Interview with the 1993 Nobel Laureate in Physiology or Medicine Richard Roberts, at the meeting of Nobel Laureates in Lindau, Germany, July 2007. The interviewer is Adam Smith, Editor-in-Chief of Nobelprize.org.

Richard Roberts welcome. You were the co-recipient with Phil Sharp of the 1993 prize in physiology or medicine for your coincidental discovery of split genes. I’d like to start by just exploring a few themes with you. If I say the word mentorship, what does that conjure up?

Richard Roberts: I think to me it always signifies a Japanese post doc that I had in my first year as a PhD chemist, who was really quite an extraordinary fellow. He had this wonderful ability, not only to tell you what you should be doing but at the end of it you understood why you’d done it and I learnt more chemistry from him I think than from anybody I’ve ever met previously. There was only certain more than from any teachers that I ever had at school or even from my professor or anyone like that in formal courses. He was amazing.

Can you pin down what it was that he …

Richard Roberts: Not really, no. The end product was that you understood why you were doing what you were doing. I think that’s terribly important in science so that if you understood why you did it you can do it again and if all you’ve done is do it, then you may or may not be able to actually do it again.

When you come to look for students, what do you look for in them?

Richard Roberts: Usually enthusiasm I would say as the single most important attribute for me. Most of the people who come to me are smart so I don’t really ever think that that’s going to be an issue but, I really look for people who have this spark of enthusiasm, the passion, because people who are passionate usually work twice as hard as those who are not.

They need to be hardworking?

Richard Roberts: I think in science you have to be hardworking, yes. If you see the competition you realise everybody else in science is absolutely working flat out most of the time and everybody else is pretty smart and so if you want to compete with them then you also have to be pretty smart and to work hard too.

The last of these themes is, how would you describe your ideal lab environment?

Richard Roberts: I think one of the things that I look for in a lab environment is an attitude of cooperation and collaboration. I like to be working with people who it’s fun to collaborate with, not who you think are trying to stab you in the back all the time and not people who are in competitive mode, at least not with you. I think competition is a good thing, but what is not good is competition within the same group, even within the same lab setting. I think it’s fine to compete with people in other institutions and I like the idea of competition where two people may be going at the same problem but going from different angles. I see no benefit in two people going at something from the same angle, but collaboration is absolutely the key.

Are there physical principles you apply to get people in your lab to collaborate?

Richard Roberts: Probably not. None that I can articulate, let’s put it that way. Maybe there are, but none than I can articulate. I always like to make sure that people have their own individual projects that are non-competitive with one another so that if people really are trying to get an answer from their particular project that it’s perfectly ok to talk to everybody else because they’re not competing with the other people.

But do you like a bustling lab or a quiet lab?

Richard Roberts: Both have their place so sometimes it’s very nice that it’s bustling. It’s good to have people in close proximity to one another because then they have to talk and very often talking is the key to success, because sometimes the only time that you really understand why you’re doing something or particularly why you made a mistake is because you’re trying to explain to someone else what you’ve been doing. Then, all of a sudden, you realise you don’t understand it yourself so terribly well. I think this is the advantage of doing research in a university environment, where you’re constantly teaching and so you’re constantly testing your own ideas in a way when you’re trying to explain what you’re doing to other people. Sometimes you get this ‘aha moment’ and you realise that you don’t understand why you were doing what you’ve just been doing. A lot of students are interested in what you’ve been doing and how you made the discovery or what it was that turned the light on from that sort of thing but some of them actually are interested in just very much more general things; how does it affect your family life, those kind of things.

Yes, the work/life balance is always a question. Looking at your own scientific beginnings, you had what, from your autobiography at least, looks like a fairly unremarkable scientific start. Was there a point at which you suddenly geared up and had a moment of realisation?

