Pathological Institute Koenigsberg

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The Pathological Institute in Königsberg existed from 1865 to 1944. The new building of the "Pathological-Pharmacological Institute" was occupied in 1890 and destroyed in 1944 as a result of the war.

History of the institute

The first director of the institute was Friedrich von Recklinghausen (1833–1910). In the surgical clinic he was given “a more than modest room for the new specialty”. Until then, the "pathological anatomy" was represented by the physiologists Hermann von Helmholtz (1821-1894) and Wilhelm von Waldeyer (1836-1921).

Friedrich von Recklinghausen stayed in Königsberg for only one year. His successor was Ernst Christian Neumann (1834–1918), son of the physicist Franz Ernst Neumann (1798–1895). Over two generations until his retirement in 1903 he founded the Neumann School of Hematology and, in which on October 10, 1868 the bone marrow was described for the first time as a blood-forming organ with its pluripotent blood stem cell.

First published in 1868: Bone marrow is the blood-forming organ

Three days after the initial publication, Neumann, as head of the Helmholtz Association for Scientific Medicine, specified his ideas of the extrauterine , regenerative "lymphoid marrow cell" that he later (1912) renamed the pluripotent large lymphocyte stem cell : contributed to the reputation of the institute Max Askanazy (1865–1940), Paul von Baumgarten (1848–1928), Georg Rosenow (1886–1985) and 54 other assistants (54 dissertations), including Ludwig Pick (1868–1944).

From the beginning, the scientists of the institute (cf. report October 13, 1868) put forward the hypothesis that all blood cells of the various blood cell series originate from a pluripotent stem cell, which is also constantly developing extrauterine from the bone marrow parenchyma (unitarianism).

The other directors of the institute were Rudolf Beneke (1861–1946) from 1903 to 1906, Friedrich Henke (1868–1943) from 1906 to 1911, Carl Kaiserling (1862–1942) from 1913 to 1935 and Karl Krauspe (1895–1965) from 1935 to 1944. They consistently continued the Königsberg school of hematology (Unitarianism). In addition, they worked on the topics of thrombosis and embolism (Beneke), infectious diseases diphtheria, appendicitis and streptococcal tonsillitis (Henke) and Königsberger Haff disease (Krauspe).

Unitarianism - dualism - strife

A pan-European controversy related to the development of the hematopoietic stem cell . The scientists at the Königsberg Pathological Institute represented the "Unitarian standpoint", which stated that "all forms of the same leukocytes can be traced back to a common stem cell that is also always present in the extrauterine". This opinion was adopted by Alexander Maximow in St. Petersburg, Max Askanazy , Geneva and Artur Pappenheim , Berlin in the "Berlin Hematological Society" he founded (1908). The story ran in favor of Nobel Prize winner Paul Ehrlich (1854–1915), Wilhelm Türk (1871–1916) from Vienna and Otto Naegeli (1871–1938) from Switzerland.

In order to settle the dispute, the Königsberg Pathological Institute suggested researching a pure culture of stem cells in 1912: “Perhaps a final decision will only be possible when the same experiment can be carried out with the colorless blood cells that Robert Koch taught to carry out with the bacteria , namely to isolate the individual cells and to follow their life processes [“in a pure culture”] in vitro for a longer period of time. ”.

The time was not yet ripe for this, so that the Königsberg Pathological Institute was forgotten with the end of the Berlin Hematological Society (1908), especially after the First World War .

Only after more than 100 years could the existence of a bone marrow stem cell, which always regenerates after birth, be confirmed by growing stem cells in a bone marrow culture.

The university building and its equipment

Hematopoietic stem cell 1874 in the native preparation in the embryonic liver resp. in postembryonic bone marrow

Between 1888 and 1890 a new building for the Pharmacological and Pathological Institute was built at Kopernikusstraße 3-4. The institute was equipped with some good microscopes . The native preparation became the most common examination method. Cells of the bone marrow juice (or the juice of the embryonic liver) squeezed out with a vice were immediately examined under the microscope while still alive, because according to the institute's opinion, chemical effects (color) changed the cell nuclei and the cytoplasm.

Drawings from 1874 have been preserved, in which the differentiation of the progenitor cells of the erythroblasts via young nucleated red blood cells is shown. Carl Kaiserling equipped the institute with state-of-the-art technology, e.g. B. with a freezing microtome, the luminescence microscopy to examine tubercle bacteria. The latest devices for photographic, microscopic and macroscopic projections with spectrography to detect thallium in tissue were also purchased.

Erythrocytopoiesis: from the hematopoietic precursor cell to the erythroblast (native preparation)

In 1903, Rudolf Beneke built a new demonstration room that had two autopsy tables. Before the Second World War , all applications were postponed for “better times”. "The destruction of the institute by an air raid on August 31, 1944 destroyed a large part of all work done there, especially the valuable collection of preparations."

