Interview: Ian Wilmut
Pioneer of Cloning

How did you become interested in science? I understand your first interest was in farming?

Ian Wilmut: Actually even that was very indirect.

The first thing that I can remember wanting to do is to go into the navy. I don't clearly recollect whether it was merchant navy, or whether it was the military service. That came because of meeting a man who I admired immensely. He was a friend of one of my grandparents and he was a super man, and so I really admired him. So, in the age sort of coming up to 10 or 11 I suppose that was my ambition. Unfortunately, I'm slightly color blind, and color of course is involved in signaling on boats, and so I sort of turned away from that.

I think the initial reason why I became interested in farming is that I wanted to be outdoors. I've always enjoyed being outdoors. And so, I looked around and when I was at high school, probably 14 or so, my parents through friends arranged for me to be able to go work on farms on the weekend. I'm of course a city boy, in other words. I was born in Coventry, we moved to the West Riding of Yorkshire, which is industrial. We lived in a woolen area, in an area where the mill was famous because it was the first in which the wool from llamas was used, alpaca. And so it was an industrial area. But I always enjoyed getting out. And I think it was through working with animals on the farm. I'm not particularly mechanically minded, so tractors never really attracted me at all. But, milking dairy cows, becoming familiar with dairy cows, understanding the biology a little bit, that's where the interest developed.

You were basically a farmhand?

Ian Wilmut: Yes, absolutely. I mucked out yards, and things like that, and as I got to be better known to them, I was allowed to milk the animals and so on, and really enjoyed that.

You've said you became interested in biology through doing those kinds of menial chores. What's the link?

Ian Wilmut: I think it was curiosity. The dairy cows giving birth, the calves and their problems, how the younger animals are trained. Certainly, the birth has always struck me as an extraordinary thing. We now live in a country area, and a number of years ago I went and assisted a friend at lambing time. It really is amazing every time. Of course, as a biologist I now know much more about what goes on inside the animal. The fact that that the whole animal comes from a single cell is really an extraordinary thing, and it's fascinating to try to understand it more. But back then it was simply wanting to understand how to improve milk production, how to improve fertility, and the collection of milk

So you could have very easily become a dairy farmer.

Ian Wilmut: Absolutely, that was my expectation. I applied to a school of agriculture, with the thought of going overseas, to go to a developing country. That was something that my wife and I (my girlfriend then) discussed at that time.

What was your interest in that?

Ian Wilmut: That's a different challenge, and it's still there for young people today. There are thousands of hungry people around the world. Probably the biggest contribution that you can make to developing countries is in simple things we take for granted like fences, rather than the very high-tech things which I've become involved in. There's still a considerable contribution to be made by agricultural specialists, veterinary surgeons, bringing things we take for granted into these different environments.

Do you regret that you didn't follow through on that goal?

Ian Wilmut: In some ways, because we didn't travel, but overall no. I've been so fortunate in my research. I think that will actually contribute more, indirectly and over a long period of time, than I could have done in that other way.

Was there a pivotal event that turned you towards the area of biology and specifically, embryology?

Ian Wilmut: I can't remember what made me start thinking about it. Everybody did the same subjects in the first year at school, and then you specialized. I was most interested in animals, but I began to realize that I wasn't really a very practical person, and that practical agriculture probably wasn't the right thing for me.

It was a relatively unusual thing to do in Britain in those days, but I arranged to go and work in a lab for a summer project on a scholarship as an intern, which students here I think almost take for granted. Not quite, but it's well been built into the routines here. In Britain it is still not a routine thing, you have to work pretty hard to get them. And I was very fortunate to get a scholarship. So, I went and worked in a lab for eight weeks, when the main function was just to do the ordinary tasks in the lab. But, there was obviously a responsibility on the senior scientists to talk to you, to explain to you what was going on and that was in my last holiday as an undergraduate and [this experience] utterly persuaded me that was what I wanted to do.

They were trying to understand at that time how it is that an animal which has been mated knows whether or not she's pregnant. Because if she's not pregnant, it's important that she comes back into heat and has another chance to mate and to conceive again. Whereas, if she is pregnant it's important that she stays pregnant. So it's obviously very subtle, but very important machinery. They were using the transfer of embryos from one animal to another to study this.

I became involved in the experimental procedures, worked with the animals, and for the first time saw embryos and assessed them. And these are -- you know, they're very small, a tenth of a millimeter across, but they're extremely beautiful little things, which grow into all of the different things and that's where the fascination in developmental biology and embryology came from.

Where did you see them? In a test tube?

