Recorded: 22 Aug 2008
My earlier career was based on trying to figure out the unknown in the Watson and Crick paper of 1953. Which was, alright, DNA replicates by a templating mechanism. Well, what is the machinery that makes it possible? And, I started…I was intrigued by this as a graduate student. In fact I got myself in big trouble by trying to show that DNA could be replicated by a single enzyme. The only one we knew at the time was DNA polymerase, which had been discovered by Arthur Kornberg and earned him the Nobel Prize. It was a beautiful enzyme turned out not to be sufficient to replicate double strand DNA. When I got to Geneva as a postdoc I had planned to continue. I wrote up an NSF application and got funded for some study of DNA replication, because I was still intrigued by the process. But almost immediately, I ran into Dick Epstein who was in Geneva and had published a classical paper in Cold Spring Harbor Symposium in 1963 that I had never seen. Which showed that all that time I was trying to replicate DNA with a single enzyme was crazy because the genetics of T4 bacteriophage showed that there were at least seven proteins, that is seven gene proteins needed to replicate DNA. And so all the prior frustration that I had had, working on this process, problem, set me up perfectly for recognizing immediately that this was a system that could be used to actually see how DNA replicated, rather than guessing how DNA replicated which is what I had done for five years as a graduate student. Unsuccessfully. And so I immediately decided to work on the T4 bacteriophage system which I eventually worked on for many, many years. Actually till I left for Academy, I was still working on that system. So I started as Assistant Professor after one year as Postdoc in Geneva. I started as Assistant Professor at Princeton with no grant for one year. It was very frustrating. No money. I had just, spent most of the year looking at most of the catalogs, making orders with things I would buy when I had any money. But, I guess the fundamental thing I decided after having so much trouble with my Ph.D. thesis, was to try to do something different than anybody else was doing. And in order to do that I had to have some new methodology. So I invested a lot of time and, even as a postdoc, trying to develop methods that we eventually called DNA-cellulose chromatography, in which you could take a crude extract of any cell, but I was of course I was using T4 bacteriophage effective cells. And find out without knowing anything about them, how many proteins bound to DNA and presumably how many proteins worked on DNA by just passing this crude mixture of proteins through a column of DNA and seeing what proteins bound to the DNA with the idea that any protein that worked on DNA inside the cell should have some affinity for DNA. Anyway, my first major paper as an independent scientist after my graduate career was actually published at Cold Spring Harbor Symposium in 1968 titled DNA-cellulose chromotagraphy . Was citation of this new method I had developed. Ah, and that paper I really hadn’t discovered anything yet. Just showed the promise of that method, and I had calibrated it with different systems including RNA polymerase. But already I had started working on T4 bacteriophage. My Al Hershey experiment - Al Hershey…talking about Hershey’s Heaven which is you get an experiment which really works and you do it over and over again - came at Princeton when I used
that column to screen the various mutants that Dick Epstein had identified in his 1963 paper by making mutant effective crude extracts and seeing…was there a band missing? And ah, turned out when I used a gene 32 T4 mutant to affect cells, one of the really major bands was missing. And that turned out to be the first single strand DNA binding protein which is now known to be a general protein in every organism. And the sort of experiment that I would have liked to have done for ever over and over again was mixing that protein. We had no idea what it did except to bond the single strand DNA very tightly and cooperatively. Mixing that protein with synthetic copolymer polyADT. And sewing [showing] that I could melt the DNA, that this would destabilize helixes. In fact we used to call the protein helix destabilizing.
Bruce Alberts, currently Editor-in-chief of Science, Professor Emeritus in the Department of Biochemistry and Biophysic at the University of California and United States Science Envoy. He received A.B. (1960) in Biochemical Science from Harvard College, Cambridge, Massachusetts and Ph.D. (1965) from Harvard University, Cambridge, Massachusetts. In 1966 he joined Department of Chemistry at the Princeton University and after 10 years he became professor and vice chair of the Department of Biochemistry and Biophysic at the UCSF.
Alberts work is best known for his work on the protein complexes that allow chromosomes to be replicated. He is one of the authors of The Molecular Biology of the Cell, a major textbook in the field. He served two-six years terms as a president of National Academy of Science (1993-2005). During his administration at NAS, he was involved in developing the landmark of National Science Education standards.
Among many honors and awards (16 honorary degrees), he is Co-chair of the InterAcademy Council and a trustee of Gordon and Betty Moore Fundation.
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