchers to only do this once and clone the resulting transgenic animal to build up a breeding stock. The development of cloning technology has led to new ways to produce medicines and is improving our understanding of development and genetics. Since Dolly Since 1996, when Dolly was born, other sheep have been cloned from adult cells, as have cats , rabbits , horses and donkeys, pigs, goats and cattle. In 2004 a mouse was cloned using a nucleus from an olfactory neuron, showing that the donor nucleus can come from a tissue of the body that does not normally divide. Improvements in the technique have meant that the cloning of animals is becoming cheaper and more reliable. This has created a market for commercial services offering to clone pets or elite breeding livestock, but still with a $100,000 price-tag.

The advances made through cloning animals have led to a potential new therapy to prevent mitochondrial diseases in humans being passed from mother to child. About 1 in 6000 people is born with faulty mitochondria, which can result in diseases like muscular dystrophy . To prevent this, genetic material from the embryo is extracted and placed in an egg cell donated by another woman, which contains functioning mitochondria. This is the same process as used in cloning of embryonic cells of animals. Without this intervention, the faulty mitochondria are certain to pass on to the next generation. The treatment is currently not permitted for use in humans. However, the Human Fertilisation & Embryology Authority in the UK has reported that there is general support in the public for legalising the therapy and making it available to patients.

Research field(s): Anatomy and development, Cell biology, Genetics, Medical technologies Medical application(s): Basic research Cloning Mammals The Cloning of Dolly, 'Cc', and other Mammals February 25 and Feb 27, 2002 Note: This is a long one..but we will take two days to discuss the material Optional Readings: Announcing Dolly : Scientific American, March 1997 Cloning Noah's Ark Scientific American, November 2000 Slouching Towards Creation (A weird but fun site; don't look at it late at night) I. What is meant by the term 'cloning'? Cloning refers to making an exact copy of an original form. The root of the word comes from the greek word for 'twin' or 'breaking in two' - klon. Computers or electronic devices that look like an original are said to be 'clones'. In science fiction books and movies, 'clones' implied replicated copies of an individual, usually resulting in some sort of 'slave army' working for an evil genius, or an evil scientist.... ; ) See this week's Warm Up to cast a vote for the cloning academy awards! !

In science, the term was originally used to refer to organisms that reproduced by asexual reproduction (like bacteria) Once biotechnology took off in the 1980s, scientists learned how to splice genes from humans or other organisms into bacteria and started to refer to 'cloned genes' - genes placed into bacteria to be replicated - 'cloning' simply meant making multiple, identical copies of a gene (or protein) in bacteria. In 1996, cloning took on a new meaning: an new individual grown from a single somatic cell of its parent and genetically identical to it... This technique is also called somatic cell nuclear transfer.... II. Hello Dolly: Cloning Mammals... July 5, 1996: First mammal cloned from adult cells: A surrogate mother sheep gives birth to Dolly, a lamb cloned from an udder cell of an adult sheep born 6 years earlier. Ian Wilmut and colleagues at the PPL Theraputics and the Roslin Institute in Scotland quietly announce the birth of Dolly in February, 1997 in the journal Nature ( Viable offspring derived from fetal and adult mammalian cells.

Nature 1997 Feb 27; 385(6619) Wilmut I, Schnieke AE, McWhir J, Kind AJ, Campbell KH Roslin Institute (Edinburgh), Roslin, Midlothian, UK.) Dolly is a later-born genetic twin of the somatic cell she was cloned from(a female Finn Dorset Ewe). Since then, much work has been done to streamline and refine the cloning process in livestock and in laboratory animals like mouse: Hello Polly (1997) The first sheep cloned by nuclear transfer technology bearing a human gene (Factor VIII), by PPL Theraputics / Roslin Institute. 'Gene' the Bull - (August 1997) cloned by ABS Global . (but cloned from fetal, not adult, cells) Cumulina : (October 1997) Three Cloned Mice: Dolly is joined on October 3, 1997 by the cloned mouse "Cumulina" and, shortly afterward, by 22 of her cloned siblings (some of whom were cloned from clones) using the 'Honolulu Technique' of nuclear transfer.

