Recorded: 08 Mar 2006
… at first glance, seemed to, uh, ramble a bit, and so on. But he had these incredible insights that he would come out with. You know I can give you two examples which are really important. Because that clued us, and certainly me, that early on that one’s dealing with a really brilliant person who has a much deeper perspective on biology than one would think at the very initial meeting. Of course this was in 1996, 7, okay. But… like, when he’s when…and this was the very early stage of molecular biology relative to today. Sort of mid-phase relative to people like him. But like for instance during this course they showed the first electron micrograph pictures of RNA polymerase that had been published by somebody. And they were these perfect hexamers. And Jim had said that he wasn’t convinced that these weren’t contaminants even though it had been published in a reputable journal. And so I remember the students looking at each other and rolling their eyes. And then sure enough, a few months later it was revealed, low and behold that it was contaminants. The real RNA polymerase is a very asymmetric molecule. And that’s when we appreciated the insight that he had. And then as a second thing when he was describing…because it was really a course on DNA synthesis as well…when he was describing all of the work done by the Kornberg group on what was then called “The Kornberg Polymerase.” Because at that point in time there was only DNA polymerase in e. coli, now called POL1, which everyone called the Kornberg polymerase. And that was supposed to be responsible for all the synthesis. And Kornberg’s lab had done this fabulous biochemistry. And Jim had said two things: He said, It’s always a little dangerous when one lab is so good that they scare away everybody else, because you always need other labs to, to, either have a different viewpoint or to check up on what the first one does. And he also said, So for example, it’s still possible that it might be a repair polymerase and not the main polymerase. And, uh, to show you how that went against the ethic of the time, one of Kornberg’s post docs came and gave a job interview seminar in Boston/Cambridge just during that period. And somebody from the audience asked at the end of the seminar, What about the traditional rebuttal that maybe that polymerase is just a repair polymerase? And everybody booed. I still remember this, okay? Boooo! Meaning, that was very impolite. How could you ask something like that? Sure enough, just a short time later, Paul De Lucia and John Cairns, and John Cairns lab at Cold Spring Harbor isolated the first polA mutants, and showed that in fact that the Kornberg polymerase wasn’t the correct polymerase. And it turns out now, it’s something else called POL3 for the gene. And that, just as Jim had said, this is really a repair polymerase. It is involved in replication in the lagging strand. But it really repairs stretches and gaps. And ah, I’ve never forgotten that, because at a very early stage I was introduced to his incredible perception. And that idea that you just can’t have one way of thinking dominate, unchallenged. Because they, uh…, nobody has a monopoly on the truth. So that’s what clued us in early on that, uh, that Jim was really a very insightful and very brilliant person. Uh, and uh, I’ve never forgotten those examples because it was really very impressive.
MP: So Jeffrey, what have you learned from him? I mean you are a, uh, uh...You keep in touch through all you scientific lifetime. So can you just name his features of his personality? Or, what particularly you have learned from him?
Jeffrey H. Miller, Ph.D., is the Distinguished Professor of the Department of Microbiology, Immunology, and Molecular Genetics at the University of California, Los Angeles. After receiving his undergraduate degree in biology from the University of Rochester, he did graduate work in biochemistry and molecular biology at Harvard in the department that included Jim Watson and Walter Gilbert, doing his thesis work under Jonathan Beckwith at Harvard Medical School. His postdoctoral work was pursued under Benno Müller-Hill at the Institute for Genetics of the University of Cologne in Germany, followed by 11 years on the faculty at the University of Geneva's Department of Molecular Biology, which was then headed by Alfred Tissières. In 1983 he joined the faculty at UCLA, where his scientific focus has been large-scale DNA sequencing and genomic analysis, the enzymology of DNA repair, protein structure, and the role of DNA repair enzymes in human cancer. He received the 2007 Career Award for Research from the Environmental Mutagen Society.
Miller has been a frequent participant at Cold Spring Harbor Symposia, a course lecturer at Cold Spring Harbor Laboratory, and a co-organizer of two meetings at the Cold Spring Harbor Laboratory's Banbury Center. He has been a consultant and principal in various biotechnology companies since the 1980s. In 1994 he co-founded Diversa Corporation, which has merged to become Verenium, a publicly owned biofuel company. He is the author of several books and laboratory manuals published by Cold Spring Harbor Laboratory Press, including "Experiments in Molecular Genetics" (1972), "A Short Course in Bacterial Genetics" (1992), and "Discovering Molecular Genetics" (1996).