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An Interview with Werner Arber Interview The Inventiveness of Nature: An Interview with Werner Arber Jane Gitschier* Departments of Medicine and Pediatrics and Institute for Human Genetics, University of California San Francisco, San Francisco, California, United States of America Image 1. Werner Arber stands outside the Biozentrum at the University of Basel, Switzerland. doi:10.1371/journal.pgen.1004879.g001 I admit to having a soft spot for the years, restriction and modification was not spawned extremely useful technology. In bacterial phenomenon of host-specific only a remarkable story in itself, but also past issues, I have interviewed Hamilton modification and restriction. I vividly remember first learning about this mech- Citation: Gitschier J (2014) The Inventiveness of Nature: An Interview with Werner Arber. PLoS Genet 10(12): anism to stave off marauding DNA as a e1004879. doi:10.1371/journal.pgen.1004879 beginning graduate student in the mid- Published December 18, 2014 1970s. Preceding the discovery of its Copyright: ß 2014 Jane Gitschier. This is an open-access article distributed under the terms of the Creative modern-day defensive counterpart, Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, CRISPR (clustered regularly interspaced provided the original author and source are credited. short palindromic repeats) by about 50 * Email: [email protected] PLOS Genetics | www.plosgenetics.org 1 December 2014 | Volume 10 | Issue 12 | e1004879 Smith, who isolated the first type II Edouard Kellenberger, who ran the La- new preparation techniques. You could restriction enzyme, as well as Herb boratoire de Biophysique in the basement spread the lysate out on the film and see Boyer, whose production of recombinant of the Institute of Physics there. It housed and count phage-related structures. In DNA in collaboration with Stan Cohen electron microscopy as well as radiation nonmutant strains of lambda, of course, launched the biotech industry. For this studies. I went there within the next few there were the nice phages with heads and interview, I was able to go back even days, and I was satisfied and accepted the tails, whereas for some of the mutants, farther into the tale and hear first-hand job. there were heads but no tails attached, and how restriction and modification came to I have to tell you the beginnings of this. sometimes the tail was missing. In some be understood at the molecular level. The Institute of Physics had been headed other cases the heads were empty. This came at the tuition of Werner by another Swiss professor, Jean Weigle. Gitschier: Where did all these mutants Arber (Image 1), who received the Nobel Weigle had agreed to help a Swiss come from? Prize together with Smith and the late company specialized in vacuum systems Arber: From the lab itself, and we got Dan Nathans. Arber remains active in to develop an electrostatic electron micro- some from the Pasteur Institute. Then one science; he heads the Pontifical Academy scope. It was given to the Institute in the day, Weigle brought me the defective of Sciences and has a keen interest in 1940s, free of charge. lambda transducing prophage that had understanding evolution’s molecular driv- Weigle then had some health problems been isolated in the Lederbergs’ lab by ers, one of which—horizontal gene trans- and later quit the directorship of Physics. Larry Morse. He asked whether lambda fer—is a direct descendent of his work on He was very interested in biology, and he could also transduce, like P22, and it did! phage transduction. In early June, after a moved to Caltech in California in 1949. But it transduced only galactose markers. quick jaunt to Paris (to watch Rafael But he still had an apartment in the old And that was only upon induction of Nadal win the French Open for the ninth town of Geneva, and he came to Geneva phage production by lysogenic bacteria, time), I popped over to Basel to reunite every summer for three months. At not after lytic infection. Now we know that with old friends and to interview Arber. Caltech, he worked with Max Delbru¨ck; the attachment site for the lambda pro- Despite that Monday being a Swiss he was a part of that relatively small, at phage is near the galactose markers… holiday, Arber suggested meeting with that moment, phage group. Gitschier: … in the E. coli genome. me in his office on the top floor of the Gitschier: Presumably, he knew Del- Arber: Yes, and at frequencies of 1025, Biozentrum. It was exceptionally hot, a bru¨ck through the physics connection. the lambda genome crosses out imprecise- record-breaking 98uF (37uC) outside, and Arber: Absolutely. He brought to ly from its attachment site to form lambda- possibly even hotter indoors. Over three Geneva the connection to the phage gal, but this hadn9t been known yet at that hours, we worked our way through a large group, as well as microbial strains. He time. So I induced the defective lysogen bottle of water, which his wife, Antonia, normally stopped over in Paris at the that we received from Weigle with UV had thoughtfully suggested he bring along. Pasteur Institute where [Franc¸ois] Jacob irradiation, and the cells lysed but I Neither of us flagged as he reminisced and [Jacques] Monod were working, and couldn9t see any phage-related structures about the field and his work in 1950s and we had, therefore, a very good connection in the lysate. 