First publications from the institute

The mesenchymal large lymphocyte stem cell in the embryonic liver, resp. lifelong in the bone marrow
  • 1868 Extrauterine, regenerative “lymphoid marrow cell” in the bone marrow or lymphoid cell in the embryonic liver for erythrocytopoiesis
  • 1870 "Myelogenic leukemia" caused by bone marrow with "Charcot-Neumann-Leyden crystals"
  • 1878 leukocytopoiesis in the bone marrow or the embryonic liver and spleen
  • 1888 Extrahepatic bilirubin formation; Pathol. Types of jaundice - Physiological neonatorial jaundice (N82, N83)
  • 1888 Exclusion law of the hemoglobin derivatives: "Hämosiderin" (Neumann) in the living organism, hematoidin as pigment symbol of necrosis (N82)
  • 1890 Blood formation in the postpartum newly formed bone marrow (N87) see Unitarianism

The drawings of the native preparation described by Ernst Neumann in 1869 may also apply to the first publications: Without chemical additives, the squeezed secretion (mostly bone marrow juice) between two fine glass panes was examined under the microscope: In 1874 Neumann described the "lymphoid marrow cell" (today's hematogenous stem cell ) with their transition to the hemoglobin-containing still nucleated erythrobastes in the embryonic liver, respectively. the postembryonic bone marrow. The further figure shows the erythrocytopoiesis after the hematopoietic stem cell via the already hemoglin-containing precursor cell to the still nucleated erythroblasts. The 3rd picture of the native preparation with the "large lymphocyte stem cell" comes from 1914 with better resolution. No. 4d is of interest here: Neumann added acetic acid to this cell so that the cell could no longer be observed in the "living state" and the hemoglobin was not displayed. For Neumann, this was proof that development processes on cells can only be observed in the native preparation and without the addition of dyes. Ultimately, this view also led to the implementation of the Unitarian standpoint against dualism.

Further results from the Pathological Institute: 1. The first description of the histology of the bone marrow tissue, including the “Neumann's law of the centripetal direction of development of fat marrow substitution” 2. Embryonic blood formation in the bone marrow, in the embryonic liver and spleen 3. Contributions to pernicious anemia 4. "Fibrinoid degeneration" and "fibroblasts" during the inflammation process (N74,1880 and N92,1896) 5. Description of the "pigment of brown lung induration" (N101,1900) 6. Recognition of the regenerative capacity of the muscle (Neumann's muscle buds "), 7. "Neumann's Nerve Development Law" (N103,1901): "Regeneration of peripheral nerves after continuity separation at the Pathological Institute in Königsberg" (Buzmann 2003). 8. "Neumann's tooth sheaths" (Neumann 1863) 9. "Neumann tumor" (congenital epulis) ( N50.1871.)

literature

  • Bernard, Cl: E. Neumann, Königsberg, Du role de la moelle des os dans la formation du sang, Oct. 1868. In: Mémoire présentée par M. Claude Bernard à l'Académie des sciences de Paris, 1869. Comptes rendue des scéances de l'Academie des Scéances de Paris Tome 68, no. 19, 1869
  • Boroviczeny, KGv et al: Introduction to the history of hematology, Georg Thieme Verlag Stuttgart 1974
  • Klinger, Y .: About the discovery of the hematopoietic function of the bone marrow and the postulate of stem cells. Dissertation from the Medical Clinic of the Ruhr University Bochum 1992
  • Neumann, E .: About the importance of the bone marrow for blood formation. Centralblatt für die Med. Wissenschaft 44 (1868) 689
  • Neumann, E .: About the importance of the bone marrow for blood formation. A contribution to the development business. of blood cells, archive f. Medicine 10 (1869) 68-102 (Wagner's archive)
  • Neumann, E .: A case of leukemia with disease of the bone marrow Appendix: Salkowski: Chemical investigations of the leukemic marrow (7/28/69) Archives of Medicine (Wagner's Archives) Vol. XI, (1871) pp. 1-15
  • Neumann, E .: New contributions to the knowledge of blood formation. E. Wagner's Archiv der Heilkunde Vol. XV, 1874 with illustration (native preparation) from nucleated red blood cells to nucleated erythrocytes (blood and pigments, pp. 63–92)
  • Neumann, E .: The law on the spread of the yellow and red bone marrow. Centralblatt für die Med. Wissenschaft. 18 (1882) pp. 321-323
  • Neumann, E .: About the development of red blood cells in the newly formed bone marrow. Virchows Archiv Vol. 119, 1890 (Blood and Pigments, pp. 201–211)
  • Neumann, E .: Hematological Studies III. Leukocytes and Leukemia, Virch. Arch. 207 (1912) pp. 379-412
  • Neumann, E .: blood and pigments. Jena Gustav Fischer 1917 (BP page numbers)
  • Neumann-Redlin von Meding , E .: The pathologist Ernst Neumann (1834-1918) and his contribution to the establishment of hematology in the 19th century, Demeter Verlag 1987
  • H. Neumann, H., Klinger, Y .: Bone marrow and stem cells - The battle for the fundamentals of hematology Blackwell Science, Ex libris Roche Vol. 1, 1994
  • Neumann-Redlin von Meding, E: Ernst Chr. Neumann (1834-1918); The description of the functional morphology of the bone marrow at the Pathological Institute in Königsberg and its influence on the hematology of the 19th century. in: Yearbook of Albertus Univ. Königsberg Vol. 29 (1994) (425-437) and Ed. Rauchning, D. et al: The Albertus University of Königsberg and its professors. Duncker et al. Humblot Berlin 1995
  • Schinck, Peter: Ernst Neumann as the founder of hematology, dissertation at the Pathological Institute in Königsberg (Prof. Kaiserling) 1920
  • Peters, Oleg: Heino Schmieden. Life and work of the architect and builder 1835 - 1913. Lukas Verlag Berlin 2016 In it: August Stüler built the new university building on Paradeplatz Königsberg in 1862 and the Pathological and Pharmacological Institute from 1888 - 90, p. 310
  • Tavassoli, M .; Yoffey, JM: Bone Marrow; Structure and Function. Alan R. Liss, Inc., 1983 New York
  • Virchow, R .: Opinion against the bone marrow as an organ of blood formation. In: Cellularpathologie 4th ed. (1871) p. 214

