The following comments are from Roland Rueckert who until recently was a Professor in the Institute of Molecular Virology, University of Wisconsin, Madison, Wisconsin. Well, my first reaction to your history request was "That's a long time ago; I'm a different person now", meaning I'm not a virologist anymore. For three years I've been thinking and breathing forestry and ecology. But he relented and continued: OK what's recorded below began as a short description, but as I typed it all came back pretty vividly. One part of Michael's history is all wrong. We were not foggy about the protomer concept in 1985 - Michael was, but I wasn't. We published a paper in 1969 (The Structure of Mouse-Elberfeld Virus: A Model, R.R. Rueckert, A.K. Dunker and C.M. Stoltzfus, Proc. Natl. Acad. Sci. 62: 912-919, 1969) and a second paper in 1971 (Fragments Generated by pH Dissociation of ME-virus and their Relation to the Structure of the Virion, A.K. Dunker and R.R. Rueckert, J. Mol. Biol. 58: 217-235, 1971) proposing the protomer concept for picornaviruses. The only uncertainty was whether VP4 was still situated close by but, even there, the simplest possibility was that it was part of the protomer. The crystallographic structure settled it. As for the relationship with Jim Hogle, you remember he was a student here with Sundaralingam. I had crystallized poliovirus by accident while post-docing with Wendall Stanley at Berkeley in 1964. Stanley made it clear that computing wasn't up to the task of determining a virus structure at that time. In 1978 when I learned Steve Harrison had solved the protein subunit structure of Tomato Bushy Stunt Virus I realized the time was ripe. I asked Sundaralingam, our only biological crystallographer at Wisconsin and himself crippled by polio. He was tempted but ultimately unwilling to make the necessary commitment. But Jim, then working on the structure of lysozyme, leapt at the opportunity. I encouraged him to do post-doctoral work in Steve's lab to learn virus crystallography; we'd send him poliovirus and if things looked promising maybe I could convince the Biochem Department to hire him with a joint appointment in our Institute (then called the Biophysics Laboratory). Because we planned to mail the virus, I suggested we'd be less liable to run into trouble with the post office if we used type 1 vaccine virus rather than Mahoney (Mahoney had been crystallized by Finch and Klug in 1960). Jim got crystals but they were very fragile in the X-ray beam. We tried lots of things to improve crystal stability, fruitlessly. I didn't want to risk sending mg quantities of polio through the mail. Finally, after considerable trepidation, I suggested to Jim he talk to David Baltimore about supplying him with Mahoney. That resulted in his collaboration with Marie Chow. Within months of the time Jim got high quality crystals he received a very attractive offer from the Scripps Laboratory in La Jolla. I tried to convince the Biochem Department to hire Jim. Neither Biochemistry nor the Biophysics Laboratory at Wisconsin were able to marshal an adequate counteroffer and, to my keen disappointment, it became clear Hogle could hardly refuse the Scripps offer. I did arrange for Joseph Icenogle, a graduate student from my laboratory, to join Hogle at La Jolla and this enabled Jim to get off to a fast start at Scripps. (Icenogle later joined the virology section at the Centers for Disease Control in Atlanta.) Meanwhile at the Strasbourg Virology Congress in 1981 Michael Rossmann, having learned of Hogle's success, told me that he planned to proceed vigorously with poliovirus crystallography. In Michael's hotel room that evening I argued against this plan on the grounds that it might jeopardize Hogle's research career and that it made better sense to study a picornavirus belonging to a different family and thereby benefit from the comparisons that would emerge as the structures were complete. I suggested human rhinovirus 14. I knew it could be produced and purified in sufficient bulk, was stable enough for crystallization and posed no health hazard to lab workers. The latter point ultimately proved crucial in a race between Hogle and Rossmann to solve the first crystallographic structure of an animal virus. I agreed to provide virus for preliminary studies and to train key personnel in Rossmann's laboratory with skills necessary for growing and purifying virus. To promote communication and maintain momentum we initiated regular annual meetings at Wisconsin. I was interested in correlating picornavirus structure with its functions. How did they attach to cells and what kind of structural rearrangements are involved in the infection step, i.e. release of its RNA genome from the shell into the cytoplasm of the host cell? I hoped that neutralizing monoclonal antibodies might provide a key tool. That antibodies might be useful for this purpose was first suggested by Dulbecco and coworkers in their 1956 paper on neutralization of animal viruses. They interpreted kinetic evidence, much like that used in radiation target theory, to mean that a single antibody molecule could neutralize a poliovirus particle. Moreover they argued this was not at an attachment step. But because of the complexity of antibodies in antiserum, purification of the antibodies in question was technically infeasible. The arrival of monoclonal antibody technology changed all that. Inspired by Phil Minor's preliminary work on neutralization resistant mutants of poliovirus, we launched a program aimed at defining neutralization sites on HRV14. Ann Mosser began with poliovirus and then taught Barbara Sherry how to make neutralizing monoclonal antibodies against HRV14. Barbara eventually isolated 35 B-cell clones producing neutralizing antibodies. These she used to isolate neutralization-resistant ("escape") mutants. These mutants were then used to classify the panel of antibodies into four groups using a microtiter neutralization assay. Sequencing the RNA showed that most of the escape mutants differed by substitution of one amino acid for a patch at the surface of the virus. Moreover each patch was correlated with one of the four antigenic groups previously defined in a novel way by screening for cross-resistance. Within a month of the time Barbara located the four escape mutation patterns, Rossmann and his coworkers had solved the rhinovirus structure to a resolution good enough to see that at least two of the mutable residues resided on the surface of the protein shell. He invited us to bring our collection of mutations to Purdue and help them trace their location in the electron density map. The map consisted of over a hundred planes stacked in a pile some 15 inches high. We color coded each alpha carbon in the chain, blue for VP1, green for VP2 and VP4, and red for VP3. It was a tedious process - and a tense one! One by one, over the course of a long day, we identified one after another of Barbara's mutants. At the end our hearts jumped for joy. Every single one of the escape mutations was located at the surface of the shell. Moreover the mutations were organized in four patches with each mutable side chain projecting into the patch to which it had been assigned by the cross-resistance mapping. No exceptions. It was an incredible high - total intoxicating elation. It gave us an unanticipated conviction of certainty in our results that one almost never experiences in experimental science. I realized at this moment the privilege of working with Michael Rossmann - and the luck of it. Michael accepted the disadvantages of working on the rhinovirus project, thus protecting Hogle's career. Poliovirus was known to form crystals of high quality, its sequence was known and antibody resistant mutants were already accessible. None of these advantages were available for HRV14. Yet Michael conquered these disadvantages, including a late start by his daring, determination and skill. Oh, and the element of luck? Rossmann was able to use the synchrotron to collect diffraction data while Hogle was not. That is because HRV14, unlike the Mahoney strain of poliovirus, was not considered a safety hazard. That, in the end, may have been the clinching factor in that exciting race for the first animal virus structure. There is more about Roland in the Viruses From Structure to Biology site at: http://medicine.wustl.edu/~virology/rueckert.htm