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 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.
Read about more breakthrough advances in science made through animal research in our timeline
- Year: 1996
- Scientist(s): The Roslin Institute
- Animal(s): Sheep
- Countries: United Kingdom
- Research field(s): Anatomy and development, Cell biology, Genetics, Medical technologies
- Medical application(s): Basic research
Dolly, the world’s most famous and controversial sheep, was born twenty years ago – on July 5, 1996 to be precise. She was the first mammal to enter the world following a process of reproductive cloning, making the event a spectacular scientific breakthrough.
To create Dolly, researchers at the Roslin Institute in Scotland employed a technique known as somatic cell nuclear transfer (SCNT). With SCNT, DNA from the nucleus of an ordinary cell - obtained from anywhere in an animal’s body - is transferred into an enucleated oocyte (egg cell), typically from a different animal.
In Dolly’s case, her DNA came from one sheep’s mammary cell; it was implanted into an egg from another sheep; and the resulting tiny biological entity was implanted into the uterus of yet a third sheep, where it grew until birth.
The result of SCNT is a creature with almost the same genetic potential as the one providing the nuclear DNA. SCNT is thus a powerful, and often effective, form of animal cloning.
Dolly is born! Announcement and reaction
Subsequently, in February 1997, Ian (now Sir Ian) Wilmut and his research team at the Roslin Institute announced Dolly’s birth in the prestigious science journal Nature. This provoked political and ethical debates that have never truly stopped.
Public discussion of cloning gradually receded in prominence as new issues arose to dominate the airwaves and the headlines, notably the threat of jihadist terrorism following the attacks on September 11, 2001. But issues relating to cloning technology remain crucial to debates over biomedical research and its regulation.
The announcement – with a description of the method used to bring Dolly into existence – triggered a feverish worldwide response because of the possible implications for human cloning. It was immediately obvious that SCNT could, in principle, be used to create human babies. Across the world, many countries banned human cloning - often with significant punishments, such as lengthy jail terms, even for attempting such a thing.
The case against cloning
The actual arguments against human cloning are extremely varied, and I cannot elaborate them all here. (I go into more of them, and in far more depth, in my 2014 book, Humanity Enhanced: Genetic Choice and the Challenge for Liberal Democracies).
One common claim is that bringing children into the world in this way is somehow a violation of the natural order, or of human dignity; or perhaps it would be an act of “playing God”. Unfortunately, it can be very difficult to pin down precisely what any of these claims really mean in the context of bioethical debate. I am, for example, sceptical about the existence of anything that can correctly be called “human dignity”.
Some critics fear that children created via SCNT would be subjected to unfair expectations of duplicating the talents and achievements of whoever provided their nuclear DNA. Sometimes the critics speak in terms of the autonomy of the child being violated, diminished or denied, although it can be very difficult to spell out exactly what this amounts to. In Humanity Enhanced, I challenge the idea that children conceived through SCNT would have their autonomy violated – or would somehow lack or lose autonomy – in any sense inapplicable to “ordinary” children.
Some critics worry about a larger social effect, or even an effect on our species, if cloning restricted the diversity of children being born (perhaps because parents and doctors might look for donors with a narrow range of characteristics, such as possessing high intelligence and meeting certain standards of physical beauty).
Yet other arguments acknowledge that reproductive cloning in itself might not have a great social or species-wide impact; however, it’s claimed, cloning could place human societies on a slippery slope toward accepting even more radical technological interventions such as genetic engineering of human traits. On one version of the approach, this would, in turn, set us upon a path to unequivocally horrible social outcomes. Thus cloning supposedly confronts us with a slippery slope to another slippery slope … which seems like a tenuous style of argument.
Though some of these fears may have an element of truth, they are all exaggerated. In my view, which I’ve defended in Humanity Enhanced and other publications, human cloning would not be a seriously worrying action if we could carry it out safely.
To some extent, however, all of this is moot. Over the past twenty years, we have enjoyed success in cloning many mammalian species, but no one has cloned a human being. Indeed, we have been frustrated in efforts to clone other primates such as apes and monkeys.
In the upshot, human reproductive cloning is not yet feasible, and indeed there’s no current prospect that it could be carried out effectively and safely in the foreseeable future. Even if we did conceive a human embryo through SCNT, and we then managed to bring it to term, the odds are very high that the result would be a seriously deformed child.
That’s a good pragmatic reason not to make attempts until we know a lot more, and even then we’d need to have developed the technology to a point where we are about as likely as with ordinary births to end up with a healthy baby.
I don’t rule out that someone might accomplish this technological feat one day, but, once again, there is no sign of it happening. Nor is it what SCNT research is really about from the point of view of reputable medical researchers. The real action is with what is known as “therapeutic cloning”. Allow me to explain.
Reproductive and therapeutic cloning
So far I’ve focused on “reproductive cloning”, and more specifically on human reproductive cloning: the postulated use of SCNT (or any other technique that might have a similar result) to bring about the birth of a human child.
By contrast, the expression “therapeutic cloning” refers to the creation of human embryos by SCNT for some other purpose, such as for biomedical research or for harvesting cells or tissues to be used in therapies.
Although some ethical issues are raised with therapeutic cloning – including a concern that the associated research destroys human embryos – the idea has been obtaining legal acceptance in some countries, usually subject to tight government regulation. If we start to see impressive results from therapeutic cloning, with new therapies emerging from the research, I expect that it will eventually obtain the same wide acceptance that IVF – in vitro fertilization – now enjoys in Western countries. (It’s not that long ago that IVF was also widely regarded as abhorrent.)
More generally, people come to embrace new technologies, even those that initially seemed shocking and “unnatural”, once concrete benefits become clear.
Twenty years later
Two decades later, I’m not sure that the ethical arguments advanced for and against human cloning are greatly different from those we saw back 1997. However, the early debate was very one-sided. The initial response to the dramatic Nature article by Wilmut et al. was largely one of fear, mingled with disgust, with too little rational reflection. Since then, the fear-mongering has partly died down, but not before a great deal of draconian legislation was enacted across the world. Little chance was given for calmer voices - or any dissenting voices - to be heard before governments took action.
As it seems to me, calmer voices eventually won the academic debate. There is a strong sense, within the field of secular bioethics, that the early arguments against human reproductive and therapeutic cloning were flawed. However, dissenters lost the political debate almost before it began. Politicians, journalists, many academics, and the general public in our Western liberal democracies greeted the very idea of human cloning with a cascade of hostility.
The expressions of fear, disgust, and moral outrage appeared immediately; in response, highly illiberal laws were enacted without due consideration of the issues.
But more reasonable people are slowly winning back the central political ground, gradually making the public case that technologies based on SCNT may bring many benefits. That, perhaps, will be the story of the next twenty years.