The journalists who flocked to the Roslin Institute, near Edinburgh in Scotland, on Tuesday, February 25, came to witness one of the most extraordinary scientific developments of the 20th century. Dolly is only a seven-month-old sheep, but she will go down in history as the most famous of them all. For she wasn't brought into this world by normal reproduction-She has been cloned from an adult sheep.
It is the first time a mammal has ever been created from the non-reproductive tissue of an adult animal, and the implications are momentous. If the same technique can be applied to humans-and there is evidence that it can-then we are not far off an age when each of us could have our very own clones, made from our own tissue.
"We know we can use this method to grow animals like Dolly," explained Dr. Ian Wilmut, head of the team from the Roslin Institute and the pharmaceuticals company PPL Therapeutics which made the breakthrough. "And there is no practical reason why we could not do it with humans. The technology is out there. It is now up to society to decide how it should be used, and we welcome any discussion of these matters."
The discussion, however, started the moment The Observer newspaper in London ran a front-page exclusive on February 23 about Dr. Wilmut's achievement. Exact details were due to be revealed later in the week in Nature, the respected scientific journal, but news leaked out and the speculation began. Was mankind about to embark on a Brave New world, reminiscent of Aldous Huxley's nightmare vision of a scientifically engineered society? Would we be faced with not one, but fifty Saddam Husseins? (In Ira Levin's book The Boys From Brazil, Adolf Hitler is cloned fifty times.)
The story might have remained in the realms of fantasy for most journalists had not US President Bill Clinton ordered a report from his medical committee into the Edinburgh breakthrough. He claimed there were "serious ethical questions" to be answered and demanded a report on his desk within 90 days, instantly introducing gravitas and a mild state of panic to the proceedings.
Joseph Rotblat, the British Nobel Prize-winning nuclear physicist, joined in with a weighty salvo, warning that Wilmut's experiments "represent science out to control- a means of mass destruction." On a lighter note, an ABC comedy show in America convened an all-day meeting to come up with new sheep jokes.
By February 25, Dr Wilmut felt it necessary to face the press and tackle some of the issues which had raised. First, though, there was the more serious matter of Dolly's name. (When the British journalists are presented with an important scientific discovery, you an count on them to pose the crucial questions.) Who was she named after, someone asked.
"She was derived from mammary cells and the people looking after her couldn't think of a more impressive set of mammary cells than Dolly Parton's," said Dr. Wilmut, referring to the American country and western singer who is famous for her ample breasts. Already sated on sheep puns, the tabloid newspapers couldn't believe their luck! An excuse to show Parton's cleavage in the honourable pursuit of science.
Dr Wilmut then went on to admit that, yes, his technique could be used for humans, but not in the way envisaged by the nation's febrile imaginations. "You cannot blame the scientist for making these kind of discoveries," he said. " We are not Frankenstein type people. If we hadn't made the breakthrough, somebody else would."
To appreciate the full significance of Dolly's humble life, and how it might lead to human cloning, it is necessary to understand the scientific process by which Dr Wilmut and his team created her. A clone is an organism which is genetically identical to another. Unlike a number of other organisms, adult mammals are not able to clone themselves. (All mammals reproduce sexually, except in the case of twins, triplets, etc.) In the past few years, however, scientists have been able to clone mammals by copying what happens during the formation of twins. While an embryo is still developing, it is deliberately split into two. Each cell,at this early stage, is capable of growing into a complete being.
Last year, Dr Wilmut and his team produced two identical lambs, named Megan and Morag, from the same embryo, a feat which was also written up in Nature, though with less fanfare. In the latest round of experiments, Dr Wilmut produced four more sheep from an embryo-three from a sheep foetus which was aborted after 26 days-and, of course," said Dr Wilmut. "This time, we thought we would take them from a foetus and an adult as well. It worked with all three."
Dolly, however, is quite different from these other clones. The technique used by scientists to clone mammals is called "nuclear transfer" and has been around for some time. It involves fusing two cells together: a donor cell containing all of its DNA, and an immature, unfertilized egg cell, known as an "oocycte", which has been stripped of its original chromosomes to leave it DNA-free.
Up until now, the donor cells have belonged to embryos or foetuses. It is not all that difficult to clone embryos-researchers at the George Washington University even cloned human embryos four years ago. But all attempts to use mature donor cells from adult mammals had ended in failure.
The main hurdle was 'specialization' by mature cells. All the cells have the same genetic blue-print but once a cell assumes the role of an organ it loses its innate ability perform the functions of any other organ. It was thought that these cells switch off some genes permanently, and take on an irreversible identity in keeping with their adult role. The skin cell, for instance, takes no interest in producing insulin and specializes in matters like melanin.
