Is Ziegler one of the forgotten founders of experimental neuromuscular physiology?

The problem of how muscles contract (how living tissue transforms stimulus into movement) has shaped the long dialogue between anatomy, physiology and physics. From Galen's (129–216) spiritus animales to Borelli's (1608–1679) geometric levers (Borelli, 1680), explanations alternated between metaphysical and mechanical extremes. By the mid-18th century, when Johan Jacobus Ziegler (1733–1768), Swiss physician, defended his medical thesis in Basel, a new epistemological stance was emerging (Ziegler, 1752). Ziegler belonged to the generation trained under the influence of Albrecht von Haller (1708–1777), Swiss physiologist and botanist, whose experimental demonstration of muscular ‘irritability’ separated sensory from motor functions (Haller, 1747, 1760). At the same time, the Borellian legacy of iatromechanism, a medical sect that sought to explain major organic functions and diseases through pure physical laws, still dominated physiology. Ziegler's thesis, Specimen Inaugurale Medicum de Mechanismo Contractionis Musculorum (Ziegler, 1752) sits precisely at this crossroad; neither purely mechanical nor mystical, but an attempt to construct an empirical anatomy of movement. Although forgotten for two centuries, Ziegler's thesis deserves attention because it contains the seeds of what would become neuromuscular physiology, i.e. a model in which muscle fibre, nerve impulse and circulatory energy interact as parts of one functional system. Jakob Ziegler (1733–1768) was a Swiss physician of the mid-18th century, born in Winterthur, into an artisan family. He was the eldest son of the tanner David Ziegler (1690–1764) and the brother of Johann Heinrich Ziegler zum Steinberg (1738–1818). He belonged to a generation of practitioners trained at major European universities during a period of significant transition in medicine. He pursued his medical studies in Strasbourg, Basel and Tübingen, following an itinerant educational path characteristic of medical training at the time. He defended his medical dissertation in 1752, at a moment when experimental physiology, particularly that associated with Albrecht von Haller, was expanding. Upon returning to Winterthur, Jakob Ziegler opened a medical practice in the house zum Tiger (Steinberggasse 33), where he worked as a general practitioner. No scientific publications or original theoretical contributions are attributed to him, and his professional activity appears to have been thereafter confined to local medical practice. He died prematurely in 1768, at the age of 35 years, bringing to an end a career that did not have time to leave a lasting mark on scholarly medical production. Ziegler's text, divided into 34 numbered paragraphs, follows the academic format of mid-18th-century disputations: short propositions meant for public defence. Its method is anatomico-mechanica: anatomical observation combined with rational deduction. The young physician describes the muscle as composed of: (i) longitudinal fibres, responsible for shortening; (ii) transverse fibres, ensuring cohesion and thickness; (iii) membranous sheaths binding fascicles; (iv) blood vessels nourishing the tissue; and (v) nerves entering the muscle to trigger movement. His empirical observations (ligating arteries, cutting nerves and stimulating muscle mechanically or chemically) reflect a clear experimental mind. Ziegler notes that when the nerve is severed, voluntary movement disappears; when blood flow is stopped, the muscle loses ‘vital heat’, yet the isolated fibre may still respond briefly to touch or incision, suggesting an intrinsic force, which Haller had termed vis irritabilis (Haller, 1778). These demonstrations, as basic as they were, constitute an early experimental analysis of the muscle–nerve–blood triad. Ziegler's insistence on combining anatomical structure with physiological response follows the emergence of experimental physiology distinct from both pure mechanics and speculative vitalism. In Ziegler's model, muscle contraction is not a simple linear shortening but a dual transformation, with simultaneous shortening and thickening. This morphological intuition, seemingly trivial today, contradicted the dominant Borellian image of muscle as a contracting rope. By distinguishing longitudinal and transverse elements, Ziegler implicitly proposed a multi-axial fibre architecture, anticipating what 19th century histologists would later reveal as sarcomeric periodicity. At Ziegler's time, actin–myosin interactions were unknown, and he tried to imagine a broken line pattern that would allow muscle fibres to be shortened (Fig. 1, right, his figs 1 and 2) or reduced in diameter (Fig. 1, right, his fig. 4). These hypothetical segments could be considered as pioneer reasoning in muscle fibre-contraction mechanisms, even if not confirmed later. He discussed several hypotheses: the fluid theory (contraction results from a nervous or vascular influx) fails, he wrote, to explain the speed of motion; the mechanical theory (fibres coil like springs) could explain shape change but