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Elizabeth Blackburn
 
Elizabeth Blackburn
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Elizabeth Blackburn Interview

Nobel Prize in Medicine

June 16, 2000
Scottsdale, Arizona

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  Elizabeth Blackburn

Dr. Blackburn, how did you become interested in this field of telomeres? Why do you think they're so significant?


Elizabeth Blackburn: I was trained with somebody called Fred Sanger, who won a Nobel Prize, first for sequencing proteins, and he was working on the sequencing of nucleic acids, DNA and RNA, but then DNA when I was a Ph.D. student with him. And so there was very few ways of sequencing DNA then, and one of the things you could do was sequence DNA at the very ends of the long DNA molecules that make up genomes, and so I saw that there would be a feasibility, a way of looking at the ends of DNA, whereas perhaps in those days you couldn't look at the middle of DNA so well. And I went to Joe Gall's lab, and was interested in pursuing this, and Joe Gall, who I mentioned before was a really good mentor, is also an extremely good biologist in recognizing there are good biological systems for asking certain questions. And he was the one who said, "There is this system that has very small short chromosomes," and lots of them, meaning lots of ends, so that this would be something that -- you know, this would be a system. And I was excited because I wanted to look at the ends of things, the ends of DNA, which nobody really had been able to look at in eukaryotes, organisms like us that had nuclei in their cells. And so it was partly that it was doable, and partly because there was a good system to do it in.

[ Key to Success ] Vision



As soon as I started looking at the molecular behavior, there was something unusual about the way the DNA was behaving, and then subsequent experiments by us and by others, over the next few years said, "Ah, there's something going on here which is different." So now, why are they important? So now, fast forwarding and jump ahead now to much more what we know. We know that the genetic material is in long thread-like molecules, DNA molecules, and they have -- each DNA molecule has two ends, and the ends have to be protected. Otherwise they kind of chemically fray away every time the cells multiply. So it turned out to be particularly important to cells that they protect the ends, and furthermore that they replenish the ends of DNA. It was that replenishment that was going on and giving rise to the strange behavior of the DNA that made us first suspicious. And then Carol and I then, you know, we'll look for telomerase. So we didn't stumble over telomerase. It was something that, there was some reason to think might exist, but it would take some real digging to get it.

[ Key to Success ] Preparation


Why did you think it might exist? What function did you think it would perform?


Elizabeth Blackburn: If you put in a certain kind of telomere into a cell of a different species, then you could see telomeric DNA being added directly on to the end of the DNA that it was put in, and that was something that was not predicted. There were also a few other little hints. There was the behavior of telomeres. As you watched the behavior of telomeres, as cells continued to multiply, then the telomeres would get longer and shorter sometimes, so that was odd behavior. And there was a genetic argument in corn, which -- you know, none of this is proof positive. These were all interesting things that came together into one idea. There was genetic evidence in corn that was suggestive that there might be a real function for doing something at the ends of chromosomes, and that could have been lots of things, but it happened that this idea that was coming together from these different kinds of observations -- it was fitting into one kind of possibility, and that was that there was something new there. So those are the things that led into thinking that there might be such an activity, a set of experimental observations that did not fit into the previously known facts, and that is because nobody had looked at telomeres before. It wasn't as if people had been looking at them before and not seeing it. It really was something relatively new to even be looking at the telomeric DNA.


Could you define a telomere for a lay audience?

Elizabeth Blackburn: Yes. It's the protective end of the chromosome, and the chromosome is this thread-like body, there's lots of them in our cells, and each chromosome carries some of our genetic blueprint. So together, all the chromosomes add up to our total genetic blueprint, but it's packaged in the form of lots of chromosomes and each chromosome has to have its end protected, and that's because essentially, things in the cell attack DNA ends unless they have special protective mechanisms.

You undertook your study of telomeres in an organism called tetrahymena. How did you happen upon that particular organism?