Dr Wilmut has succeeded where others have failed by managing to wind back the biological development of an adult cell. In the case of Dolly, he took a cell from the udder of six-year-old pregnant sheep (a Dorset Finn ewe, no less) and reprogrammed it to forget its current role and begin life all over again. In other worlds, it was no longer a dedicated udder cell; instead, it had the same youthful, carefree qualities as a cells taken from an embryo.
Dr Wilmut believes that the key to his success was the method in which he manipulated the adult donor cell. he did this by starving it into a state of hibernation. He placed it in a hostile salt solution, to send almost all its genes to sleep, and later introduced it to an unfertilized egg cell (which had its own nucleus and genes removed) from another sheep.
The actual fusion was encouraged by a small electric nudge, and the cells were then allowed to grow and divide in a culture dish, where they formed a blastocyst-an embryo cell. This was then implanted into a third sheep, which gave birth five months later to Dolly.
Dr Wilmut's cloning technique still has considerable teething problems. He fused 277 udder cells and eggs but only 29 eggs grew into embryos. And only 13 of the surrogate mother sheep became pregnant and just one gave birth. all other embryos perished in the womb.
Nobody knows how quickly dolly will age. And it is unclear whether cells from other parts of a body (the heart, or nerve cells) can be made to forget their specialist roles as successfully as udder cells. Still, even one Dolly is an unprecedented achievement.
It remains to be seen what the full implications will be for humans. Some people are already musing on the creation of brain-dead clones as a source of perfectly matched organ transplants. At present, however, the more likely scenario-conceded by Dr Wilmut- is one in which human embryos could be allowed to grow to a certain stage, allowing bone marrow, for example, to be removed. The embryo would then dies before it was born.
"In many ways, cloning could offer enormous benefits," says Silmon Fishel, embryologist and scientific director of the Nurturer fertility clinic in Nottingham. "You could alone from an adult or a child that is sick to produce embryonic stem cells that could be used to repair that individual's damaged tissues."
Following the Warnock report on test-tube babies in the 1980s, legislation was drawn up in Britain to make human cloning illegal. But that was human cloning illegal. But that was before Dolly. The law might now have to be tightened up, or slackened, depending on how the government ultimately views that latest changes. minds are still being made up, although the ministry of agriculture has just announced that its government funding for Dr Wilmut's project will be withdrawn in April next year.
"In my view, the current prohibition should remain in force," says Margaret Brazier, professor of law at Manchester University. " Brain-dead clones nurtured as organ banks would radically change the nature of what it is to be human. If a clone was allowed to develop as a normal child, who would be responsible for her welfare, who would be her parents, how would she cope psychologically and socially?"
Followings the Warnock report on test-tube babies in the 1980s, legislation was drawn upon Britain to make human cloning illegal. But that was before Dolly. The law might now have to be tightened up, or slackened, depending on how the government ultimately views that latest changes. Minds are still being made up, although the ministry of agriculture has just announced that its government funding for Dr. Wilmut’s project will be withdrawn in April next year.
"You can call them hair-raising scenarios, but I know of very wealthy, egocentric people who have in the past expressed an interest in cloning themselves," says Martin Johnson, professor of reproductive sciences at Cambridge University. "There is the theoretical possibility of funding the application of this technology in countries where it not forbidden. It is unlikely, however, that asexual reproduction will ever catch on amongst humans.
As the economist said so succinctly in its leader: "It would be suicidal, not just dispiriting, for the species to give up sexual reproduction in favour of cloning. Sex creates new gene combinations that confer new strengths, especially resistant to disease. The distinguished biologist, George C. Williams, once said that asexual reproduction is like xeroxing your lottery ticket. Even if you have the winning number, making many copies won’t help unless the winning number is the same every time."
Dr. Wilmut and his team have just won the lottery, but nobody is quite sure about the prize.
DOLLY’S creator lives a quiet life in Scotland, in a hamlet outside Edinburgh, with his wife Vivienne, enjoys bracing mountain walks and likes to relax with " a good malt Scottish Whisdy". But he was actually born in England, near Warwick, in 1944-the year the first ever in vitro fertilisation was attempted.
Wilmut studied embryology at Nottingham University under the famous G. Eric Lamming, and soon after completing his doctorate at Cambridge (the thesis was on boar semen) he produced a calf from a frozen embryo in 1973. His work helped breeders improve the yield of their cattle.
He had by then joined then Roslin Institute, known till four years ago as Animal Breeding Research Organisation. It was born in the war years, just as Wilmut was, and its birth, like Dolly’s, had a link with starvation. If Dolly’s parent cell was starved of nutrients before cloning, the institute was set up for genetics research to help ward off famine in Britain.
It was his taste for Scotch that eventually led Wilmut to Dolly. Ten years ago he heard at a bar in Ireland that a Danish scientist in Texas, Dr Steen M. Willadsen, had cloned a sheep from a developing embryo cell. That made Wilmut wonder: why not clone an adult animal?