Author Teruhiko Wakayama concludes that "contrary to previous opinion, mammals can be reproducibly cloned from adult somatic cells" [Image] Dolly gives birth to Bonnie : (April 1998) conceived in the good old-fashined way. (ie: Dolly was healthy and fertile). Triplets the year after. Dolly's telomeres are shorter than other 3-year-old sheep, (May 27 1999 Nature) but Dolly seems to be just fine, maybe just a bit more obese that other sheep her age... 1999, Roslin Bio-Med becomes Geron Bio-Med . Geron buys part of the Roslin Institute. Gotta love their patent position: telomerase, hES cells, AND somatic cell nuclear transfer! Mice cloned from ES cells (December 1999), Teruhiko Wakayama and colleagues are at it again - "Our findings demonstrate that ES cell nuclei can be used to produce viable cloned mice and provide a link between the technologies of ES cells and animal cloning. It thus may be possible to clone from a single cell a large number of individuals over an extended period." III.

Somatic Cell Nuclear Transfer: (aka cloning). A how-to: Ingredients: 1 somatic (diploid) donor cell, containing the complete genome of that individual + 1 unfertilized recipient egg with its haploid nucleus removed (or 'e-nucleated') + 1 electric shock to get them together... Images from Time Magazine, March 10, 1997 More detail on those Early Steps: Scientific American, November 2000 Quiescence: The state in which all but the most basic functions of a cell or group of cells has stopped. This is usually a response to an unfavourable environment, such as one in which the food supply is low or absent. The cell becomes dormant until its surroundings are more favourable. In this state the genes that define the specialist function of a cell "switch off" making the cell suitable for nuclear transfer. IV. Why do scientists want to clone animals?!?!? 1. The Potential of cloned livestock : (September 1997) Scientific American.

Cloning livestock allow for the genetic replication of animals that are expecially high producers of a desired product, allowing for the creation of animal herds that can be farmed for milk, blood and organs: [Image] * Human therapeutic proteins (hormomes, clotting factors, etc) * Organs and tissues for transplants * 'Humanized' cows milk The Roslin Institute 2. A second reason: Saving endangered species: Cloning Noah's Ark (November 2000) Scientific American. The inspiring (but ultimately sad) story of the cloning of the baby Guar, Noah. See this week's Good For. (Even sadder than NOT being able to clone endangered species? - the daily extinction of species due to the continual, daily habitat destruction for numerous species worldwide....thanks to humans...) Bank your pet's DNA at the Genetic Savings & Clone The Missyplicity Project is a project funded by the Genetic Savings & Clone to produce the first cloned dog. They have invested $2.3 million to produce a clone of a beloved pet dog, Missy, a mixed breed border collie. A team of about 20 researchers is working on the Missyplicity Project.

2/14/02 Operation Copycat First Cloned Cat is born . "Texas A&M announced today the first cloned kitten, appropriately named Cc. 'She is as cute as a button,' said a spokeswoman for Texas A&M, where the work was done using a grant from philanthropist John Sperling's Genetic Savings & Clone . 'The kitten was vigorous at birth and appears to be completely normal,' Mark Westhusin and colleagues write in their report in a letter published in the science journal Nature. The kitten is a calico-and-white shorthair that looks similar to, but not exactly like, her genetic mother. The scientists said her coat coloring was unique because not only genetics contribute to an animal's markings, but also conditions in the womb. Cc, like cumulina, was cloned from a cumulus cell. These cells nurture the developing eggs in a female's ovary and have been used to clone other animals as well, as they seem particularly adaptable to the process." [ Image and quotes ] Wondering what to give that special someone who has everything?? Why not a gift certificate good at any Genetic Savings and Clone? V. Cloning Human Beings...?

(Will there ever be another 'ewe'?) "There is no clinical reason why you would clone humans. Why would you make another human being? We think it would be ethically unacceptable and certainly would not want to be involved in that project.'' Dr. Ian Wilmut, The Roslin Institute "We will get there, because very simply it's a matter of determination. And I think we are determined to get there," Dr. Panos Zavos, University of Kentucky, who, beginning in November 2001, will attempt to clone the first human, with the help of over 200 volunteer infertile couples. (Check back in 9 months..) One reason to not pursue human cloning: July 16 2001: H.R. 2505, Human Cloning Prohibition Act of 2001, Introduced by Rep Dave Weldon. Passed by a vote of 265 to 162 in the US House of Representatives a ban on all human cloning, either for reproduction or for therapeutic cloning. The bill, if passed into law, would make cloning a crime punishable by up to 10 years in prison and outlaw the sale of any treatments developed from cloning.

