Das neue digitale ‚Shakespeare-Bildarchiv Oppel-Hammerschmidt‘ an der Universitätsbibliothek Mainz : Reden und Beiträge anlässlich seiner öffentlichen Vorstellung am 17. November 2008 an der Johannes Gutenberg-Universität Mainz

On the basis of illustrations of Shakespeare's Hamlet, the new digital 'Oppel-Hammerschmidt Shakespeare Illustration Archive' at the Mainz University Library - together with a lavishly-constructed and multiply-linked Web interface version - was presented to the public on 17 November 2008. This e-book, edited by Andreas Anderhub and Hildegard Hammerschmidt-Hummel, contains the speeches and presentations given on the occasion of the opening ceremony of the electronic archive. The collection of the new archive, published here for the first time, holds about 3,500 images and is part of the only Shakespeare illustration archive in the world. The Shakespeare Illustration Archive was founded in 1946 by the internationally acclaimed Shakespeare and Goethe scholar, Prof. Horst Oppel. This part of the archive was donated to the Mainz University Library on condition that its holdings be digitalised and made available to the public. The collection has been named 'The Oppel-Hammerschmidt Shakespeare Illustration Archive' in accordance with the terms of the Agreement of Donation of 9, 15, and 16 September 2005, and honouring the 16 March 1988 Delegation of Authority and Declaration of Intent by Frau Ingeborg Oppel, Prof. Oppel's widow and legal assignee. Vice-President Prof. Jürgen Oldenstein opened the proceedings by noting that 2008 had been a good year for international Shakespeare scholarship. For, in London, the site of the 'Theatre' in Shoreditch, where Shakespeare's company performed, had been unearthed, and in Mainz the Shakespeare Archive had gone online with thousands of illustrations. The Dean of the Faculty of Philosophy and Philology, Prof. Mechthild Dreyer, who mentioned that she herself had long been successfully employing interdisciplinary research methods, took particular pleasure in the transdisciplinary approach to research resolutely pursued by Prof. Hammerschmidt-Hummel. Prof. Clemens Zintzen (Cologne), former President of the Mainz Academy of Literature and Sciences, recalled highlights from the more than sixty-year-long history of the Shakespeare Illustration Archive. Prof. Kurt Otten (Heidelberg and Cambridge) drew an impressive portrait of Horst Oppel's personality as an academic and praised his influential books on Goethe and Shakespeare. He pointed out that Oppel's Shakespeare Illustration Archive, the basis for many a dissertation, had enjoyed great popularity around the world. Prof. Otten also delineated the academic career of Prof. Hammerschmidt-Hummel and her new findings regarding Shakespeare's time, life and work. Prof. Rüdiger Ahrens OBE (Würzburg) drew attention to Prof. Hammerschmidt-Hummel's research results, directly or indirectly arising out of her work on the Shakespeare Illustration Archive. This research had centred on proving the authenticity of four visual representations of Shakespeare (the Chandos and Flower portraits, the Davenant bust and the Darmstadt Shakespeare death mask); solving the mystery around Shakespeare's 'Dark Lady'; and establishing the dramatist's Catholic religion. Prof. Hammerschmidt-Hummel reported on her 'Shakespeare Illustration' project, describing the nature, dimensions and significance of the Archive's pictorial material, which relates to all of Shakespeare's plays and stretches over five centuries. She explained that the digital 'Oppel-Hammerschmidt Illustration Archive' was an addition to the three-volume edition she had compiled, authored and edited for publication in 2003. Unlike the print version, however, the digital collection had only been partly editorially prepared. It represented source material and a basis for further work. Hammerschmidt-Hummel expressed her thanks to the Head of the Central University Library, Dr Andreas Anderhub, for his untiring commitment. After the initial donation had been made, he had entered enthusiastically into setting up the necessary contacts, getting all the work underway, and clearing the legal hurdles. Hammerschmidt-Hummel was especially grateful to University of Mainz librarian Heike Geisel, who had worked for nearly five years to carry out the large-scale digitalization of a total of 8,800 items. Frau Geisel was also extremely resourceful in devising ways of making the collection yield even more, e.g. by classifying and cross-linking the data, assembling clusters of individual topics that lend themselves to research, and (in collaboration with the art historian Dr Klaus Weber) making the archive's index of artists compatible with the data-bank of artists held by the University of Mainz Institute of Art History. In addition, she compiled an extremely helpful 'users' guide' to the new digital collection. Frau Geisel had enjoyed invaluable support from Dr Annette Holzapfel-Pschorn, the leading academic in the Central IT Department at the University, who set up an intelligent, most impressive Web interface using the latest application technologies. Frau Geisel and Dr Holzapfel-Pschorn were highly praised for their convincing demonstration, using illustrations to Hamlet, of how to access this well-devised and exceptionally user-friendly Web version. For legal reasons, Prof. Hammerschmidt-Hummel pointed out, the collection could not be released for open access on the internet. The media - as Dr Anderhub stressed in his foreword - had shown great interest in the new digital collection of thousands of Shakespearean illustrations (cf. Benjamin Cor's TV feature in "Tagesthemen", 17 November 2008, presented by Tom Buhrow). The ‘Oppel-Hammerschmidt Shakespeare Illustration Archive’ should also meet with particular interest not only among academic specialists, but also among the performers of the arts and persons active in the cultural realm in general, as well as theatre and film directors, literary managers, teachers, and countless Shakespeare enthusiasts.

