Elizabeth Blackburn Interview (page: 7 / 8) Nobel Prize in Medicine	Print Interview

Could you explain the connection between telomerase and the aging process? There's been a lot of excitement about that.

Elizabeth Blackburn: A lot of interest. I think it attracted interest, partly, because things looked much simpler than of course they were.

Get the Flash Player to see this video. The basic observation is that without telomerase, then the DNA of chromosomes kind of wears down a little bit each time cells multiply. What telomerase does is replenish that DNA, and adds it back on again so that there's no overall continuous loss, and cells continue multiplying. And then eventually, as they continue multiplying and start losing DNA a little bit too much, then this "talking to the cells" that I mentioned goes on, where a cell will get a message from its telomeres that says, "I'm not being replenished. Hey, stop multiplying!" to put it in anthropomorphic terms. And that's partly because the cells have to protect their genetic material, and they say, this DNA sends a signal, "Stop everything. Don't go any further. We've got a problem here." And some cells just simply sit there and never multiply again. Some cells in our body altruistically commit suicide for you, and they say, "This is a dangerous situation. This DNA can go badly awry," and they kindly commit suicide when that happens. So there are ways in which not having the DNA replenished, through having active telomerase, sets off signals in cells which stop then multiplying.

We know that as we age, certain cells do lose some of their ability to multiply, so it's very tempting to think that perhaps if one could replenish back telomerase, perhaps one could keep that multiplying capability of cells. So would that be good or would that be bad? This is where we get completely into the unknown complexity of the whole human body.

Get the Flash Player to see this video. We can't just have cells multiplying out of sight. There's a very bad category of cells that keep multiplying, of course, and those are cancer cells. And one thing cancer cells do is they just love telomerase. That's very unscientific. What I mean is that telomerase gets selected for in cancer cells. It helps them keep proliferating against all the odds. And so in that way, an activity of cells, which when it's not regulated, helps cancer cells to keep on multiplying. So clearly there's one extreme, and the other extreme is no telomerase, and somewhere is some biological window in which there may be some useful potential applications. I don't think there's a single panacea. Far from it. Would that biology was so simple, but we can't fool ourselves. There might be useful applications for sure. So I think this is something that shouldn't be allowed to just be dropped, but on the other hand we shouldn't have unrealistic hopes either.

You won't be buying a bottle of it in the drug store next week to combat aging?

Elizabeth Blackburn: Well, who knows? I have my daily dose of telomerase, but it's in the mind. I mean it's the intellectual fun of it. But people joke about that. It's sort of an attractive idea without any particular immediate outlook right now, but on paper it's okay. How many wonderful ideas have been thought of to cure cancer or aging on paper? We're inching forward. There are other things that we are starting to understand about aging, and the interplay of all the cells in our body as aging goes on. So it's not as if it's hopeless, and it may very well have some part. I think it's interesting. I talked once to somebody who said the idea of the DNA wearing down, this sort of metaphor of the candle burning down, this idea seems to have a very deep appeal to people, and maybe this is partly why this idea caught on. There's something about the metaphor that we like. So it's going to be interesting to see what can be done, and what directions this will all go.

Dr. Greider, could you talk about some of the potential medical applications of telomerase? Researchers have already engineered laboratory mice with extra telomerase. You bet a co-worker a six pack of beer that these mice would get cancer.

Carol Greider: That's my typical bet.

Get the Flash Player to see this video. The idea of telomerase, either turning it on or turning it off, has been talked about in sort of two separate realms. So people talk about the aging aspect and the cancer aspect. And, I think that it's not two separate realms. It's really one and the same. The aging realm that people talk about is that cells have a limited capacity to divide. They only divide for certain number of times and then they stop. And then the cancer realm is that telomerase is needed for cancer cells to keep on growing. It's really the same thing. If you take normal cells and allow them to divide more times than they normally would, then what you have is a cancer cell. Or potentially, that you at least have the potential for a cell that could divide more times than it should. So I don't see these as a dichotomy. I see them as really the same thing, because I believe that the aspects in which telomerase is going to be important for "aging" will be really age-related disease.

Get the Flash Player to see this video. When you hear about it a lot of times in the media, you'll hear that telomeres have to do with aging, and people automatically think, "organismal lifespan." By changing the length of the telomeres, they're going to change how long the human species can live. There are books written about this, and fiction books that put telomerase in the middle of this whole thing. There's no evidence that the telomere length really has anything to do with the organismal lifespan, but rather, potentially, with age-related diseases, that this inability of cells to divide indefinitely may play out in certain disease models. So I certainly think that there are some implications in those diseases that are associated with aging -- that don't determine lifespan but are age-related diseases-- but there may be some role for telomerase to increase the lifespan of cells, and therefore be able to ameliorate some diseases that require more cell divisions.

Get the Flash Player to see this video. And then the flip side is the cancer side. It's pretty clear that cancer cells -- many cancer cells -- have activated telomerase. And it's been shown in a number of different systems that if you take cells that have short telomeres, as tumors normally do, and you inhibit the telomerase by a variety of mechanisms, that telomeres get short and then the cells die. So that's a very good basic set of experiments that suggest that, in fact, when telomeres are short, cells die and so you might be able to target telomerase, in certain cancers, for telomerase inhibition being a cancer chemotherapeutic. I think that the error that people make -- and it's again a generalization -- we talk about cancer all the time as if it's a disease when, in fact, cancer is not one disease. It's a whole bunch of different related diseases, all of which have to do with the increased ability of cells to divide. And so I don't think that -- as has been written in some press accounts -- that telomerase is the final magic bullet that will finally cure cancer, but rather that there will be certain cancers in which inhibition of telomerase may play a very key role, but what one needs to do now is to go and find out what are those particular diseases where inhibition of telomerase might play a role. That's really the next step. A lot of the basic cell biology has been worked out to suggest there is some promise here, and now some of the more clinical studies need to be carried out.

What are you working on now, Dr. Greider?

Get the Flash Player to see this video. Carol Greider: We're still interested in a lot of the basic questions, and we've created some tools. For instance, a mouse that completely lacks the telomerase enzyme, where we can find out what happens in a normal organism in the absence of telomerase. And it turns out that we initially created that tool as a means to get to the cancer question. What happens if a mouse doesn't have telomerase? Can it get cancer? But we find that with that tool we can ask some really fundamental questions about what happens when a chromosome loses its telomere. Does it fuse to other chromosomes? Yes, as we expected it would. And what chromosomes does it fuse to? And what is it that determines which chromosome fuses to which? Very basic questions about how telomeres normally function. And so we have these tools, and we're having a really good time sort of trying to think of some of the fundamental questions that we want to ask that's going to be true probably for many cells, if not all cells, in terms of how they maintain chromosome integrity during normal cell division.

Are you focusing on the cancer application at this point or is the whole thing open to you in this realm of research?

Carol Greider: Yeah, the whole thing is open but we're not really getting into the clinical side of things. We're not working with inhibiting telomerase in human tumors. There are a lot of major pharmaceutical companies and some biotech companies that are out there doing that. We're happy to talk to them, but that's not really where I think my strengths are. What I'd really like to be able to do is come into the lab and have an idea, "I wonder how that works," and go and do it. And there are so many areas right now, in how our chromosomes are maintained during cell division. How do the telomeres play a role in that? I can probably ask questions for a number of years and still be excited by the very fundamental questions. So that's where I see our work going.

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