Ian Wilmut: No, what you have to do in this sort of experimentation is to push sterile fluid through the reproductive tract to take the eggs out, and then to put them into a dish. You can only just see them with the naked eye, they're so small, one 200th of an inch roughly. Looking at them with the naked eye, you'd just see a tiny little dot, like a period at the end of a sentence, and that's all. You can't tell anything about it, you can't move them about or anything.

If you put your flat dish onto the microscope, as you turn the magnification up, then you can begin to assess them. Usually by the time you transfer the egg it should have divided into a number of cells. You can see if that division has taken place and whether it's all even and whether the cells look normal. There's a shell around these things called the zone of pellucida, the clear zone, which shines in the light. The cells are darker, because they have fat in them. So you have these lovely single spheres to start with, which then divide into the smaller cells, which really look beautiful. I was learning from casual conversations in the lab, as well as from the work itself.

This will horrify people now, but this was before health and safety regulations came in, so we actually had coffee in the lab. This is, you know, absolutely illegal and not very safe, but at that time people didn't think about it. And, a cart went round the corridor every morning delivering tea, coffee and so on to people. And people -- the senior person in the lab -- would come out and we'd sit and talk, and it might be last night's TV program, or a game of cricket, or the girlfriends that we had -- whatever it was -- or science. And, in my experience, this is where science makes progress often because somebody will put in an idea, or a new observation, and it sparks something else in somebody else's mind.

In my own experience, I think a lot of these things go on in your subconscious. I find myself saying something and almost seeing it go past and thinking, "Hey, that's a good idea." Apart from the social fun, this is also when scientific ideas get discussed. Somebody will develop a hypothesis in a conversation.

People still think of the lab as a pretty serious place.

Ian Wilmut: That's not my experience at all. When I first became a postgraduate student, there were a number of people who wrote essays like, "Science should be fun." Reproduction should be fun, because that's my specialty. If you're not enjoying it, if it's not fun, you should be doing something else. I'm sure that there are some jobs which are very boring, assembling cars for example. I can only imagine that the fun there comes from conversations with people, which is important in science, as well, but we have the privilege of doing something interesting as well.

So was it after these lab jobs in the summer that you started getting serious about the formal study of biology?

Ian Wilmut: That's right. When I went back it was absolutely clear.

In the last year as undergraduates we did a short research project which we built around the course work. And, I worked on the methods of recovering embryos, increasing the yield of embryos from new lambs, working with a postgraduate student. I guess that was the first time I was up through the night, giving them treatments, taking blood samples and so on. And using the new experience that I had about embryos. The university that I was at at that time, there was nobody who had seen an embryo. And so, I used this skill that I'd got. Remember, "embryos" sometimes gives the impression of something which has already got heads and legs and so on, is recognizably a sheep. This is not like that. And so, I brought into the university the training that I'd had away at the research lab.

Once you started with this kind of research, did you have any idea where your work in embryology could go?

Ian Wilmut: No. As a Ph.D. student I had a chance to do a project working with sperm. At that stage I moved to the University of Cambridge, working with Chris Polge, who is best known because he identified the compounds which provide protection during freezing of cells.

The particular niche which was open for me was to try to understand why it was that the same procedures which enable us to freeze and thaw bull sperm effectively wouldn't work for boar sperm. It's always been very important and exciting to try to understand the basic mechanisms as well as I can, and then to seek an application. So, I'd like to think that I wrote an essay on freezing -- the technical name for freezing cells is cryobiology, "cryo" being low temperature -- which would have stood comparison with many at that time. Drawing on research from all sorts of other cells, different species and so on. But, at the same time with Chris Polge I was going out onto one or two pig farms to see whether the method that we developed was going to work or not. And, bridging that gap has always been something which has been important to me.

What was the practical application?

Ian Wilmut: You can make comparisons between the pigs that are here now in 1998, with ones which were there in say 1958. It lets you measure of whether or not there is genetic progress. Whether the pigs really are different as a result of all the selection, or whether all you're doing is feeding them better and that's the reason why they perform better.

You can also use it as a healthier way of importing genes. You might like to import some pigs from Britain. One of the healthiest ways to do that is to collect semen from a boar to freeze it. You can study the boar to make sure that he doesn't show any infections over as long an incubation period as you wish, and then ship the semen to the United States. It's cheap and safe, from a health point of view.

Were you caught up in the excitement of the genetics field?