Generation of FLT3-ITD-reactive T-cell populations from different sources

Approximately 25% of acute myeloid leukemias (AMLs) carry internal tandem duplications (ITD) of various lengths within the gene encoding the FMS-like tyrosine kinase receptor 3 (FLT3). Although varying duplication sites exist, most of these length mutations affect the protein´s juxtamembrane domain. FLT3-ITDs support leukemic transformation by constitutive phosphorylation resulting in uncontrolled activation, and their presence is associated with worse prognosis. As known form previous work, they represent leukemia- and patient-specific neoantigens that can be recognized by autologous AML-reactive CD8+ T cells (Graf et al., 2007; Graf et al., unpublished). Herein, in patient FL, diagnosed with FLT3-ITD+ AML and in first complete remission after induction chemotherapy, T cells against her leukemia´s individual FLT3-ITD were detected at a frequency up to 1.7x10-3 among peripheral blood CD8+ T lymphocytes. This rather high frequency suggested, that FLT3-ITD-reactive T cells had been expanded in vivo due to the induction of an anti-leukemia response.rnrnCell material from AML patients is limited, and the patients´ anti-leukemia T-cell repertoire might be skewed, e.g. due to complex previous leukemia-host interactions and chemotherapy. Therefore, allogeneic sources, i.e. buffy coats (BCs) from health donors and umbilical cord blood (UCB) donations, were exploited for the presence and the expansion of FLT3-ITD-reactive T-cell populations. BC- and UCB-derived CD8+ T cells, were distributed at 105 cells per well on microtiter plates and, were stimulated with antigen-presenting cells (APCs) transfected with in vitro-transcribed mRNA (IVT-mRNA) encoding selected FTL3-ITDs. APCs were autologous CD8- blood mononuclear cells, monocytes or FastDCs.rnrnBuffy coat lymphocytes from 19 healthy individuals were analyzed for CD8+ T-cell reactivity against three immunogenic FLT3-ITDs previously identified in patients VE, IN and QQ and designated as VE_, IN_ and QQ_FLT3-ITD, respectively. These healthy donors carried at least one of the HLA I alleles known to present an ITD-derived peptide from one of these FLT3-ITDs. Reactivities against single ITDs were observed in 8/19 donors. In 4 donors the frequencies of ITD-reactive T cells were determined and were estimated to be in the range of 1.25x10-6 to 2.83x10-7 CD8+ T cells. These frequencies were 1,000- to 10,000-fold lower than the frequency of autologous FLT3-ITD-reactive T cells observed in patient FL. Restricting HLA I molecules were identified in two donors. In one of them, the recognition of VE_FLT3-ITD was found to be restricted by HLA-C*07:02, which is different from the HLA allele restricting the anti-ITD T cells of patient VE. In another donor, the recognition of IN_FLT3-ITD was restricted by HLA-B*35:01, which also had been observed in patient IN (Graf et al., unpublished). By gradual 3´-fragmentation of the IN_FLT3-ITD cDNA, the 10-mer peptide CPSDNEYFYV was identified as the target of allogeneic T cells against IN_FLT3-ITD. rnLymphocytes in umbilical cord blood predominantly exhibit a naïve phenotype. Seven UCB donations were analyzed for T-cell responses against the FLT3-ITDs of patients VE, IN, QQ, JC and FL irrespective of their HLA phenotype. ITD-reactive responses against all stimulatory FLT3-ITDs were observed in 5/7 UCB donations. The frequencies of T cells against single FLT3-ITDs in CD8+ lymphocytes were estimated to be in the range of 1.8x10-5 to 3.6x10-6, which is nearly 15-fold higher than the frequencies observed in BCs. Restricting HLA I molecules were identified in 4 of these 5 positive UCB donations. They were mostly different from those observed in the respective patients. But in one UCB donation T cells against the JC_FLT3-ITD had exactly the same peptide specificity and HLA restriction as seen before in patient JC (Graf et al., 2007). Analyses of UCB responder lymphocytes led to the identification of the 10-mer peptide YESDNEYFYV, encoded by FL_FLT3-ITD, that was recognized in association with the frequent allele HLA-A*02:01. This peptide was able to stimulate and enrich ITD-reactive T cells from UCB lymphocytes in vitro. Peptide responders not only recognized the peptide, but also COS-7 cells co-transfected with FL_FLT3-ITD and HLA-A*02:01.rnrnIn conclusion, T cells against AML- and individual-specific FLT3-ITDs were successfully generated not only from patient-derived blood, but also from allogeneic sources. Thereby, ITD-reactive T cells were detected more readily and at higher frequencies in umbilical cord blood than in buffy coat lymphocytes. It occurred that peptide specificity and HLA restriction of allogeneic, ITD-reactive T cells were identical to autologous patient-derived T cells. As shown herein, allogeneic, FLT3-ITD-reactive T cells can be used for the identification of FLT3-ITD-encoded peptides, e.g. for future therapeutic vaccination studies. In addition, these T cells or their receptors can be applied to adoptive transfer.