Currently faces uncertain prospects on the Senate Calendar, particularly after September 11 (other things to worry about...). Note: Two dozen countries ban human cloning, but there is no such cloning ban in England and many other countries...and really none now in our country...until this act works its way through Congress and the White House. Two reasons some scientists and physicians want to pursue human cloning: 1. Reproductive cloning: making babies for infertile couples created from a single somatic cell without sexual reproduction. 2. Therapeutic cloning: making immunologically compatible hES cells (tissues and maybe someday organs...) for a person who has disease, a disorder, or an injury (diabetes, leukemia, spinal cord injury, etc. etc.). Some scientists advocate calling this technique " nuclear transplantation " to avoid the negative connotations of cloning. VI. Future Games: Reproductive Cloning: Time Magazine, August 2001 Is Cloning an Inevitability? (Time: moral compass) First human clone bid planned : Despite warnings, on August 7th, 2001 , at a National Academy of Sciences meeting, 3 privately-funded US / European groups vow to contunue their programs on Human Cloning.

Dr. Severino Antinori : of Italy, who became well-known in 1994 when he helped a 63-year-old woman to have a baby by implanting a donor's fertilised egg in her uterus, making her the oldest known women in the world to give birth. Plans to clone babies starting November 2001! - for couples who are infertile because the man is unable to make sperm, using the man's genetic material and the woman's egg (and egg cytoplasm, which contains mitochondria). Dr. Panos Zavos : of Lexington KY, director of the Andrology Institute of America, and the Kentucky Center for Reproductive Medicine. Would like to clone humans by 2003, collaborating with Dr. Antinori to impregnate up to 200 women from infertile couples with cloned embryos in hopes that at least a few of the women will carry a child to term.. (Note from Dr. Marrs: In the immortal words of Buzz Lightyear, from Toy Story (1995) , "I don't believe that man has ever been to medical school".) Dr.

Brigitte Boisselier : scientific director of Clonaid , "The First Human Cloning Company". Founded three years ago by Rael, a spiritual leader of the Raelian Movement, who believes that human life is the result of extraterrestrial genetic experiments. (Note from Dr. Marrs: In the immortal words of Fozzie Bear, from The Muppet Movie (1979) , "We picked up a weirdo...!") Scientist's responses : not good. "Practice, it is said, makes perfect. But is it ethical to practice? And I absolutely think it is not, in the human context," said Alan Colman, a researcher for Scotland's PPL Therapeutics. Jeremy Rifkin, do you have anything to add? (Jeremy Rifkin is a vocal opponent of the Biotechnology industry) VII. Therapeutic Cloning: Teruhiko Wakayama cloned mice from ES cells and other labs have done this with livestock. This provides a link between the technologies of ES cells and animal cloning.

Therapeutic cloning involves the creation of an embryo via somatic cell nuclear transfer (cloning) from an animal (ie: a person) with a disease, to derive hES cells immunologically identical to donor, in hopes of treating the disease. The cloned embryo would exist only until day 5, when it would be used to isolate hES cells. The nucleus of a somatic cell from the donor (ie: you?) would be removed and placed into an enucleated human egg. "Fertilization" would be simulated with electric shock. The inner cell mass would be removed from the 5-day old blastocyst, which is genetically identical to the donor. hES cells would be cultured into the tissue type needed by the donor. This immunologically identical tissue would be placed back into the donor, hopefully curing the donor's disease Eventually, growing replacement organs (heart, liver, pancreas, skin, etc) MAY be possible - however I think we can conservatively say we are many years away from producing needed tissues, let alone whole organs. A step forward...or back?

Thanksgiving weekend, 2001: Sunday, November 25, 2001: The First Cloned Human Embryo "ACT scientists reported that they had used somatic cell nuclear transplantation to create several human embryos. Unfortunately, only one of the embryos progressed to a 6-cell stage, at which point it stopped dividing and died (note from KM: the numbers go: 1 cell, 2 cells, 4 cells, 8 cells....obviously something was wrong there!) and none were able to get to the 5-day blastocyst stage. E-biomed Rapid Communication: Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development the Journal of Regenerative Medicine 2 (25 - 31) Jose B. Cibelli; Ann A. Kiessling; Kerrianne Cunniff; Charlotte Richards; Robert P. Lanza; Michael D. West Monday, November 26, 2001: Scientific criticism: Experts rip cloning 'story' "Glenn McGee, a University of Pennsylvania bioethicist resigned today from Advanced Cell Technology's ethics advisory board, calling the announcement 'nothing but hype.