Ian Wilmut: Actually, not at all, no. My interest was still very much in the gametes and the embryos. And I had a different fortunate opportunity. My wife and I were hoping to work overseas. The particular post we applied for, we were successful, but the money wasn't available for a number of months, and we weren't able to bridge that financial gap. We were offered the post in Cambridge and stayed. It was during that period that we produced the first calf from a frozen embryo, applying the same sorts of things I'd learned with boar sperm. That laid the foundations for a different agricultural application, and also a medical one, because the procedures we followed in 1973 are essentially the same ones used to freeze human embryos as part of fertility treatment programs.

What did you call the calf?

Ian Wilmut: Frosty. Chris Polge had been involved a number of years earlier in producing the first calf from a frozen semen, using his new freezing technologies. His calf was Frosty One and mine was Frosty Two.

What was the big discovery there?

Ian Wilmut: Until then, almost all of the freezing had been done with single cells. Embryos are already small groups of cells, beginning to function together, and quite a lot larger. The volume of an embryo would be I guess a hundred times the volume of a typical cell. It's by far the largest cell in the body. And things get that much more difficult if you're working with bigger cells. So people had not previously been able to work with embryos.

So it was exciting from a cryobiology point of view, and also from an agricultural point of view. Even in human patients when you're trying to just produce one child, there is this occasional response which can produce up to seven or eight fetuses. Extraordinary variability in the response to the same treatment. The same thing happens in all mammals. Now, what this means if you're wanting to do a transfer from one animal into another is that you get no embryos, or 30, and before we had freezing you needed to put them into another animal that day, within a few hours.

From a commercial point of view it was very difficult. If you knew that somebody was bringing in a particularly valuable cow, did you arrange four recipients, five recipients, 20? How many? Once the techniques were refined, it was possible to arrange, let's say six recipients, which is probably the typical figure of eggs that you recover, and to store any that were recovered above that. So it's had a quite significant impact in animal breeding through embryo transfer.

Were there a lot of failures before the technique was perfected?

Ian Wilmut: It was actually the other way around. The two calves that we had were from very early on in the research. And then we spent a period wondering why we couldn't do it again. Actually, the refinement of the technique was left to a successor of mine, Steve Willitsen, a Dane who has made a number of important contributions to embryo research.

Following the experience with the freezing technique, was there a clear path to the next step?

Ian Wilmut: It was one of a small number of opportunities. There was an institute in Edinburgh which was associated with animal genetics. I knew that the physiology techniques I was associated with could contribute to genetic research. That's the reason we went up to Edinburgh in 1973 and have been there ever since.

When you got there, was your intuition confirmed, that this was the right place to be?

Ian Wilmut: No, they were extremely slow in building up resources. Professional career advisors would probably say we should have moved. But we lived about 20 miles south of Edinburgh in a beautiful place. You never have a perfect set of things in life, but our children were roughly three and five, we had a nice place to live, a good place to bring up children, and we decided to settle for that. We've been very fortunate, and over 20 years the Roslin Institute has developed.

Do you think that decision set you apart from a lot of other scientists?

Ian Wilmut: I don't know. Maybe we were just indecisive.

You talk about "we" a lot. I take it your spouse is an important factor.

Ian Wilmut: Absolutely. We met at high school. In those days, Scarborough had separate-sex schools, so we weren't at school together strictly, but met at that time. We stayed in touch whilst I was at university, and my wife was working somewhere else. We married after I graduated, so that we were in Cambridge together. We had our first child after the second year, and a second child once it was clear that I had a post-doctoral fellowship to stay on. We debated what we would do if we had children of the same sex. We felt that if that happened to us we would adopt, because then you help a child that's stuck a little bit, and have the sex of the children that you want. We adopted a son, so now we have three children.

Is your wife at all interested in your field?

Ian Wilmut: Her original subjects at school were physical sciences. She did maths, physics and chemistry. She had no particular training in this; she became interested in it through living with me for 30 years.

Do you use her as a sounding board?

Ian Wilmut: Sometimes, because we have very different views.

I don't have a religious faith, but my wife is now an elder of the Church of Scotland; she does have a very strong religious faith. And so, on some of the ethical issues, I would put to her, what do you think about this? And, we don't necessarily expect to agree, obviously. But, I can get help from her on the way to discuss things and describe things, which is very important. These are very complicated issues and difficult to describe.

You're dealing with technology that raises difficult moral issues. Do you come down on opposite sides?

Ian Wilmut: Not often. She has a different perspective. Over 30 years we've probably come together a little bit. The other thing which I think is important in a slightly different perspective, is that my wife's never had a career, in a formal sense. She's brilliant with young children. For a while she ran a play group and looked after children in the village. She's always done a lot of things with charities, with women's organizations, and the church. She's a busy lady. But she hasn't had the same sort of demands that are made on my time now. That makes it very much easier.

