WHEN she was born human cloning seemed only a matter of time. But six years on Dolly is sick and copying humans remains a distant prospect. So is this the end of the road?
The most famous sheep in the world ambles over to greet me from the far end of the paddock. There is an expression of affectionate resignation on her face at the prospect of the photographic ordeal she has learned to associate with visitors. She is a pro.
Like most stars, she isn’t the size you expect from her pictures. In Dolly’s case she’s a lot bulkier. Habituated to human attention, she is friendly and gentle and convincingly feigns interest in the affairs of strangers.
Dolly looks healthy, but she is on a course of anti-inflammatories for the arthritis that struck her, unusually early for a sheep, a few months ago. It’s hard to say – sheep don’t normally live to pensionable age – but, at six years old in July, she is probably approaching her forties in human terms.
The medicine seems to be working. Her arthritic limp is gone. The illness may be a sign that, as some scientists believe, even apparently healthy clones are doomed to suffering and an early grave. Or it may be just a coincidence. Either way, the first animal in the world to be cloned from another adult animal is getting old. It is virtually certain that she will be put down before the end of the decade, and with her ageing comes the question: where are the clones? Where are the replicas, human and animal, that the media and public dreamed of back in 1997, when Dolly’s existence was revealed to the world?
True, every few months a new addition is made to the list of animal species to have been cloned, but each clone is made with enormous difficulty, at great cost and with a huge loss of unviable embryos, such that they are not ready to be of practical use to farmers or scientists.
True, there have been repeated promises by a Bedlam of eccentric egoists that a cloned baby is just around the corner – the latest by Italian fertility doctor Severino Antinori at the beginning of this month – but this dangerous experiment with human lives carries with it doubts that any of the participants is up to the job.
It is beginning to look as if the incredible achievement of cloning an animal will mean something entirely different from what we thought it meant at the time. When we heard about cloning, we thought: “Identical copies.” The true significance of Dolly may be the opposite: diversity.
Nearly six years of furious experiments have shown that making replicas of animals is hard and gets no easier, but it has confirmed what Dolly was extraordinary evidence of: that our cells can be persuaded, given enough time and effort, to remodel themselves, to change their nature and to travel back in time.
Doctor Ian Wilmut, who led the team that cloned Dolly, has always been opposed to the reproductive cloning of humans. At the time Dolly was born, and for some years afterwards, he thought of cloning as a means of making copies of animals. Sitting in his office at the Roslin Institute near Edinburgh he told me that he had changed his mind. The persistent failure of scientists to make animal cloning a more reliable procedure over the years had left him, not disillusioned exactly, but feeling vaguely let down.
“I suppose I would say I’m disappointed, yes,” he said. “Scientists by nature are optimists. You have to be, don’t you. So … I suppose I might have hoped that by refinement of the techniques there might have been more progress.”
Dolly was born and grew up apparently healthy after 276 failed attempts. Since then none of the other species to have been cloned has improved much on that appalling failure rate. Research on cloned mice in Japan suggests they live sick and die early. Some species – dogs, horses, monkeys – have resisted attempts to clone them altogether.
“There’s been zero progress. I mean it. Zero,” says Rudolf Jaenisch of the Massachusetts Institute of Technology, a leading cloning researcher.
Wilmut doesn’t rule out or rule in the idea that Dolly’s arthritis is a symptom of her clonal origins. But the Japanese mice study clearly bothers him.
“There appear to be two schools. I think the reality is somewhere between the two extremes. One group of people says of course there are lots of problems with healthy clones; another group – Jaenisch would be an extreme member – says probably there aren’t any perfectly normal clones. The scientific answer, of course, is that we don’t know. Even the people who are saying how normal their cloned calves are – their oldest animals are four years old, in a species which can live up to 20.”
Given the difficulties, Wilmut doubts that men like Antinori have the ability to clone a human being. His fears are less that Antinori might succeed than that he might try and hurt women and destroy embryos in the attempt; and that he gives the field a bad name.
“I think we treat people like Antinori far too seriously,” he says. “I would encourage people like you to ask them about the pigs they claim to have cloned, the monkeys they claim to have cloned. Unless they will actually show you those animals, we should start to ignore them.”
What is the point of cloning, without clones? If there were one word Wilmut would use to sum up the point, it would be “plasticity”. If that’s not much help, think of the difference between Plasticine and fired clay. The old model of life was like the clay. The cells that make up living things are assembled according to the pattern in DNA and then fixed in their role, as if they were clay models fired in a furnace. Dolly showed that life was more like Plasticine: that you can take a lump of it, fashion it into an intricate shape, and then roll it into a ball and model it into something else.
The single cell from which Dolly grew had seemed fixed in its highly specialised role in a sheep’s udder. The cell had the same set of genes as all the others in the animal, but an array of tens of thousands of chemical switches had been set so that most of those genes were not being used. The creation of the embryo from which Dolly was born showed that it was possible to strip away those switches, to take the cell back in time to a point where it had the potential to turn into anything.
There will be more animal clones. There may be human clones, and the world will be amazed, and perhaps appalled. But to Wilmut clones are beginning to seem something of a vaudeville sideshow next to the real enterprise of learning how to manipulate individual cells and the genes within them, to fabricate replacement cells for transplant and to alter the DNA in living people.
“I think there are several reasons why cloning could be useful, but for me, the main one is not for cloning itself. I think that the Dolly experiment is one of several experiments that more or less at the same time suggested there is far greater plasticity in mammalian development than we had expected, and that we are going to be able to manipulate that much more effectively than we’d expected,” he says.
Roslin is turning its research away from cloning whole animals towards basic research at the cellular level Wilmut intends to apply to the Human Fertilisation and Embryology Authority for a licence to work with donated surplus human embryos from an in vitro fertilisation programme. He hopes to derive lines of embryonic stem cells, cells at their most plastic. He is reluctant to acknowledge how great a change this is for him, but he will allow that his view of the significance of cloning has altered.
“We concentrated [in the mid-1990s] on trying to use cloning to make genetic changes in animals for biomedical purposes … My personal view would be that, in the longer run, understanding developmental plasticity and manipulating it will be much more important. I see this as a shift in my thinking, rather than a revelation.”
Wilmut doesn’t think the media will lose interest in him and the institute when Dolly dies. Their names, and destinies, will be forever linked. I ask Wilmut whether, if he were a hill farmer, he would have put Dolly down already. “Yes,” he says. “You couldn’t afford the veterinary surgeon’s fees.”
So was it simply a question of a calculation about the degree of suffering she was going through? “That’s correct. At the present time I don’t think she is suffering, but if she were suffering significantly, she would have to be euthanised, just out of kindness.”
After she dies, Dolly will undergo an exhaustive postmortem, before being stuffed and put on display in the National Museum of Scotland. Wilmut says he isn’t holding back from signing her death warrant only because of her scientific value. The other reason is “just straight sentimentality”. Did he feel affection towards Dolly? “Oh, yeah.”
Dolly’s life is a plain one. She divides her time between the paddock and the straw-floored byre where she sleeps. She drinks out of a grubby yellow plastic bucket and eats grass, hay and sheep nuts.
Douglas McGavin, an assistant on the farm, says he thinks sheep are intelligent, although he never explains what it is about Dolly that is intelligent apart from her learning to associate him with food.
Does he think sheep got bored? “No. I think she gets programmed to her surroundings and that’s a completely normal life to her.”
Just like us, then? “Just like us.”