Horizon (1964) s34e06 Episode Script
Dawn of The Clone Age
1 Archive programmes chosen by experts.
For this collection, Prof Alice Roberts has selected a range of programmes to celebrate Horizon's 50th anniversary.
More Horizon programmes and other BBC Four Collections are available on BBC iPlayer.
'There are many people who think there's a territory 'called God's Domain that we should not cross over into.
' 'To me, although we've made a new life in a new embryo, 'it isn't really a person.
' 'Cloning a whole human embryo for spare-parts surgery, 'that would be murder.
' 'And it's possible to clone people without their consent.
' 'We are in the shadow of that knowledge 'and it came to us without us being properly prepared.
' # Hello, Dolly .
.
It's so nice to have you back where you belong On February 23rd 1997, the first cloned adult animal became a superstar.
This is the story of the cloning of Dolly and the remarkable implications of her birth.
As the news broke, the scientists who made her at the little-known Roslin Institute near Edinburgh found themselves thrust onto the world stage.
It was really rather overwhelming.
There was just a flood of requests for information.
And we were occupied for, I guess, almost 12 hours on that Sunday dealing with phone-calls from newspapers and radios all around the world.
We were beginning to get phone-calls from the States, first from the east coast, then from the west coast, and then from Australia and New Zealand.
And we realised this was a continuous 24-hour operation.
When we were wandering round the institute, there was a phone ringing from the cleaner's closet.
I wasn't aware there was a phone in this particular small room.
Going inside into an even smaller cubbyhole, I saw a phone, picked it up - it was the Daily Mirror.
It was chaotic here.
NEWS: The world's first clone has been produced of an adult mammal We had TV crews from CNN, ABC, CBS, NBC - all the American networks - beaming live broadcasts to the early morning news on the east coast.
In the first 10 days after the story broke, we estimate that collectively we've handled 2,000 calls from the media and we've provided in-depth interviews to at least 100 reporters from all over the world.
The Science Museum in London have offered to stuff Dolly for posterity when she dies.
We've had requests for Dolly to appear on a US chat show.
NEWS: International pressure for a ban grows following news last week that scientists had successfully cloned a sheep.
NEWS: Some critics say human cloning has become a step closer.
How easy might it be scientifically for someone, somewhere, to apply your method to the cloning of humans? It would be my belief that if you really wanted to do it, it could be done.
'The President today has asked 'his National Bioethics Advisory Commission to make a judgement' I personally have still not heard a potential use of this technique to produce a new person that I would find ethically acceptable.
'The Pope implied such experiments were dangerous.
'Today, Italy banned cloning experiments.
So did Argentina.
' 'President Clinton favours a total ban on human cloning' Dolly isn't science fiction come true.
She is a sheep, and the jump from the cloning of one sheep to the cloning of humans is a large one.
For those at the centre of the storm, all this was an extraordinary over-reaction.
Their aim was something else entirely.
According to local legend, the Holy Grail is buried somewhere in the Rosslyn Chapel.
Dolly's creators were not thinking about human clones or spare parts.
For them, the Holy Grail was rather different - to engineer a better glass of milk.
It all started years ago at the Roslin Institute.
In the early '80s, people discovered the techniques for moving genes between species.
And, after quite a bit of deliberation, we thought one application of this would be to make so-called transgenic sheep, in which we gave them quite new properties.
In fact, what we wanted to do was to put human genes into these animals so that these animals produced human proteins.
There are a number of diseases which simply reflect the absence of one particular protein.
Haemophiliacs bleed spontaneously and fail to have clotting because of the absence of one particular protein in their blood.
This is simply reflecting the fact that one gene is not functioning properly.
Their ambitious plan was to get human genes expressed in sheep's milk to treat diseases like cystic fibrosis and haemophilia.
We were really excited to calculate that a flock of sheep would be capable of producing all of the clotting factor that was necessary for the whole world.
In the '80s, even publicly funded science was meant to make money, so the Roslin team sold the rights to their idea to a new company and together they made a number of famous sheep.
The first one was a sheep called Tracey and she produced 30 grams of AAT, still our lead protein, in every litre of her milk.
And nothing had ever produced that amount of protein before.
Following on from Tracey, we worked on protein C, which is an anti-clotting protein, and the first sheep there was called Hillary, and her daughter was naturally called Chelsea.
After that, we worked on the protein that becomes fibrin, which was the matrix of clots.
And here our star performer is Fifi and her daughter is called Fraufrau.
We recently announced that Rosie, a cow, had produced 2.
4 grammes of a HUMAN milk protein in her milk for feeding to very premature infants.
There are probably already 50 or 60 proteins which are known to be therapeutically useful and more are being discovered all the time.
But their business success was limited.
The technique everyone was using involved genetic manipulations in eggs, only obtainable by surgery.
It's a really inefficient procedure.
The problem is only a small proportion of those eggs will take up the DNA and become a transgenic.
So we're talking about maybe 1-3% of the eggs that we inject and transfer come on to be a transgenic.
The rest of them don't.
The technique for doing this has been around now for nearly 15 years and it's really not improved, so we really do need a new way to make transgenic animals.
'These problems were very much on Ian Wilmut's mind.
' 'He realised there might be a way round the problem - cloning.
' 'But cloning had long been regarded as the enfant terrible of science.
'Brave New World.
' "Identical twins, but not in piddling twos and threes.
"The whole of a small factory staffed with the products "of a single bokanovskified egg.
"96 identical twins working 96 identical machines.
" MUSIC: "Carmina Burana" by Orff 'Science fiction opened a Pandora's box, 'creating spare parts, 'bringing dictators back to life, 'shaping our own evolution.
' 'In reality, it all started with frogs.
'Cloning was done in the 1960s 'to tackle a fundamental question in development.
' How does an egg, just a single cell, turn itself into a complete organism, consisting of brain, blood, intestine, skin, and so on? This was a very critical question to try and provide an answer to because at that time we had no idea how an egg forms an adult and therefore how specialised organs of our bodies come to exist and to function.
'As a single cell develops into an embryo, 'are the genetic instructions in cells in some way removed 'to allow the specialised parts of the body to form?' 'Or does every cell in every tissue 'always contain a complete set of genes to make an entire animal? 'To answer this, Gurdon cloned tadpoles.
'No fertilisation was needed.
' 'A cell from a tadpole's intestine was sucked into a fine pipette.
' 'And then injected into a frog's egg 'in which the nucleus had been destroyed.
'It's a technique known as nuclear transfer.
' If you could put the genes from an intestine cell into an egg that doesn't have its own genes and nevertheless get a normal individual, like a tadpole or frog, then it is clear that that intestine cell must have had a complete set of genes needed for normal development in that intestine cell.
'Amazingly, these did develop into tadpoles, 'proving that the genes for an entire animal are in every cell in the body.
'But although they could clone cells from tadpoles, 'adult frogs were another matter.
' We did try for many years to transplant a nucleus from an adult and to get back another cloned adult.
We did not succeed and it was surprising to us that this did not work.
What we found was that the abnormalities arising from the transplanted nuclear adult cells were severe.
Many of the tadpoles we obtained from adult nuclear transfers swelled up with water and progressively died, not at any one particular point - the best ones would finally cease to feed and die for no obvious reason.
'Early attempts to clone adult mammals also failed.
'Scientists concluded that cloning adult animals was impossible.
'It seemed the Holy Grail would always be out of reach.
'Quite how the cells in an embryo 'specialise into the myriad of different tissues in the body, 'and whether this could be reversed, was to remain a mystery.
' 'But in the mid-'80s, a chance conversation changed everything.
' What really lit me up was when I was at a scientific meeting in Ireland.
I was in a conversation in a bar, speaking to the manager of a Danish friend of mine, Steen Willadsen.
I was extremely excited to be told that he had been able to obtain calves by doing nuclear transfer from cells which had begun to differentiate.
