Recorded: 01 Jun 2001
Harry Noller: There was a meeting here in ‘73 on the ribosome, from which the ribosome book came out, and I was thrilled because I was an assistant professor and they asked me to write a chapter for it. And I thought, “God! I get to tell the story about the ribosomal RNA.” And a couple of months before it was due I get a phone call dis-inviting me to write it because they had too many chapters. I was probably the only person who was disappointed to learn they didn’t have to write a chapter. I’d be delighted now to hear that I don’t have to write a chapter for whatever book, but I was crushed. And so people—that was one sort of level of recognition that was taken away from us. If we had gone into that book, at least in flipping through that book people would have been reminded, instead of just having to find our paper. But then it was [when] we got all these results and even the very ones that you did, Winship, the modification-interference experiments, on subunit association. It was very clear that the RNA is functional. Well, there was the Shine-Dalgarno result, but people said, “Well, that’s just base pairing,” and that that was sort of an exception. But Joan Steitz was starting to wonder about the ribosomal RNA, not only the Shine-Dalgarno. She wrote a chapter once in which she had a little table speculating on what functions might be attributable to the RNA. There were some Russians who were cross-linking the tRNA to the ribosomal RNA and not to proteins and we found that, too. And there was just more and more evidence, but no one was listening to it because the protein paradigm was so strong. It wasn’t until Tom Cech, and I guess the ‘82 RNA processing meeting here, I think, or ’81.
Winship Herr: ’81, I think.
Harry Noller: ’81, ok. I remember coming to that, hearing the rumor not long before from Christine Guthrie, that Tom Cech had shown that this thing was splicing itself. I remember, I just went down the hall announcing it to everybody the minute I hung up the phone in Santa Cruz. I came to that meeting and I was just really excited. And we celebrated afterwards. This is part of the tape you may edit if you wish. But Tom Cech, Olke Uhlenbeck, and Christine Guthrie and I went to my room in Blackford and smoked a joint in celebration of that event.
Harry Noller: Then people—then it become okay to think of the functional RNA and then people started looking at the ribosome saying “Oh…”
Harry Noller: We had a decade, but it was wonderful in that there was no competition for ten years. You get to work on the most interesting problem in biology all by yourself. It was great. There were other things too that were bubbling to the surface. We were sequencing the ribosomal RNAs and [Carl] Woese had sequenced the oligonucleotides from around a hundred different organisms. He had noticed that many of these oligonucleotides were quite conserved—that is, they were absolutely conserved—across all species in all kingdoms. And he also pointed out that—we noticed this, of course—that the sites that we were finding—that kethoxal was hitting—some of which were causing the inactivation, were among these universally conserved sequences. These sequences were so conserved—John Abelson called it “eerie.” Three and a half billion years, you know, a 20-nucleotide sequence that had not changed one base in any organism. We knew by that time, this was real.
Winship Herr: No coat hanger.
Harry Noller: No. But you could say all this to people and it would run off them like water off a duck.
Winship Herr: Because you presented in the ‘73 meeting. You presented the diagonal method, right, which was the mapping of these kethoxal sites. So the year before
He had shown kethoxal inactivated, then he developed a method to sequence the actual sites of modification. That experiment is not mentioned in that book anywhere, in the Ribosome book, that came out. The only reference to your kethoxal paper, kethoxal work, is to the PNAS paper, where it’s two brief mentions. It’s almost like they’re writing a review and they have to make sure they capture all of the papers.
Winship Herr, director of the University of Lausanne School of Biology and member of EMBO. He earned his Bachelor of Arts degree at the University of California in 1974 and Ph.D. for studies on recombinant retroviruses in leukemogenic mice with Walter Gilbert from Harvard University in 1982. He completed his postdoctoral research studies in Cambridge (England) with Frederick Sanger and with Joe Sambrook in Cold Spring Harbor. After that he joined the Cold Spring Harbor Laboratory faculty in 1984. From 1994 till 2002 he was an assistant director of the Laboratory and founding dean of the Watson School of Biological Sciences from 1998 till 2004. He is a professor of the Center for Integrative Genomics at the University of Lausanne.
Winship Herr is a former National Science Foundation predoctoral fellow, Rita Allen Foundation Scholar, Helen Hay Whitney postdoctoral fellow, and Lita Annenberg Hazen Professor of Biological Sciences.
Harry Noller, is best known for his work on on ribosomal RNA structure and function, currently the director of the University of California, Santa Cruz's Center for the Molecular Biology of RNA. He received his B.S. in biochemistry at the University of California, Berkeley and his Ph.D. in chemistry from the University of Oregon.
He received the Rosenstiel Award for Distinguished Work in Basic Medical Sciences together with Drs. Moore and Steitz for their research on the ribosome. Harry Noller has been awarded Paul Ehrlich and Ludwig Darmstaedter Prize granted by the Paul Ehrlich Foundation.
He is a member of National Academy of Science, RNA Society and American Academy of Art and Science.