The Scottish scientist behind Dolly, the first cloned animal, talks about extracting stem cells from animal-human hybrid embryos and using them for drug screening.

Corie Lok

In town for a stem cell conference earlier this week, Ian Wilmut, director of the new interdisciplinary Center for Regenerative Medicine at the University of Edinburgh, sat down for a chat with Nature Network Boston. He talked about regional differences in stem cell research, the next steps in his research, and the near-term benefits of stem cells (and it’s not cell transplants for tissue repair).

Ian Wilmut (Credit: University of Edinburgh)

What differences do you see in the culture of stem cell research between the U.K. and, say, Boston?

People in the U.K. are concerned about the enormous investment which has been made in different parts of the United States. There’s a real concern that we’ll just be swamped. Boston appears to have found ways of expanding and creating new opportunities even in this difficult political environment, which is very impressive.

Any other differences?

Britain had a debate about research with embryos around the time when the first IVF (in vitro fertilization) baby was born, Louise Brown. It was both a debate in public and in Parliament. That set the framework for the regulation of those procedures. Clearly there are differences of opinion and clearly some people find embryo research deeply offensive, but broadly our society has accepted it. There’s clear government support and funding for research with embryos, both for fertility treatments and for stem cell research.

I’d have to say that, in a rather British way, the regulations are a little bit cumbersome and slow, but at least there’s a framework for discussing the new things that have come along, like nuclear transfer and deriving stem cells from cloned human embryos, which actually went through fairly quickly. There is broad public support. It does make a big difference.

The U.K. authority that regulates embryo research recently decided, after public consultation, that it was acceptable to create animal-human hybrid embryos from which stem cell lines can be generated for research. Will you be pursuing work in this area?

Yes, we want to put in an application later this year. What would be interesting to do would be to put nuclei from the same cell population into both human and animal oocytes (eggs) and compare how they develop. There are all sorts of reasons for doing this. One is that the number of human oocytes would actually be very small. It would be difficult to organize a project using only human oocytes. It appears terribly ungrateful for a man to say something like that, but it’s a fact.

What do you ultimately hope to do with embryos from animal eggs, if they’re found to be equivalent to those from human eggs?

We’ve always had ALS (amyotrophic lateral sclerosis) as our first target disease, to be able to have cell lines from inherited cases of ALS.

So taking DNA from cells from ALS patients and putting it into animal eggs and then looking for changes in those embryos and cells as they develop that might be associated with the disease, right?

Yes. There are an awful lot of uncertainties, a lot that still needs to be proved. If you go to an ALS meeting, you’ll find a pretty vigorous debate about the mechanisms behind the disease.

The aim would be to have a number of cell lines—differentiated neurons, in this case—with different mutations and try to figure out a common disease mechanism that’s present in them all, presuming there is a common mechanism. Once you have done that, you would then use that observation as the basis for a high-throughput drug screen.

So using stem cells as the basis for a drug screening tool?

Yes. If you could demonstrate the disease mechanism within a cell culture and come up with a good assay for measuring changes in the cells that may associated with the disease, then the question would be: can you find a small molecule that would stop this mechanism in the cells? That would be a preliminary screen.

A lot of drug screening happens in animals, which is slow and expensive. With human cell cultures, you could do a preliminary screen of thousands of molecules.

What are the challenges in developing this kind of cell-based drug screening tool?

Identifying the disease mechanism and producing a stable cell line that you could use time and time again over a period of months or years…those are the real challenges.

I believe that, in the short-term, in the next 20 years or so, the main benefit to come from embryonic stem cells will be this kind of screening. It will be after that before we get, if it happens, the use of cells for therapy. I would argue that in the haste to think of using cells for therapy, people overlook the potential benefit for research and drug therapy, and that’s a mistake.