Nissl, Franz

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(b. Frankenthal, Germany, 9 September 1860; d. Munich, Germany, 11 August 1919)

psychiatry, neuropathology.

Nissl was the son of Theodor Nissl and Maria Haas. He is known for the discovery of a granular basophilic substance, now called Nissl’s bodies, that is found in the nerve cell body and the dendrites. In connection with this discovery he classified changes in the distribution and number of these granules following disease or the severing of the axon; coined the term nervöses grau, or gray nerve network, a misleading concept of a diffuse interconnection of all nerve processes; and, both alone and with Alois Alzheimer, made a detailed study of dementia paralytica, paying special attention to the behavior of microglia (rod cells).

Niss’s father, who taught Latin in a Catholic school, intended his son to become a priest but, against his parents’ wishes, Nissl studied medicine at Munich University. His interest in the nervous system was firmly established by his first scientific effort. He entered a competition for a prize in neurology offered by the Medical Faculty at Munich. The judge was Bernard von Gudden, a scientist and psychiatrist. Gudden was so impressed by Nissl’s work on the pathological changes of cortical neurons that he offered him an assistantship in 1884. Gudden drowned in the lake of Starnberg with his patient, King Ludwig of Bavaria, in 1886, and Nissl then became an assistant at the psychiatric hospital in Frankfurt. There he met the comparative neurologist Ludwig Edinger and the neuropathologist Carl Weigert. Nissl worked for seven years with Alzheimer, a psychiatrist and an outstanding neuropathologist. Together they edited the Histologische und Histopathologische Arbeiten über die Grosshirnrinde (1904–1921). In 1895 Nissl moved to the University of Heidelberg, becoming university lecture in 1896, associate professor of psychiatry in 1901, and full professor and director of the department of psychiatry in 1904.

The burden of teaching and administration, combined with poor research facilities, forced Nissl to leave many scientific projects unfinished. He also suffered from a kidney disease. World War I proved to be an even greater burden for he was commissioned to administer a large military hospital as well. In 1918 Nissl moved to Munich to take a research position at the Deutsche Forschungsanstalt für Psychiatria. He died a year alter, before deriving any benefit from these new opportunities.

The present stage of development of neurohistological techniques, inculding electron microscopy, makes possible an appraisal of Nissl’s real scientific achievements. The granular basophilic Nissl’s substance is an important ultrastructure of nerve cells, composed of ribosomes and the membranes of the endoplasmic reticulum. The Nissl bodies, in reacting to injury and toxins, mirror the life cycle of a neuron very closely, and the importance Nissl attached to them was fully justified. The gray nerve network, however, proved to be untenable and demonstrates that the use of only one technique leads to faulty interpretation. Nissl and his contemporaries fought for recognition of their respective views. His only monograph, Die Neuronenlehre und ihre Anhänger (1903), is a sad and depressing account of a speculative mind incapable of listening to other scientists’ arguments. His attitude was rigid, and his stature in German neurology was one of the reasons that after the magnificent start given to German neuropathology by the studies of Nissl, W. Spielmeyer, Alzheimer, Weigert, and others, no real advances were made by fully experimental methods. Such studies would have early revealed that many observations of cellilar changes or of the gray nerve network resulted from bad fixation and application of only one technique.

Nevertheless, Nissl’s arguments against the neuron doctrine, which is based on areas of contact between neurons, survived in many quarters until recent times, when electron microscopy amply confirmed the early observations of his contemporary Ramón y Cajal, which Nissl’s studies on dementia paralytica are still valid, his admirable attempt to discover a neuropathological cause for mental diseases failed. This is not to detract from Nissl, however, for the cause of these mainly functional diseases is neurobiochemical, not morphological.