They are doing science by press release,' he said." Scientific criticism from every direction directed at ACT, Scientific American, and the Journal of Regenerative Medicinebecause it was not good science. Tuesday, November 27, 2001: Bush denounces ACT WASHINGTON- AP: "President Bush, joined by a chorus of religious and political leaders in the United States and abroad, today condemned the work of a Massachusetts biotechnology company that says it has created human embryos through cloning. The White House called on lawmakers to ban the practice. 'The use of embryos to clone is wrong,' Mr. Bush said this morning at a Rose Garden ceremony 'We should not as a society grow life to destroy it.' "The president's comments, coming on the heels of the company's announcement on Sunday, reignite an intense debate that had been all but extinguished by the Sept. 11 attacks. The Senate is facing increased pressure to consider legislation, similar to a bill passed by the House of Representatives in July, that would prohibit human cloning either for reproduction or to create tissue for treating disease. Hours after Mr. Bush spoke, Senator Sam Brownback, Republican of Kansas, said he would push the Senate to adopt the bill before its Christmas recess.

If lawmakers refuse to do so, Mr. Brownback said, he will press for a six-month moratorium that would temporarily ban the cloning research." [ Quotes and image from the New York TImes ] IV. Safety Issues: Clone Snafu suspected Wired, May 2001 The rate of success of cloning is currently very low - cloned animals rarely make it to adulthood - or sometimes even birth. It took 277 attempts (failed pregnancies) to get 1 cloned sheep - Dolly. It took 188 tries (failed pregnancies) to get just one 'Cc'. Some labs are better at it than others, but typically a hundred or so attempts are made before one 'successful' clone is born alive and well. Many times, the placenta of the animal is abnormal, contributing to a miscarriage. Many animal embryos spontaneously miscarry or the animal dies shortly after birth. Cloned animals often have problems with their immune systems, lungs, and livers, causing death at an early age. They also have problems with obesity.

A recent study in Science and another in Nature in which researchers monitored gene expression in embryo and fetal development showed that mice cloned from ES cells had subtle changes in many of the genes involved in early development of the embryo and of the mouse after birth - changes that may not cause noticible defects in physiology or behavior, but may alter individuals slightly. Often genes are 'imprinted' during development - turned on or off depending on whether they came from the maternal or paternal parent. Changes in imprinting are seen when examining different clones of an organisms, suggesting again that subtle changes in gene expression occur during the cloning process. Although telomeres of cloned animals can be shorter than their non-cloned relatives, the significance of this finding is not yet known. PS. Happy Birthday to ewe, Happy Birthday to ewe...Dolly turned 5 (or is it 11?) on July 5, 2001. The lifespan of a sheep is about 6 years. V. Ethical Issues (we will do some worksheets about this both Monday and Wednesday): What are the benefits of and who benefits from reproductive cloning? What are the potential drawbacks or harmful things that could result from reproductive cloning?

Imagine a child growing up as a 'clone' of an adult from a member of her family. What are some of the 'issues' she might have to deal with (besides the usual issues like "nobody understands me" and "why can't I get my ears pierced?") What are the benefits of and who benefits from therapeutic cloning? What are the potential drawbacks or harmful things that could result from therapeutic cloning? Would you be willing to have rules or decisions about human cloning applied to you or your family members? Read if you are interested: 21 arguments against human cloning and their responses Objectives: 1. Please be able to state 'who' these cloned animals are and why we are discussing them: Dolly, Polly, Cumulina, Noah, and Cc. 2. Who is Ian Wilmut? (no, he is not a cloned mammal!) 3. Define cloning as it relates to mammals. 4. Describe the 'ingredients' needed to make a cloned mammal. What is the purpose of the diploid nucleus? Why is the recipient egg enucleated before the procedure? What is left in the recipient egg after e-nucleation and why is this important for the developing animal?