Obviously, when one's working in science, one always has to keep one eye on the future.
And one is always looking around to see what possibilities there are in the area.
Embryo manipulation was one very big possibility.
'Steen Willadsen had a brilliant reputation for entering new fields, 'which he established working at 'the Animal Research Station in Cambridge.
' 'He had applied Gurdon's cloning techniques in frogs to livestock.
'He was the first to take a nucleus from a sheep's embryo 'and then implant it into a sheep's egg, 'from which the nucleus had been removed.
'He produced the first live clone of a sheep embryo, 'but the news had been slow to break.
' 'Willadsen, with his expertise in cloning livestock, 'decided to leave the publicly funded institute in Cambridge.
' Just before I left, I did write a paper which I sent to Nature.
I wasn't in any great hurry to publish the work.
I was sort of holding back a little bit on the publication.
I had now decided to embark on a more independent career and I really needed the advantage that I had at the time, timewise.
'He wanted to develop the technique commercially.
'He joined a livestock company in Texas - the Granada Corporation.
' CATTLE BELLOW 'Here he applied his work in the sheep to the cow.
' The work was hugely successful.
We were way ahead of anybody else that was in the field, and so they didn't have anything to complain about there, but when it came to negotiations about continuing working together, I've got to say that they were not people that I would want to continue to work with.
'He fell out with Granada and left after a dispute with management.
' 'Willadsen's paper on cloning calf embryos was not yet published.
' 'But this work showed it WAS possible to clone or transfer nuclei 'from cells in embryos that were several days old - 'cells that had begun the process of differentiating 'into the various parts of the body.
'For Wilmut, this was the key.
' For the first time, it began to occur to me that it would be possible to use cloning as a way of introducing precise genetic changes into the livestock, which was our objective.
So, from then on, it was important to me to try to find out more about the technique of nuclear transfer to confirm that the story that I'd heard in the bar really WAS true.
So we swung into action as quickly as we could.
It so happened that in a few weeks I was going to Australia to work and I was able to re-arrange my travel plans so that I came back through Calgary to go and visit Steen.
So, having spoken to him and seeing that he was able to use these cells which had begun differentiation, I came back to Britain already beginning to plan how it was that we could get together the team to develop this technique of cloning.
'He needed specialists in growing cells, in reading DNA 'and manipulating eggs under the microscope.
' You also need to have scientists who carry out the basic research to understand the mechanisms and what's going on inside the cells that you're using.
'They appointed Keith Campbell.
' The reasons I was interested in cloning was because I'd spent time working on the frog, I got to know the work of John Gurdon, and I found it fascinating that it was able to cause, effectively, the reprogramming of DNA.
I was very passionately interested in that aspect.
'Campbell believed that Gurdon had failed to get adult clones 'from adult cells for technical reasons 'and not because it was impossible.
' When I saw this opportunity at Roslin, I tried to grab it with two hands, and, as luck would have it, here I am.
'His earlier work in other species and on cancer cells 'also suggested that cloning would be possible.
' A lot of people are very sceptical about my ideas, maybe a bit more tied up with the dogma of what had been published, and other results that had been obtained.
Whereas I think my wide experience from a range of species had taught me one thing - the basic mechanisms underlying all of these processes are very similar.
And I'd worked in the frog and the yeast, and now in cattle and sheep and felt that there were so many similarities that we should be able to obtain development from these adult cell types.
'They were beginning to realise 'there was something extraordinary about the cell 'which could be the key to nuclear transfer.
' 'Every cell of every living thing goes through different phases 'as it grows and divides.
'These phases are known as the cell cycle.
' If we consider that the cell consists of a nucleus which contains the instructions, which is surrounded by a soup of proteins, there's continuous talking between the nucleus and the soup of proteins.
When we create an embryo by nuclear transfer, we're taking a nucleus from one cytoplasmic, or soup, environment and placing it into the egg, which is a different environment.
Now, if we're not careful about co-ordinating these two environments, we can end up causing a lot of damage to the DNA or the instructions.
We can cause duplication of some of the instructions and breakage of the chromosomes, which leads to damage of the instructions.
'When the DNA was damaged, the embryos couldn't survive.
'He realised the way forward was to co-ordinate the different phases 'of the cells used in nuclear transfer.
' 'But he had competition.
' 'Dr Charles Looney and Dr Frank Barnes 'had been brought into the Granada Corporation 'to develop the work started by Steen Willadsen.
' I think beef is probably the best food that God allowed us to have.
It's just that we have it in all kinds of colours and types.
Every time you go into a restaurant to have a steak, there's a question about what it's gonna taste like.
We wanted to be able to produce literally thousands of identical offspring, and cloning gave us that opportunity.
'Granada aimed to use cloning 'to improve beef production and create the perfect steak.
' The current dogma at the time was that cloning was impossible, and so we set out to disprove the dogma.
After all, we were students and we were on a mission, you know.
'Like the Edinburgh team, they too were interested in cell cycles.
' There was a ton of literature coming out on the cell cycle.
We saw a paper from Ian Wilmut's team - I think that was '88 or '89 - that definitely indicated an influence of the cell cycle on the cloning process, and that put me to digging a lot deeper into which phase of the cell cycle might be optimal.
Imagine coming from high school and your first job out, you're meeting scientists with some sort of international acclaim.
Scientists were calling in to Granada to find out what we were doing in Texas.
Probably the most recognisable scientist was Ian Wilmut.
He basically came in on a daily basis and looked up our skirt just to find out what was going on.
And we were proud of that, because we felt that he was going to share information with us and we were going to share information with him and make the whole programme better.
'Money was poured into an ambitious large-scale field trial.
' When I visited the group at Granada, I was really surprised to learn that they were aiming to produce 1,000 pregnancies in cattle.
Which, if you assume that only a third of the embryos that they transfer will become calves, it means they were planning to transfer 3,000 embryos, which, even for quite a large American company, is a phenomenal amount of work to contemplate, simply to assess a product before you begin to use it.
'But they succeeded.
' In the initial stages, we were so delighted that you could manually tear an embryo apart and then manually rip the nucleus from an egg and then put the two together with electricity and come up with something that was alive.
That was incredibly exciting.
And then all of a sudden we realised that there was a sad side to this - that some of these calves were abnormal.
When we were birthing some of the cows, the calves were extremely large - some calves, 180lb.
That's twice as large as what they normally would be.
A normal calf should be about 75lb.
This alarmed us.
This definitely was a show stopper.
The calves were dying at a rate of about 18-20% and therefore it wasn't commercially feasible to continue the process until we could understand what was causing this increased birth weight.
We looked at the gestational growth of the calf while they're in utero, we measured for all types of growth hormone production, we looked at insulin A lot of calves were being born with diabetes, some had enlarged hearts.
We threw everything we could at it.
We brought in people from all over the country.
And it was the first time that something which we call "cowboy science", embryo transfer, all of a sudden now had a detrimental effect.
And it killed the commercial interest.
'As Granada Genetics' profits began to plummet, 'the scientific expertise started to leave.
'Frank Barnes wanted to understand this disturbing failure 'and continued research on cell cycles 'in a company in Salt Lake City - Genmark.
' We discovered we could manipulate the cell cycle either chemically or by altering the conditions in which it was cultured.
That took us to testing individual stages of the cell cycle.
It took us to characterising what stage of the cell cycle each cell of an embryo was in.
'Frank Barnes and his team were on the verge of solving the puzzle 'when the new company also folded.
' 'Although he hadn't known it, he had been incredibly close to the answer, 'but before he could prove it, his funding had gone 'and he left the field for good.
' 'Although they had glimpsed the Holy Grail, 'once more it escaped their grasp.
' 'Meanwhile, Keith Campbell thought he'd got it.
