The Nobel Prize in Physiology or Medicine 2006
Andrew Z. Fire, Craig C. Mello
"Unrelated looking stories just keep coming together and
unfolding in beautiful ways"
Telephone interview with Professor Craig C. Mello immediately following the announcement of the 2006 Nobel Prize in Physiology or Medicine, October 2, 2006. The interviewer is Adam Smith, Editor-in-Chief of Nobelprize.org.
[Unidentified] – Hello?
[Adam Smith] – Hello, may I speak to Professor Mello please?
[Unidentified] – Hold on for one second.
[AS] – Thank you.
[Craig Mello] – Hello.
[AS] – Hello, Professor Mello, my name is Adam Smith and I'm calling from the official website of the Nobel Foundation.
[CM] – Yes, hi.
[AS] – Well first of all many, many congratulations on being awarded the prize.
[CM] – Thank you so much.
[AS] – Where were you when you heard the news?
[CM] – I was checking my daughter's blood sugar. She has type 1 diabetes so I was actually up, one of the few, I guess, in the North Americas who was awake.
[AS] – Yes, I imagine so.
[CM] – We check her frequently and I just happened to be up, checking her blood sugar. And she had a good sugar actually, 95, which is normal.
[AS] – That's good news, yes.
[CM] – I was on my way back to bed and the phone rang.
[AS] – So two good pieces of news at once! I imagine you were thinking of other things but what was your first thought on being told?
[CM] – Well, you know, gee, that's a really hard question! You know first it's disbelief, and I don't think it sinks in quickly. I felt I was sort of too young to get it this soon and thought, if it happened, it would be a few years from now. So I wasn't ready at all.
[AS] – It has been quite a short gap, a relatively short gap, between the discovery and the prize.
[CM] – Yes, it has. Is it unusually short for Physiology and Medicine?
[AS] – I don't know about unusually, but certainly than some years recently, yes.
[CM] – But of course I was, you know, now it's starting to sink in, I don't think I still really appreciate how this might change everything, in terms of ... we'll see later today how it goes! But no, I was actually ... now what was your question?
[AS] – It was just what your first thought was, but ...
[CM] – There were lots of thoughts going through my head and it was a big surprise.
[AS] – Indeed. The prize has been awarded specifically for the phenomenon of gene silencing by RNA interference that you and Andrew Fire published. Was there a single Eureka moment you can recall when you realized what was going on?
[CM] – There really wasn't for me until we got to understanding of the gene, the first gene we cloned, and for me that was very much like a Eureka moment because the phenomenology was exciting and interesting – the fact that this silencing was occurring and the fact that it could be transmitted from one generation to the next and spread from tissue to tissue – all of those things were amazing and exciting and of course inspired us to work hard at understanding the mechanism. But not until we cloned the first gene, which we had called rde1 for RNAi decision gene number one, did we realize that the gene had homologues in essentially every organism including humans and plants and even fungi. And that, to me, was extremely exciting, especially because it was a novel gene and yet highly conserved, with extensive sequence conservations.
[AS] – Yes, yet more evidence that RNA cannot possibly be viewed as just the passive messenger of DNA.
[CM] – Exactly. And I think there's more coming, I think this is just the beginning. I'm very excited now in thinking in terms of the role of this type of silencing in evolutionary change, rather than simply as something involved in regulating gene expression. Actually I think it has an impact, or a potential impact, on evolution on a broader scale as a source of inheritance and variation. And that's something that I'm thinking about writing right now, a paper, essentially a hypothesis, that this may play a very important role in evolutionary change.
[AS] – Right. So your interest really remains very much on the basic science side.
[CM] – Yes. It has and it still is, although there are many applications for RNAi, to me there's still a lot we don't understand about the mechanism. And it's then just really, really exciting how many different fields, seemingly unrelated, have just merged together with the understanding of the mechanism. As the understanding grows we just seem to be bringing together these very distant looking - sort of unrelated looking stories just keep coming together and unfolding in beautiful ways. So, there have been so many contributions from people all around the world, scientists who have been working on phenomena that we didn't know were related to the one that we discovered. And all of their work has really helped to make this something that has been so widely recognized as a fundamental discovery, because lots of work was already being done. So I think that's one reason it happened so quickly. It just was the last, but a very important piece in a puzzle that quickly fell together.
[AS] – Yes, because there really has been an explosion of interest in it. But what a lovely, unexpected consequence that it brought all these fields together.
[CM] – It is wonderful, and they're great people and I just really loved meeting all the other scientists working on RNAi. They're just a tremendous group of people, and I think the Nobel Committee should, at some point in the future, recognize the small RNA discovery itself, which is a different story. I don't know if that's something that could be taken up by Chemistry or Physiology and Medicine, but small RNAs, microRNAs (I'm sure you've heard of the little RNAs that are developmentally regulating gene expression) are one of the major discoveries that was made shortly after ours and was very exciting.
[AS] – That opens a whole new chapter. And we talk at greater length with the Laureates when they visit Stockholm in December, so hopefully that's something we'll have a chance to talk about then. One, just last question; any ideas how you're intending to celebrate today?
[CM] – Uh, I haven't gotten that far, but I'll call my family and we'll take it from there.
[AS] – Well, once again, many, many congratulations and thank you very much indeed for talking to us.
[CM] – Thank you.
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