INTERVIEW

Ian Wilmut Interviewed by Suzanne Berry

This article will also appear in Trends in Biotechnology.

Posted November 23, 2001 · Issue 115

Background

Biography
Ian Wilmut is the joint head of the Department of Gene Expression at the Roslin Institute (Edinburgh, UK) - one of eight research institutes in the UK sponsored by the Biotechnology and Biological Sciences Research Council (BBSRC). His main research interests include early mammalian development; embryo manipulation; and nuclear transfer and gene targeting in mice, cattle, sheep, and pigs. Wilmut grew up in Coventry and read agricultural science at the University of Nottingham. He went on to earn a Ph.D. from Darwin College, Cambridge on a postgraduate scholarship, specializing in the deep-freeze preservation of boar semen. He then received a postdoctoral fellowship to research frozen embryos at the ARC Unit of Reproductive Physiology and Biochemistry at Cambridge. In 1973 he was appointed research leader at the Animal Breeding Research Organization, which is located just outside Edinburgh, Scotland.

Do you get bored of the public asking about human cloning? Or do you like the chance to be able to explain the good things that can come from the technology?

I guess it's a bit of both of those, really, as there is a good side and a bad side. There are tremendous opportunities out there. The probability is not very high but by coming and speaking at this conference, which I don't normally come to, there is a possibility that somebody will get in touch and say to you, "Have you thought about this idea?" The other side of the coin is that there is a responsibility to explain things, which is fine, it goes with the territory.

Are you going to continue to patent the technologies you come up with?

It's the structure we have at the Institute, so it's not really whether or not we choose to patent them. A significant part of our money comes from patenting new ideas and then licensing them off. It would be a serious disciplinary offense not to take commercial advantage of research we developed. I am a head of department and I focus on managing patents. The strengths of the patenting and our commercial involvement is that we are now spending far more money on research, even though we do still get some government funding. As long as you have any commercial involvement, you need patents.

Companies sponsor a lot of our research, and Geron actually encourages us to communicate to the outside world. The first time we got to the stage of asking for publication it was very clear that they wanted us to publish. That particular case was where various groups were trying to achieve a particular objective, and we had one piece of the jigsaw puzzle. Geron could easily have argued that we'd rather keep that piece for ourselves because it might have been the last piece that someone else needed, but they did not stop us publishing it, and I was very impressed.

What do you do on a day-to-day basis?

It's years since I was in the lab - I'm too clumsy and absent-minded. My job, whether it's for a postdoc or a student, is to provide an environment in which they can work. For example, many lines of research depend on different disciplines coming together, so we tend to work in groups. My job is make that link together, discuss ideas, sort out problems, and so on; I enjoy that.

What do you think will be the next thing to hit the headlines from Roslin?

I've no idea; whatever does hit the headlines will be something you wouldn't expect! The logic suggests, looking at papers that are coming out now, that there will be new insights into the problems associated with nuclear transfer technology, differences in methylation, gene expression and so on. It's not just the Roslin Institute that is working on these problems. The people working in the mouse have some advantage (the shorter generation time, the availability of gene databases) so I think that we'll see advances there. The most exciting thing is that somebody somewhere, by chance, is manipulating cells in such a way to solve the current problems and make cloning become more dramatic. The problems are solvable but it wouldn't surprise me if it took 50 years, or certainly 20.

What would you especially like to achieve by the end of your career? Do you have one goal or several?

If we understood the whole process of reproduction and the problems with cloning technology, you might be able to improve the efficiency of nuclear transfer, and then you might be able to come up with methods of directly programming the cell - and it would be nice to contribute something to that.

To learn more about how the transferred nucleus is reprogrammed, we have to find out how many oocyte proteins are involved. If the answer is only two or three then it would be a system easy to look at. If it's 200, it's not going to be worth looking at. Until we get somewhere down that line of research, we're not going to know if it will be viable. Some people are already very skeptical about it but I can't see the grounds on which they are skeptical. To me it's very important that we try to identify some of the oocyte proteins, to try to mimic that function in other proteins and it would be good to contribute to that.

Being able to enhance nuclear transfer technology would also help us in therapeutic cloning using stem cells to treat people with degenerative diseases. My father was diabetic for more than 50 years; by the time he died he'd been blind for almost 30 years so I know all about diabetes. The other degenerative diseases are equally unpleasant, so I'd like to contribute towards therapy for them but there are two limiting things - one is that there is an effective treatment for diabetes already and the other is that I'm 57!

There seems to be a big swing against xenotransplantation. Initially one of our major objectives was in that field, and then it sort of disappeared. The companies are turning away, and yet they are turning away just at the time when people are beginning to get a little bit more comfortable with the concept. The ironic thing is that the technology is almost there now, in terms of gene targeting in pigs, which is the way we need to go to prevent hyperacute rejection, which is caused by a particular sugar residue. People are swinging away from xenotransplantation at the time when we can deal with some of the major issues. Also, people naively think that cell therapy will remove the need for xeontransplantation but I just don't see that; I can't imagine growing something as complex as kidneys, for example. So to think that you could derive all the things from cell therapy might be overly optimistic, and it would be a shame if no one were pushing xenotransplantation to see how far it can go. We're still quite a way away because we still have to work out gene targeting in pigs to get the cells surviving for longer, etc., and only then will people really be able to see what is the effect of removing a particular sugar molecule; not only in hyperacute rejection but in later rejection stages as well.

What do you think about cloning endangered animals for conservation?

You need a species that is sufficiently close to the endangered species to be able to provide oocytes and be able to reprogram the transferred nuclei. People always mention mitochondria in terms of endangered species conservation using cloning. The mitochondria need to match but the proteins in the cytoplasm worry me too. The reconstructed embryo will then be transferred into a recipient and you need to have a good knowledge of reproductive biology to have control over it all.

Although our knowledge of reproductive biology in "zoo" species will increase it seems very unlikely that cloning would work at all. I agree with the campaigners who say that we should store cells and so on but I think that it would be totally misleading, to do it on the basis of looking towards getting those species back. Also, we can't let people off the hook as it were, the main thing we have to do is retain an environment for animals to live in using modern technology, not just clone them.

Do you think you'll ever go back to being a farmer as you used to want to?

Ha ha. Probably not! Although I like working with animals.