' When I had these thoughts and they came together, I was actually sitting at the computer, but I often sit at the computer, typing away, thinking of other things! So I can't actually remember what I was working on at the time but sometimes it's difficult to get I've been working on this for six years and sometimes I even dream it.
'He realised there was something critical that he had overlooked.
' 'Every cell in every living thing 'can go into a special state known as quiescence.
' Quiescenceis a cell cycle phase which has been ignored, really, for a lot of years.
The cell only performs the function it needs just to stay alive, just maintenance functions.
The cell is getting its genetic material ready to maybe specialise into another direction or into another cell type.
'If the donor cells used in nuclear transfer were in a quiescent state, 'Campbell was convinced it would work.
' The real flash was that maybe the most important aspect of it was the quiescence, rather than the co-ordination of the cell cycle.
Ian came wandering past and I told him about these thoughts on quiescence and he went away and had a think to himself.
It's in conversations like this that you have some of the greatest excitement in science because it's a new idea, and if what Keith was suggesting was correct, it was opening up entirely new ways of thinking.
You have the opening of a new understanding and then from time to time after that, there'll be sort of little ricochets where you suddenly realise, "Yes, well, if that's right, something else will flow," but it's really the idea itself which gives you the excitement and, perhaps, for most of us, the reason for doing science.
'After all these years of work, the trick - 'to put cells into quiescence - was breathtakingly simple.
'All they had to do was starve the donor cells of food.
' I think what we began to realise was that, instead of making just a very small step forward, this might be very big.
We became very secretive for a few months until we'd had the opportunity to put in a patent, because, of course, here in Britain, if we discuss an idea at all in public then it is no longer patentable, and so it was absolutely essential, if we were to have the opportunity of patenting the idea, that nobody knew about it.
So for several months, I guess there were only about four of us who knew the basis of our success.
'To test out quiescence, they tried a number of cell types.
' It was really just chance that we came to make Dolly.
The aim of the experiment was to compare cells taken from a number of different sources, and the collaborators that we had from PPL remembered that there was a cell line that they had, which was taken from the mammary gland of a six-year-old ewe, actually cultured for a completely different reason.
'This was the Holy Grail - 'to create new life from cells taken from an adult animal.
'To create the clone, the nucleus of a sheep's egg was removed.
'The expert in micro-manipulation, Bill Ritchie, 'put the six-year-old donor cells under the microscope.
'With a pipette not much wider than a hair, one donor cell was selected.
'It was inserted into the egg cell.
'Electricity gently fused the two cells.
'The egg with the donor nucleus was placed between two fine electrodes.
'A sharp burst of 25 volts brought it to life, 'mimicking aspects of fertilisation.
'The embryos which developed were then implanted into surrogate ewes.
' In many of these cases, the embryos which you produce and which you transfer into a foster mother appear to be perfectly normal at that stage, but most of them die and so you cannot be sure, simply because you've got something which is developing for a week, you can't be sure at all that it will come through and become a live lamb, and so we have to commit ourselves to that whole period of work at the beginning of each experiment.
We've got foetal movement.
Here are the ribs on either side, going towards this V.
In the middle of the V, right at the point, is the heart.
CAMPBELL: Seeing these baby sheep foetuses moving about was really exciting, to see that they'd got legs and heartbeats, and you could see this whole little sheep sitting in there, it was amazing, it was a really good feeling.
'It took 277 attempts to get Dolly.
' We were not only working pretty hard during the day in the lab, we were also spending our nights "watching over our flock," as they say, and checking on the sheep every hour between 11.
30 and 5.
30 in the morning, just to make sure that if they did give birth, they didn't get into any difficulty.
McGAVIN: When Dolly's mother started to go into labour, she started getting restless and moving round in circles and pawing at the ground.
Dolly's birth was very natural and, at the end, came very quickly.
WILMUT: As far as I was concerned, it was just an ordinary day.
Unfortunately, at that time, quite a few of the team were away, so we didn't actually celebrate, because it seemed to me to be important that, since this was such a team effort, that if we were going to celebrate by drinking the champagne that I'd actually already bought, that we should all be there to take part in it.
But nevertheless, there was the great personal satisfaction that this little lamb here was showing that our nuclear transfer technology was a very important step forward and that we were going to be able to tackle a whole new range of biological opportunities.
'At last, a central tenet of developmental biology was overturned.
'Their results proved that a nucleus from an adult cell 'could be reprogrammed to clone animals.
' I'm full of admiration.
I think it's a great technical achievement.
I'm also particularly proud that it was done at Roslin, as well, by my colleagues there.
- This is a great achievement.
- It's a wonderful piece of science.
I think it's always better to be the bride instead of the bridesmaid, but I can honestly say that, er, not for a moment was I ever jealous of Ian Wilmut.
Ian was a colleague, he was a collaborator, he was a friend, and when we saw that they had got it right, it was.
it was fantastic.
It was kind of a kick in the pants.
I said, "We could probably have done that!" We have simply been the fortunate people who put the last brick in place and completed the understanding.
Watch your backs.
'Even three months after the announcement, 'Dolly's shearing was still front-page news.
' Can you come round the other side? Kneel down, put your arms round her.
That's right.
We're very pleased to have the world champion here to shear Dolly today.
As you probably are aware 'The director of the institute hopes to use the advance 'to genetically engineer livestock to make pharmaceuticals.
' .
.
and we hope will be useful to treat lung disease such as emphysema and cystic fibrosis.
'But as Dolly became an icon of biological control, 'the real fears were for human cloning.
' MUSIC: "Carmina Burana" by Orff We don't, ourselves, under any circumstances intend to do it, and we don't intend to license the technology to anyone who wishes to do it and it's illegal in most Western European countries, including the UK.
'But lawyers told Horizon that human cloning 'may not be against the law in Britain.
'The act defines an embryo as 'an "embryo where fertilisation is complete", 'but a cloned embryo has not been fertilised.
'Parliament's Science and Technology Committee 'has found it is not satisfactory for issues as momentous as this 'to be left until they're decided through test cases, 'but, so far, the law has not been changed.
'In America, too, human cloning has not been banned 'and there are fears it may prove unpoliceable.
' Within a week of the announcement of Dolly's birth, there was a company that advertised itself on the World Wide Web, called CLONAID, that was offering to use cloning technology for a fee of 200,000.
It's not clear whether this company is really legitimate or not, but it certainly indicates that companies will be able to set up their services on offshore islands where the laws won't interfere with their practice of the technology.
'CLONAID told Horizon they aim to create a human clone 'within two years, using IVF laboratories 'which they weren't prepared to name.
'All this despite the fact that 'any human clone could be physically damaged.
' WILMUT: The cells that were used to produce Dolly were from a ewe that was six years old when they were taken, so there's an interesting question as to whether Dolly, who's now approaching a year old, is really a year old, or whether she's really seven years old.
There are changes in our cells as we grow older, as we age, and the question is, how many of these changes have been reversed as part of the reprogramming events during nuclear transplantation? The simple answer is that we don't know.
'So a human clone created from cells of an 80-year-old 'might have only a few years to live.
'Would women undergo the countless egg donations 'and pregnancies needed to create Dolly? 'If they did, it's possible a human clone 'might grow too large in the womb, 'like some of the giant calves in Texas.
'Jonathan King is a molecular biologist who has voiced concerns.
' Technologies like nuclear weapons, chemical warfare, nasty pesticides, these all have the potential to do a lot of direct human harm - to damage, to maim hundreds of thousands of people.
Cloning isn't going to be like that.
Cloning maims the relationship between humans, the notion of what it is to be human, the notion of what it is to regard other people as human, as having a common heritage, common values, needing to take care of each other.
Any technology that makes humans into objects, like slavery 200 years ago, sets back human history, it doesn't advance it.
SILVER: I think the cloning technology could be used to end anguish with a number of people.
All you are doing with cloning is having another child be born with the same genes as the person who donated the cell.