Elizabeth Blackburn: As a postdoctoral fellow I'd gone to Joe Gall's lab, and he had suggested -- he had found small linear molecules, short DNAs in high copy number, and that gave an unusual opportunity to look at the ends of the molecules, because if you have very few, very long molecules, you don't have too many ends, but if you have lots and lots of very short linear molecules, you have lots of ends. So he knew that biological system, and had found these molecules, and so the two came together. So it was just a little pond scum organism, you know. It doesn't do anybody any harm. It swims in ponds and happens to have lots of chromosomes, so that was the way I had got into looking at the DNA. And then it seemed reasonable, and luckily it was true, that if there was lots of DNA ends then, as we were going to embark on the hunt for this new enzyme, that there might be lots of the enzyme that made this extra DNA. So I stayed with tetrahymena, and you can grow buckets and buckets of it, and get lots of material to work with, not too expensively.


And how did you begin working with Dr. Greider, looking for this unknown enzyme?


Elizabeth Blackburn: I was a professor at the University of California, Berkeley, and we have a graduate research program. A graduate program, students come to the program to do their Ph.D. work, which means doing research in molecular biology. So the program attracts terrific students, and one of them was Carol, and then the students choose a lab and a project that they'll do research in, and I had the great good fortune that Carol chose to work in my lab.

Carol Greider: I remember the day that we actually met. It was during the interviews when I was interviewing for graduate schools, and I guess at Berkeley I had actually been accepted, and then I went around to talk to professors, just to decide whether I wanted to go there or not. And I had a great time in my conversation with Liz, and she was just very excited about what she was doing, and I was having such a great time talking to her, that the time went by so fast and I really wanted to know more. I remember I asked you if I could come back and talk a little bit more, because I was staying just up the road in Davis. And then, between when I came back and when I'd left, my father had a heart attack and ended up in the hospital, but I did everything I could to come down, because I was going to go back and talk to you some more. And that was sort of the thing that clinched for me that what I wanted to do was to go to Berkeley and to work in Liz's lab. Typically, one goes to a university and then chooses a lab once you go there, but that was my goal after meeting her.

[ Key to Success ] Passion


Elizabeth Blackburn: Carol is not your typical person. I think you see things and you say, "I'm going to go for it!" And you go for it.

Carol Greider: It was guaranteed, the way the program was set up. You had to do three lab rotations, so I did a little project in three different labs. Officially, you're not allowed to make any agreements about where you're going to go until the end of those rotations. I don't know if it was because everyone else in my class knew that what I wanted to do was to go back and work for Liz, or how it worked out but...

Elizabeth Blackburn: It worked.

Carol Greider: I do remember, at the very end of the third rotation, when I came in and said, "I'd like to come back," and she said, "Sure." I was quite happy about that.

So there was sort of a chemistry, if you'll pardon the expression, between the two of you?

Elizabeth Blackburn: Yes. Yes, I could tell Carol was terrific.

How long after that did you make the big discovery of telomerase?

Elizabeth Blackburn Interview Photo
Carol Greider: The first piece of evidence that we had telomerase was Christmas Day of '84. December 25th. And then another year until our first publication.

Elizabeth Blackburn: Right. But you jumped right in right from the start, knowing what you wanted to do. Sometimes people sort of cast around a little bit here and there for a project, but Carol knew that this was one she wanted to get involved in.

Carol Greider: I remember asking you, when I first came: (a) could I work in your lab, and (b) could I do this project. You said yes to both.

Elizabeth Blackburn: Yes. I was so happy to have someone to agree to do this project, which was a daring thing, because the idea was, "Maybe there's something that hadn't been described before." To look for something new is not something that wise people -- prudent people -- would normally do.

Carol Greider: Young and naive!

Elizabeth Blackburn: Yeah. So being young and hopeful -- I had just got tenure and I had research money -- and that gave me a lot of mental freedom to say, okay, I can do something which, if I had written it as a planned research project, funding agencies would have said, "Is this even feasible?" Of course, you don't know. If there's something that's new, you don't know if it's feasible. I had the confidence to go ahead and have the lab and have our energies go into something new.

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