What is the purpose of the electric shock? What is quiescence and why does it appear to be crucial to cloning mammals? 5. List three reasons scientists are interested in cloning livestock animals or research animals like mice. 6. List two reasons scientists are interested in cloning animals like guars, and like cats and dogs. 7. What is the Human Cloning Prohibition Act of 2001? What has prevented this Act from progressing through the Senate and George Bush's desk? 8. What is human Reproductive Cloning? Who is pursuing this procedure? 9. What is human Therapeutic Cloning? Why may this procedure be needed to realize the potential of hES cells? 10. List 4 medical and safety issues concerning cloned animals. Dolly the sheep Dolly the sheep 5 min read Share As the first cloned mammal ever to be created from an adult cell, her birth was of huge excitement both to the scientific world and to the public. Dolly the sheep fact file Born Gifted by the Roslin Institute, University of Edinburgh Museum reference Dolly is on display again in our new science and technology galleries . Did you know? Dolly was named after the legendary country and western singer Dolly Parton.

Why clone a sheep? The development of cloning technology was an extension of the Roslin Institute's interest in the application of transgenic technology to farm animals. Transgenesis is the process of introducing an external gene, called a transgene, into a living organism so that the organism will display a new trait, which it may then pass on to its offspring. Transgenesis has been practised on mice since the early 1980s, producing so-called 'super mice' through a very sophisticated genetic modification technology using embryonic stem cells. Since embryonic stem cells had not been isolated from farm animals, this method of genetic modification was not available. Cloning was therefore a potential alternative way of achieving the same end. Hello Dolly As with all other cloned animals, Dolly started her life in a test tube. Once normal development was confirmed at six days, the embryo, which was eventually to become Dolly, was transferred into a surrogate mother. The pregnancy went without a problem and Dolly was born on 5 July 1996. The birth of Dolly was kept under wraps until the publication of the Roslin Institute's research results could be prepared.

Once these results were released, the full impact of the discovery became plain, as the world’s press descended on Roslin. Dolly's family In an attempt to allow Dolly to have as normal a life as possible, it was decided that she should be allowed to breed. A small Welsh mountain ram was selected as her mate and between them they successfully produced six lambs. Their first lamb, Bonny, was born in the spring of 1998. Twins followed the next year and triplets the year after that. Dolly as a lamb with her surrogate mother. © Roslin Institute. Dolly and her first lamb Bonnie. © Roslin Institute. Dolly the sheep being scanned. © Roslin Institute. Dolly's arthritis In the autumn of 2001, Dolly was seen to be walking stiffly. X-rays confirmed that Dolly did indeed have arthritis. It fueled the suspicion that cloned animals were destined to age prematurely. The cause of the arthritis was never established but daily anti-inflammatory treatment resolved the clinical signs within a few months. Dolly's final illness Although the arthritis was a concern for the animal carers at Roslin, a much more serious problem was feared.

In January 2000, another cloned sheep, Cedric, died. The post mortem revealed that Cedric had died of sheep pulmonary adenomatosis (SPA). This disease is caused by a virus that induces tumours to grow in the lungs of affected animals and is incurable. Dolly remained healthy until Monday 10 February 2003, when an animal care worker reported that he had noted her coughing. Full veterinary examinations and blood tests were conducted but failed to establish a diagnosis. A CT scan was carried out on 14 February 2003. The scan confirmed the team's worst fears: tumours were growing in Dolly's chest. Since a general anaesthetic had been necessary to perform the CT scan it was decided that it would be best if Dolly did not regain consciousness and she was put to sleep. Why is Dolly important? Dolly was important because she captured the public imagination. The idea that there might be an exact copy of oneself somewhere in the world is a theme that has been often pursued in science fiction and the prospect that it might be possible to clone a human being has excited a lot of speculation and interest.

Likewise, plans to clone extinct species such as mammoths have attracted a lot of publicity, but at present such ideas must remain, like Jurassic Park, firmly in the realm of fiction. Dolly on film This short animation about Dolly was made by young volunteers at National Museum of Scotland working with curators from our Science and Technology department and animator Cameron Duguid. Dolly takes on the Atom Smasher Dolly and the Atom Smasher was designed and made as part of a National Museums Scotland project, Game Jam, which brought together schools pupils, game developers and museum objects. Pupils from Craigie High School in Dundee worked with Dundee Games Collective (DGC) and staff from the museum’s Community Engagement team.

Question: What was the name of the first cloned mammal?
Answer: Dolly