Richard Roberts: You say ‘unremarkable’, I think if you compare my start with what is possible today it would start to look quite remarkable, because I got interested in chemistry through making fireworks. I just thought fireworks were fantastic. I thoroughly understand why terrorists like a big bomb. There’s something about explosions and bright lights and so on and when I was growing up it was easy to do that. You could buy chemistry sets, you could buy the chemicals you needed to make fireworks very easily, there were books that told you how to make them and a lot of my friends, and I think a number of my fellow laureates also got their interest in science in a very hands on manner; by making fireworks, by making explosives, by doing home chemistry kinds of things and that is something that’s very difficult to do these days. We’ve reached this point in society where we feel we’ve got to protect the kids from anything, we can’t let them do anything dangerous, God forbid they should be doing something where they might lose a finger or an eye or something like that.

They’re not even allowed to take a bus to school.

Richard Roberts: I think we’ve actually done a great disservice to the young scientists or the potential young scientists by not giving them those same opportunities to experiment and do stuff at home. There’s nothing more boring in a chemistry class than watching a teacher do something. Much more fun to do it yourself and especially if you have some leeway to do things that was not in the curriculum and that you just want to do yourself. That was the thing that led me to science I think without a doubt, it’s this hands-on experimental work that I was able to do at home, that you simply can’t do so easily today, much, much more difficult to do anything like that today.

When did the parallel tracks of your home interest in science and your standard educational interest meet?

Richard Roberts: Probably when I went to university. I would say at school I was always, certainly in chemistry, I was always way ahead of anything that was being taught in the classroom because I’d been buying textbooks at home and doing stuff at home. I didn’t find chemistry terribly interesting at school, certainly didn’t care for physics at school. I liked mathematics, I always liked math and in fact math was always my best subject. I was much better at that even than chemistry or anything of that sort, but I had a problem. When I was doing mathematics, when it came to distinguishing between pure and applied mathematics, and it wasn’t until I got to university that I realised applied mathematics was really purely math, and it was just the way you phrase the question and the way you interpreted the question that made it either applied or pure and so then I was ok once I figured that out I was ok. All of my life I’d always thought I was going to be a chemist and my aspirations at school were really to be an industrial chemist. It seemed to me that this was a place where you were going to constantly be able to actually get to the lab bench and do lab work. Then when I started doing my PhD I was fortunate, thanks to this Japanese post doc who really taught me how to do chemistry I got everything I needed for my thesis in the first year. So, after one year as a PhD student I could have easily written my thesis and got the thing but in England, of course, you have to do it for three years. That gave me two years to really go looking around and browsing around and thinking about other things and it was during that time that I discovered molecular biology, through reading, and decided I wanted to be a molecular biologist.

Because you were working on flavonoids?

Richard Roberts: Yes, right. My PhD thesis I was basically given a piece of tree from a Brazilian tree called Machaerium and asked to find out what was in it. We knew that there would be interesting flavonoids, neoflavonoids in it and there were. There were loads and I was lucky. I’ve always been very lucky. One of the compounds, one of the new compounds was a key intermediate in the biosynthesis of these neoflavonoids that my professor had predicted should exist, but it was unstable when it had come out of other things, but in my hands it was stable and so it was the missing intermediate and I had it and he was very happy, so that was nice.

Seven years, then you had freedom to explore. Your move to molecular biology, did you think that you were moving away from chemistry or were you being a chemist who was becoming a molecular biologist?

Richard Roberts: I thought I was moving away from chemistry a little bit but taking advantage of the chemical training. At the time if you wanted to proceed to the frontier of chemistry you had to one of two things. You either had to go theoretical because there was a desperate need for a new theory of organic chemistry. You had the Woodward-Hoffmann rules but you didn’t have a lot else and I didn’t have any good ideas as to what one might do theory wise and the other was to go biological. It was clear that there was a frontier of chemistry that was out there in the biological world and I just found that far more interesting and something that I might actually be able to do.

That took you to Harvard and your work there led really to the job offer from Jim Watson, which seems to have been, from my reading, the seminal event?

