To the Editor:—

Within the anesthesia community, it is commonly believed that Professor Claude Bernard, M.D. (1813–1878), was the first to postulate the motor end-plate as the point of action of curare.

It is certain that he demonstrated experimentally first on a whole curarized frog, that muscle retained its activity when directly stimulated, and second, in the frog model of Galvani in which one leg was protected from the curare by a vascular ligature, that sensory nerves were not affected by curare. However, his position regarding the effect of curare on motor nerve is not so clear. After these experiments he concluded that the motor nerve itself was paralyzed. 1However, in an experiment with a nerve-muscle preparation where the nerve and then the muscle were successively bathed in a curare solution, he noted that the nerve could be immersed in the curare without loosing its function. 2He proposed to the Academy of Sciences that the nerve was affected right next to the muscle during its final ramuscules  (ramifications). 3He was therefore very close to the correct interpretation, and indeed, the term motor end-plate would later appear in his writing. 4Nevertheless at the same time, he continued to defend the idea that nerve was destroyed by curare. 5In addition, he later arrived at an another strange conclusion. He based his view on one observation (whose validity was questioned by Professor Alfred Vulpian, M.D.) where, in a lightly curarized frog, electrical stimulation of the medullar roots leading to the motor nerves was without effect while stimulation of the nerve still produced a response. He concluded that curare uncoupled the nerve from the cord, i.e. , the reflex arc was interrupted at the level of the spinal cord and that this was the point of action of curare. Using his own term, curare somehow unhooks (décroche ) the nerve from the cord. These theories were set out in his “Leçons” of 1865 4and were again asserted in his last published text about curare where he talked of an unhooking and paralysis coming from the central and not peripheral nervous system. 6At the end of his life, he still planned new experiments. In his personal notebook, edited long after his death, there are 21 references to curare. For example, he wrote, “One could do a neat experiment with curare and strychnine, with the aim of showing that the motor nerve becomes separated from the cord.”7He illustrated his ideas with diagrams, one of which is shown in figure 1. Had he more time to live and to perform these experiments, perhaps Claude Bernard would have been aware of his error.

Fig. 1. Notes illustrating a research project (from reference 7, p. 182) 7:“Fonder mon expérience pour l'action du curare sur la mort du nerf (…); en touchant l'artère, il n'y a plus de mouvements réflexes. En excitant le nerf en A, il y a contraction, donc conclure: le nerf est décroché. Quand les … (?) reflexes cessent, le nerf est décroché.”“Basing my experiment about the action of curare on nerve death (…); When touching the artery (i.e. stimulation of the reflex arc ) there is no longer any reflex movement. When stimulating the nerve at point A there is a contraction. Therefore conclusion: the nerve is unhooked. When the …(?) reflexes cease, the nerve is unhooked.”

Fig. 1. Notes illustrating a research project (from reference 7, p. 182) 7:“Fonder mon expérience pour l'action du curare sur la mort du nerf (…); en touchant l'artère, il n'y a plus de mouvements réflexes. En excitant le nerf en A, il y a contraction, donc conclure: le nerf est décroché. Quand les … (?) reflexes cessent, le nerf est décroché.”“Basing my experiment about the action of curare on nerve death (…); When touching the artery (i.e. stimulation of the reflex arc ) there is no longer any reflex movement. When stimulating the nerve at point A there is a contraction. Therefore conclusion: the nerve is unhooked. When the …(?) reflexes cease, the nerve is unhooked.”

It was Alfred Vulpian (1826–1887) who refuted Claude Bernard's hypothesis. Drawing on the publications of contemporary physiologists (especially Wilhelm Kühne, a Berliner physiologist, and Dr. Charles Rouget, Professor of Physiology at Montpellier Faculty) and his own research and reasoning, it is evident from his notes that he had concluded the action of curare to be on the motor end-plate, a concept that was clearly stated in 1875. 8The fact that Vulpian's work is not widely known outside of France may have led to a mistaken view of the role of Claude Bernard in correctly identifying the true nature of the neuromuscular junction.

The author thanks David J. Baker, M.Phil., D.M., F.R.C.A, (attaché-Consultant, Hôpital Necker Enfants- Malades, Paris, France) for his informed translation.

References

1.
Bernard C, Pelouze IJ: Curare: Recherches sur la composition et les effets de ce même poison végétal. CR Acad Sci, 1850; 30: 533–7
2.
Bernard C: Leçons sur les effets des substances toxiques et médicamenteuses. Paris, Baillière, 1857, p 309
3.
Bernard C: Analyse physiologique des propriétés des systèmes musculaires et nerveux au moyen du curare. CR Acad Sci, 1856; 43: 825–9
4.
Bernard C: Cours de médecine expérimentale, Revue des Cours Scientifiques. Paris, 1864–1865, 3: 242–6
5.
Bernard C: Leçons sur la physiologie et la pathologie du système nerveux. Paris, Baillière, 1858, p. 199
6.
Bernard C: De la physiologie générale. Paris Hachette, 1872; 230–7
7.
Bernard C: Pensées: Notes détachées. Paris, Baillière 1937; 193
8.
Vulpian A: Leçons sur l'action physiologique des substances médicamenteuses et toxiques. Paris, Doin, 1882, pp. IV, 220, 240, 255, 268