François Magendie — Nux Vomica, Pure Alkaloids and the Birth of Experimental Pharmacology

In April 1809 a twenty-five-year-old Paris doctor named François Magendie (1783–1855) stood before the Institut de France and reported that a Javanese arrow poison and two bitter seeds familiar to apothecaries — nux vomica and the Saint-Ignatius bean — all did the same thing to an animal: they threw it into convulsions by acting on the spinal cord. Different plants, from different countries, produced one effect in one place in the body. To Magendie that meant they shared a single chemical substance, and that the substance could be found. The historian of medicine Mirko Grmek wrote that these experiments mark the beginning of modern pharmacology.

Twelve years later Magendie published the Formulaire of 1821, the first handbook to carry the newly purified plant alkaloids — strychnine, morphine, emetine, quinine and others — into the doctor’s prescription, each first tested on animals in his own laboratory. This wing tells the story in four deep-dive articles: the man, the poison experiments and the Formulaire, the plants behind his medicines, and his legacy in physiology and in his pupil Claude Bernard. The overview below gives the whole story on one page. Many of the substances involved are deadly poisons; they appear here as history and pharmacology only, and no dose or preparation is given.

Table of Contents

  1. Deep-Dive Articles
  2. 1. Who François Magendie Was
  3. 2. The Discovery on One Page
  4. 3. The Natural Sources: Strychnos Seeds, Upas and Ipecac Root
  5. 4. The Formulaire of 1821
  6. 5. Timeline at a Glance
  7. 6. Later Significance: Claude Bernard and Experimental Medicine
  8. Key Research Papers
  9. Connections

Deep-Dive Articles

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François Magendie: Life and Career (1783–1855)

A Rousseau-inspired childhood in Bordeaux and Paris, surgical apprenticeship, the manifesto of 1809, the quarrel with the Faculty, his journal, the Collège de France chair, two famous public-health errors and Balzac’s “Docteur Maugredie”.

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The Formulaire of 1821: Magendie and the First Pure Medicines

The 1809 upas and nux vomica experiments, the poison that acts on the spinal cord, the prediction of strychnine, emetine with Pelletier, and the handbook that brought pure alkaloids into practice.

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Strychnos, Ipecac and the Plants Behind Magendie’s Medicines

Nux vomica, the Saint-Ignatius bean and the Javanese upas, how strychnine blocks the spinal cord’s glycine brake, ipecac root and emetine’s later career against amoebic dysentery, and the other Formulaire sources.

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Magendie’s Legacy: Claude Bernard, the Bell–Magendie Law and Experimental Medicine

The pupil who inherited his chair, the spinal nerve roots and the priority dispute with Charles Bell, cerebrospinal fluid, early diet experiments, anaphylaxis in 1839 and the vivisection controversy.

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1. Who François Magendie Was

François Magendie was born in Bordeaux on 6 October 1783, the son of the surgeon Antoine Magendie and Marie Nicole de Perey. According to Grmek’s article in the Dictionary of Scientific Biography, his father was an ardent republican and a follower of Jean-Jacques Rousseau, and the boy was raised so strictly on Rousseau’s principles that at ten he had not been to school and could neither read nor write. The family moved to Paris in 1791; there he asked to be sent to school, progressed quickly and won a prize in a national essay contest at fourteen.

At sixteen he was apprenticed to the Paris surgeon Alexis Boyer. In 1803 he passed the hospital internship examination, and on 24 March 1808 he took his medical doctorate. In 1809 he published a sharp critique of the admired physiologist Xavier Bichat — the paper the historian William Albury called “Magendie’s manifesto of 1809” — arguing that most physiological facts had to be checked again by new experiments. An anatomy demonstrator at the Paris Faculty of Medicine by 1811, he quarrelled with the professors François Chaussier and Guillaume Dupuytren and resigned in 1813, living instead from private practice and popular private courses in experimental physiology.

Recognition followed. His Précis élémentaire de physiologie (1816–1817) was a textbook built on experimental fact. In 1821 he founded the Journal de physiologie expérimentale, the first periodical given over entirely to physiology, and was elected to the Académie des sciences. He took charge of a ward at the Hôtel-Dieu in 1830 and, on 4 April 1831, the chair of medicine at the Collège de France, which he held until his death. Not every judgement went his way: Grmek records that he held cholera and yellow fever to be non-contagious and opposed ether anaesthesia in 1847. He died at his country house in Sannois on 7 October 1855. The full story is in François Magendie: Life and Career.

