Recorded: 22 Mar 2003
So, Rich Roberts and I were postdoctoral fellows at the same time. I was in Mark Ptashne's lab and Rich was in Jack Strominger’s lab. And Jack Strominger had discovered some tRNAs that were part of the membrane in bacteria and he recruited Rich who was in England at the time to sequence tRNAs. And both of us, at separate times, went to the MRC in Cambridge to learn to sequence. Rich [learned] RNA sequence and I learned to sequence DNA. And so I knew Rich kind of at a distance when I was there. The most remarkable thing at the time was that he had a lab not too far from where I was that he purified these tRNA molecules and at that time the only way you could do it is by uniformly labeling so you grow the bacteria in the organic phosphate with this labeled P32. And you’d walk into this room and he had all these columns fractionating tRNAs. And if you turned on the Geiger counter it would just go off scale, the whole room. And he worked in there, day and night, you know. I couldn’t imagine. And he seemed to be totally, it had no effect on him. This was probably in ’72, 1972.
And so I was, and again I didn’t know him that well. But because of our interest in sequencing and so on we talked from time to time. And then he came by my lab one afternoon and said, “You know, I just got a call from Jim Watson.” And of course this is before I got the call to, because you know I was still very much working on Lambda. And Jim hired him to come to Cold Spring Harbor to sequence because there was no one at Cold Spring Harbor that was doing RNA or DNA sequencing. And so Rich was flattered and thought it was a great opportunity. And actually when I was thinking of going down myself later I spoke with him.
So when I arrived at Cold Spring Harbor Jim found a place for us to live and the place was in the firehouse. And the first floor was Terri Grodzicker and we were on the second floor and Rich Roberts and his wife were on the third floor. And so we got to know them quite well. We both had—you know, at the time I had one child. My now older son was just six months old or something like that. And Rich had two children who were somewhat older. And so and as it turns out my lab was close to his as well. It was right down the hall. And so probably the people at Cold Spring Harbor at the time I interacted with him the most.
And he’s an unusual scientist in that he thinks about things in a very narrow and specific way. He’s able to focus in ways that a lot of people aren’t. And he focused on the sequencing and actually, I have to say it, it didn’t turn out well. You know, he really sort of didn’t make that leap into—his objective was to sequence adenovirus DNA. And he managed to grind some out but it didn’t turn out to be highly successful. But while I was there Joe Sambrook and actually Phil Sharp who had just left were beginning to use restriction enzymes to map DNA. And, in fact, Joe and Terri Grodzicker collaborated to use a combination of adenovirus genetics and restriction enzymes to begin to map adenovirus genome, and that of course helped a lot.
And what developed was an amazingly competitive and antagonizing relationship between Joe Sambrook and Rich Roberts. They were so different personalities. Rich was kind of formal, British, sort of upper class. Joe, of course, was from Liverpool, worked in Australia and was very much at the opposite end of the spectrum. They respected each other at some level but there was just a personal friction between them. And the reason for stating this is this later became a bone of contention that still exists today about restriction enzymes.
So Joe and various people in James were using restriction enzymes to map DNA. And Joe actually suggested to Rich that it might be worth looking for new restriction enzymes. And so Rich started doing that and that’s something he was really good at, you know. He’s a good biochemist. I mean, he knows how to purify things, whether it be nucleic acids or proteins. And he managed to hire this woman whose name I can’t remember.
And she was an amazing woman. Absolutely brusque, impersonal, but she took on as her life goal purifying as many restriction enzymes as she possibly could. And she was terrific. She would never leave her bench. She would go in there and just—you know, completely dedicated.
And so this combination of this woman who was just absolutely dedicated to this job and Rich who was out looking for these things and so on. They had a huge impact. In fact, most restriction enzymes we use today came from his lab. And that’s sort of one of the things that I think that a lot of people in the outside world are not fully aware of. Is that many ways, in terms of a practical implication, that work was a bigger contribution than the work that led to the Nobel Prize.
So, I socialized with his family. His wife, as you may know, was very difficult and that led to a terrible tragedy in the end. But she, I’d say more than anyone I knew at Cold Spring Harbor, was extremely bitter about being there. And she tortured him daily over that. And you could just see the conflict between his work and his family.
So he was doing research in enzymes and actually I had left just about the time they were getting the first data that led to splicing. And at that time it was very confusing. They were isolating RNAs that all had the same five-prime end and they couldn’t really understand what was going on. We discussed it quite a bit at that time. Nobody could really make sense of what was going on there. It was after that, about six months after I left, is when they did the famous EM picture with Louise Chow, Tom Broker, and Rich.
And so Rich, I think, always felt that Jim [Watson] never really respected him. And I think he felt that Jim saw him as a technician. And even though he ultimately brought tremendous prestige and fame to the lab, years later when the choice had to be made for director and Rich desperately wanted that job, Jim passed him over. And I think—shortly after Rich left to go to the New England Biolabs—and actually I’ve never heard each of them talk about each other in that context. I mean Rich was very opinionated about Jim. He said a lot of things about him, but I never really sort of got the inside story, you know.
So Rich Roberts is an unusual scientist in that he, on the one hand, is very technically oriented, but is able to see beyond that. But his greatest strength is his ability to focus. I think that when many scientists are thinking about very complex problems and trying to put models together and so on, Rich really could focus on the details of a certain, a certain problem and did very well in solving it. And I think that was really the story in splicing is that he was an excellent nucleic acid chemist and really focused on trying to understand how RNAs are generated in adenovirus and obviously did that very successfully.
Tom Maniatis, molecular biologist, is a leader in the field of recombinant DNA. At Vanderbilt University he completed his Ph.D. studying DNA wide-angle scattering. He became a postdoctoral fellow and professor at Harvard University and met Jim Watson just before he became director of Cold Spring Harbor Laboratory.
While Maniatis was beginning experimentation with cDNA cloning and gene regulation of higher cells, the controversy over recombinant DNA in Cambridge stunted his progression. Watson offered Maniatis a position at CSHL where he could work more efficiently to understand the methods of recombinant DNA. At CSHL, Maniatis completed full-length synthesis of double stranded DNA and actual cloning of cDNA.
He is currently a professor of molecular and cellular biology at Harvard University studying the mechanisms involved in the regulation of RNA transciption and pre-messenger RNA splicing. He studies transcription to understand how eukaryotic genes are activated by viral infection and extracellular signals.