And we already know from identical twins - identical twins ARE nothing more than clones - identical twins have their own personalities, they are their own persons, they are their own individuals.
'Even Lee Silver, who's in favour of cloning 'to tackle infertility and other problems, has his concerns.
' The cloning technology, all of a sudden, allows genetic engineering to be feasible with human beings and this is what I really fear, because, with genetic engineering, it is possible that those who have money would be able to provide genetic advantages to their children, and those who do not have money will not be able to use this technology.
And what will happen is that the two social classes will diverge into two genetic classes, where there could actually be two different races of human beings, based on those who have been enhanced genetically and those who have not been enhanced.
We as human beings now, for the very first time, have the ability to evolve ourselves, to choose what genes we want to put into our children, and so, in a sense, the entire process of evolution is now changing and we have the ability to make that change right now.
KING: Very often, the scientific community, technologists, imply that every more sophisticated application of science and technology is progress.
But, in fact, that's not the case.
It's only progress if it solves a real problem.
There are plenty of applications of science and technology that set us back, they're inappropriate, they violate what it is to be human.
The application of modern cell biology, modern genetic engineering, for human cloning That is a genie that we should put back in the bottle, cork it and carefully label, "Danger, this is not in the interest of human society.
" INTERVIEWER: Haven't your team unleashed some terrible genie on the world? Well, in many ways, the genie was let out of the bottle by Pasteur in the 19th century when he first started applying science to medicine and science has gone on throughout the world, in many, many laboratories, over the last 120 years and this is just another example of it.
It's moving forward at a really broad sweep, it's almost like the tide coming in.
We're just a little bit ahead of somebody else, maybe just only a year or two ahead of somebody else, so if we hadn't have made this discovery now, somebody else would have made it in a few years' time.
'But leaving aside the cloning of individuals, 'there is another ethical minefield - 'the use of cloned embryos in medicine.
' WILMUT: We're very excited about the idea that we may be able to use this technique to bring forward a particular way of treating some diseases.
What you'd do would be to take cells from a patient and fuse them to unfertilised eggs in order to obtain undifferentiated cells of an early embryo.
You would then, very quickly, in culture, cause these to differentiate into the cell type that was needed to correct that particular disease.
I think we can look forward to this being used to treat not only specific conditions like Parkinson's disease or leukaemia, but also, perhaps, for providing quite complex tissues or even complex organs like hearts.
You do have to produce a small bundle of cells, but you would cause these to differentiate into the tissues that you needed within the period of a week or so.
I recognise that there are people who feel that, even at the moment of conception, there is aa soul present in this very small bundle of cells.
To me, this is something This is a view of life that I don't share.
I don't regard an embryo at that stage, that little ball of cells, as being a person.
'But how is life to be defined 'if cloned embryos could be used for spare-part surgery? 'Biologists are already mastering the reconstruction of the body in frogs.
' At an early stage of development, a frog embryo consists just of an undifferentiated ball of cells and we've been interested for some time in how the pattern of the embryo develops from this featureless ball of cells and, in particular, we have been interested in the question of why the head comes from one end and the tail from another end.
'They found they could control the series of genes that form 'the different parts of the animal.
' If you inhibit any member of this gene cascade, then the embryo can't make a trunk and a tail and it becomes just an isolated head.
If, on the other hand, you over-express any of the genes in the cascade, that is to say you turn them on all over the embryo, not just in the posterior end where they're normally on, then the whole embryo becomes a trunk and the tail and you don't get a head.
'Could this technology be used in humans to create spare parts?' I think we probably do know enough about animal development that we could imagine reprogramming an egg in such a way that it didn't form a whole embryo, but it just formed the organ you wanted plus the heart and circulatory system.
Let's say you wanted a pancreas and you created an embryo consisting of a pancreas and a heart, surrounded by skin.
I think, if you could grow it in a bottle, perhaps one could begin to discuss whether this would be acceptable or not, but at present I think the idea of growing it in a human female volunteer really is completely unacceptable.
I'd feel a bit insecure about the possibility that such an organ could be grown in an animal host as well, although thatthat's not currently practical, although that's something that might become a practical possibility in the next few years.
'But where is the line to be drawn 'when creating potential new life and then destroying it to save another?' It would certainly be unacceptable to create a whole human embryo by cloning for some purpose such as spare-parts surgery.
That would That would be murder and that would be quite out of the question.
I think if it was just an isolated organ, erm, that is a greyer area and it's something which does very much depend on what society as a whole feels about it and I think if such a thing is repugnant, then it should not be proceeded with.
If it's seen as being aa new lifeline to people who are dying provided by biological technology and if it's generally welcomed, then it could be proceeded with.
'The reconstruction of a cloned embryo to make spare parts, 'a much easier way of genetically engineering animals, 'and the cloning of humans - 'these may no longer be the realms of science fiction.
' I know that scientists sometimes say, "Well, this work is so dangerous, "I don't want to be involved in it any more, "I'm now going to get out of the field.
" I think that is also a dangerous way.
If you felt that this science was dangerous in some way, your best route is to stay with it, so that, as it develops, you can communicate it to the world, and in our particular case, that's what we believe is our primary responsibility - to communicate all this information to the world so that they understand what we're doing and they understand the ramifications of it.
You can't then put a gate and say, "Well, I've communicated it.
I'm no longer responsible.
" No, you have to shepherd it through, help people interpret it.
Is it properly used? Does it reach the people who need to have it? And if you see that it's being misused, right, you can't say, "Oh, well, that's notthat's not my fault.
" INTERVIEWER: So, do you see yourselves as primarily whistle-blowers on cloning technology or as the prime beneficiaries of it? We see ourselves both as the scientists that are doing the work and as the whistle-blowers on the technology.
We also see ourselves as profiting from it scientifically, because it's exciting and it's an intellectual breakthrough, it is a major intellectual breakthrough, and hopefully we will profit from it as a research organisation from some licensing of the technology to bring some income into the research institute.
KING: What's going on everywhere in the world really is an enormous commercialisation of forms of life that we never thought of previously as private property - human genes, cell lines and entire organisms.
But what this is really about is being able to get economic control over animal breeding at a much, much broader scale than has ever happened before.
400-500 years ago the frontiers were geographic.
Adventurers, sailors, very intrepid ones, sailed out to the New World and they claimed all the land they could see for themselves or for the king, regardless of who was there beforehand.
Now we have a new frontier in which corporations and institutions claim, as their private property, all of the genes and cells and organs and genetically modified organisms that depend on millions of years of evolution.
Many people call it "bio-piracy", robbing from the whole species for a very particular gain.
WILMUT: During the last few months there's been enormous interest, not only from the media, press and TV and so on, but also from fellow scientists, enormous flow of requests for information, so there have been times when I haven't known whether it was going to be either a heart attack or a nervous breakdown which was going to get me.
INTERVIEWER: People have compared this to nuclear weapons, chemical weapons and some of the worst things that have come out of scientific laboratories this century.
What do you feel about this? I I think that the, erm potential misuses of the nuclear transplantation are a lot less dangerous than, er, atomic weapons, a lot less dangerous than that.
Erm But I think, perhaps, this illustrates the whole point that, if you like, knowledge itself is a neutral thing and it's important we go on gaining knowledge and understanding things.
What's critical is the way in which we use that new knowledge.
Not only can you not stop science, but I really think it would be a mistake to try to do so.
Just think how many things there are which we take for granted which have come from biological research in the last 50 or 100 years.
What's going to happen in the next 20 or 50 years is that the genetic research, which is just beginning, is going to produce a whole range of similar opportunities which we can't even begin to predict, but it's quite clear that they are going to be as important as the biological research that has already gone on this century.
'As the age of biological control dawns 'and the biologist has the same mastery of the genes 'that the chemist has over the elements, 'our power to alter our destiny is changing for ever.