Richard Roberts: Yes, maybe. It’s hard to know. When I was a post doc at Harvard I discovered nucleic acids and sequencing and went to Fred Sanger’s lab to learn how to do RNA sequencing. That really gave me an interest in the structure of biological molecules, not structure in the sense of 3D structure, but structure in the sense of knowing exactly what all the atoms were within the molecule. Of course, for DNA or RNA it’s just really what is the sequence of basis and that seems something relatively straightforward that I might be able to understand and do. I got interested in sequencing and methodology for doing the same. I tried to get back to England, I’d originally gone to the US thinking I was just going to spend two years in the US. As soon as I got there I realised having changed fields at two years wasn’t going to be long enough to do anything in a new field and I did two years and then I got appointed as some sort of … I forget what the exact thing was but it was slightly better than post doc. Then I started to look for jobs and I was told there was a nice job in Edinburgh, which I applied for but I never heard anything back from them and then I was offered a job by Jim Watson, came completely out of the blue. I’d spent a lot of time with Mark Ptashne, who was at the time, I guess, either assistant or associate professor at Harvard. I taught him how to do RNA sequencing and we’d become reasonably friendly and he apparently had spoken to Jim and said, There’s this guy Roberts that you should offer a job to. He came up to me in a seminar and said, Jim Watson wants to talk to you, and since I’d never met Jim at the time I said, Oh yes, that’s nice and waited and nothing happened. A couple of weeks later Mark came along and said, Well, you know, Jim says he doesn’t know you so perhaps you could go and introduce yourself, so I trotted off to his office and said, I’m Rich Roberts and he basically opened the conversation saying, We want someone to sequence DNA at Cold Spring Harbor, I’d like it to be you and this was kind of it. I was in his office no more than five minutes and as I was leaving he said, Oh, and by the way, as a formality, you’d probably better come down and give a talk but, don’t worry, you’ve got the job.

Nice but slightly disconcerting.

Richard Roberts: Yes. I was in Jack Strominger’s lab and I went and talked to Jack and I said, Jim just told me he’s offered me a job. I assume he’s talked to you about it, and Jack said, No, it’s the first I’ve heard about. It’s fairly typical of the way that Jim I think still does stuff. He has people who he trusts and talks to and if they tell him they think something is worth doing then he’ll often just follow their advice and do it. Then, at the same time, the biology department at Harvard asked me if I would be interested in a job and they offered me something. So here I was, I had two jobs in hand, as it were, and one I really wanted was back in England but I’d not heard whether I was even being considered, I mean I never even got an acknowledgement for my letter of application so it seemed the thing to do. I had a wife and two kids, I’d better take one of these jobs that was offered me.

What do you think was creating these job offers? Was it primarily the fact that you had RNA sequencing?

Richard Roberts: Yes, completely.

It was having the right technology at the right time that everybody wanted.

Richard Roberts: Yes. I was the first person in the Boston area to be doing the Sanger method of sequencing RNA, so anybody there who wanted to learn how to do it came along and talked to me and I showed them how to do it. I could do something that a lot of other people couldn’t do but lots of people wanted to do.

When you found yourself at Cold Spring Harbor you were then working primarily on sequencing?

Richard Roberts: Yes, when I first went there what Jim wanted was to have SV40 sequenced but as soon as I got there I realised there were two other groups already doing that; Walter Fiers in Belgium was doing it and Sherman Weissman at Yale was doing it and it seemed stupid for a third group to do the same thing. This certainly caused Jim some consternation because this was what he wanted sequenced. Jim always likes competition.

So having a group internally doing it as well is great, yes.

Richard Roberts: But I wouldn’t do that. It just seemed to me a waste of time. If these two other groups were going to get the sequence it was not as though there was any shortage of things to sequence, the entire world was out there made of DNAs, lots of stuff to sequence. But I’d actually, during my last year at Harvard had heard Dan Nathans give a talk about restriction enzymes and particularly about how you could use HindII, actually they called it Endonuclease R at the time, it was a mixture of two enzymes that Ham Smith had discovered and Dan Nathans was using to map DNA.

This gave you the possibility of sequencing DNA?

