Do good scientists aim for fixed goals or follow their curiosity? And do they ever worry that they’re barking up the wrong tree?

Question: Is your research highly targeted or guided by curiosity?

Carol Greider: Well, I've always been somebody that likes to follow interesting questions, and that initial work in Liz's lab was really a curiosity-driven question: how can the cell maintain its chromosome ends when we know that they should be getting shorter? So it was a puzzle that we needed to solve. But it was an important puzzle because all cells need to solve this problem of replicating the chromosome ends. But I feel like I've been really fortunate because at every step then along the way I've been able to follow my curiosity and see where the next step led. So, for instance, I started off working on this enzyme telomerase and trying to understand how the enzyme actually functions. What are the different components? Can we find out the mechanism by which this enzyme operates? And then the question came up about cells, and if the telomeres are shortening every time, what would happen to cells? And I got then into this field of cellular senescence, which is that cells can divide a certain number of times and then they stop dividing. And it turns out that the short telomeres play a role in that. So that was a very interesting discovery, and that then led to the next question, which is: if the cells normally stop dividing, why don't cancer cells stop dividing? That's a cell type that has to divide many times. So then our interest went into the area of cancer research, and I was able to follow that because it's very nice to be able to be in this kind of environment where you can just do science, and as long as you're learning something interesting and you can get funded—and I've been funded continuously by the National Institutes of Health, and so that's been very nice—to then be able to follow the next steps along the way in terms of what the most interesting question was to me.

Question: Did you ever doubt that you were on the right track with your telomere hypothesis? 

Carol Greider: Well, at the time there were really two main hypotheses for how telomeres may be elongated: that there could be a recombination-based model or this hypothetical enzyme. And I just thought it was like an exciting puzzle to see which might be true. And so I chose one because I was working with Liz, which was to look for an enzyme which might lengthen telomeres. And it was really just fun to be part of solving that puzzle.

Question: Do scientists fear chasing false hypotheses?

Carol Greider: Of course it could have been possible that there was another mechanism that lengthened telomeres, and it's not clear how long one would then keep looking for something without any success. Luckily, in my case it was about nine months of trying various things, and then I had some success. But yes, there are a number of dead ends in science, and you may be doing experiments along one track, and either technically the experiments don't work, or you get something slightly wrong. And that's what's really important about the whole scientific process, is that it's really about what the results are. And either you or somebody else will be able to determine whether or not the result of your research are correct. And so being able to let go of ideas and move forward I think is just as important as having good new ideas.

Recorded November 10th, 2009
Interviewed by Austin Allen