' MUSIC: "Requiem" by Mozart
For this collection, Prof Alice Roberts has selected a range of programmes to celebrate Horizon's 50th anniversary.
More Horizon programmes and other BBC Four Collections are available on BBC iPlayer.
'There are many people who think there's a territory 'called God's Domain that we should not cross over into.
' 'To me, although we've made a new life in a new embryo, 'it isn't really a person.
' 'Cloning a whole human embryo for spare-parts surgery, 'that would be murder.
' 'And it's possible to clone people without their consent.
' 'We are in the shadow of that knowledge 'and it came to us without us being properly prepared.
' # Hello, Dolly .
.
It's so nice to have you back where you belong On February 23rd 1997, the first cloned adult animal became a superstar.
This is the story of the cloning of Dolly and the remarkable implications of her birth.
As the news broke, the scientists who made her at the little-known Roslin Institute near Edinburgh found themselves thrust onto the world stage.
It was really rather overwhelming.
There was just a flood of requests for information.
And we were occupied for, I guess, almost 12 hours on that Sunday dealing with phone-calls from newspapers and radios all around the world.
We were beginning to get phone-calls from the States, first from the east coast, then from the west coast, and then from Australia and New Zealand.
And we realised this was a continuous 24-hour operation.
When we were wandering round the institute, there was a phone ringing from the cleaner's closet.
I wasn't aware there was a phone in this particular small room.
Going inside into an even smaller cubbyhole, I saw a phone, picked it up - it was the Daily Mirror.
It was chaotic here.
NEWS: The world's first clone has been produced of an adult mammal We had TV crews from CNN, ABC, CBS, NBC - all the American networks - beaming live broadcasts to the early morning news on the east coast.
In the first 10 days after the story broke, we estimate that collectively we've handled 2,000 calls from the media and we've provided in-depth interviews to at least 100 reporters from all over the world.
The Science Museum in London have offered to stuff Dolly for posterity when she dies.
We've had requests for Dolly to appear on a US chat show.
NEWS: International pressure for a ban grows following news last week that scientists had successfully cloned a sheep.
NEWS: Some critics say human cloning has become a step closer.
How easy might it be scientifically for someone, somewhere, to apply your method to the cloning of humans? It would be my belief that if you really wanted to do it, it could be done.
'The President today has asked 'his National Bioethics Advisory Commission to make a judgement' I personally have still not heard a potential use of this technique to produce a new person that I would find ethically acceptable.
'The Pope implied such experiments were dangerous.
'Today, Italy banned cloning experiments.
So did Argentina.
' 'President Clinton favours a total ban on human cloning' Dolly isn't science fiction come true.
She is a sheep, and the jump from the cloning of one sheep to the cloning of humans is a large one.
For those at the centre of the storm, all this was an extraordinary over-reaction.
Their aim was something else entirely.
According to local legend, the Holy Grail is buried somewhere in the Rosslyn Chapel.
Dolly's creators were not thinking about human clones or spare parts.
For them, the Holy Grail was rather different - to engineer a better glass of milk.
It all started years ago at the Roslin Institute.
In the early '80s, people discovered the techniques for moving genes between species.
And, after quite a bit of deliberation, we thought one application of this would be to make so-called transgenic sheep, in which we gave them quite new properties.
In fact, what we wanted to do was to put human genes into these animals so that these animals produced human proteins.
There are a number of diseases which simply reflect the absence of one particular protein.
Haemophiliacs bleed spontaneously and fail to have clotting because of the absence of one particular protein in their blood.
This is simply reflecting the fact that one gene is not functioning properly.
Their ambitious plan was to get human genes expressed in sheep's milk to treat diseases like cystic fibrosis and haemophilia.
We were really excited to calculate that a flock of sheep would be capable of producing all of the clotting factor that was necessary for the whole world.
In the '80s, even publicly funded science was meant to make money, so the Roslin team sold the rights to their idea to a new company and together they made a number of famous sheep.
The first one was a sheep called Tracey and she produced 30 grams of AAT, still our lead protein, in every litre of her milk.
And nothing had ever produced that amount of protein before.
Following on from Tracey, we worked on protein C, which is an anti-clotting protein, and the first sheep there was called Hillary, and her daughter was naturally called Chelsea.
After that, we worked on the protein that becomes fibrin, which was the matrix of clots.
And here our star performer is Fifi and her daughter is called Fraufrau.
We recently announced that Rosie, a cow, had produced 2.
4 grammes of a HUMAN milk protein in her milk for feeding to very premature infants.
There are probably already 50 or 60 proteins which are known to be therapeutically useful and more are being discovered all the time.
But their business success was limited.
The technique everyone was using involved genetic manipulations in eggs, only obtainable by surgery.
It's a really inefficient procedure.
The problem is only a small proportion of those eggs will take up the DNA and become a transgenic.
So we're talking about maybe 1-3% of the eggs that we inject and transfer come on to be a transgenic.
The rest of them don't.
The technique for doing this has been around now for nearly 15 years and it's really not improved, so we really do need a new way to make transgenic animals.
'These problems were very much on Ian Wilmut's mind.
' 'He realised there might be a way round the problem - cloning.
' 'But cloning had long been regarded as the enfant terrible of science.
'Brave New World.
' "Identical twins, but not in piddling twos and threes.
"The whole of a small factory staffed with the products "of a single bokanovskified egg.
"96 identical twins working 96 identical machines.
" MUSIC: "Carmina Burana" by Orff 'Science fiction opened a Pandora's box, 'creating spare parts, 'bringing dictators back to life, 'shaping our own evolution.
' 'In reality, it all started with frogs.
'Cloning was done in the 1960s 'to tackle a fundamental question in development.
' How does an egg, just a single cell, turn itself into a complete organism, consisting of brain, blood, intestine, skin, and so on? This was a very critical question to try and provide an answer to because at that time we had no idea how an egg forms an adult and therefore how specialised organs of our bodies come to exist and to function.
'As a single cell develops into an embryo, 'are the genetic instructions in cells in some way removed 'to allow the specialised parts of the body to form?' 'Or does every cell in every tissue 'always contain a complete set of genes to make an entire animal? 'To answer this, Gurdon cloned tadpoles.
'No fertilisation was needed.
' 'A cell from a tadpole's intestine was sucked into a fine pipette.
' 'And then injected into a frog's egg 'in which the nucleus had been destroyed.
'It's a technique known as nuclear transfer.
' If you could put the genes from an intestine cell into an egg that doesn't have its own genes and nevertheless get a normal individual, like a tadpole or frog, then it is clear that that intestine cell must have had a complete set of genes needed for normal development in that intestine cell.
'Amazingly, these did develop into tadpoles, 'proving that the genes for an entire animal are in every cell in the body.
'But although they could clone cells from tadpoles, 'adult frogs were another matter.
' We did try for many years to transplant a nucleus from an adult and to get back another cloned adult.
We did not succeed and it was surprising to us that this did not work.
What we found was that the abnormalities arising from the transplanted nuclear adult cells were severe.
Many of the tadpoles we obtained from adult nuclear transfers swelled up with water and progressively died, not at any one particular point - the best ones would finally cease to feed and die for no obvious reason.
'Early attempts to clone adult mammals also failed.
'Scientists concluded that cloning adult animals was impossible.
'It seemed the Holy Grail would always be out of reach.
'Quite how the cells in an embryo 'specialise into the myriad of different tissues in the body, 'and whether this could be reversed, was to remain a mystery.
' 'But in the mid-'80s, a chance conversation changed everything.
' What really lit me up was when I was at a scientific meeting in Ireland.
I was in a conversation in a bar, speaking to the manager of a Danish friend of mine, Steen Willadsen.
I was extremely excited to be told that he had been able to obtain calves by doing nuclear transfer from cells which had begun to differentiate.