Richard Roberts: The reason that RNA sequencing had been developed first was because there was small molecules to practice on and in DNA there were no small molecules but these restriction enzymes gave you the opportunity to make some small molecules of DNA. I thought that would be very useful that one could get the small molecules to practice on and I was initially interested in developing methods for sequencing DNA but then the restriction enzymes themselves it turned out that there was not only the one that Ham Smith had found but there were others around too. I got into the idea that one might be able to just use the restriction enzymes as sequencing reagents because wherever they cut they gave you five or six bases at a time and so this might be developed into a sequencing methodology. We started to make restriction enzymes and look for new restriction enzymes and it became slowly clear they weren’t going to be very much use directly for sequencing DNA, useful as intermediary agents to make fragments. They were interesting for mapping and then recombinant DNA came along and so they were useful in that context. They just became general useful reagents for doing much more than sequencing.

You became a big producer of restriction enzymes, indeed which of course led to future things which we’ll talk about. Your discovery of the split gene nature of Adenovirus was something that came quite quickly, and I’d like to just talk about the conceptual side of it. It was, presumably when you joined Watson’s lab, fairly inconceivable that genes were not a continuous stretch. Was the indication there that they were discontinuous prior to your first findings or was it a complete surprise when you started seeing discontinuous sequences?

Richard Roberts: It was a complete surprise and completely against the dogma because Francis Crick had come out with this central dogma DNA makes RNA makes protein and that was based upon everything that we knew about bacteria and bacteriophages where you had a contiguous gene, you had a continuous piece of RNA made from it and you just read the bases off three at a time as codons. It never really occurred to anybody that the arrangement of DNA sequences in eukaryotes would be any different from the arrangement of DNA sequences in prokaryotes. We got involved in this because I was interested in trying to characterise a promoter, the region upstream of the gene that says where the gene should begin. We wanted to know if eukaryotic promoters were different from prokaryotic promoters. There was no inherent reason to think that they would be but nevertheless, until you look and see you’ll never know.

That’s interesting that you chose to look at something that you thought was going to just yield a null result.

Richard Roberts: I wouldn’t say a null result. We thought there might be at least one or two interesting differences but nothing really spectacular. We certainly didn’t think there would be a spectacular difference when we got started.

You were investigating it because you could, there must have been something about the search?

Richard Roberts: I would say we did it because we could. We thought in order to do it you needed to be able to do a little more DNA sequencing than was possible and so in one sense it was pushing technology a little bit and it was also clearly a doable problem. It was something that could be done and it would give you an answer. Either these things were the same or they were different. That was kind of a nice yes/no answer that could come from it. But the methodology for doing it was not straightforward so how you would identify the 5′-end of a message. You knew they had triphosphates at the end so that gave you a handle from an RNA sequence standpoint, here was a special feature, a label if you like that you could look for so that you can in fact find the 5′-end of the RNA. The idea was to then figure out where that was being located on the DNA then just look upstream and that would be the promoter. Adenovirus seemed very nice for that because Adenovirus was a linear virus and we knew that transcription early during infection was coming in from the two ends and that meant that between the end and the start point of the message that’s where the promoter must be. You could just sequence basically the ends of that DNA, which at the time, that was a lot of sequence, people were typically doing just a few nucleotides, nothing quite as long as that.

Anyway we set off to do that, discovered that the amounts of RNA that were present early during infection were simply not enough to get a sufficient amount of the terminal oligonucleotides to actually map the message. We turned our attention to late Adenovirus messages and there we knew that they were making huge amounts of message, essentially once Adenovirus infects and you get a good infection going then they produce almost all Adenovirus message, very, very little cellular message being made. That was nice and then along, while we were during that, caps were discovered, these funny modifications that take place at the 5′-ends of RNAs and so that actually gave you an even better tag with which to look at these messages. When we started to do that we also realised that there was a possibility of doing a more interesting experiment than the just finding the messages and that was we knew that late during Adenovirus infection the genes, there were a whole bunch of genes laid out along the genome and there were at least eight or ten different messages that one expected. The thought was if you could characterise the short oligonucleotides at the very beginning of these messages each one would be different and there were display methodologies that would allow you to actually look at all of these different oligonucleotides at the same time.

You could map?

Richard Roberts: You could see what was happening during the course of infection; which messages were going up, which were going down, actually do the kind of functional genomics people now do on micro erase but this in a much simpler system long before one had thought about all these other kinds of things.

