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Elizabeth Blackburn
Elizabeth Blackburn
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Elizabeth Blackburn Interview (page: 2 / 8)

Nobel Prize in Medicine

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  Elizabeth Blackburn

Was there an actual moment when you knew that you were seeing something that hadn't been described before?

Elizabeth Blackburn Interview Photo
Carol Greider: When I first saw the first result that Christmas Day, there was a pretty clear recognition of what it might be. I remember being very excited, but within hours, all the things went through my mind about what else it could be, but not what I thought. What other things could be fooling me, and look like that, and not really be a new enzyme? So then we set about challenging ourselves to prove that it wasn't a lot of other things that were already known that were fooling us. I think that the point where I really believed that it really was real -- because I wouldn't even allow myself to believe it -- was an experiment. I guess it was the experiment using the yeast oligo, and getting the yeast oligo to do the same thing.

Elizabeth Blackburn: Yes, right.

Carol Greider: It was maybe five or six months later that we actually did that experiment and got the result. I do remember going home that night, having had that result, and just being very excited about it, and thinking, "Okay, this really is something new." So it was probably a good six months of testing various other alternative hypotheses before really believing it. I remember turning up the rock and roll and dancing all by myself in my room at home.

What song were you dancing to?

Carol Greider: It was Springsteen. Born in the U.S.A. I'm not sure which song, but that's what the album was.

How about you, Dr. Blackburn? When did you have that feeling you'd got it?

Elizabeth Blackburn: Actually, that first gel really sort of -- it said so -- it was such an unusual pattern to see, that it really spoke and said, "Yes, I think this is it. "And then, of course, as you say, all the questions that any responsible person is going to ask, that this isn't just wishful thinking. You can always wish to see what you want to see, but there was this real qualitative difference in the previous -- you know, there had been a little hint here and this sort of thing -- but this was kind of, "Ah!" There was a pattern. You know, I think we love patterns. This produced a kind of pattern of tiger stripes. I think our eyes like to see these sorts of things, and I think our view of how this enzyme works is still very dominated by this kind of visual pattern, but I did have this real gut sense. "Ah yes. This really, really looks important and new here. So you have these two things that go on inside, so you have this "Yes, this is really good, and I want to do this," and then at the same time, as Carol was saying this morning, we have to also be very sort of strict, because you know yourself. You're the most likely to be deluded, because you're the one who wants it to work, all right. So you also have to kind of play these two things off against each other, where your enthusiasm for the project has to kind of feed into your enthusiasm to make it sure as well, because in science you are trying to get at what is real. Right?

[ Key to Success ] Integrity

It sounds like it was a pretty clear path to this discovery. Did you have some setbacks along the way, or moments of doubts?

Elizabeth Blackburn: Experiments don't work much of the time. The very easy ones have been done, so when you do things, you know that there'll be a certain number of times things just won't work. You keep trying. You try a different way.

With telomerase, the initial experiments have been done with trying to make certain kinds of fragments of DNA into a kind of a bait, or a lure, to try and lure out telomerase to show us its existence. I'd done a little tiny bit of work with this and seen the tiniest hint, maybe there was something working, and Carol then took this on and said, "Okay, we're really going to make this work." But then the breakthrough was to not use fragments of DNA grown in bacteria, but to use very small -- what are called oligonucleotides of DNA made in a chemical synthesizer where you can make more, and that is the thing that made a big difference. So you know, it was very hard going, and it wasn't at all assured of success. So even though it sounds smooth in retrospect, there's lots of things that didn't work, and to this day you try things out, and some of them work and some of them don't. There's a lot of unpredictability in doing biology experiments, so you have to be able to put up with a lot of times things not appearing to work.

Dr. Greider, could you tell us a little bit more about the discovery of the enzyme itself, telomerase. How did you know you had something?

Carol Greider: We started some time around in May, trying various things to try to devise a way to find something that nobody had ever seen before. So what we had to do was to test out a whole bunch of different things, just empirically, to determine whether or not we could see something. So it was probably seven or eight months of doing that before we made this particular change in the way we did the experiment. So I did the experiment. The experiment was actually set up some time before Christmas time -- and these kinds of experiments take four or five days for you to actually get the results. It was on Christmas Day that I came back in and developed the gel and saw this result. That Christmas, and other Christmases, it was important to be in the lab, because family things were very difficult, so I wanted to have something to do. So it was very nice that here I was, trying to keep focused, and something great came out of it.

So I developed the gel that showed this pattern. It looked like the kind of pattern that we might expect, and so I was able to think about it.

One of the things about my interaction with Liz is I always would try and sort of hide away for at least an hour or two with new results. I recall at other times actually turning and going into another room when I saw her coming down the hall, so I could sit and think with my data for about ten minutes because she was always so much quicker than I was at getting to what this essential thing meant. So I did have -- because I did develop it on Christmas Day -- I had at least a day and a half to sit and think with the results and sort of mull over what they might mean. And then, of course, met with Liz and we went over them together, and because again it was Christmas time, just after that I took off for a trip that I was going to take. So I had another two or three weeks to sit on my own and try and plan out, what did I think the next set of experiments might be, so that I could have some time to sort of think things through, and then was able to come back and we could sit down together with Liz and go over things.

It was a lot of fun doing the interactions, the day-to-day interactions, but because she had already thought about things, sometimes much more than I had, I tried to get some independence, so that I could think about them, and then we would put our two heads together, over a matter of days, and come up with new ideas.

Dr. Blackburn, can you remember what you thought when Carol first showed you these results?

Elizabeth Blackburn: Carol had done this experiment, and we stood, just in the lab, and I remember sort of standing there, and she had this -- we call it a gel. It's an autoradiogram, because there was trace amounts of radioactivity that were used to develop an image of the separated DNA products of what turned out to be the telomerase enzyme reaction. I remember looking at it and just thinking, "Ah! This could be very big. This looks just right." It had a pattern to it. There was a regularity to it. There was something that was not just sort of garbage there, and that was really kind of coming through, even though we look back at it now, we'd say, technically, there was this, that and the other, but it was a pattern shining through, and it just had this sort of sense, "Ah! There's something real here." But then of course, the good scientist has to be very skeptical and immediately say, "Okay, we're going to test this every way around here, and really nail this one way or the other." If it's going to be true, you have to make sure that it's true, because you can get a lot of false leads, especially if you're wanting something to work.

Was it just the two of you in the lab?

Elizabeth Blackburn: Yes, yes, yes.

Did you share a moment of joy, or were you both immediately skeptical?

Elizabeth Blackburn: I think there was excitement, and then sort of, "Well, what does one do next?"

You don't dare dwell too long on excitement but -- but I did have this, "Ah, yes. This is looking very..." This sort of gut feeling. "This is looking good." Carol had it. She knew. But again, we had to both do this sort of tough testing of it, and there wasn't a set of rules by which to test it, so we had to sort of imagine -- day, week, month after month -- had to imagine all the possible things it could be that would make the whole thing fall on its face and look like it was just a false lead. You had to keep thinking of more and more possibilities, because nature is kind of complicated, and there's lots of things that can go wrong, and you don't want to fool yourself. So that process went on for quite a while, but in a way it's sort of like an intellectual thing. You're trying to say, "Can you be smarter than nature?" in a way. Can you dig something out that has been hard to find? Telomerase -- there's not a lot of telomerase. This is why it didn't show up 20 or 30 years ago. There's not a lot of it. It had to be teased out and distinguished against all of the other kinds of things, all of the other enzymes in cells that do related -- but not the same -- kinds of things.

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