Obviously, when one's working in science, one always has to keep one eye on the future.
And one is always looking around to see what possibilities there are in the area.
Embryo manipulation was one very big possibility.
'Steen Willadsen had a brilliant reputation for entering new fields, 'which he established working at 'the Animal Research Station in Cambridge.
' 'He had applied Gurdon's cloning techniques in frogs to livestock.
'He was the first to take a nucleus from a sheep's embryo 'and then implant it into a sheep's egg, 'from which the nucleus had been removed.
'He produced the first live clone of a sheep embryo, 'but the news had been slow to break.
' 'Willadsen, with his expertise in cloning livestock, 'decided to leave the publicly funded institute in Cambridge.
' Just before I left, I did write a paper which I sent to Nature.
I wasn't in any great hurry to publish the work.
I was sort of holding back a little bit on the publication.
I had now decided to embark on a more independent career and I really needed the advantage that I had at the time, timewise.
'He wanted to develop the technique commercially.
'He joined a livestock company in Texas - the Granada Corporation.
' CATTLE BELLOW 'Here he applied his work in the sheep to the cow.
' The work was hugely successful.
We were way ahead of anybody else that was in the field, and so they didn't have anything to complain about there, but when it came to negotiations about continuing working together, I've got to say that they were not people that I would want to continue to work with.
'He fell out with Granada and left after a dispute with management.
' 'Willadsen's paper on cloning calf embryos was not yet published.
' 'But this work showed it WAS possible to clone or transfer nuclei 'from cells in embryos that were several days old - 'cells that had begun the process of differentiating 'into the various parts of the body.
'For Wilmut, this was the key.
' For the first time, it began to occur to me that it would be possible to use cloning as a way of introducing precise genetic changes into the livestock, which was our objective.
So, from then on, it was important to me to try to find out more about the technique of nuclear transfer to confirm that the story that I'd heard in the bar really WAS true.
So we swung into action as quickly as we could.
It so happened that in a few weeks I was going to Australia to work and I was able to re-arrange my travel plans so that I came back through Calgary to go and visit Steen.
So, having spoken to him and seeing that he was able to use these cells which had begun differentiation, I came back to Britain already beginning to plan how it was that we could get together the team to develop this technique of cloning.
'He needed specialists in growing cells, in reading DNA 'and manipulating eggs under the microscope.
' You also need to have scientists who carry out the basic research to understand the mechanisms and what's going on inside the cells that you're using.
'They appointed Keith Campbell.
' The reasons I was interested in cloning was because I'd spent time working on the frog, I got to know the work of John Gurdon, and I found it fascinating that it was able to cause, effectively, the reprogramming of DNA.
I was very passionately interested in that aspect.
'Campbell believed that Gurdon had failed to get adult clones 'from adult cells for technical reasons 'and not because it was impossible.
' When I saw this opportunity at Roslin, I tried to grab it with two hands, and, as luck would have it, here I am.
'His earlier work in other species and on cancer cells 'also suggested that cloning would be possible.
' A lot of people are very sceptical about my ideas, maybe a bit more tied up with the dogma of what had been published, and other results that had been obtained.
Whereas I think my wide experience from a range of species had taught me one thing - the basic mechanisms underlying all of these processes are very similar.
And I'd worked in the frog and the yeast, and now in cattle and sheep and felt that there were so many similarities that we should be able to obtain development from these adult cell types.
'They were beginning to realise 'there was something extraordinary about the cell 'which could be the key to nuclear transfer.
' 'Every cell of every living thing goes through different phases 'as it grows and divides.
'These phases are known as the cell cycle.
' If we consider that the cell consists of a nucleus which contains the instructions, which is surrounded by a soup of proteins, there's continuous talking between the nucleus and the soup of proteins.
When we create an embryo by nuclear transfer, we're taking a nucleus from one cytoplasmic, or soup, environment and placing it into the egg, which is a different environment.
Now, if we're not careful about co-ordinating these two environments, we can end up causing a lot of damage to the DNA or the instructions.
We can cause duplication of some of the instructions and breakage of the chromosomes, which leads to damage of the instructions.
'When the DNA was damaged, the embryos couldn't survive.
'He realised the way forward was to co-ordinate the different phases 'of the cells used in nuclear transfer.
' 'But he had competition.
' 'Dr Charles Looney and Dr Frank Barnes 'had been brought into the Granada Corporation 'to develop the work started by Steen Willadsen.
' I think beef is probably the best food that God allowed us to have.
It's just that we have it in all kinds of colours and types.
Every time you go into a restaurant to have a steak, there's a question about what it's gonna taste like.
We wanted to be able to produce literally thousands of identical offspring, and cloning gave us that opportunity.
'Granada aimed to use cloning 'to improve beef production and create the perfect steak.
' The current dogma at the time was that cloning was impossible, and so we set out to disprove the dogma.
After all, we were students and we were on a mission, you know.
'Like the Edinburgh team, they too were interested in cell cycles.
' There was a ton of literature coming out on the cell cycle.
We saw a paper from Ian Wilmut's team - I think that was '88 or '89 - that definitely indicated an influence of the cell cycle on the cloning process, and that put me to digging a lot deeper into which phase of the cell cycle might be optimal.
Imagine coming from high school and your first job out, you're meeting scientists with some sort of international acclaim.
Scientists were calling in to Granada to find out what we were doing in Texas.
Probably the most recognisable scientist was Ian Wilmut.
He basically came in on a daily basis and looked up our skirt just to find out what was going on.
And we were proud of that, because we felt that he was going to share information with us and we were going to share information with him and make the whole programme better.
'Money was poured into an ambitious large-scale field trial.
' When I visited the group at Granada, I was really surprised to learn that they were aiming to produce 1,000 pregnancies in cattle.
Which, if you assume that only a third of the embryos that they transfer will become calves, it means they were planning to transfer 3,000 embryos, which, even for quite a large American company, is a phenomenal amount of work to contemplate, simply to assess a product before you begin to use it.
'But they succeeded.
' In the initial stages, we were so delighted that you could manually tear an embryo apart and then manually rip the nucleus from an egg and then put the two together with electricity and come up with something that was alive.
That was incredibly exciting.
And then all of a sudden we realised that there was a sad side to this - that some of these calves were abnormal.
When we were birthing some of the cows, the calves were extremely large - some calves, 180lb.
That's twice as large as what they normally would be.
A normal calf should be about 75lb.
This alarmed us.
This definitely was a show stopper.
The calves were dying at a rate of about 18-20% and therefore it wasn't commercially feasible to continue the process until we could understand what was causing this increased birth weight.
We looked at the gestational growth of the calf while they're in utero, we measured for all types of growth hormone production, we looked at insulin A lot of calves were being born with diabetes, some had enlarged hearts.
We threw everything we could at it.
We brought in people from all over the country.
And it was the first time that something which we call "cowboy science", embryo transfer, all of a sudden now had a detrimental effect.
And it killed the commercial interest.
'As Granada Genetics' profits began to plummet, 'the scientific expertise started to leave.
'Frank Barnes wanted to understand this disturbing failure 'and continued research on cell cycles 'in a company in Salt Lake City - Genmark.
' We discovered we could manipulate the cell cycle either chemically or by altering the conditions in which it was cultured.
That took us to testing individual stages of the cell cycle.
It took us to characterising what stage of the cell cycle each cell of an embryo was in.
'Frank Barnes and his team were on the verge of solving the puzzle 'when the new company also folded.
' 'Although he hadn't known it, he had been incredibly close to the answer, 'but before he could prove it, his funding had gone 'and he left the field for good.
' 'Although they had glimpsed the Holy Grail, 'once more it escaped their grasp.
' 'Meanwhile, Keith Campbell thought he'd got it.
' When I had these thoughts and they came together, I was actually sitting at the computer, but I often sit at the computer, typing away, thinking of other things! So I can't actually remember what I was working on at the time but sometimes it's difficult to get I've been working on this for six years and sometimes I even dream it.