Long before the term functional genomics?

Richard Roberts: We thought this would be a really neat methodology and there might be a nice paper out of that and we started to do those experiments and I had a post doc, Richard Gelinas, who I’d first met when I’d been a post doc at Harvard; he was a student up there and he’d come down to join me. Very talented fellow and this became his post doc project, to do this functional mapping of the Adeno messages. When he did the first experiment, oh, and we dreamt up this nice way to actually select for just these termini, the 5 prime termini, and we set that up and got it going and he did the experiment and instead of seeing eight or ten mRNAs he only saw Ns, he only saw one. I said, Well, you better go back do it again and we looked through his notes and he went back and did it again and got the same result. I told him he must have screwed up the experiment and I would do it and show him how it should be done properly and so I did the experiment, got the same results and of course then I believed it at that point. I guess that was a point at which we knew that there was something interesting and unusual going on, didn’t know what it was, no idea what it was but I would say that was the moment when I knew that there was an interesting finding to be made, whatever it might be.

Still no guess as to what it would be, no?

Richard Roberts: One always has a guess as to what it should be and the guess was based upon the fact that by in vitro biochemistry at that time, RNA polymerase and the eukaryotic RNA polymerase that Bob Roeder had been working on was not a terribly good polymerase unless you gave it a primer. If you gave it a short RNA primer then it worked pretty well as a polymerase but if you were asking it to make things de novo it really couldn’t do it terribly well, it was rather poor. We had the idea that perhaps what we were looking at was the end of the primer and that the same primer was being used for all adenovirus mRNAs and perhaps it was just folding differently at different points on the genome. This became my favourite hypothesis as to what was going on and was ultimately the hypothesis that we ended up testing when we did the key experiment. But in the meantime we were just trying to get good biochemical evidence to prove that what we were looking at was real and not some artefact as everybody wanted to tell us, it was all an artefact of course because it just didn’t’ make any sense, everybody knew how you made RNA, you’ve got an RNA polymerase just gets in there and does stuff. We spent almost a year, I would say, gathering more and more evidence in favour of the idea that all of these messages had the same 5′-end but we really couldn’t prove it to anyone’s satisfaction. Biochemistry is not always a good way to convince people of what’s going on. People like a visualisation of some description.

It’s a bit abstract, yes.

Richard Roberts: It requires an act of faith almost, that the biochemistry’s being done properly and it’s not always easy to convince people, especially when something goes against dogma. If you’re doing your biochemistry and everybody accepts the basic premises of how things work and the biochemistry says sure that’s clearly how it works, then it’s much easier to accept it, but we were saying something that completely went against the dogma.

Something had to be wrong?

Richard Roberts: Something had to be wrong, yes, and it was us. Anyway, we spent about a year trying to really come up with a good experiment and then one morning early in March of 1977 we’d gotten into the habit of every Saturday morning we would sit and have a postmortem on what had gone wrong the week before and why we hadn’t had the success that we were hoping for and then dream up the next set of experiments. I remember this one Saturday morning Richard was up at the blackboard and was writing out some horrendously complicated set of experiments we were going to do and I really wasn’t paying as much attention as I should and all of a sudden it struck me what we should do. I said, Sit down, and I rubbed off all his scribblings and drew out this experiment that I thought would be a nice experiment to do. The only problem with it was it was an electron microscopy experiment and neither of us were electron microscopists but fortunately we had a couple of colleagues down the hall, Tom Broker and Louise Chow who were just superb electron microscopists, just as good as they come. After I’d drawn out the experiment, Richard said, Yes, that would be a great experiment if it works. We went down and talked to them and said, If we make the reagents could you do the experiment? and they said, Sure. Didn’t know it would work but it looked as though it should, no-one had quite done it that way before. We made the reagents and on the Tuesday morning they did the experiment and the very first molecule they looked at in EM looked exactly the way I’d drawn it up on the blackboard, with one difference that it was folded a little more than we’d expected it to be. Then they looked at some more and they also turned out to be folded in the same way and we realised that this piece of RNA that was at the 5′-end  of the messages was actually itself split into two pieces and so the experiment told us really two things; one was that the 5′-ends of the RNA clearly were coded somewhere quite differently from the main body but that this piece of the 5′-end itself was composed of two parts. Once you could do that you could begin to map exactly where everything was being coded.