not vitality; and the vital theory (muscle has its own intrinsic irritability) best matched experiments, but required nerve and blood for initiation and maintenance. In his thesis, Ziegler therefore proposed a hybrid mechanism, whereby contraction originates in the fibres, is triggered by the nerve and is sustained by the blood. In modern terms, one could call this a qualitative sketch of excitation–contraction coupling and metabolic support. He also reported contractions persisting after death, induced by physical stimuli, a direct observation of what would later be known as post-mortem contractility or rigor phenomena. With no knowledge about calcium or ATP, he got the idea that contractile capacity survives neural control for a short period; a clue to the independence of muscle tissue. The connexions between Ziegler (1752) and 20th century molecular physiology are theoretical but potentially strong when viewed retrospectively. In 1859, Willy Kühne isolated myosin as the primary contractile protein (Kühne, 1859). Wilhelm Krause identified the Z-discs delimiting the repeating contractile units, the sarcomeres (Krause, 1869). Theodor Engelmann observed that striations change during contraction, suggesting an internal rearrangement of fibres (Engelmann, 1873). W. M. Fletcher, F. G. Hopkins and Otto Meyerhof clarified the biochemical energy exchange between oxygen, lactic acid and contraction (Fletcher & Hopkins, 1907; Meyerhof, 1920). Finally, Huxley and Hanson visualized the sliding filament mechanism, uniting structure and function at the molecular level (Huxley & Hanson, 1954). A posteriori, Ziegler's ‘longitudinal and transverse fibres’ evoke actin and myosin filaments and their Z-line anchorage. His insistence on blood as the ‘vital maintainer’ echoes the later discovery of ATP as the energy currency of contraction. His notion of the nerve as the trigger parallels modern understanding of calcium release following membrane depolarization. Ziegler described in morphological language what modern physiology reports in molecular terms, i.e. a structurally organized system transforming energy into movement. Does Ziegler matter today? First, his thesis, in the mid-18th century, exemplifies how scientific intuition can precede experimental tools. Without microscopy, he suggested structural differentiation; without chemistry, he proposed energetic dependence; and without electrophysiology, he described nerve triggering. His reasoning shows that progress often begins with conceptual imagination. Second, the 1752 thesis bridges philosophical and physiological traditions. Ziegler stays in the middle, between Borelli's mechanistic rigour and Haller's experimental empiricism. He thus personifies the 18th century shift from descriptive anatomy to physiology as a laboratory experimental science. Third, revisiting Ziegler illuminates the continuity of neuromuscular research. The modern concepts of excitation–contraction coupling (Shishmarev, 2020), myofibril properties and energy metabolism were expressed in this early hybrid language of anatomy and mechanics. Finally, Ziegler's thesis reminds us that historiography is part of scientific understanding. Recognizing early conceptual frameworks encourages a deeper appreciation for how experimental physiology evolved. The boundary between 18th century observation and modern molecular analysis is not discontinuous but cumulative; a layering of perspectives across time. Jacobus Ziegler's Specimen Inaugurale Medicum de Mechanismo Contractionis Musculorum (1752) represents a transitional moment in the history of neuromuscular physiology. Situated between iatromechanist models and later experimental physiology (Bernard, 1865), his thesis articulated an integrated view of muscle contraction based on the interaction between muscle fibres, nerves and blood. Without access to microscopy, biochemistry or electrophysiology, Ziegler proposed that contraction is an intrinsic property of muscle fibres, initiated by neural input and sustained by circulatory support. His distinction between longitudinal and transverse fibres, his recognition of post-mortem contractility and his emphasis on nerve triggering anticipate, in qualitative terms, core principles of modern neuromuscular physiology. Although his work had little direct influence on subsequent investigators, largely owing to his early death and limited dissemination, Ziegler's thesis illustrates how conceptual insight can precede experimental verification. Reconsidering this neglected text highlights the cumulative nature of scientific knowledge and the deep historical roots of contemporary muscle and nerve physiology. Too bad that Ziegler died so young. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. The authors declare that they have no competing interests. E.D.: conception and first draft of the manuscript. Y.P.: revision of the manuscript and clinical commentaries. Both authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All persons designated as authors qualify for authorship, and all those who qualify for authorship are listed. None. The authors have nothing to report.