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2. The Discovery on One Page

At the start of the nineteenth century almost every medicine was a whole natural material — a root, a bark, a seed — whose strength varied from batch to batch, and nobody could say exactly where in the body a drug acted or how it got there. Magendie set out to answer those questions by experiment.

On 14 April 1809 he read to the First Class of the Institut de France a memoir, Examen de l’action de quelques végétaux sur la moelle épinière, based on work done with the botanist and physician Alire Raffeneau-Delile. They began with upas, a Javanese arrow poison; because it could not be bought in commerce, they looked for something with the same action and found it in nux vomica and the Saint-Ignatius bean. All three threw animals into convulsions. Cutting the spinal cord from the brain did not stop the convulsions; destroying the spinal cord abolished them. The action lay in the spinal cord. Looking back in the 1822 edition of his Formulaire, Magendie wrote that the work had shown “qu’une famille entière de végétaux (les strychnos amers) a la propriété singulière d’exciter fortement la moelle épinière” — that a whole family of plants, the bitter strychnos, strongly excites the spinal cord.

From this he drew the idea at the heart of modern pharmacology: that a plant drug acts because of a particular chemical substance inside it, which ought to be obtainable pure. He suspected such a substance in the strychnos seeds a decade before the Paris pharmacists Pierre-Joseph Pelletier and Joseph-Bienaimé Caventou isolated strychnine (found in 1818, published in 1819). In 1817 Magendie and Pelletier had already isolated emetine, the active principle of ipecacuanha root. He also showed that poisons are absorbed through the blood vessels, not only the lymphatics, and act where the blood carries them. The historian José Ramón Bertomeu-Sánchez has traced how this animal work on poisons fed into the forensic toxicology of the period. The full account is in The Formulaire of 1821: Magendie and the First Pure Medicines.

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3. The Natural Sources: Strychnos Seeds, Upas and Ipecac Root

Every medicine in the Formulaire began as a plant or a mineral. Nux vomica is the flat grey seed of Strychnos nux-vomica, a tree of India and Southeast Asia; the Saint-Ignatius bean is the seed of Strychnos ignatii, a climber of the Philippines. Raffeneau-Delile’s 1809 thesis named the Javanese poison they studied upas tieuté, a Strychnos preparation — not to be confused with upas antiar, the heart poison of the unrelated tree Antiaris toxicaria. From the strychnos seeds came strychnine and its weaker cousin brucine.

Magendie could only locate strychnine’s action. The explanation came in 1973, when Anne Young and Solomon Snyder showed that strychnine binds to glycine receptors in the spinal cord. Glycine is one of the cord’s main “brake” messengers; strychnine blocks the brake, so the slightest stimulus sets off uncontrolled muscle spasm — the convulsions Magendie and Delile recorded 164 years earlier. Strychnine went on to a long nineteenth-century career as a so-called tonic and stimulant, a history surveyed by John Haller; it is also an extremely toxic poison.

Ipecacuanha is a knotted root from the Brazilian forest, long used to cause vomiting. Its alkaloid emetine, isolated by Magendie and Pelletier in 1817, had a second career a century later: in 1912 Leonard Rogers reported treating amoebic dysentery and amoebic liver disease with injected emetine salts, and emetine became a standard treatment for infection with Entamoeba histolytica for decades, though its toxicity to the heart is well documented. The Formulaire’s other sources included the opium poppy (morphine and narcotine), cinchona bark (quinine and cinchonine — see Malaria: History and Discovery), white hellebore and sabadilla (veratrine), gentian root, prussic acid, and iodine from seaweed. The plants are covered in Strychnos, Ipecac and the Plants Behind Magendie’s Medicines.

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4. The Formulaire of 1821

In 1821 Magendie published Formulaire pour la préparation et l’emploi de plusieurs nouveaux médicamens — a handbook for preparing and using several new medicines. It was short, and it offered not new herbs but pure chemical substances recently drawn out of plants by the Paris chemists. The second edition of 1822, revised and enlarged, lists on its title page nux vomica, morphine, prussic acid, strychnine, veratrine, the cinchona alkaloids, emetine and iodine.

Its preface sets out the case. Magendie wrote that ten years of experiments in the laboratory and at the bedside had convinced him “que la manière d’agir des médicamens et des poisons est la même sur l’homme et sur les animaux” — that medicines and poisons act the same way in humans and in animals — and that because the chemistry of a pure substance is fixed, there need be no fear of variation in its strength. He reported that he had tried on himself substances he had first found harmless in animals; that is recorded here as history only.