That itself told you that there was coding in different places?

Richard Roberts: Yes. It just all confirmed the biochemistry, absolutely confirmed the biochemistry but it provided the visualisation that was needed. The thing is normally you do an electron microscopy experiment and everyone says but it’s just one molecule, there’s an awful lot of molecules in a mixture and not just the one that you happen to see on the electron micrograph. We had both things. We had the electron microscopy and the biochemistry already done so we didn’t really have to convince anybody of too much after that.

Just going back to the conceptualisation, those must have been heady days? It was quite a long period during which you were playing with this idea that you were really going to smash the dogma. Exciting to have that internal discussion; you must have longed to talk about it.

Richard Roberts: Oh, but I talked to everybody about it.

I see.

Richard Roberts: I can’t shut up once … I think the reason a lot of people do science is when you come across something interesting you want to go and tell everybody about it. There’s nothing better than that.

What about the often talked of fear of being scooped?

Richard Roberts: Never crossed my mind.

That’s nice. Do you think that was different days or is that just the way you are?

Richard Roberts: It’s the way I am, I think.

In fact, after the fact one knows you were in competition with Phil Sharp who was coming up with the same stuff.

Richard Roberts: Not really. I went to Phil Sharp’s office probably two months before the final discovery was made. I explained my ideas on the blackboard to him and he never said a word about it and didn’t immediately then go and do the experiment that we ended up doing. It was interesting because whenever you’re really going against dogma and breaking dogma, in general people just don’t believe you. It’s not that everyone was saying, Oh wow, great, let’s go and see if we can beat him to it. I think they just didn’t believe it. They didn’t believe it was possible and probably thought I was full of shit. During that time, it turned out Richard Gelinas was the person who actually needed the most encouragement because he was getting quite discouraged, because he’d do experiment after experiment and we couldn’t quite nail it. He was, on a number of occasions, all for packing up and the only thing that kept him going was the fact, I’d say, I know we’ve got a really big discovery here and this is going to be the make-or-break great experiment, great discovery. I was, in a way, a little like a cheerleader every Saturday morning to make sure that he got up the energy to do the experiments the next day.

Good that you were. It opened up a whole world. It opened up RNA editing, it opened up alternative splicing and then 15 years later you were awarded the Nobel Prize. Do you think it took 15 years because that world had to develop in order for the real importance of the dogma smashing idea to come through?

Richard Roberts: No. I think everybody accepted immediately that it was all correct, that was never an issue. Phil Sharp won every prize going in the intervening time because he got nominated for every prize going and I didn’t.

Ok. It took its time but everybody knew the importance?

Richard Roberts: Yes.

Then your lab continued along the previous track of making restriction enzymes?

Richard Roberts: We continued that on a smallish scale. We followed through on the splicing event. Because my interest had mainly been in sequencing and sequences, we wanted to know what were the sequences that were required in order to be able to do this. What were the sequences at the intronics on junction? In between the bits that were going to be spliced out, what were the sequences? There must be some sequence there, specific sequence, that the protein machinery would recognise to do the splicing. We set out to try to do that and that led us, ultimately, to sequence the whole Adenovirus genome. That became a project all in itself to do the Adeno sequence and then the other thing, we were trying to recapitulate the reaction in vitro by setting up an in vitro splicing system. That turned out to be a lot more difficult and complicated than we had thought and we were in competition then, we didn’t really realise it at the time, with Tom Maniatis’ group and we picked one, we picked the /- – -/ promoter as a way of making transcripts in vitro and he picked the promoter from another phage, SB6. It turned out he’d made a better choice than we did because his promoter made really nice discreet transcripts that had a single starting point whereas the /- – -/ promoter seemed to give two or three different starting points and that proved too confusing. We couldn’t then get the nice clean transcripts that we needed to set up the in vitro transcription splicing system. He won out on that one and there were a bunch of discoveries came from that and we also spent so much time doing the Adeno sequencing that that kind of distracted a little bit from the in vitro splicing work.