'He realised there was something critical that he had overlooked.
' 'Every cell in every living thing 'can go into a special state known as quiescence.
' Quiescenceis a cell cycle phase which has been ignored, really, for a lot of years.
The cell only performs the function it needs just to stay alive, just maintenance functions.
The cell is getting its genetic material ready to maybe specialise into another direction or into another cell type.
'If the donor cells used in nuclear transfer were in a quiescent state, 'Campbell was convinced it would work.
' The real flash was that maybe the most important aspect of it was the quiescence, rather than the co-ordination of the cell cycle.
Ian came wandering past and I told him about these thoughts on quiescence and he went away and had a think to himself.
It's in conversations like this that you have some of the greatest excitement in science because it's a new idea, and if what Keith was suggesting was correct, it was opening up entirely new ways of thinking.
You have the opening of a new understanding and then from time to time after that, there'll be sort of little ricochets where you suddenly realise, "Yes, well, if that's right, something else will flow," but it's really the idea itself which gives you the excitement and, perhaps, for most of us, the reason for doing science.
'After all these years of work, the trick - 'to put cells into quiescence - was breathtakingly simple.
'All they had to do was starve the donor cells of food.
' I think what we began to realise was that, instead of making just a very small step forward, this might be very big.
We became very secretive for a few months until we'd had the opportunity to put in a patent, because, of course, here in Britain, if we discuss an idea at all in public then it is no longer patentable, and so it was absolutely essential, if we were to have the opportunity of patenting the idea, that nobody knew about it.
So for several months, I guess there were only about four of us who knew the basis of our success.
'To test out quiescence, they tried a number of cell types.
' It was really just chance that we came to make Dolly.
The aim of the experiment was to compare cells taken from a number of different sources, and the collaborators that we had from PPL remembered that there was a cell line that they had, which was taken from the mammary gland of a six-year-old ewe, actually cultured for a completely different reason.
'This was the Holy Grail - 'to create new life from cells taken from an adult animal.
'To create the clone, the nucleus of a sheep's egg was removed.
'The expert in micro-manipulation, Bill Ritchie, 'put the six-year-old donor cells under the microscope.
'With a pipette not much wider than a hair, one donor cell was selected.
'It was inserted into the egg cell.
'Electricity gently fused the two cells.
'The egg with the donor nucleus was placed between two fine electrodes.
'A sharp burst of 25 volts brought it to life, 'mimicking aspects of fertilisation.
'The embryos which developed were then implanted into surrogate ewes.
' In many of these cases, the embryos which you produce and which you transfer into a foster mother appear to be perfectly normal at that stage, but most of them die and so you cannot be sure, simply because you've got something which is developing for a week, you can't be sure at all that it will come through and become a live lamb, and so we have to commit ourselves to that whole period of work at the beginning of each experiment.
We've got foetal movement.
Here are the ribs on either side, going towards this V.
In the middle of the V, right at the point, is the heart.
CAMPBELL: Seeing these baby sheep foetuses moving about was really exciting, to see that they'd got legs and heartbeats, and you could see this whole little sheep sitting in there, it was amazing, it was a really good feeling.
'It took 277 attempts to get Dolly.
' We were not only working pretty hard during the day in the lab, we were also spending our nights "watching over our flock," as they say, and checking on the sheep every hour between 11.
30 and 5.
30 in the morning, just to make sure that if they did give birth, they didn't get into any difficulty.
McGAVIN: When Dolly's mother started to go into labour, she started getting restless and moving round in circles and pawing at the ground.
Dolly's birth was very natural and, at the end, came very quickly.
WILMUT: As far as I was concerned, it was just an ordinary day.
Unfortunately, at that time, quite a few of the team were away, so we didn't actually celebrate, because it seemed to me to be important that, since this was such a team effort, that if we were going to celebrate by drinking the champagne that I'd actually already bought, that we should all be there to take part in it.
But nevertheless, there was the great personal satisfaction that this little lamb here was showing that our nuclear transfer technology was a very important step forward and that we were going to be able to tackle a whole new range of biological opportunities.
'At last, a central tenet of developmental biology was overturned.
'Their results proved that a nucleus from an adult cell 'could be reprogrammed to clone animals.
' I'm full of admiration.
I think it's a great technical achievement.
I'm also particularly proud that it was done at Roslin, as well, by my colleagues there.
- This is a great achievement.
- It's a wonderful piece of science.
I think it's always better to be the bride instead of the bridesmaid, but I can honestly say that, er, not for a moment was I ever jealous of Ian Wilmut.
Ian was a colleague, he was a collaborator, he was a friend, and when we saw that they had got it right, it was.
it was fantastic.
It was kind of a kick in the pants.
I said, "We could probably have done that!" We have simply been the fortunate people who put the last brick in place and completed the understanding.
Watch your backs.
'Even three months after the announcement, 'Dolly's shearing was still front-page news.
' Can you come round the other side? Kneel down, put your arms round her.
That's right.
We're very pleased to have the world champion here to shear Dolly today.
As you probably are aware 'The director of the institute hopes to use the advance 'to genetically engineer livestock to make pharmaceuticals.
' .
.
and we hope will be useful to treat lung disease such as emphysema and cystic fibrosis.
'But as Dolly became an icon of biological control, 'the real fears were for human cloning.
' MUSIC: "Carmina Burana" by Orff We don't, ourselves, under any circumstances intend to do it, and we don't intend to license the technology to anyone who wishes to do it and it's illegal in most Western European countries, including the UK.
'But lawyers told Horizon that human cloning 'may not be against the law in Britain.
'The act defines an embryo as 'an "embryo where fertilisation is complete", 'but a cloned embryo has not been fertilised.
'Parliament's Science and Technology Committee 'has found it is not satisfactory for issues as momentous as this 'to be left until they're decided through test cases, 'but, so far, the law has not been changed.
'In America, too, human cloning has not been banned 'and there are fears it may prove unpoliceable.
' Within a week of the announcement of Dolly's birth, there was a company that advertised itself on the World Wide Web, called CLONAID, that was offering to use cloning technology for a fee of 200,000.
It's not clear whether this company is really legitimate or not, but it certainly indicates that companies will be able to set up their services on offshore islands where the laws won't interfere with their practice of the technology.
'CLONAID told Horizon they aim to create a human clone 'within two years, using IVF laboratories 'which they weren't prepared to name.
'All this despite the fact that 'any human clone could be physically damaged.
' WILMUT: The cells that were used to produce Dolly were from a ewe that was six years old when they were taken, so there's an interesting question as to whether Dolly, who's now approaching a year old, is really a year old, or whether she's really seven years old.
There are changes in our cells as we grow older, as we age, and the question is, how many of these changes have been reversed as part of the reprogramming events during nuclear transplantation? The simple answer is that we don't know.
'So a human clone created from cells of an 80-year-old 'might have only a few years to live.
'Would women undergo the countless egg donations 'and pregnancies needed to create Dolly? 'If they did, it's possible a human clone 'might grow too large in the womb, 'like some of the giant calves in Texas.
'Jonathan King is a molecular biologist who has voiced concerns.
' Technologies like nuclear weapons, chemical warfare, nasty pesticides, these all have the potential to do a lot of direct human harm - to damage, to maim hundreds of thousands of people.
Cloning isn't going to be like that.
Cloning maims the relationship between humans, the notion of what it is to be human, the notion of what it is to regard other people as human, as having a common heritage, common values, needing to take care of each other.
Any technology that makes humans into objects, like slavery 200 years ago, sets back human history, it doesn't advance it.
SILVER: I think the cloning technology could be used to end anguish with a number of people.
All you are doing with cloning is having another child be born with the same genes as the person who donated the cell.
