Lucky Day For Two Neuropathologists And More Luck On A Sabbatical

In discussions with Dr. Chou, we decided to give another project priority, namely, the clarification of the mystery of the abnormal oligodendrocytes in PML. We felt unencumbered by the strict rules for optimal ultrastructural images as worked out by cell biologists. The structural proteins of viruses were perhaps still preserved despite postmortem delays in fixation and immersion in 10% formalin for 2 years. What was there to lose in trying? On August 7, 1964, Dr. Chou and myself attended a celebration for a student friend who had passed her preliminary examination. My diary shows the following entry, in mixed English and German: ''Pink Bacardi mit cherry!! Dann erste EM session mit Sam, 62-393. CRYSTAL INTRANUCLEAR VIRUS!!!! POLYOMA?? Bis 5 h.'' We found the crystalloid aggregate (Fig. 2.2) in the first ultrathin section,

Figure 2.2. Electron micrograph obtained on the day of the discovery of the papova virions, here arranged in a crystalloid pattern. x65,000 orig. mag.


and we could not believe our luck and kidded about the influence of the Bacardi. After Dr. Chou developed the first photographic plates that also revealed scattered virions and filamentous forms, we hugged in the dark room; what an exciting day in our lives it was. Whereas the tissue in general showed moderate autolysis, the virions were so well preserved that their images compared favorably with those in the literature. The virions belonged to an identifiable group, with oncogenic potential, perhaps explaining the bizarre shapes of as-trocytes, and this virus had penetrated deep into the brain, unlike papilloma viruses. Yet no human polyoma virus was known at that time. When we showed the plates to Dr. Angevine, his dry comment was: "This is the way discoveries are being made.''

In early September, I arrived at Montefiore Hospital equipped with Epon blocks of the esophagitis case and PML case 62-393, with the first prints of the latter and with Ludwik Gross's book titled Oncogenic Viruses (Gross, 1961), which became my ''bible.'' When Dr. Zimmerman saw the prints, he found them exciting enough to add a presentation, belatedly, to the program of the forthcoming ARNMD (Association for Research in Nervous and Mental Diseases) symposium entitled ''Infections of the Nervous System.'' Dr. Zimmerman, at that time, was President of the ARNMD and the program coordinator.

In addition to continuing electron microscopy now also on our second case of PML, I was forced to rapidly pursue library studies. Which journals and books was I to read in a field at the crossroads of virus and cancer research and cell biology? It required a fast reorientation for a diagnostic neuropathologist. In September, I was able to resolve the nature of the nuclear inclusion bodies of the esophagitis case: They consisted of herpes-type virions, well preserved in this autopsy tissue. In mid-November, I got a phone call from Dr. Lucien Rubinstein, of Stanford University. He had just received the ARNMD program with the listing of ''Papova Virus in Progressive Multifocal Leukoen-cephalopathy'' by Zu Rhein and Chou and wanted to inform me that he and Dr. Silverman had found similar virus particles in a recent case of PML (Sil-verman and Rubinstein, 1965). He offered to back us up in the meeting, with Dr. Zimmerman's consent.

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