The Formulaire went through nine issues between 1821 and 1836, adding bromine, potassium cyanide, salicin, codeine and more as chemists isolated them. Alain Ségal and François Trépardoux, historians of pharmacy, write that Magendie standardised animal tests of each substance’s activity and safety, in a way that anticipated the evaluation of new drugs for registration in the twentieth century.

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5. Timeline at a Glance

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6. Later Significance: Claude Bernard and Experimental Medicine

Magendie’s most famous legacy is a person. According to the Collège de France, Claude Bernard was the préparateur for Magendie’s course from 1841 to 1844, his substitute lecturer from 1847 to 1852, and his successor in the chair in 1855. Bernard carried on the arrow-poison work — his unpublished notes on curare, upas, strychnine and other arrow poisons were edited by Grmek in 1966 — and turned Magendie’s method into the founding text of experimental medicine. Paul Mazliak’s 2013 portrait calls Magendie the creator of pharmacology and the inspirer of Bernard’s research.

His name also survives in physiology. In 1822 he showed that the front roots of the spinal nerves carry movement and the back roots sensation — the Bell–Magendie law, whose two names record a documented priority dispute with the Scottish anatomist Charles Bell. The foramen of Magendie, the opening in the roof of the brain’s fourth ventricle through which cerebrospinal fluid flows, carries his name, and Tubbs and colleagues list his work on the fluid and the nerve roots among the foundations of neuroscience. His dogs fed only sugar and water declined and died, and the corneal ulcers he described in 1817 are now recognised as vitamin A deficiency, though he blamed a lack of nitrogen. Historians credit him with an early description, in 1839, of what Charles Richet later named anaphylaxis. His public demonstrations on living animals, including in England in 1824, provoked early antivivisection campaigns. These threads are followed in Magendie’s Legacy.

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Key Research Papers

  1. Ségal A, Trépardoux F. [The Formulaires of Magendie (1821-1840) of the chemical pharmacy to pharmacology]. Hist Sci Med. 2015;49(2):141-56. PubMed PMID: 26492670
  2. Mazliak P. [Medical recollections. François Magendie, creator of the pharmacology, inspirer of Claude Bernard's researches]. Rev Prat. 2013;63(7):1030-3. PubMed PMID: 24167908
  3. Bertomeu-Sánchez JR. Animal experiments, vital forces and courtrooms: Mateu Orfila, François Magendie and the study of poisons in nineteenth-century France. Ann Sci. 2012;69(1):1-26. PubMed PMID: 22530381
  4. Stahnisch FW. François Magendie (1783-1855). J Neurol. 2009;256(11):1950-2. PubMed PMID: 19693629
  5. Tubbs RS, Loukas M, Shoja MM, Shokouhi G, Oakes WJ. François Magendie (1783-1855) and his contributions to the foundations of neuroscience and neurosurgery. J Neurosurg. 2008;108(5):1038-42. PubMed PMID: 18447728
  6. Albury WR. Physiological explanation in Magendie's manifesto of 1809. Bull Hist Med. 1974;48(1):90-9. PubMed PMID: 4608397
  7. Young AB, Snyder SH. Strychnine binding associated with glycine receptors of the central nervous system. Proc Natl Acad Sci U S A. 1973;70(10):2832-6. PubMed PMID: 4200724
  8. Haller JS Jr. The history of strychnine in the nineteenth-century materia medica. Trans Stud Coll Physicians Phila. 1973;40(4):226-38. PubMed PMID: 4574625
  9. Rogers L. THE RAPID CURE OF AMOEBIC DYSENTERY AND HEPATITIS BY HYPODERMIC INJECTIONS OF SOLUBLE SALTS OF EMETINE. Br Med J. 1912;1(2686):1424-5. PubMed PMID: 20766221
  10. Lanska DJ. Chapter 29: historical aspects of the major neurological vitamin deficiency disorders: overview and fat-soluble vitamin A. Handb Clin Neurol. 2010;95:435-44. PubMed PMID: 19892132

PubMed Topic Searches

  1. PubMed: Magendie history
  2. PubMed: Magendie Formulaire
  3. PubMed: Bell–Magendie law
  4. PubMed: strychnine history
  5. PubMed: emetine ipecacuanha

Further Reading

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Connections

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