And we already know from identical twins - identical twins ARE nothing more than clones - identical twins have their own personalities, they are their own persons, they are their own individuals.
'Even Lee Silver, who's in favour of cloning 'to tackle infertility and other problems, has his concerns.
' The cloning technology, all of a sudden, allows genetic engineering to be feasible with human beings and this is what I really fear, because, with genetic engineering, it is possible that those who have money would be able to provide genetic advantages to their children, and those who do not have money will not be able to use this technology.
And what will happen is that the two social classes will diverge into two genetic classes, where there could actually be two different races of human beings, based on those who have been enhanced genetically and those who have not been enhanced.
We as human beings now, for the very first time, have the ability to evolve ourselves, to choose what genes we want to put into our children, and so, in a sense, the entire process of evolution is now changing and we have the ability to make that change right now.
KING: Very often, the scientific community, technologists, imply that every more sophisticated application of science and technology is progress.
But, in fact, that's not the case.
It's only progress if it solves a real problem.
There are plenty of applications of science and technology that set us back, they're inappropriate, they violate what it is to be human.
The application of modern cell biology, modern genetic engineering, for human cloning That is a genie that we should put back in the bottle, cork it and carefully label, "Danger, this is not in the interest of human society.
" INTERVIEWER: Haven't your team unleashed some terrible genie on the world? Well, in many ways, the genie was let out of the bottle by Pasteur in the 19th century when he first started applying science to medicine and science has gone on throughout the world, in many, many laboratories, over the last 120 years and this is just another example of it.
It's moving forward at a really broad sweep, it's almost like the tide coming in.
We're just a little bit ahead of somebody else, maybe just only a year or two ahead of somebody else, so if we hadn't have made this discovery now, somebody else would have made it in a few years' time.
'But leaving aside the cloning of individuals, 'there is another ethical minefield - 'the use of cloned embryos in medicine.
' WILMUT: We're very excited about the idea that we may be able to use this technique to bring forward a particular way of treating some diseases.
What you'd do would be to take cells from a patient and fuse them to unfertilised eggs in order to obtain undifferentiated cells of an early embryo.
You would then, very quickly, in culture, cause these to differentiate into the cell type that was needed to correct that particular disease.
I think we can look forward to this being used to treat not only specific conditions like Parkinson's disease or leukaemia, but also, perhaps, for providing quite complex tissues or even complex organs like hearts.
You do have to produce a small bundle of cells, but you would cause these to differentiate into the tissues that you needed within the period of a week or so.
I recognise that there are people who feel that, even at the moment of conception, there is aa soul present in this very small bundle of cells.
To me, this is something This is a view of life that I don't share.
I don't regard an embryo at that stage, that little ball of cells, as being a person.
'But how is life to be defined 'if cloned embryos could be used for spare-part surgery? 'Biologists are already mastering the reconstruction of the body in frogs.
' At an early stage of development, a frog embryo consists just of an undifferentiated ball of cells and we've been interested for some time in how the pattern of the embryo develops from this featureless ball of cells and, in particular, we have been interested in the question of why the head comes from one end and the tail from another end.
'They found they could control the series of genes that form 'the different parts of the animal.
' If you inhibit any member of this gene cascade, then the embryo can't make a trunk and a tail and it becomes just an isolated head.
If, on the other hand, you over-express any of the genes in the cascade, that is to say you turn them on all over the embryo, not just in the posterior end where they're normally on, then the whole embryo becomes a trunk and the tail and you don't get a head.
'Could this technology be used in humans to create spare parts?' I think we probably do know enough about animal development that we could imagine reprogramming an egg in such a way that it didn't form a whole embryo, but it just formed the organ you wanted plus the heart and circulatory system.
Let's say you wanted a pancreas and you created an embryo consisting of a pancreas and a heart, surrounded by skin.
I think, if you could grow it in a bottle, perhaps one could begin to discuss whether this would be acceptable or not, but at present I think the idea of growing it in a human female volunteer really is completely unacceptable.
I'd feel a bit insecure about the possibility that such an organ could be grown in an animal host as well, although thatthat's not currently practical, although that's something that might become a practical possibility in the next few years.
'But where is the line to be drawn 'when creating potential new life and then destroying it to save another?' It would certainly be unacceptable to create a whole human embryo by cloning for some purpose such as spare-parts surgery.
That would That would be murder and that would be quite out of the question.
I think if it was just an isolated organ, erm, that is a greyer area and it's something which does very much depend on what society as a whole feels about it and I think if such a thing is repugnant, then it should not be proceeded with.
If it's seen as being aa new lifeline to people who are dying provided by biological technology and if it's generally welcomed, then it could be proceeded with.
'The reconstruction of a cloned embryo to make spare parts, 'a much easier way of genetically engineering animals, 'and the cloning of humans - 'these may no longer be the realms of science fiction.
' I know that scientists sometimes say, "Well, this work is so dangerous, "I don't want to be involved in it any more, "I'm now going to get out of the field.
" I think that is also a dangerous way.
If you felt that this science was dangerous in some way, your best route is to stay with it, so that, as it develops, you can communicate it to the world, and in our particular case, that's what we believe is our primary responsibility - to communicate all this information to the world so that they understand what we're doing and they understand the ramifications of it.
You can't then put a gate and say, "Well, I've communicated it.
I'm no longer responsible.
" No, you have to shepherd it through, help people interpret it.
Is it properly used? Does it reach the people who need to have it? And if you see that it's being misused, right, you can't say, "Oh, well, that's notthat's not my fault.
" INTERVIEWER: So, do you see yourselves as primarily whistle-blowers on cloning technology or as the prime beneficiaries of it? We see ourselves both as the scientists that are doing the work and as the whistle-blowers on the technology.
We also see ourselves as profiting from it scientifically, because it's exciting and it's an intellectual breakthrough, it is a major intellectual breakthrough, and hopefully we will profit from it as a research organisation from some licensing of the technology to bring some income into the research institute.
KING: What's going on everywhere in the world really is an enormous commercialisation of forms of life that we never thought of previously as private property - human genes, cell lines and entire organisms.
But what this is really about is being able to get economic control over animal breeding at a much, much broader scale than has ever happened before.
400-500 years ago the frontiers were geographic.
Adventurers, sailors, very intrepid ones, sailed out to the New World and they claimed all the land they could see for themselves or for the king, regardless of who was there beforehand.
Now we have a new frontier in which corporations and institutions claim, as their private property, all of the genes and cells and organs and genetically modified organisms that depend on millions of years of evolution.
Many people call it "bio-piracy", robbing from the whole species for a very particular gain.
WILMUT: During the last few months there's been enormous interest, not only from the media, press and TV and so on, but also from fellow scientists, enormous flow of requests for information, so there have been times when I haven't known whether it was going to be either a heart attack or a nervous breakdown which was going to get me.
INTERVIEWER: People have compared this to nuclear weapons, chemical weapons and some of the worst things that have come out of scientific laboratories this century.
What do you feel about this? I I think that the, erm potential misuses of the nuclear transplantation are a lot less dangerous than, er, atomic weapons, a lot less dangerous than that.
Erm But I think, perhaps, this illustrates the whole point that, if you like, knowledge itself is a neutral thing and it's important we go on gaining knowledge and understanding things.
What's critical is the way in which we use that new knowledge.
Not only can you not stop science, but I really think it would be a mistake to try to do so.
Just think how many things there are which we take for granted which have come from biological research in the last 50 or 100 years.
What's going to happen in the next 20 or 50 years is that the genetic research, which is just beginning, is going to produce a whole range of similar opportunities which we can't even begin to predict, but it's quite clear that they are going to be as important as the biological research that has already gone on this century.
'As the age of biological control dawns 'and the biologist has the same mastery of the genes 'that the chemist has over the elements, 'our power to alter our destiny is changing for ever.
' MUSIC: "Requiem" by Mozart