Because she's not part of the scientific community, I imagine she can relate to what you're doing in very human and everyday terms.

Ian Wilmut: Absolutely. In this particular case it has been important for us.

You say the laboratory at what became the Roslin Institute was under-financed when you started there. What were the challenges there?

Ian Wilmut: Paperwork, bureaucracy and persuading people.

You'll either think I'm very persistent, or very unimaginative because I think it took about nine years to actually get the surgical facilities that we really wanted. We could do some things beforehand, but it took about nine years to sort of launch and to really get the excellent facilities, which you have, which are world-class, but that's the sort of response time of the system: very, very slow.

In doing this, you were writing proposals?

Ian Wilmut: Yes, and helping other people and talking to assessment committees. In government terms, it was a fairly large amount of money. The total costs would have been about a million dollars. Quite a lot of money.

Was it frustrating to want to get your hands on this stuff and have to sit there and beg?

Ian Wilmut: Absolutely. And you never know how long to go on being an optimist. You face a situation where there is going to be a committee two or three months hence, so you think maybe that will sort it out. You go through that committee and then something else appears. You never know how long to persist or whether to sort of throw in the towel and go away and do something different. We just persisted all the way.

When you first came to Roslin, weren't you working in a different direction?

Ian Wilmut: I started on a completely different area. It's scenario biology, which hasn't had a fraction as much notice. When I was at Cambridge I'd become fascinated by a particular question. Quite a proportion of embryos which are formed at fertilization die. It's a particularly high proportion in humans. Some estimates are that more than half die. Why? For several years I worked on trying to understand that. It was very difficult to work with.

Why?

Ian Wilmut: The reproductive system is sort of flexible in the way in which fertilization takes place, the way in which the potential mother will begin to produce hormones in response to changes in nutrition or temperature. An animal can reproduce in a great variety of different environments, but the price it pays is that on a certain proportion of occasions it will fail. Overall that's a net gain. It's much, much better to be able to reproduce at 70 percent efficiency in an enormous range of environments, rather than 100 percent efficiency in only one. Because if the environment changed, you're gone.

If, in the species we were working with, 30 percent of the embryos are dying, let's say five percent of it could be because of changes in nutrition. So you're dissecting it down to the individual issues. Very difficult indeed. In human medicine I think it is practicable, because the monitoring, and the interest and the motivation is so much greater. People are able to identify some of these factors, and are helping more women to have children successfully.

But in animal science?

Ian Wilmut: I think it's been put to one side. It's very difficult to cope with.

How did this lead you to cloning?

Ian Wilmut: There was a major change in the institute.

The institute wanted to bring in molecular biology. As I said, biologists have discovered molecules, and this is becoming a very important thing. And in being able to change genes in animals, you need to work with embryos. And very, very unusually, but I was essentially told to stop working on the cause of embryo loss, and to begin working on this area. An instruction which I deeply resented, deeply, deeply resented. Scientists don't like being told what to do at all.

You could have left, what made you stay?

Ian Wilmut: I'm very cautious, I suspect we both are. We had children in high school, which is a critical age for them. The opportunity that came along though, was to work in molecular biology, in modern genetics. After a few months of working with the microbiologists for the first time, that is when I began to understand the power of genetics. We're talking about 1983.

Was that a sudden breakthrough for you?

Ian Wilmut: A steady evolution. Fifteen years later, I'm heavily committed and impassioned about it. I think this area of biology is just exploding. I'm privileged to be in it at the right time.

If someone hadn't come along and said, stop doing what you're doing, would we have had Dolly?

Ian Wilmut: You probably would, but through somebody else. There are other labs around the world -- one at Texas A&M which subsequently moved to Salt Lake City -- and one of them would have had the good fortune at some point, not too much later.

You have said on occasion that if not for a conversation you had in a bar, a major development would not have occurred. Can you explain that?

Ian Wilmut: Absolutely right. We were using the technology which we had at the time to add genes into sheep. It's a very inefficient process. You can only add a gene, whereas what we often want to do is to change genes that are there, but it does work. The director and I were at a meeting in Ireland talking about the work, and listening for ideas, thinking of different approaches to use.

In a conversation in a bar one evening we were told that somebody working in that lab that I mentioned in Texas had achieved a step forward with nuclear transfer and was getting development from cells taken from embryo. And, it sparked across to the fact that in mouse there are ways of culturing those cells in the lab, they're called embryonic stem cells. A specialist population of cells which can give rise to every other tissue. Now, what the person in Texas had done was to take cells from just a day or two earlier than that, so there's sort of a short gap. But, the point that excited me was that if we could bridge that gap, then we would be able to have ways of being able to make genetic changes in animals and make lots of copies of animals.