960s. with these microbial geneticists. Gitschier: No phage particles? Arber developed his interest in natural Weigle also had bacteriophage lambda, Arber: Indeed, no phage particles, no science as a child growing up on a farm which originally had been discovered by empty heads, no tails! near Aarau, south of the Jura Mountain Esther Lederberg as prophage in E coli At that moment, I decided to start range of Switzerland. After attending the K12 bacteria. genetic experiments. There were a certain local gymnasium, he studied at the Swiss The problem was that everybody had number of already mapped mutants avail- Polytechnical School in Zurich to become K12, which was lysogenic, but they didn9t able—for head, tail, and other properties. a science teacher, rather than pursuing his have lambda-sensitive, nonimmune From induction of double lysogens— mother’s hopes for his priesthood in the strains. And Weigle brought us both from having one lambda-gal and one active Protestant church. He majored in exper- Esther—the lysogenic and the sensitive phage—you get both active and transduc- imental physics and completed his under- strains. In fact, that was not easy because ing particles. In a series of genetic graduate degree in 1953, just after the Esther said she wanted to do some experiments, I could show that in the structure of DNA was discovered, and experiments with that phage herself. But lambda-gal genome, a few head and a few went on to the University of Geneva for Weigle said, ‘‘We have an electron micro- tail genes were just missing. Then we his PhD. We pick up the conversation at scope and we can look at it,’’ and realized that instead of having these head this transition. everybody was interested to see what it and tail genes, they must carry gal genes. Gitschier: You finished your teaching looked like! And that was what Kellenber- That was one of the early clear proofs that degree, but you were thinking about doing ger did—he pleased the involved scientists some viruses can serve as vectors for host basic research? with a nice electron micrograph of phage DNA integrated into the viral genome. Arber: Yes. Most of the physicists did lambda. This is now called specialized transduc- not take the broad curriculum I had, Gitschier: And were there other types tion. I reported our findings at the including biology and so on. So Paul of bacteriophage that they looked at? Assembly of the Swiss Society for Micro- Scherrer [the prominent Swiss physicist Arber: Of course, the T-evens and a biology. A few people may have under- who was Arber’s advisor] suggested I go to number of other phages. One of my jobs stood it. the University of Geneva where they had in the lab was to look at mutant bacterio- Gitschier: What year? an electron microscope, which needed phages; there were about ten different Arber: That was in 1957. With the daily care by a physicist. There they mutants of lambda available. These were impulsion of Edouard, I was invited to a looked at a variety of biological objects: prophages, so I could induce by UV conference of microbial geneticists at bacterial extracts, viruses, bacteriophages, irradiation and then look at the lysate. Royaumont near Paris, to present my and so on. Right away he phoned Kellenberger was very good at inventing work, and that had a really big echo. PLOS Genetics | www.plosgenetics.org 2 December 2014 | Volume 10 | Issue 12 | e1004879 On the spot I got two invitations for looking for conjugation in Salmonella develop atomic power plants in order to post-doc—one by Joe Bertani in Los strains. And at first view, it seemed that get a new energy supply. Paul Scherrer Angeles, and the other by Franc¸ois Jacob there was recombination. But then they managed to convince the Swiss Parliament at the Pasteur Institute. I thought both could show that there were no cell–cell to vote for a big financial credit just for would be interesting, but I could only contacts. In the conjugation mixture some that. And Edouard had made a request accept one; I chose the United States of the cells lysed, being lysogenic for phage that a very small part of that big credit rather than France.
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