Web links

Individual evidence

  1. Scholz, H .: Doctors in West and East Prussia. Holzner-Verlag Würzburg, 1970
  2. Askanazy, M .: Ernst Neumann, Verh. Dt. Path.Ges. 28 (1935) pp. 363-372
  3. Rutisheimer, E .: Necrologica - Max Askanazy. Switzerland. Magazine f. General Path. and Bakteriologie, Basel 4 (1941) 174-176
  4. Lecture text before the Association for Scientific Medicine on October 13, 1868 - Lymphoid medullary cell is the cell of origin of erythropoiesis
  5. Askanazy, Max: Neumann explains on the frog that these stem cells, the "lymphocytes" in the broader sense of the word, i. H. the unstained parenchymal cells of the blood formation tissue are to be assigned. There is no question of the endothelium or the reticular cells. "Lecture in Geneva 1935, printed in the Verh. Dt. Gesell. F. Pathol. Vol. 28, 1935, p. 369
  6. ^ The Institut of Koenigsberg (E. Neumann) and Turin ( G. Bizzozero ) "reported observations and drew conclusions that were so revolutionary that they were not accepted" Wintrobe, M .: Hematology, the Blossoming of a Science; a story of inspiration and effort. Lea & Febiger Philadelphia 1985. "The beginning of Stem Cell research can be dated back to Ernst Neumann, who was appointed professor of pathology at the University of Koenigsberg in 1868. He described in a preliminary communication the presence of nucleated red blood cells in bone marrow (BM) saps (Fig. 2). Neumann concluded in his subsequent papers, that during postembryonic life, erythropoiesis and leukopoiesis are taking place in the BM. On the basis of his observations, Neumann was the first to postulate the BM as blood Forming organ with a common SC for all hematopoietic cells "Zech, NH, Shkumatov, A. Koestenbauer, S .: The magic behind stem cells. Journal of Assisted Reproduction and Genetics Vo. 24, No. 6 (2007) 208-214
  7. ^ Krauspe, C .: Ernst Neumann. The Pathological Institute Koenigsberg. In: The East Prussian Doctor's Family, Osterrundbrief (1969) p. 15 ff
  8. ^ Neumann, E .: Hematological Studies III. Leukocytes and Leukemia, Virch. Arch. 207 (1912) pp. 379-412
  9. ^ Neumann, E .: Hematological Studies III. Leukocytes and Leukemia, Virch. Arch. 207 (1912) pp. 379-412
  10. ^ Voswinckel, Peter: 50 years of the German Society for Hematology and Oncology. Würzburg, 1987
  11. Fauser, AA et al .: Cytotoxic T-cell clones derived from pluripotent stem cells (CFU-GEMM) of patients with Hodgkins Lymphoma Blood 60 No. 6 (1982) pp 1317-1320
  12. Neumann, E .: About the importance of the bone marrow for blood formation, A contribution to the development. the blood cell archive f. Medicine 10 (1869) 68-102 (Wagner's archive)
  13. ^ Gutzeit, R .: The Pathological Institute of the Albertina at the time of Ernst Neumann. Yearbook of the Albertus University vol. II, Göttingen working group, Dikreiter Verlagsges. GmbH, Freiburg, Frankfurt 1952, pp. 253-254.
  14. Scholz, H .: Doctors in West and East Prussia. Holzner-Verlag Würzburg, 1970
  15. Scholz, H .: Doctors in West and East Prussia. Holzner-Verlag Würzburg, 1970
  16. Scholz, H .: Doctors in West and East Prussia. Holzner-Verlag Würzburg, 1970
  17. ^ E. Neumann: New contributions to the knowledge of blood formation. In: E. Wagner's archive of medicine. Volume XV, 1874, Fig. 6fß with transition to erythroblasts 6fa
  18. ^ E. Neumann: New contribution to the knowledge of the embryonic liver. In: Arch.f.mikr. Anat. Volume 85, Abt. I, 1914, pp. 480-520