Interview, February 2021

On 9 February 2021, Venkatraman Ramakrishnan spoke to students and scientists at the European Molecular Biology Laboratory, EMBL. He answered wide-ranging questions, tackling topics such as mentorship, work-life balance, and competition and collaboration.

Interview transcript

[Venkatraman Ramakrishnan] Hello?

[Adam Smith] Hello. Professor Ramakrishnan?

[VR] Yes.

[AS] Hello, my name’s Adam Smith. I’m calling from the official web site of the Nobel Foundation in Stockholm.

[VR] Yes.

[AS] We have a tradition of recording very short interviews with new Laureates. May I offer you my congratulations and speak to you for a few minutes?

[VR] Yes. Thank you.

[AS] You started out as a physicist, and I just wanted to ask what attracted you to biology in the first place?

[VR] Well, I’ll be honest with you. I was a theoretical physicist but my Ph.D. work was on a problem that was not particularly interesting to me at the time. And I used to subscribe to Scientific American and I found that there were all these wonderful discoveries happening in biology and I also knew that a number of physicists had gone into biology and been successful. So, I decided to switch.

[AS] Well so many, like Francis Crick, and so many others who moved into molecular biology for instance …

[VR] Yes, exactly. In fact many from my own lab, you know, where I work.

[AS] That’s right. And you do work at the LMB in Cambridge, this marvelous place where so many great ideas have come from. What is it that makes it so special?

[VR] I think it’s the ability to tackle difficult problems in a sort of stable and supportive environment. I think that’s the real key to it.

[AS] So one is challenged, always, to address the most difficult problem one can think of?

[VR] That’s right. And I think, you know, the history of the place means that you don’t waste your time doing sort of mundane or routine things.

[AS] And in particular, the problem of the ribosome, this extraordinarily complicated structure. It perhaps seems like a mountain that’s too high to climb, but that itself attracted you?

[VR] No, because I started working on ribosomes when I was a post doc, in 1978, when it would have been impossible, really, to solve it. But, it was just a fundamental problem in biology. And we felt, no matter, anything we do to chip away at the problem would be useful. So it was more that that attracted me. And I think the fact that it was large and kind of difficult to come to grips with, yes, it was attractive. Really what was attractive was that it was a fundamental problem.

[AS] And Francis Crick had made this proposal in the 60s, that it might perhaps be the link between the pre-DNA world and life now as we know it.

[VR] Yes. And the structures have definitely shown, or confirmed, earlier biochemical work, mainly by people like Harry Noller, that the key elements of the ribosome that are involved in function are made of RNA. And so a primordial ribosome could very well have consisted entirely of RNA. And, so, yes it does … But Crick was amazingly, I think, prescient to have thought about it.

[AS] There’s a marvelous video on your web site showing the ribosome in action, which indicates that really we understand its workings pretty well.

[VR] Well, only if you don’t think of it as chemistry. Because we understand in a sort of fuzzy way that something has to come in, and something has to move, and so on. But, if you really want to understand the detailed molecular interactions that make it go in a particular direction, make certain contacts, break other contacts, hydrolyze GTP, you know, form bonds, etcetera, and do it all amazingly accurately, then you do need a high resolution picture of those states. But, that’s not going to be enough. It’s going to take a lot of work by biochemists, by computational people who do molecular dynamics and things like that to really, eventually, understand it in the sense that we would understand, say, a more typical reaction.

[AS] And, the three of you who’ve been rewarded with the Nobel Prize today, have all worked on bacterial ribosomes. Is it the case that bacterial ribosomes are a good model for our ribosomes?

[VR] They are good for certain things, but they’re not good for initiation where it’s very, very difficult so … But there are people working on trying to get eukaryotic ribosomes crystallized and trying to study it, but I think that will be a difficult problem for quite a while.

[AS] And just as a last topic, one thing that the committee have emphasized is all three of your work on antibiotics and ribosomes and the structural work on antibiotics interacting with ribosomes. Do you have high hopes that this structural biology will lead to new antibiotics to treat resistant strains of bacteria.

[VR] Yes. So the fact is that … You know, having a high resolution structure in hand, one of the first things that those of us who were working on it did was to try and determine the structure with antibiotics, with known antibiotics that bind to the ribosome. And those gave us a very good idea of how they interacted with the ribosome. And it also gave us an idea of why certain mutations would cause resistance and how you might design better antibiotics. And, indeed, one of my co-winners, Tom Steitz, founded a company in New Haven and that company is devoted to making new antibiotics based on the structure of the ribosome and they have, actually, new potential drugs in clinical trials. So that’s one of the more satisfying things to come out of it.

[AS] OK, well thank you very much. I can hear behind you what sounds like a celebrating lab. What do you think is about to happen?

[VR] It looks like, from the way the phone’s ringing, that today’s going to be written-off. But I haven’t even told my wife yet. I couldn’t reach her. She’s probably gone for a walk, and she doesn’t use a mobile phone, so it will be interesting. And my father lives in Seattle and I don’t want to wake him up because it’s three in the morning, so …

[AS] So, you’ll be held on the phone for a while more before you can speak to the family. Well, good luck good luck with the rest of today and we look forward to meeting you when you come to Stockholm in December.

[VR] Thank you, bye, bye.

[AS] Bye, bye.

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