After that meeting in -- I think -- January 1986, I went back with the director, very excitedly trying to persuade him that this was the way that we had to go. And so it was just that chance conversation that brought a number of ideas together.

Was it easy to convince the director?

Ian Wilmut: Fairly easy with the director. Not too difficult with the potential sponsors of the work, but it all takes time. It took a couple of years to get the money in, then we began to work on this area in a systematic way.

Along the way, the field went through its ups and downs. Can you talk about the controversies?

Ian Wilmut: There are two issues which were very important, and had a big influence on the process. There was a suggestion that an experiment that had been reported was a complete fraud. There was evidence of tampering with the data. Actually, since Dolly and since the technique which led to the production of Dolly, the group at Roslin have come to think that there may actually have been some truth in that report as well. Some people have always felt that, but because there was evidence of tampering with the data, it was dismissed.

Now, developmental biology in mammals is mostly done in mouse, but the embryology of mice is extreme in one particular facet. Very early development in all mammals is initially controlled by proteins and things which are produced before ovulation. At a specific time the genes in the embryo take over. In the mouse it's very early on, when there's only two cells. In sheep, cattle, humans, it's eight cells. In frogs it's about 5,000.

Nuclear transfers have always been much more efficient in frogs and least efficient in the mouse, and it seems to be an important relationship. People had tried doing nuclear transfer in mouse, and they'd drawn a conclusion and said, "It's just not going to go." That massively dominated the view of nuclear transfer that people had, and that was misleading.

The initial step which Steve Willitsen had done in Texas was to show that you could go past that barrier. He was working with cattle embryos, probably with 32 cells, well past this barrier of eight. That led to my optimism. If you could get to there, maybe you could get to this specialist population of cells.

You met with a lot of skepticism. How do you deal with that as a scientist?

Ian Wilmut: You just have to believe it, don't you? You have to be prepared to defend your interpretations and to justify them as well as you can. Science makes progress by advancing new ideas, hypotheses which can be tested by designing good experiments. I just had faith in my hypothesis.

There were unsuccessful attempts. What were the problems?

Ian Wilmut: When you do nuclear transfer you're taking two cells and putting them together. Cells have mechanisms which enable them to grow and then divide. It's called the cell cycle, because it is a cyclical sort of process. You need to coordinate that. A colleague, Keith Campbell, came into the group in '93, and with him, we not only proved this was important, but figured out how to do it. So the first step forward that we made was how to coordinate cell cycles and that gave us a significant step forward.

It was limited though. It was useful, but not eye catching. That led us to investigate other ways of coordinating cell cycles. I had always expected that the particular cell populations I was hunting for would work. When we got lambs from a similar type of cell, I wasn't too surprised. But then as things progressed we began to realize that it was much more powerful than we'd expected and that it was going to work with a variety of different cell types, including some from adult animals.

Was that very exciting?

Ian Wilmut: Oh, absolutely. But often what happens is that there's sort of theoretical moment, if you like. In the case of adult cells that would have been two or three years before the event. It takes quite a long time then to bring the thing to fruition.

Is it hard to keep the excitement going through two or three years?

Ian Wilmut: No. I would characterize myself usually as a naive optimist, and so no, it's not a problem.

You eventually used a mammary cell. Was that just an arbitrary decision to try this cell?

Ian Wilmut: We had shown that you could work with the embryo cells, and we had money to take it on to different cells. We collaborated with a company and set up a project to test two or three cell lines for them, which they could then go away and use. The sheep season in the northern hemisphere goes from roughly October to March, that's when we can work with the sheep. And by Christmas, we had tested a new embryo line for them and got pregnancy started.

They had contracted us to test three new embryo lines, but they'd only got one to work; they'd had technical failures. So we were looking for other things to test. The mammary cells were in the lab for a completely different purpose, so why not use them? I can't believe that we would have used mammary cells if we'd been starting with a clean slate.

What did you have to do to the cell?