Das Biobankgeheimnis : Schutz der Persönlichkeitsrechte in der biomedizinischen Forschung

Biobanken sind Sammlungen von Körpersubstanzen, die mit umfangreichen gesundheits- und lebensstilbezogenen sowie geneologischen Daten ihrer Spender verknüpft sind. Sie dienen der Erforschung weit verbreiteter Krankheiten. Diese sog. Volkskrankheiten sind multifaktoriell bedingte Krankheiten. Dies bedeutet, dass diese Krankheiten das Ergebnis eines komplizierten Zusammenspiels von umwelt- und verhaltensrelevanten Faktoren mit individuellen genetischen Prädispositionen sind. Forschungen im Bereich von Pharmakogenomik und Pharmakogenetik untersuchen den Einfluss von Genen und Genexpressionen auf die individuelle Wirksamkeit von Medikamenten sowie auf die Entstehung ungewollter Nebenwirkungen und könnten so den Weg zu einer individualisierten Medizin ebnen. Menschliches Material ist ein wichtiger Bestandteil dieser Forschungen und die Nachfrage nach Sammlungen, die Proben mit Daten verknüpfen, steigt. Einerseits sehen Mediziner in Biobanken eine Chance für die Weiterentwicklung der medizinischen Forschung und des Gesundheitswesens. Andererseits lösen Biobanken auch Ängste und Misstrauen aus. Insbesondere wird befürchtet, dass Proben und Daten unkontrolliert verwendet werden und sensible Bereiche des Persönlichkeitsrechts und der persönlichen Identität betroffen sind. Diese Gefahren und Befürchtungen sind nicht neu, sondern bestanden schon in der Vergangenheit bei jeglicher Form der Spende von Körpersubstanzen. Neu ist aber der Umfang an Informationen, der durch die Genanalyse entsteht und den Spender in ganz besonderer Weise betreffen kann. Bei der Speicherung und Nutzung der medizinischen und genetischen Daten ergibt sich somit ein Spannungsfeld insbesondere zwischen dem Recht der betroffenen Datenspender auf informationelle Selbstbestimmung und den Forschungsinteressen der Datennutzer. Im Kern dreht sich die ethisch-rechtliche Bewertung der Biobanken um die Frage, ob diese Forschung zusätzliche Regeln braucht, und falls ja, wie umfassend diese sein müssten. Im Zentrum dieser Diskussion stehen dabei v.a. ethische Fragen im Zusammenhang mit der informierten Einwilligung, dem Datenschutz, der Wiederverwendung von Proben und Daten, der Information der Spender über Forschungsergebnisse und der Nutzungsrechte an den Daten. Ziel dieser Arbeit ist es, vor dem Hintergrund des Verfassungsrechts, insbesondere dem Recht auf informationelle Selbstbestimmung, das Datenschutzrecht im Hinblick auf die Risiken zu untersuchen, die sich aus der Speicherung, Verarbeitung und Kommunikation von persönlichen genetischen Informationen beim Aufbau von Biobanken ergeben. Daraus ergibt sich die weitere Untersuchung, ob und unter welchen Voraussetzungen die sich entgegenstehenden Interessen und Rechte aus verfassungsrechtlichem Blickwinkel in Einklang zu bringen sind. Eine wesentliche Frage lautet, ob die bisherigen rechtlichen Rahmenbedingungen ausreichen, um den Schutz der gespeicherten höchstpersönlichen Daten und zugleich ihre angemessene Nutzung zu gewährleisten. Das Thema ist interdisziplinär im Schnittfeld von Datenschutz, Verfassungsrecht sowie Rechts- und Medizinethik angelegt. Aus dem Inhalt: Naturwissenschaftliche und empirische Grundlagen von Biobanken – Überblick über Biobankprojekte in Europa und im außereuropäischen Ausland – Rechtsgrundlagen für Biobanken - Recht auf informationelle Selbstbestimmung - Recht auf Nichtwissen - Forschungsfreiheit - Qualitätssicherung und Verfahren – informierte Einwilligung – globale Einwilligung - Datenschutzkonzepte - Forschungsgeheimnis –– Biobankgeheimnis - Biobankgesetz