Yes indeed. Then, some time later, in fact just before the award of the Nobel Prize, you moved from Cold Spring Harbor to New England Biolabs, you moved into the industry. A small company but industry. What prompted that move?

Richard Roberts: I’d done everything that was possible at Cold Spring Harbor. I was assistant director for research there, overseeing the research operation and frankly I’d done everything that I could do at Cold Spring Harbor, I mean short of becoming director, and Jim showed no signs of stepping down and if he had wouldn’t have picked me anyway. He and I always had a somewhat testy relationship, shall we say.

From the very beginning?

Richard Roberts: Yes, pretty much from the very beginning. As soon as I said I wasn’t going to sequence SV40 DNA, which he’d hired me for.

That was like day one.

Richard Roberts: Yes, right. He was not completely happy, shall we say about that.

In retrospect he must have been happy that he had you there?

Richard Roberts: I don’t know. You’d have to ask him that. Anyway, I’d been thinking about doing something other than Cold Spring Harbor. One of the things, it occurred to me that with the advances in DNA sequencing technology that there was a lot of DNA sequencing, that it would be fun to do and I was thinking of setting up a DNA sequencing company. I talked to a couple of people about this, one of whom I think was seriously trying to recruit me. Then Biolabs heard that I was thinking of leaving Cold Spring Harbor and going to industry and they said, If you’re going to go to industry, why don’t you come up and join us? We talked about it a little bit and they made me an offer that I think was just too good to turn down and plus, you know, I always had a great love for this company. I’d helped set them up back in 1975 and I’d been their chief consultant all the way through, and I really admired the philosophy of the owner and I admired the way the company had done and they were doing good research up there so it seemed to me a good move.

Did the environment you found at New England Biolabs meet your expectations?

Richard Roberts: Oh absolutely. I’d known the company since 1975 and so I knew exactly what I was going into and yes, it was very nice. In retrospect I wish I’d moved there earlier.

Do you spend most of your time there running commercial operations?

Richard Roberts: I have as little as possible to do with the commerce. I’m chief scientific officer, which means I oversee the research that goes on there. My responsibilities are all for research, for bringing new ideas into the company, for bringing in research directions that we’re going to go into and then I do my own research.

What’s the overall remit for research at the company?

Richard Roberts: The way in which it was originally set up is anybody who came in as a researcher was expected to spend one third of their time doing something that would be useful to the company. That’s pretty broadly defined actually and then two-thirds of the time they could do whatever they want. That ended up mainly selecting for people who were interested in projects related to what was good for the company. Obviously restriction enzymes; more than half our business is selling restriction enzymes and anything connected with that is useful for the company. We sell DNA polymerases, anything connected with that is useful and a bunch of other kinds of reagents but the majority of the people who go there and enjoy being there enjoy the fact that they can do both pretty basic research as well as applied research and can lead to the prosperity of the company.

It seems remarkably generous allowing two-thirds. Google are often proud of promoting the fact that they give 30% of peoples’ time to off the wall projects as they call them. How do your researchers get funding?

Richard Roberts: From the company.

From the company. All of it’s from the company?

Richard Roberts: Some people have grants. There’s a mechanism in the US called Small Business Grants, SBIRs, we have a few of those. We’ve also in the past we have a big programme in parasitology, working on filariasis, and this was a deliberate programme set up a long time ago when we were reasonably profitable and wanted to put some money back into a humanitarian project. I organised a small conference. We got the people to tell us about the key diseases that World Health Organisation was interested in and we picked one. We ended up picking the one where we thought molecular biology could be helpful and where there was very little government funding. Over the last 22-23 years we’ve been working in the area of filariasis and recently had quite a big breakthrough, two or three years ago, in which we and a bunch of other groups discovered that there’s a little endosymbiotic bacteria called Wolbachia that lives inside the worm that causes filariasis and if you can kill the bacteria, you kill the worm. This means that if you could get the right sort of antibiotic into that bacterium then you should be able to get rid of the worm and kill the worm that causes filariasis.