Ian Wilmut: The trick that we introduced to coordinate them was to starve them, to make them inactive, there's a technical name of quiescence. And, there are two reasons why we think that's important. One is it's this process of coordinating the cells cycles, so that they begin to go off at the same time. The other is that they're easier to make go back to the beginning of development. And, I think we need to think about this for a minute, what happens in development is that a single cell will become all of the different tissues of an animal, and it happens by cells dividing and then becoming more and more different. And, what biology said was that this process will become more complex, and more difficult to reverse. Now, what happens when we make a cell go relatively inactive is that we think that there are differences in structure in the nucleus, in the genetic information. Which then allow the factors which are in the egg, which really are the magic ingredients, to act on that nucleus and to bring about the complete reversal of development. Now, we haven't formally proved that and we certainly have no idea how it works, but that is our current hypothesis as to why we produced Dolly.

Is that going to be a new area?

Ian Wilmut: Absolutely, and it's very important for a whole range of other things.

Once you've shown that you can do this with an egg by taking a nucleus and an egg, you can ask, what are the factors? Can we find ways of putting those factors into the cell without doing a nuclear transfer? If you can do that, then you can find a way of -- let's say you have a patient with Parkinson's disease, taking a cell from that patient, treating it in the sort of ways that we're beginning to dream about now and it will go back to a very early stage of development. Now, the value of that in principle is that if you got a cell back at that stage you can make it differentiating to everything else, including the nervous cells which are damaged in Parkinson's disease. So I'm quite sure that one day somebody will be describing to you how to do this and to provide cells to treat Parkinson's disease, diabetes, perhaps to reconstitute the immune system in somebody who's had leukemia. To reconstruct the immune system with AIDS, all sorts of different treatments like that.

After you planted this embryo in the surrogate mother, were there sleepless nights waiting to see whether this was going to go?

Ian Wilmut: I suppose there were. We transfer the egg after a week. We use ultrasound to monitor pregnancy, in just the same way as you would in a human patient. So at 50 days we knew there was just one pregnancy. A sad fact that isn't mentioned quite so often, is that half of all pregnancies fail, don't go to term, the equivalent of a miscarriage. So the probabilities were not very high. I don't do the ultrasound myself, so I was just waiting for the call to say, "It's still there, it's still looking really good." People have an idea that all of a sudden there'll be a click and you'll go from having no lamb, to having Dolly. In reality, what happens is that for a hundred days you're monitoring this thing, and it isn't quite such an explosive surprise. It's almost a sigh of relief that the lamb has made it and is obviously so healthy.

When was Dolly born?

Ian Wilmut: July 5th, 1996.

Did everybody celebrate?

Ian Wilmut: This is really strange, because the answer is no. I actually bought some champagne and it was in the fridge, but this is a team effort. My colleague Keith Campbell was on holiday, and at the time I felt that it was more important that the team celebrated together. We tried to wait until Keith and everybody else had come back. With hindsight, that was a mistake. What we should have done is celebrate twice, once when he was away and once when he came back.

You kept this a secret.

Ian Wilmut: The reason's quite simple. The particular journal, Nature, will not publish things if they are in the public domain. It's trying to hype the publicity of the announcement. If we had discussed it in public, it would not get a proper scientific review. And, of course, my career ultimately depends on publishing scientific papers.

It also took us a number of weeks to do the tests to prove her parentage, and to confirm that we really had done what we were describing. There were a lot of other lambs born at the same time. And then it took us until the 22nd of November to prepare the manuscript.

The remaining three or four months are taken up by the journal. The paper is sent out to people to assess, to referee. They make comments and we made some minor changes and then it went in for publication. If you asked a hundred scientists at random if they've had a paper published within six months of the experiment, they'd tell you it's usually a bit more than that, eight or nine months. Not many have got a publication in that period of time, it was very quick.

In all of those months, did you have any inkling of the momentous kind of reaction that would come from this?

Ian Wilmut: No. We expected some reaction.

We expected probably most of the questions, but not the scale of the reaction. You know, we were visited by almost tens of TV companies, straight off. The number of phone calls which you had was logged and it ran into hundreds, thousands, probably, just within a week or two. Still now, there's just a steady trickle of requests for interviews, and that's what, 15 months or so later. At the time, the peak time, The New York Times sent not just one journalist, but one from Moscow, one from Frankfurt, one from New York, and a photographer from New York. It was just way beyond our greatest expectation.

What do you attribute it to?

Ian Wilmut: I'm never quite sure. I think the main thing is probably just the realization that this was now a biological possibility, something people had written about for a number of years. And there's a little bit of fear and anxiety, because the stories that are written about it tend to have a bad element to them. For some people the whole idea has bad associations. You know...