I . Original Works. Nissl’s writings inculde “Resultate und Erfahrungen bei der Untersuchung der pathologischen Veränderungen der Nervenzellen in der Grosshirnrinde” his diss. (unpublished) (1884); “Über die Veränderungen der Ganglienzellen am Facialiskern des Kaninchens nach Ausreissung des Nerven,” in Versammlungen des Südwestdeutschen Psychiatervereins in Karlsruhe,”22 (1890); “Über experimentell erzeugte Veränderungen an den Vorderhornzellen des Rückenmarkes bei Kaninchen,” in Zeitschrift für Neurologie, 48 (1892), 675–682; Über die sogenannten Granula der Nervenze1len, in Neurologisches Zentralblatt, 13 (1894), 676-685, 781-789, 810-814; “Die Beziehungen der nervenzellsubstanzen zu den tätigen, ruhenden and ermüdeten Zellzuständen,” in Allgemeine Zeitshrift fur psychiatrie, 52 (1896), 1147-1154; “Mitteilungen zur pathologischen Anatomie der Dementia paralytica,” in Archiv für Psychiatrie, 28 (1896), 987-992; “Über die Veränderungen der Nervenzellen nach experimentell erzeugter Vergiftung. Autoreferat,” in Neurologisches Zentralblatt,15 (1896).

“Uber einige Beziehungen zwischen Nervenzellerkranklungen and gliösen Erscheinungen bei verschiedenen Psychosen,” in Archie für Psychiatrie, 32 (1899), 656-676; Die Neuronenlehre und ihre Anhäger (Jena, 1903); “Zur Histopathologie der paralytischen Rindenerkrankung,” in Histologische und histopathologische Arbeiten über die Grosshirnrinde, 1 (Jena, 1904); “Diskussionsbemerkung zu Alzheimer: Die syphilitischen Geistesstörrungen,” in Neurologisches Zentralblatt, 32 (1909), 680; and “Zur Lehre der Lokalisation in der Grosshirnrinde des Kaninchens,” in Sitzungsberichte derHeidelberger Akademie der Wissenschaften, Math-naturwiss. KI. (1911).

II. Secondary Literature. Biographies are A. Jakob, “Franz Nissl,” in Deutsche medizinische Wochenschrift, XLV, (1919), 1087; E. Kraepelin, “Franz Nissl,” in Münchener medizinische Wachenschrift (1919); and “Lebensschicksale deutscher Forscher,” ibid. (1920); H. Marcus, “Franz Nissl,” in Minnesood i Svenska läkaresällskapet (1919); P. Schröder,“Franz Nissl,” in Monatsschrift für Psychiatrie … 46 (1919), 294; H. Spatz, “Franz Nissl,” in Berliner klinische Wochenschrift (1919), 1006; and “Nissl und die theoretische Hirnanatomie,” in Archiv für Psychiatrie und Nervenkrankheiten, 87 (1929), 100–125; and W. Spielmeyer, “Franz Nissl;,” in Kirchhoffs deutsche Irrenärzte, 2 (1924), 288.

Specialized works are J. E. C. Bywater and P. Glees, Der Einfluss der Fixationsart und des Intervalles zwischen Tod und Fixation auf die Struktur der Motoneurone des Affen (Zurich, 1959), offprint from Verhandlungen der Anatomischen Gesellschaft (Jena), 55 (1959), 194–200; P. Glees, “Ludwig Edinger,” in Journal of Neurophysiology, 15 (1952), 251–2S5; and “Neuere Ergebnisse auf dem Gebiet der Neurohistologie: Nissl-Substanz, corticale Synapsen, Neuroglia und intercelluläter Raum,” in Deutsche Zeitschrift für Nervenheilkunde, 184 (1963), 607–631; P. Glees and J. E. C. Bywater, “The Effect of the Mode of Fixation and the Interval Between Death and Fixation on Monkeys’ Motoneurones,” in Proceedings of the Physiology Society Journal of Physiology, 149 (1959), 3–4P; and P. Glees and K. Meller, “The Finer Structure of Synapses and Neurones. A Review of Recent Electronmicroscopical Studies,” in Paraplegia, 2 , no. 2 (1964), 77–95.

Paul Glees