Frank W. Stahnisch

Santiago Ramón y Cajal's concept of neuronal plasticity: the ambiguity lives on

Parallel to his well-known work on the microarchitecture of the CNS, Santiago Ramón y Cajal conducted various investigations of its de- and regenerative capacities. However, Ramón y Cajals theoretical stance on the issue remains rather ambiguous and can even be assumed to reflect modern views on the potential of structural plasticity in the CNS.

Launching Invasive, First-in-Human Trials against Parkinson’s Disease: Ethical Considerations

The decision to initiate invasive, first‐in‐human trials involving Parkinsons disease presents a vexing ethical challenge. Such studies present significant surgical risks, and high degrees of uncertainty about intervention risks and biological effects. We argue that maintaining a favorable risk‐benefit balance in such circumstances requires a higher than usual degree of confidence that protocols will lead to significant direct and/or social benefits. One critical way of promoting such confidence is through the application of stringent evidentiary standards for preclinical studies. We close with a series of recommendations for strengthening the internal and external validity of preclinical studies, reducing their tendency toward optimism and publication biases, and improving the knowledge base used to design and evaluate preclinical studies.

Making the brain plastic: early neuroanatomical staining techniques and the pursuit of structural plasticity, 1910-1970.

The concept of neuronal plasticity is widely used, but seldom defined in the neurosciences. It can signify many different occurrences, such as structural alterations of axons and dendrites (Cotman & Nadler, 1978), behavioural adaptations (Rosenzweig & Bennett, 1996), or physiological changes in synapse formation (Martin et al., 2000) at different stages of health and disease. Although there is such a wealth of research from many disciplines, the neuroanatomical aspects of plasticity are the focus of this paper. It seeks to illuminate the evolution of different concepts of plasticity concerning the structure and circuitry of the central nervous system (CNS). Early modern morphological research on de- and regeneration phenomena in the 19th- and early 20th-century is well documented. These studies, however, almost exclusively concentrated on the peripheral nervous system (PNS). It was one of the major contributions of Santiago Ramón y Cajal (1852–1934), that he applied the concept of regenerative capacities to the CNS. But the term plasticity seemed to have disappeared for about two decades after his death. The ensuing comeback of the expression may be attributed, at least in part, to new neuroanatomical staining and tracing methods. The pursuit of these techniques will serve as a guidepost through varying approaches in different times: It was the 1950s which seemed to spawn the time for new departures in structural investigations of neuronal plasticity.

Three Twentieth-Century Multiauthored Neurological Handbooks – A Historical Analysis and Bibliometric Comparison

The emergence of neurology as a separate specialty from internal medicine and psychiatry took several decades, starting at the end of the nineteenth century. This can be adequately reconstructed by focusing on the establishment of specialized journals, societies, university chairs, the invention and application of specific instruments, medical practices, and certainly also the publication of pivotal textbooks in the field. Particularly around 1900, the German-speaking countries played an integral role in this process. In this article, one aspect is extensively explored, notably the publication (in the twentieth century) of three comprehensive and influential multivolume and multiauthor handbooks entirely devoted to neurology. All available volumes of Max Lewandowskys Handbuch der Neurologie (1910–1914) and the Handbuch der Neurologie (1935–1937) of Oswald Bumke and Otfrid Foerster were analyzed. The handbooks were then compared with Pierre Vinkens and George Bruyns Handbook of Clinical Neurology (1968–2002). Over the span of nearly a century these publications became ever more comprehensive and developed into a global, encompassing project as is reflected in the increasing number of foreign authors. Whereas the first two handbooks were published mainly in German, “Vinken & Bruyn” was eventually published entirely in English, indicating the general changes in the scientific language of neurology after World War II. Distinctions include the uniformity of the series, manner of editorial involvement, thematic comprehensiveness, inclusion of volume editors in “Vinken & Bruyn,” and the provision of index volumes. The increasing use of authorities in various neurological subspecialties is an important factor by which these handbooks contrast with many compact neurological textbooks that were available at the time. For historiographical purposes, the three neurological handbooks considered here were important sources for the general study of the history of medicine and science and the history of neurology in particular. Moreover, they served as important catalyzers of the emergence of neurology as a new clinical specialty during the first decades of the twentieth century.

Ludwig Edinger (1855-1918).