The Boys from Brazil, the Nazis from Germany, and that sort of thing. And you could put a good spin on it. You could say -- it's way too academic -- but let's say somebody might write about, let's say a case where there is a child, a very young child who is killed in an accident, and reproducing that. And getting people to think about whether that's something that they're comfortable with. That in itself raises a lot of ethical issues, but it's not presented in a frightening sort of way, is it? So many of the reactions that I have -- just in terms of pure number of people giving this reaction -- are of governments misusing the technology and of dictators misusing the technology. And I think those are by far the least important things to come from this technology.

Many people associate this kind of genetic research with science fiction. People make that leap right away.

Ian Wilmut: Yes, maybe. It is always very difficult to judge when you're closely involved with something.

Is it possible that science sometimes is too insular, too focused on what is happening in the lab and not looking broadly enough?

Ian Wilmut: I think that we do understand, to a considerable extent. The difficulty is in getting interest. Megan and Morac were born from a slightly simpler cell, almost exactly a year before Dolly, and the publicity was almost exactly a year before. We published in the same journal. We put out press releases and discussed the probability that it would be possible to copy adult animals. And there was so much less interest in that.

So, whilst I would be totally in favor of discussing research with anybody, at almost any time, the practical difficulty is in getting people to discuss things which are still hypothetical. It comes on with a bump once it becomes a reality. That's something that we have to live with.

Science is unpredictable. And if you could say something is going to be achieved on the 15th of June in the year 2001, we could plan from late 1999 how to use it. It would be so much easier, but it isn't like that. When should people first have started discussing this? When people first worked with frogs in the '60s? When it was first applied to mice and sheep in the early '80s? When? It's a real practical difficulty. I'm absolutely not hostile to the idea that society should be involved in these sorts of comments. But in the end, you can only make the ultimate judgments and publicity as things happen.

What was life like during that period of the immediate response?

Ian Wilmut: Very hard work. We got a massive number of requests for interviews. Television, radio, the phone to people overseas, newspaper interviews and so on. We do get a bit of preparation for that. The publicity that I mentioned in relation to Megan and Morac the year before had been a help. But in a situation like that, there's a need to focus totally on what you want to say, in the two minutes you're going to get. You really have to focus on what you want to say. It is hard work.

Has both the substance and the quantity of the reaction had an impact on how you're going to be approaching things in the future, and how you deal with the public?

Ian Wilmut: I don't think so. I've always enjoyed talking about work, and I've talked to a whole variety of different audiences all along. It's not an obligatory part of my work, but I've talked to general groups. The extent to which I do it has changed, but not the principle of doing it.

You have talked very specifically about the moral issues raised by your research. Can you define that for us?

Ian Wilmut: Well, the general question that I would ask about anything is, what are the effects of it?

Are the things which may come from something you're thinking of doing beneficial? Very often of course there's a double edge to it, and so it's a question of, does the benefit outweigh any disadvantages that there are? So it is, if you like, a pragmatic judgment that I'm making. And so, if you're thinking of experimenting with animals, that may cause distress and pain to the animal. "Is the distress that you're going to cause justified by the potential benefit in terms of new treatments for human patients?" for example, would be the sort of judgment that we have to make all the time. And, we have to not only make those judgments, but document them to a supervisory system. In terms of human applications of cloning, in terms of application of cloning, essentially the same sort of process. Is this sort of thing which has been thought about beneficial? So that if you're asking the question, for example, "Is it appropriate to think of making a copy of a person?" You have to ask not only, "What is the benefit to the people who are asking for this to be done?" But also, "What's the impact on the child that's going to be produced?" And that last bit I think often gets missed out.

Recently, there has been the suggestion of treating infertility by copying one of a couple and I would usually use my own family as an example, and would suggest that, let's say that we decided -- that we hadn't had children, and so we decided -- to copy me. Now, it so happens that we met at high school, so the child who is of course going to have a different personality is 17, 18 years old, he's going to have a substantial physical resemblance to the young man that my wife fell in love with a long time ago. How's that going to work? How am I going to cope with living with somebody who is very much like me? And, I think actually most of us would find ourselves pretty difficult to live with.

A very distinguished physicist told me how difficult he found it to live in the shadow of an older brother who'd done very well in SAT scores. How is the young man going to cope with living with somebody who has already been there? How is a person like that going to feel about being able to see what's going to happen to them, physically. That's going to have a substantial influence on their personalities. It's not a fair thing to do to a child.

You yourself have drawn a moral line there. If somebody said, "I want to give you all the money in the world to take this to the limit, but I do not want to explore the ethical side of it, what would your reaction be?