And the breakthrough that you made?

Richard Roberts: What we were doing at the time, we had a group who were busy, this was not me personally, it was another group, were busy looking at the mRNAs that were present. They were basically doing an EST project to look at the mRNAs that were being made inside the worm and when they started to analyse these discovered that some of the sequences looked as though they were bacterial and were not eukaryotic. When they followed that through they were able to show that indeed there was a bacterial genome inside there and then by normal cell biological processes you could show there was a bacterium growing inside this worm.

How big is the outfit at New England Biolabs?

Richard Roberts: New England Biolabs is now about 240-250 people, something like that. We have a little over maybe 110 who are doing research.

Are they able to build up independent groups?

Richard Roberts: Yes. What we do is when we hire a scientist we give them a post doc and a technician and then if they want to get a larger group than that occasionally, if they’re doing something that’s especially product oriented, maybe we’ll put another person into their lab to help out on that or they can apply for SBIR grants and enlarge the group that way, but usually we try to encourage people to set up collaborations, one group with another, and expand the manpower that way.

Do people stay?

Richard Roberts: People don’t like to leave New England Biolabs. It’s very difficult to get them to go. It’s a wonderful working environment, terrific working environment; a very different company. The reason is most people set up a company because the owner wants to become wealthy, the owner wants to be the next Bill Gates and Don Comb, who is the guy who started New England Biolabs, doesn’t have those same sort of ambitions; he loves research. You used to go to him and say, I’ve got this wonderful idea for a product, we can make millions and he’d say, Yes, ok, but you’d go and say, Hey we’ve got this great result in the lab today and he’d be all over you. This was what he wanted to know about. He set up the company with the idea of trying to make the money specifically to support research and using the products of the company to support research. He’s not poor but he’s not ostentatiously wealthy in the way that CEOs of most companies or owners of most companies are.

You had a tremendous success as a chemist moving into molecular biology. What do you think molecular biology needs now? What do you look for when you’re recruiting to New England Biolabs these days?

Richard Roberts: I’ve always looked for enthusiasm and passion.

But in terms of disciplines?

Richard Roberts: There are a couple of areas that we’re expanding into at the moment. One is the field of RNA biology. I’m a firm believer that RNA is doing an awful lot more inside cells than we know about at the moment. One of the problems with RNA is it’s not that easy to work with. You can degrade it rather easily. We know that they’re huge numbers of transcripts being made within the human genome that we really don’t know what they do and we’re completely unaware of what they’re doing. In bacteria we know of plenty of small RNAs that are made, some of which are doing unusual things, but in bacteria in general we don’t know a lot about what RNA is doing there. I’m talking about RNA outside of the normal coding RNA. I think RNA is doing an awful lot that we don’t know about. I feel there are some really big discoveries to be made there.

But in the way that for instance cell biology now has some need for instance for systems engineers, some people would say so, other people would say that cell biology has no need for systems engineers but it’s a debating point. Is there something that molecular biology, do you think, needs from some outside discipline to help it advance?

Richard Roberts: I would put it a little differently. I would say that whatever field you’re in you can always benefit from outside disciplines. People who move from one field to another always come at the new field with a different underlying philosophy of how to do science and that’s a good thing. People, when you move from one field to another it’s very easy to ask stupid questions and not be made to feel stupid because people will say, Oh well, they weren’t trained in the discipline so they don’t know any better than to ask that question, and it’s often the stupid questions that really allow you to make progress because then when people are trying to answer them they suddenly realise they don’t really know the answer to some of these stupid questions. Then you can go ahead and provide the answers and sometimes they’re not what you expect.

Perhaps that’s a nice end point, the thought of recruiting a few stupid people to New England Biolabs.

Richard Roberts: No, no, no. You want smart people from different fields so this is a good thing to do. Stupid people in general don’t help you all that much.

Ok. Thank you very much indeed for taking the time to speak to us.

Richard Roberts: Good, thank you.

Watch the interview

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