Ludwig Edinger is one of the lesser known forebears of 20th century neurology [2, 4, 10]. His contributions, however, to neuroanatomy, comparative neurology, and integrative diagnosis are manifold [6]. Among his famous pupils count the neurohistologist Carl Weigert (1845–1904), the holistic neurologist Kurt Goldstein (1865–1965), and the brain anatomist Cornelius Ariëns Kappers (1877–1946). Edinger put forth and explored many influential concepts, including the comparative perspective of brain development. He also introduced the “wasting theory of nerve action”; inquired further into the structure-function relationship of the brain; and succeeded in identifying the Nucleus oculomotorius accessorius mesencephali. Edinger was born in Worms and studied medicine in Heidelberg, from 1872 to 1874 with the comparative anatomist Carl Gegenbaur (1826–1903), and in Strasburg between 1874 and 1877. During his medical studies, he was taught by the pathologist Friedrich von Recklinghausen (1833–1910) who greatly influenced him, as did Adolf Kussmaul (1822–1902) in whose clinic he worked as a resident for three years. Edinger’s M.D. thesis “On the histology of the mucosa of fish and some remarks on the phylogenesis of the glands of the small intestine” (in German) was supervised by the anatomist Wilhelm Waldeyer (1836–1921) at the Strasburg Municipal Hospital. Edinger then served as an intern with Franz Riegel (1843–1904) in Giessen where he received his Habilitation (1881). He subsequently began a European pilgrimage which brought him to Sir William Gowers (1845–1915) in London, to the psychiatrist Carl Westphal (1833–1890) in Berlin, and to Leipzig where he worked with Paul Flechsig (1847–1929) and Wilhelm Erb (1840–1921). In 1883, Edinger also spent time in Paris with JeanMartin Charcot (1825–1893) before returning to Germany. One might wonder if medical historians would be as interested in Edinger’s biography if certain major upheavals had not brought him into the cultural atmosphere of Frankfurt am Main. As Edinger was of Jewish origin, his plans to lecture as a Privatdozent in Giessen were interrupted when the head of the university barred him from exercising his Venia legendi. Consequently, in 1883 Edinger established himself as the first Nervenarzt in Frankfurt. Fortunately, the Senckenberg Foundation gave him full status as a scientific member which allowed him to pursue his academic career. In the end, his work in the “medical republic of Frankfurt” [7] was very fruitful [5], the more since, in 1885, Carl Weigert was recruited as the new director of the Department of Anatomy, allowing the two neuroF. W. Stahnisch, M.D., M.Sc. ( ) Dept. of Social Studies of Medicine McGill University 3647 Peel Street H3A 1X1 Montreal, PQ, Canada Tel.: +1-514/398-4455; ext: 2058 Fax: +1-514/398-1498 E-Mail: frank.stahnisch@mail.mcgill.ca Portrait of Ludwig Edinger by Lovis Corinth (1909). Original measurements: 145 cm (height) x 110 cm (width). Source: Historisches Museum, Frankfurt am Main, Germany [8]

Alexander von Humboldt: Galvanism, Animal Electricity, and Self-Experimentation Part 2: The Electric Eel, Animal Electricity, and Later Years

After extensive experimentation during the 1790s, Alexander von Humboldt remained skeptical about “animal electricity” (and metallic electricity), writing instead about an ill-defined galvanic force. With his worldview and wishing to learn more, he studied electric eels in South America just as the new century began, again using his body as a scientific instrument in many of his experiments. As had been the case in the past and for many of the same reasons, some of his findings with the electric eel (and soon after, Italian torpedoes) seemed to argue against biological electricity. But he no longer used galvanic terminology when describing his electric fish experiments. The fact that he now wrote about animal electricity rather than a different “galvanic” force owed much to Alessandro Volta, who had come forth with his “pile” (battery) for multipling the physical and perceptable effects of otherwise weak electricity in 1800, while Humboldt was deep in South America. Humboldt probably read about and saw voltaic batteries in the United States in 1804, but the time he spent with Volta in 1805 was probably more significant in his conversion from a galvanic to an electrical framework for understanding nerve and muscle physiology. Although he did not continue his animal electricity research program after this time, Humboldt retained his worldview of a unified nature and continued to believe in intrinsic animal electricity. He also served as a patron to some of the most important figures in the new field of electrophysiology (e.g., Hermann Helmholtz and Emil du Bois-Reymond), helping to take the research that he had participated in to the next level.

Three 20th-century multiauthored handbooks serving as vital catalyzers of an emerging specialization: a case study from the history of neurology and psychiatry.

Abstract Originating in the late 19th century, psychiatry and neurology emerged during a period of several decades as two distinct fields of medical inquiry, separate from the study and practice of internal medicine. Around 1900, the German-speaking countries in Europe played an important role in this development. In this article, the publication of three influential multivolume and multiauthor handbooks are studied. All available volumes of Max Lewandowsky’s Handbuch der Neurologie (1910–1914) and the Handbuch der Neurologie (1935–1937) of Oswald Bumke and Otfrid Foerster are analyzed. The handbooks are compared with Pierre Vinken and George Bruyn’s Handbook of Clinical Neurology (1968–2002). This article is particularly timely in that it helps to reveal some of the origins of the disciplinary split—even at a moment when “brain psychiatry” (Wilhelm Griesinger), “neuropsychiatry” (Kurt Goldstein), and the German notion of Nervenheilkunde all acknowledged the interdisciplinary nature of both psychiatry and neurology. Particular emphasis is placed on the preeminent role that Jewish clinical neurologists assumed in the editing of the respective handbooks, leading to the extraordinary breadth and wealth of these publications. A great number of doyens in the fields of neurology and psychiatry—among them numerous Nobel Prize laureates—were involved in the dissemination of contemporary knowledge, including diagnostic and therapeutic procedures, which testifies to the fundamental status that these handbooks held for training purposes for both undergraduate and postgraduate students. Finally, the volumes analyzed in this article (between 1911 and 2002) are representative of a shift in the dominant scientific language, from German to English, since the 1930s and the 1940s, as well as the change in geographical distribution of the leading scientific authors, from Central Europe (Germany, Austria, Holland, France, Italy, and Scandinavia) to North America (the United States).

