Read more: Instant Expert: Cloning
When she was born in the Roslin Institute near Edinburgh, UK, on 5 July 1996, Dolly marked the beginning of a new era of biological control. With a large team, I was the first to reverse cellular time, the process by which embryo cells differentiate to become the 200 or so cell types in the body. Some pundits have even said that Dolly broke the laws of nature. But she revealed, rather than defied, those laws. She underscored how human ambition is bound by biology – and by society’s sense of right and wrong.
Dollymania
Once the news of Dolly’s birth became public, in February 1997, she made headlines and captured the imagination of commentators, politicians and headline writers across the planet.
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“Researchers astounded… Fiction becomes true and dreaded possibilities are raised.” That was the quaint way that one newspaper greeted the news of Dolly’s birth, but it was not the only one to sound the alarm. In the US, President Bill Clinton responded by asking the National Bioethics Advisory Commission to report on the ethical and legal issues relating to the cloning not just of animals, but of human beings. The Vatican and the European Commission swiftly followed suit.
Within a few months came the first claims – never substantiated – that human pregnancies were under way with cloned embryos. Rumours along similar lines have circulated ever since, courtesy of cults and maverick scientists.
The life of Dolly
Dolly became a global celebrity. She starred in photo-shoots for People magazine, and became a cover girl. Plays, cartoons and operas were inspired by her story, and advertisers traded on her image. Her birth also raised many profound ethical and moral issues, and shocked lay people who were disconcerted by the implications of reproduction without a male and female being involved.
“Her birth raised many profound ethical and moral issues, and shocked many people”
Many scientists were shocked, too, but for a different reason: Dolly had been cloned from the DNA of an adult cell. Previously, it had been thought that the mechanisms that read the DNA code to generate a particular type of adult cell – skin, muscle, brain, or whatever – were so complex and so rigidly fixed that it would not be possible to undo them. By showing it was possible to turn back the clock of development, Dolly overturned this deeply held conviction. This feat had numerous potential applications, from cloning elite animals to making replacement cells and tissue in the laboratory that is identical to a patient’s own.
Death of Dolly
After a few years as the world’s number one celebrity sheep, Dolly developed breathing problems and a cough in February 2003. We suspected she was suffering from pulmonary adenomatosis, a disease that is not uncommon in adult sheep, which is caused by the jaagsiekte retrovirus.
The virus infects lung cells, making them divide uncontrollably. The resulting lung tumours cause emaciation, weight loss and shortness of breath.
Dolly was sent for a CT scan at the Scottish College of Agriculture in Edinburgh, and that same afternoon the vet told me that Dolly’s infection was worse than we had thought. The scan revealed the full extent of her lung tumours, and it became clear that her suffering should end. Dolly was never allowed to recover from the effects of the general anaesthetic she’d been given for the scan, and was dispatched with an injection of barbiturates.
The autopsy confirmed that Dolly’s lungs contained large areas of firm, grey solid tumour. There were also signs of pleurisy, and her larger airways and trachea contained white, frothy fluid. Although there has been much speculation about how the process of cloning had affected Dolly, the post-mortem revealed nothing particularly unusual for an animal of her age and her weight.
Megan and Morag
Dolly was not the first sheep to have been cloned from cells that had progressed beyond the early embryonic stage. That distinction goes to Megan and Morag, twin Welsh mountain sheep that were created from partly differentiated cells by Keith Campbell of the Roslin Institute near Edinburgh in the UK, where I led a large team conducting nuclear transfer.
Campbell came up with a profound insight into how an embryo could result from implanting a differentiated cell into an egg that had been emptied of genetic material, then using an electric shock to fuse the contents. The key to success was to put the differentiated donor cells into a resting state called quiescence. This was done with differentiated embryo cells to make Megan and Morag.
But Campbell had always believed that cloning with adult cells would become possible, and we all set out to test the idea. This time we implanted a cell from the mammary gland of an adult ewe into an emptied egg – which is how we came to choose her name, a reference to singer Dolly Parton.
The birth of Dolly on 5 July 1996 marked the dawn of a new era. Her very existence overturned the biological understanding of the day – the dogma that development runs only in one direction in nature. Until then, it was it was thought that once cells had differentiated into the many specialised cell types that make up an adult animal’s different organs and tissues, this can’t be reversed. Dolly showed it was, after all, possible to turn back biological time.
