“It was just, you know, diving into the unknown”
Transcript of the telephone interview with Carol W. Greider immediately following the announcement of the 2009 Nobel Prize in Physiology or Medicine, 5 October 2009. The interview was recorded on the morning of the Prize announcement, and the interviewer is Adam Smith, Editor-in-Chief of Nobelprize.org.
[Carol Greider] Hello
[Adam Smith] Oh good morning. May I speak to Carol Greider please?
[CG] Yes, speaking.
[AS] Oh, hello, this is Adam Smith, calling from the Nobel Foundation website.
[CG] Yes, they said that you would be calling me.
[AS] Yes, well, many, many congratulations of course.
[CG] Well, thank you very much.
[AS] I imagine you might have been asleep when the call came from Stockholm?
[CG] Well, actually I usually wake up a little bit early, so I was actually doing the laundry when the call came.
[AS] Did you carry on doing the laundry after the call came?
[CG] Ah, no! I decided we could do that later.
[AS] You’ve been the recipient of quite a few prizes in recent years, so I imagine there was always the suspicion that this might be coming
[CG] I mean you can’t really ever expect something. I mean I had no expectation but, you know, people had certainly had, you know said that there was information out in the press about predications and things like that. But, I don’t really follow those sorts of things very much.
[AS] No, of course, one can’t. You were awarded the Nobel Prize for your discovery of telomerase together with Elizabeth Blackburn when you were a graduate student in her lab. And, it seems, I suppose, to those who might be choosing their graduate projects that you made an absolutely dream choice. It was the perfect one. What attracted you to it?
[CG] Oh, it was just the most interesting question at the time. You know, I had been working in the lab before I chose a project and, it just seemed like the unanswered question, and so why not, you know, go for the most interesting thing that there is to work on. It really was, you know, curiosity that just drove me there.
[AS] Was it a difficult question to answer?
[CG] It was really unknown. It wasn’t clear whether it was going to be difficult or not. We basically had to make things up as we went along because there had been no previous, you know, examples of such an unknown kind of polymerase. So, we took examples from people that had worked on other kinds of polymerases and made our best creative guesses about what kind of experiments to do. But it wasn’t clear whether it would be hard or not. It was just, you know, diving into the unknown.
[AS] And, I gather that the first evidence for the activity that was later shown to be telomerase came Christmas day, 1984. Was it normal that you would work every day of the year?
[CG] Most of the time. I was just very excited about what I was doing at the time. We had kind of been chasing potential activities and … so I had actually done the experiment several days before but then it takes a few days for the autoradiograph to develop. So I went in on Christmas day just to see what was there.
[AS] Perhaps there’s a lesson there for others wanting to emulate you that.
[CG] I wouldn’t necessarily say that it’s a requirement to be out on Christmas day. I was just curious about that particular experiment at that time. I wouldn’t necessarily say that it’s a, you know … that one shouldn’t take breaks and take Christmas off. But, if you’re excited about something and you want to go see, then go ahead and do it.
[AS] As you mentioned, telomerase, was a novel sort of DNA-synthesizing enzyme; it’s a reverse transcriptase, containing both protein and RNA. So, presumably, it took a long time and is taking a long time to untangle it. Do we yet understand it?
[CG] I think we understand a lot about telomerase. There are, still large unanswered questions. Some of the detailed biochemistry isn’t yet entirely worked out, about how the enzyme actually uses a small template reiteratively and, probably more importantly, exactly how it’s regulated in elongating the telomere. Very clearly the establishment of length equilibrium in cells so that telomeres can maintain their length is really critical. And, both the level of telomerase as well as its, regulation by other proteins and modifications clearly plays a role in establishing that equilibrium. And, given the recent, exciting work showing telomerase levels involved in human genetic disease, I think understanding that length equilibrium is going to be really paramount.
[AS] That’s interesting because, yes, I suppose one’s always focused when talking in the sort of popular way about telomeres on maintaining them at a sufficient length to protect the chromosome, but I suppose there’s a balance. You can’t get too long otherwise it becomes damaging also.
[CG] Precisely. So the cell goes to a lot of trouble to establish an equilibrium and regulate that very tightly, so that telomeres are neither too long nor too short. And, how, that regulation comes about really is going to be questioned for the next several years. We know that telomerase is the enzyme that is needed to put the repeats on. But, there are many other factors that go into the establishment of the equilibrium length.
[AS] Right, right. And, one of the things that’s come out of your laboratory with these telomerase null mice. Mice that are born without any telomerase.
[AS] And, yet they are born and they live. Is that saying that telomerase’s role is, again, more complicated than …
[CG] It’s really what we’ve been able to show is that what really matters is the telomere length. So, when a telomere gets short, that’s when either senescence or apoptosis is triggered. So, short telomeres are the things that are really critical and will cause disease as well as problems with tissue turnover. The telomerase just needs to maintain the telomere length equilibrium, as I said, to be able to keep the telomeres from getting short. So, in the telomerase null mice, in the first few generations, the telomeres are still long. So, it takes several generations of cell division before the telomeres get short. So, it’s not the telomerase enzyme per se that causes these phenotypes that we see in the mice but rather it’s the short telomeres.
[AS] Right, right. I wanted to ask about women in telomere research because it’s been commented before that it’s a field where, happily a large number of women have contributed. Is there something particular about the subject, do you think, that has made that happen?
[CG] I don’t think it’s necessarily about the subject. I think it’s one of those examples of a jackpot effect, where you have somebody that trains a lot of women, and then there’s a slight gravitation of women to work in the labs of other women. I don’t think it’s a large effect but a small effect. And so, because the founding group was women, it tends to then, you know, sort of grow out as a jackpot effect. So then, Joe Gall, with whom Liz Blackburn worked was extremely supportive of the women that worked in his lab and he trained a number of telomere biologists – Liz and Ginger Zakian and others. And so, I really think that the fact that he sort of founded a group of strong women that then went on and had other women in their labs was most likely the reason that there was so many in the telomere field.
[AS] Right, right, so …
[CG] It’s a founder effect, sort of.
[AS] Exactly, from small seeds, yes. And is it something that you continue to propagate? You said that there is a sort of slight gravitation. Is it something that one has to actively promote, do you think?
[CG] I think actively promoting women in science is very important because the data has certainly shown that there has been an under-representation and I think that the things that contribute to that are very many social … subtle, social kinds of things. So, yes, I think that one should definitely be cognizant of that and be aware of it.
[AS] Ok, well, thank you very much indeed. I was just going to finish by asking whether you have any idea how today’s going to pan out now?
[CG] I don’t! I heard that you were going to call and then I’m supposed to call the Johns Hopkins Press Office. They said if I got a call, I should call them. But, I was waiting to talk to you first before everything starts happening.
[AS] Well, thank you very much. And, best of luck with it all and, when you come to Stockholm, we’ll have a chance to speak at greater length so I very much look forward to that.
[CG] Thank you very much.
[AS] Thank you, bye, bye.
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