My life with Mu.

To write this essay I received a series of questions aiming at guiding my writing. Reading them made me realize that the phage I chose to study Mu, and the group of people who shared my enthusiasm for that transposable phage have been the main drive of my scientific path. Fascinating findings readily started and kept accumulating through the years and the dual nature of the organism (a phage and a transposon) led the group to be part not only of the phage but also of e.g., the plasmid and transposon scientific communities. Today, the number of scientists working on the development of transposable phages and its regulation has shrunk so much that a significant part of the knowledge accumulated through over 40 y of research is at high risk of extinction! A historical survey of Mu biology and the Mu community appeared in the book “Phage Mu” (Neville Symonds et al., CSHL press, 1987), a tribute to Ahmad Bukhari, a leading figure in the Mu field, who passed away at the end of 1983, in his middle 40s. His memory inspires more than any other when going back to the most productive years in Mu biology from 1970 to the late 90s. My first encounter with Mu occurred in 1968. It was a time of intense political discussions and reinvention of authority! I was working on my PhD thesis in Ren e Thomas’s lab. Ren e, with whom I spent the largest part of my scientific life at the Universit e Libre de Bruxelles, Belgium, taught me scientific rigour and freedom. To some of us, he had suggested to work in pairs, to produce 2 collaborative theses! That’s how, for over 3 years, I had the compelling experience to share ideas, conceive and run experiments, write papers and much more with Nicole Douat. Nicole and I were desperate to isolate polar mutations in phage l. We convinced Ren e to invite Pieter Starlinger (Professor at the University K€ oln) for a seminar. Pieter’s group had isolated strong polar mutations in the E.coli gal operon, using, among other procedures, bacteriophage Mu insertions. Our last hope for getting l polar mutations was this new phage. Pieter brought us a sample of Mu and a few months later we had all the lmutants we needed to show that its late genes form an operon. In the summer of 1970, with Bill Dove, Ren e taught the last phage course at CSHL. I was in the US as a “post-doc” at that time (quoted because I still hadn’t finished writing my thesis!) and by a happy set of circumstances, Ren e asked me to join as a technician to help teaching the course. There, I met Ahmad Bukhari for the first time. He had just been appointed by Jim Watson to work on Mu at CSHL after his post-doc with Larry Taylor, the discoverer of Mu in the early 1960s. Ahmad was soon to be joined by Martha Howe and Ernesto Bade. From then on the Mu community built up and we shared exceptional moments when meeting and discovering the intricacies of the Mu system bit by bit (most bits being completely unexpected). We enthusiastically discussed the most eccentric possibilities and explored the scientific and nonscientific world. It was not a fairy tale, but, as usual, as time passes, the good aspects tend to dominate. Mu research has certainly been influenced by the number of people working on the phage remaining small through the years, allowing easy contacts between the different laboratories (We had no fax or internet at the time!) enabling the “Mukaryots” in Cold Spring Harbor, the “Rhodomu’s” in Brussels and other groups to maintain an overview of what was going on. Many of us started to work on Mu at the same time, in the late 1960s. Both in the US and in Europe, the few people involved tried to get in touch, looking for counterparts because they felt isolated in the phage world dominated at the time by e.g., MS2, FX174, l, P2 and T4, but also because they did not want their work to overlap too much. It took about 4 y before we all met for the first time at Cold Spring Harbor Laboratory (CSHL) in July 1972. From then on, contacts were maintained between the different groups, especially at phage meetings at CSHL and in Salamanca (organized by Margarita Salas), and at recombination meetings in Nethybridge, (organized by Neville and Robin Holliday). There was an intense sharing not only of results, but also of ideas for future experiments and of possible models for those results that, when they first appeared, were so difficult to put into a known context. Everyone seemed very excited about the ideas, without worrying about others knowing of them. But once we were back in our respective laboratories, we started to work frantically, trying to be the first to solve the problem. This might have been why we always had a tendency to “transpose” by intra-molecular reaction from one end to the other on the Mu genome, whenever something exciting showed up in the transposase A gene or in the invertible G region. Of course, because of those transposition events, some political problems arose, but frank and stable friendship nevertheless developed. One consequence of entertaining such close contacts was that information had a tendency to remain within the Mu circle. This was reinforced by a general tendency of those involved to publish only part of their work, not to keep people in the dark, but just because writing was no fun (there was not as much pressure to publish at the time!), and there were always important experiments to be done right away. The book “Phage Mu” was not only the Mu community tribute to Ahmad, but also an attempt to allow all our phage colleagues to finally find the answers to some of the questions they always asked about Mu that never got an answer! This was because most of us only did the experiments we enjoyed doing, even though that meant leaving aside basic questions to which other phage workers were anxiously awaiting for an answer. In the early 1970s, Mu was felt as a marvelous and easy virgin field, even though we soon realized that Larry Taylor had already done so much! At a time when research on eukaryotes was starting to take the lead over that on prokaryotes, our motivation to start