Ian Wilmut: I wouldn't do it. My first question would be "Why?" Now, as we think about this more, there may be reasons for doing it and I might say yes. But I am not interested in helping people to copy themselves as a cure for infertility. There is no cause for infertility which can only be cured by cloning. None. All of the other approaches are proven. They're safe, which cloning isn't, and have reasonable track records, from the point of view of the environment that the child had.

I suppose every scientist draws that moral line individually. But when you bring a new technology or discovery into the world, you know that there are individuals who can use it who may draw the moral lines in a different place. A few months ago there was a man in Chicago who was making rather incredible statements about taking this offshore and doing something with it. As one of the people who brought this technology into the world, how do you feel about that?

Ian Wilmut: First of all, he got far more attention than he deserved, because it's nonsense to suggest you can do it at the present time. I actually also think that it's rather sick. If you think that half the pregnancies we start don't make it. A fifth of the lambs that are born alive die within a few days. That's distressing enough if it happens to sheep. If you're talking about a woman having a miscarriage within days of term, of young children dying, I'm sad that people are even thinking about it. That's the immediate safety issue, it's appalling.

I don't think this is a new philosophical position for people to be in. Sadly, each day people in this country and everywhere around the world will be killed by cars, which we all take for granted. We all use them because they're such a contribution to our life.

I think of the analogy of Oppenheimer and the bomb.

Ian Wilmut: I don't understand physics very well at all and I think you have to think in terms of the broader area of physics because if it hadn't been Oppenheimer, it would have been somebody else in just the same way that somebody else would have produced a Dolly. Do the disadvantages that come from knowing that we can blow the whole place up outweigh the advantages which come from all of physics? And I would suspect the answer is, no. It is not a new aspect of life to have two-edged swords.

You have talked about cutting back the workload and getting a life again. Are you going to really slow down?

Ian Wilmut: I'm going to do different things. I enjoy traveling, I enjoy talking. I've been really privileged, for the last 15 months or so, to meet a lot of really fascinating people. It's also had the desired effect of attracting interest in the biology, and hopefully will bring in more funding. So I think my function changes slightly now. I want to be in Roslin when the new people arrive and begin developing and using this technique. They will share some of the load of traveling and giving talks. So frankly, I imagine I will work as hard, but in a slightly different way. Spending more time at home, more time in the institute.

There is another clone called Polly now.

Ian Wilmut: Polly was derived from a fetal cell and she has a gene added. When she grows up and lactates, she will produce clotting factor 9, which is one of the proteins needed by hemophiliacs. The value of this in medicine is really only just beginning to be understood. There are a whole range of proteins which are needed to treat disease. We use very large amounts of serum albumin during surgeries and so on, and it could possibly be used out of the milk of cows.

We are starting a project now to try to make genetic changes in pigs, so that they can be used to provide organs for human patients. Now, if you take a pig organ and put it into a human it's destroyed immediately by an immune response, so we have to find a way of making a genetic change in a pig, so that that particular response is prevented. Now, of course, to some people that whole idea is really appalling. And, I think that it's important that there is discussion about this, so that there can be a social judgment for each country as to whether this is an acceptable thing to do.

Will you be on the front line of the discussion?

Ian Wilmut: I would be very happy to do that, yes. Because I think it now is part of my responsibility. But I think there's a distinction between being involved in the discussion and making the decisions.

Before you go, was there a particular book that influenced you growing up?

Ian Wilmut: I've thought about this a bit and I think the answer is probably no. From my father's father, and from my father himself, I have been interested in philosophy, particularly. I was an undergraduate at Nottingham when Bertrand Russell's autobiography came out. I read that at the time. At much the same time, I read Somerset Maugham's The Razor's Edge and a number of his other essays. I think his essays are beautiful little vignettes. I read The Razor's Edge when I was working on a farm in Denmark, for summer vacation and enjoyed that.

Did you see yourself in the role of Maugham's hero, going off on his spiritual quest?

Ian Wilmut: I think not. The reason he went off was to understand the world and himself. I think I'm doing that in a different way. My understanding of the world is in biology. I have a busy and a full life in the community that I live in. I do things in the community as well as work, and that's where I find the meaning of life.

People have raised questions about the soul of a person that's been cloned. Do you have any thoughts on that?

Ian Wilmut: I don't believe in the soul, so I find the whole thing difficult to handle. Because you can have genetically identical twins which come about simply by separating the egg. If there is a soul there is a means of handling this particular issue. I don't know what it would be. To me, it's not necessary to, you know, sort of believe in that sort of world, that sort of god. There is enough in the world, if you like, to understand what makes us what we are. And that, I must admit, is what I enjoy contributing to a bit.

Thank you very much. It's been fascinating.