He found another man thinking along the same lines when biologist Keith Campbell, now 42, joined the institute in 1991. Campbell believed that if one could clone a mammal one could clone any mammal. And he had the vim: he was a science fiction buff, which Wilmut never was.
Eventually it was Campbell’s imagination that helped them break through the barrier. He guessed, ingeniously, that an egg could be persuaded to accept an adult cell if the latter did not make a fuss about it. In other words, the activity in the cell(creation of new chromosomes) had to be near-inert during the union.
Campbell proposed that the cell be put on a starvation diet to tame it. Wilmut did just that: he took an udder cell from a sheep and fed it just one twentieth of the nutrients it normally got. When it became quiet and inactive, he fused it with another sheep’s egg from which he had removed the nucleus. An embryo was born without fertilisation.
That was in the last week of January 1996. Six days later Wilmut put the embryo in the womb of a third sheep, and Dolly was born in a shed near the institute on July 5 at 4 p.m. Wilmut learnt of it only the next day, and the donor sheep wasn’t bleating in joy: it had died.
There was wild breast-beating when Wilmut, after patenting the technique, announced the birth this February and admitted that it was possible to clone humans. Scientists, politicians and priests conjured up horrors of human cloning: megalomaniac tyrants filling the earth with their own cruel clones, mummies stalking out of human spare parts springing up like the old slave markets, a Pandora’s box of new genetic diseases being prised open, the concept of family collapsing…..
While the British government planned to cut funds for Roslin Institute, Clinton cried a halt to all experiments in human cloning in the US. The Vatican warned against "abuses of all kinds that threaten the dignity of life." What would happen to a clone’s soul and karma, wailed a Buddhist monk in consternation.
Such reactions were hardly surprising. Worse intellectual violence and deeper anguish were on display when Copernicus moved the earth from the centre into an insignificant part of the universe and Darwin found man closer to the ape that to God.
The church appeared aghast that powers of ‘immaculate conception’ and ‘resurrection’ were within man’s reach. Wilmut, an atheist, wan’t trying any such thing; he found that idea of cloning a human being repugnant. But who could stop the march of science? "If you asked, "Could you start tomorrow and in months’ time produce a cloned human?’ the answer would be ‘Absolutely, definitely, no’. A huge amount of experimental work would have to be done before that," he said.
Many embryologists agreed with the comment by Nature: "Cloning humans from adults ‘tissues is likely to be achievable any time from one to ten years now." As if in confirmation, came the news that Dr Don Wolf of Oregaon, US, had cloned two monkeys, a species far closer to humans than sheep.
It was not such a scientific triumph as Dolly - the monkeys were cloned from a developed embryo rather than an adult-but it brought ever closer the possibility of human clones. Among those who hailed the news were hopelessly infertile couples, besides lesbians who exulted over the prospect of making babies without dealing with disgusting sperm. Someone even claimed that, with cloning, the world could do without men.
More excited were cryogenics freaks like David Pizer, a real estate broker of Arizona who would have himself frozen on death-so that scientists might eventually resurrect him. " I want to be able to live forever, in some form, some place," he said. " I want to be either myself or an exact duplicate copy of myself."
He as asking for cloning the body and mind, though he knew science was incapable of cloning consciousness. Making even an exact physical copy is a tall order because many factors such as diet and environment play major roles in the growth. One can at best get a somewhat identical twin, who may not behave like the person cloned. Twins share the same genetic makeup but have separate identities and characters.
Yearning for cloning is fervent in parents of dying children. "People say that if a child dies, you can get that child back," Wilmut said. " It is heart-wrenching. You could never get that child back. It would be something different. People are not genes. They are much more than that."
That is why he wants to carry on cloning "to enable us to study genetic diseases for which there are no cures." Like him, many scientists believe that experiments in cloning will help man conquer cancer and other genetic diseases and delay the process of aging.
The next animal to be cloned, it seems, is the cow. Scientists at Wisconsin University plan to clone a ‘supercow’ to triple its milk yield to 40,000 gallons a year. The technology will than be used to clone disease-free cattle which produce ore beef, chickens which lay more eggs and sheeps which produce more wool.
Researchers at PPL Therapeutics, which spent $750,000 on Dolly, recently produced a transgenic cow, Rosie, by injecting human genes into her embryonic cells. Rosie’s milk contains almost all the amino acids that a newborn baby needs and might be used as a substitute for breast milk. But all that pales in comparison with Wilmut’s giant scientific leap with Dolly.
As PPL chief executive Dr Ron James said, Wilmut "is careful, diligent, honest and thoughtful." He will need all those qualities in the coming years. The genie he has let out of the bottle has made him the target of rival commercial companies and ethical vigilantes of science and religion.
Has he beaten God? Nah! The Bible-bangers would scream. ‘Didn’t God take Adam’s rib and make Eve? Wilmut just made a ewe!’
