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Nobel Prize Winner for Medicine Details Gene Modification Work

October 8, 2007 at 6:20 PM EDT

JUDY WOODRUFF: And now, the Nobel Prize in Medicine for pioneering work in the field of genetics. Gwen Ifill has the story.

GWEN IFILL: This year’s prize was awarded to a trio of scientists for modifying genes in mice and creating better animal models for understanding human disease. The Nobel Committee said the scientists’ work is “being applied to virtually all areas of biomedicine.”

Mario Capecchi is one of the winners. He joins us tonight from the University of Utah in Salt Lake City, where he is a professor of biology and human genetics.

First of all, Professor Capecchi, congratulations.

MARIO CAPECCHI, Winner, Nobel Prize in Medicine: Good evening. Thank you.

GWEN IFILL: So the best successful description I heard of your work today described it as you’re creating designer mice. Is that accurate?

MARIO CAPECCHI: That is accurate. What we can do is to change the DNA, the composition of the genes, in any way that one can conceive of, for example, inactivate a particular gene, and then look at the effects of that inactivation on the mouse, and thereby infer the function of those genes.

GWEN IFILL: And when you say “inactivation,” is that like a scientific process of elimination?

MARIO CAPECCHI: For example, a gene is made up of four letters. It’s the sequence of four letters. Instead of using 26 letters, it’s written in a language of four letters. And one thing we can do is simply delete out that text and then say, what happens to that mouse?

GWEN IFILL: And in the case of the mice that you are looking at here, there’s no limit — the desire or the good thing that you get out of this is that there’s no limit on the uses of this kind of manipulated genetic material.

MARIO CAPECCHI: That’s correct. I mean, one use, for example, is to model different genetic diseases. An example would be cancer. Make a mouse modeled with a particular cancer, use the mouse to study that cancer, and then, once we understand it, then use it also to develop therapies.

Using stem cells to fight disease

GWEN IFILL: And what other kinds of diseases? You said cancer, but that's not the only example here. Even though I know there were three of you and you each worked on a different segment of this...

MARIO CAPECCHI: That's right. No, it could be blood pressure, high blood pressure. It could be psychological disorders. It could be heart disease. It's applicable to all diseases, because all of them have a genetic component. Some of them are only caused by a single gene mutation; others are more complex.

GWEN IFILL: One of the very first things that we all thought, laypeople here, as we read about this, this morning, is we saw the term "embryonic stem cells," and immediately that stirred up the nature of the human embryonic stem cell debate we've been having. Is this very much the same or very much different?

MARIO CAPECCHI: Well, we use embryonic stem cells to do our experiments. The actual initial genetic modifications are done in embryonic stem cells of mouse. And then you use those cells then by reintroducing them back into a pre--implantation embryo to generate a mouse with that genetic modification.

And the cells that we introduce contribute to making all the tissues of the mouse -- hair, skin, liver, every tissue -- but, most importantly, also the germ cells, that is the eggs and the sperm, and thereby propagating that mutation or change that we introduced into the DNA to many generations of mice. And we can then generate as many of those mice as we want in order to study, for example, cancer, or heart disease, or a psychiatric disorder.

GWEN IFILL: Or cystic fibrosis, I read today.

MARIO CAPECCHI: Or cystic fibrosis is an excellent example of a single gene defect.

GWEN IFILL: So this has been going on for some time. This is not a brand-new strain of research. In fact, you won the Lasker Prize, kind of the pre-Nobel for this, already. So how much farther do you have to go following this strain of research?

MARIO CAPECCHI: Well, I think we can go on for quite a while. For example, instead of just inactivating the gene, now we have the capability of inactivating the gene in a specific cell type and at a particular time chosen by the investigator, for example, by introducing a small molecule by injecting it into the bloodstream of the mouse.

So that allows us to control very precisely where the defect occurs and when it occurs. And this becomes very important, for example, if you want to study how the brain works. Is a gene involved in initial acquisition information, the storage of that information, or the retrieval of that information? And so you have very different time points in order to see, when is that gene active? And you want to have that ability to do those manipulations.

Capecchi's life in science

GWEN IFILL: How did you come to this point in your life, Professor Capecchi? You have an interesting childhood story, and you've come quite some distance from then.

MARIO CAPECCHI: Yes, it started out fairly bleak. I grew up in Italy during the Second World War. And I lived in the streets for many years, from four-and-a-half until I was nine. And then, fortunately, the war ended. My mother was released from Dachau. She took about a year-and-a-half to retrace my footsteps, found me, and then brought me to the United States. And there my schooling started.

GWEN IFILL: Do you think some of that experience taught you how to be persistent, perhaps, in coming up with solutions like this?

MARIO CAPECCHI: Yes. Some people say stubborn rather than persistent, but I like to consider it as persistence...

GWEN IFILL: This is the second...

MARIO CAPECCHI: ... and, also, I think it's resourceful. I think, you know, you have to take care of yourself, and you can only depend on yourself in order to accomplish a particular goal. And that's essentially what you also have to do in science. You initially get some funds, and then you have to use your own resources in order to utilize those funds effectively.

Focusing on predictive research

GWEN IFILL: This is the second year in a row that the medicine prize of the Nobel has gone to genetics research. I wonder if that's now where it's at in science and whether that means that everyone is beginning to see this as a way of being predictive in our medicine rather than reactive.

MARIO CAPECCHI: No, I think it certainly is true, it is important to be predictive. That is, in a sense, really understand the problem, design drugs that are -- I mean, for example, with neuropsychiatric disorders right now, we simply try drugs off the shelf. If they work, we continue to use them. If they don't work, we move onto another. But we don't have a real understanding of what that drug is doing.

But once you understand how the brain works, then you will be able to design drugs that are specific, for example, for monopolar depression, or schizophrenia, or any OCD, obsessive-compulsive disorder, whatever. So I think you need an understanding, a deep understanding of the pathology, and then, once you have that, then you can design a drug that's very specific.

GWEN IFILL: Well, thank you for sharing some of your deep understanding with us, Professor Mario Capecchi. Once again, congratulations.

MARIO CAPECCHI: It's been my pleasure. Thank you very much for having me on.

GWEN IFILL: Happy to.