Read more: Instant Expert: Cloning
The birth of Dolly opened the door to an unexplored realm of biology. At first, it was thought that a key application of the nuclear transfer method we used to create her would be to generate stem cells for use in medicine but in recent years it has mainly been used for genetic modification and for cloning rare and elite animals.
Cloning rare and elite animals
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Nuclear transfer has been used by teams who want to copy endangered species and elite breeds. Wildcats have been bred this way at the Audubon Center for Research of Endangered Species, New Orleans, Louisiana. A rare breed of wild ox called the gaur was cloned by the Massachusetts-based company Advanced Cell Technology. And a mouflon, an endangered species of sheep, was copied by a team at the University of Teramo in Italy.
Cloning has also been used to copy elite animals, which can then be used for breeding in the normal way. Idaho Gem, a mule born on 4 May 2003, and Prometea, a Haflinger female born 28 May 2003, led the way in cloned equine species. As part of an effort to preserve the bloodline of racing camels, Injaz was born on 8 April 2009 in the Camel Reproduction Center, Dubai. ViaGen, a company based in Austin, Texas, clones cattle, horses and pigs.
Others have cloned pet animals. In 2004 a cat called Little Nicky was produced by a California-based company from the DNA of a 17-year-old cat that had died the year before.
Then came Afghan hound Snuppy, in April 2005. The dog was cloned by a team in South Korea led by Woo Suk Hwang, then at Seoul National University (and who has since been censured for misconduct relating to other aspects of his cloning research).
Some have speculated that cloning could be combined with efforts to reconstruct the genetic code of extinct species such as the mammoth, allowing such species to walk the Earth again.
Therapeutic cloning
In the decade after Dolly, the most hotly anticipated use of cloning by nuclear transfer was to create embryos using the DNA of people with certain serious illnesses. From these embryos would come the stem cells that are the parent cells of the 200-plus different types in the body. This technique, known as therapeutic cloning, began to be eclipsed in 2006 when Shinya Yamanaka at Kyoto University, Japan, came up with an alternative way of creating human embryonic stem cells.
Yamanaka showed that it is possible to directly convert adult cells into embryo-like induced pluripotent stem (iPS) cells without resorting to cloning. This suggests that one day, after a heart attack, for example, you might manipulate skin cells from the patient by adding a cocktail of chemicals to form muscle cells. These cells could then be used to repair the damage to the heart. Or in the case of Parkinson鈥檚 you might make brain cells from iPS cells to counter the effects of the disease.
Unlike therapeutic cloning, Yamanaka鈥檚 technique does not need human eggs, which are in short supply. Nor does it create and destroy cloned human embryos, a practice some people find morally objectionable. In my own laboratory we are turning iPS cells into the two main cell types known to be involved in motor neuron disease 鈥� the motor neurons themselves and support cells called astrocytes 鈥� to help unlock the secrets of this fatal neurological condition.
After Dolly
Paradoxical as it may seem, the ability to create genetically identical offspring by cloning can help introduce highly desirable genetic changes into animals. In fact it was this possibility that motivated the project that led to my team creating Dolly.
In the 1980s, Martin Evans and Matt Kaufman at the University of Cambridge found a way to grow and multiply cells from the inner cell mass of a mouse embryo when it is a blastocyst 鈥� the part that will turn into the fetus and most of the placenta. These embryonic stem cells have unusual properties. They can be grown indefinitely, and they also retain the unique ability to form all of the many different tissues that make up an adult animal.
It occurred to me that you could use cloning to make a whole animal from a single cell on which you have succeeded in carrying out precise genetic surgery. That cell would be selected from among the millions of cells in which the surgery was botched or incomplete or had failed. That would offer huge advantages over old-fashioned brute-force methods for introducing the DNA of foreign genes into the cells of a developing embryo.
In these traditional methods, of 10,000 embryos injected with foreign DNA, only a handful would make it to productive adulthood in a typical experiment. Efficiency can be improved with methods to test if the DNA has been incorporated, but there鈥檚 another snag: the novel DNA can be incorporated randomly in an animal鈥檚 genome, with unexpected effects. There is also a danger that a newly introduced gene can be turned on in the wrong tissue.
This is what damaged the so-called Beltsville pigs, the result of an American team鈥檚 attempt to boost the growth of swine with a human growth hormone. The plan went awry when the hormone was made and used in the wrong tissues. The result was arthritis, lameness, mammary development in males, and a host of other problems.
The first demonstration that cloning would also make it easier to carry out the genetic alteration of animals came with the birth of the sheep Polly at the Roslin Institute. She carried a human gene for a blood-clotting protein in every cell of her body: it got there because the DNA of the cell nucleus from which she was cloned had been engineered to contain the human gene.
At GTC Biotherapeutics in Framingham, Massachusetts, transgenic goats produced using a similar technique are making a human anticoagulant protein. This is used to treat people whose blood is deficient in this type of protein, and so are vulnerable to dangerous blood clots and deep-vein thrombosis. Hematech in Sioux Falls, South Dakota, has unveiled cattle which can make human polyclonal antibodies that can help fight antibiotic-resistant infections, and treat immune deficiencies and other illnesses.
The introduction or deletion of genes offers the means to make animals that grow faster for meat production or are resistant to diseases such as BSE, and mastitis, an infection of milk glands. Revivicor of Blacksburg, Virginia, hopes that cloned transgenic pigs can eventually provide suitable organs to overcome the chronic shortage of suitable organs for transplant.
The biotech company Genoway, based in Lyon, France, specialises in creating rats with human gene sequences and mutations that can be used to investigate diseases of people.
And, to help study cystic fibrosis, a team at the University of Iowa has pigs containing the faulty human gene that causes the condition.
The possibilities appear almost endless.
Human cloning
Maverick scientists often claim that the work on Dolly and other animals has prepared the ground for cloning human beings.
However, the experience of cloning animals so far has shown that the possibility for harm far outweighs any currently conceivable benefits.
To make Dolly, my team at the Roslin Institute started with 277 reprogrammed eggs. Only 29 made it to the stage where they could be implanted into 13 surrogate mothers. Of those sheep, only one became pregnant, carrying Dolly.
To repeat the Dolly experience in humans would mean obtaining around 300 human eggs, which are already in short supply, and persuading 29 women to agree to having an embryo implanted. Of those, 28 would risk the hurt and emotional turmoil of failed pregnancies, miscarriages and deformed fetuses so that one embryo would 鈥渢ake鈥� to produce a child. It adds up to an intolerable exercise in human misery and suffering.
There are also concerns regarding the psychological and social impacts on any child brought into being by cloning, which have been explored by the psychiatrist Stephen Levick in his book Clone Being.
The pressures on a cloned child during their upbringing could be extreme. Take, for example, a situation in which parents might attempt to undo the loss of a dead daughter by cloning another child from one of the dead child鈥檚 cells.
With parents who regard her as a replacement, a living memorial to the dead, the clone would have difficulty in developing her own identity. And she would, in any case, be unlikely to fill the shoes of the ghost sibling.
For reasons such as these, I oppose human reproductive cloning. To clone humans would be utterly irresponsible.