François Magendie (1783–1855)

François Magendie is often referred to as the ‘father of experimental physiology’ [2]. He introduced animal experimentation to scientific medicine and conducted pioneering neurophysiological work in several fields. These included the cerebrospinal fluid system (‘foramen of Magendie’), enhanced understanding of facial nerve functions, and the differentiation of the sensory and motor properties of the spinal nerves (‘Bell-Magendie law’) [5]. Over and above, Magendie was an ‘all-rounder,’ who investigated many body systems, including the heart, blood vessels and liver, and who conducted research over breathtakingly long periods. For example, his work on absorption in the intestines, lymphatic and venous system stretched more than 40 years (1809–1850) [8]. Magendie was educated not only in medicine, graduating with a M.D. from Paris University (1808), but he also received training as a resident (interne) at the Hôtel Dieu, becoming an adjunct clinician (docteur agrégé) to the Parisian hospitals [7]. Unlike many nineteenth century physiologists— including his pupil Claude Bernard (1813–1878) or Johannes Mueller (1801–1858) in Germany—Magendie’s hospital work enabled him to develop many scientific hypotheses from clinical observations. In addition, he learned to test laboratory results in patients, use physiological protocols to improve clinical practice, and facilitate the emergence of his discipline [10]. Magendie (Fig. 1) was born to a surgeon, Antoine Magendie, and his wife, Marie Nicole de Perey, in Bordeaux. His father was a supporter of the French Revolution, immersing young François in the philosophical ideas of Jean Jacques Rousseau (1712–1778). In 1792, Antoine Magendie moved his family to Paris to assume a role in the revolutionary administration [9]. From 1789 to 1796 the revolutionary government dissolved French medical schools, which were considered ‘royalist strongholds’; the Paris University had by the time of Magendie’s inscription not fully recovered from these changes. Consequently, after graduating from the lycée, Magendie began to study medicine in peripheral collèges and as an apprentice to senior physicians. Following Maximilien de Robespierre’s (1758–1794) death, the idéologues Étienne Bonnet de Condillac (1715– 1780), Destutt de Tracy (1754–1836), and the physicianphilosopher Pierre Cabanis (1757–1808) became the most influential intellectuals in French academia, philosophy,

Chapter 11: on the use of animal experimentation in the history of neurology.

Publisher Summary This chapter gives an overview of the use of wild and laboratory animals in the history of neurology. This overview covers several landmark experiments, and, in doing so, it pays particular attention to the transfer of knowledge derived from animal experimentation to human physiology and clinical phenomena in neurology. Additionally, various social backgrounds of the Western research endeavor in biomedicine, such as the influence of conflicting religious and cultural beliefs held by neuroscientists or the public, will be touched upon to illustrate the complex efforts of different historical contexts. In Greek medical culture, the unifying concepts of form and function in living animals merged with broader ideas on the nerves as the seat of bodily formae, that is, the coordinated functioning and essential integration of the physical body through the dynamic structure of the soul. Animals that displayed certain anatomical resemblances to humans were likewise seen to possess the same formae and suffer from diseases similar to those found in man.

The language of visual representations in the neurosciences — relating past and future

In theoretical accounts of the neurosciences, investigative research programs have often been separated into the morphological and physiological tradition. The morphological tradition is seen as describing the structure and form of the external and interior parts of the brain and spinal cord. The physiological tradition is interpreted as a compilation of those approaches which investigate cerebral functions particularly in their dynamic interactions. It must be regarded as an open question, though, whether the distinction between the morphological and physiological tradition in modern clinical and basic neuroscience has now become obsolete with the most recent neuroimaging techniques, such as fMRI, PET scans, SPECT, etc. Taken at face value, these new imaging techniques seem to relate, overlap, and even identify the anatomical with the functional substrate, when mapping individual patterns of neural activity across the visually delineated morphological structures. The particular focus of this review article is primarily on the morphological tradition, beginning with German neuroanatomist Samuel Thomas Soemmerring and leading to recent approaches in the neurohistological work of neuroscience centres in the United States and morphophysiological neuroimaging techniques in Canada. Following some landmark research steps in neuroanatomy detailed in the first section, this article analyzes the changing trajectories to an integrative theory of the brain in its second section. An examination of the relationship between form and function within the material culture of neuroscience in the third and final part, will further reveal an astonishingly heterogeneous investigative and conceptual terrain.