Claude Bernard: Curare, Carbon Monoxide and the Milieu Intérieur

Table of Contents

1. Deep-Dive Articles
2. 1. Who Claude Bernard Was
3. 2. Curare: The Discovery on One Page
4. 3. Carbon Monoxide and the Scarlet Blood
5. 4. The Natural Source: Curare Vines of South America
6. 5. Timeline at a Glance
7. 6. Later Significance: Inner Environment, Method and the Operating Room
8. Key Research Papers
9. Connections

Deep-Dive Articles

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1. Who Claude Bernard Was

Claude Bernard was born on 12 July 1813 at Saint-Julien, a vine-growing village near Villefranche in the Rhône region of France. After a local schooling with the Jesuits and college at Lyon, he went to Paris at about twenty hoping to become a dramatist, and was steered instead into medicine. He studied in Paris from 1834 to 1843, attended the physiology lectures of François Magendie at the Collège de France, and in 1841 became Magendie’s laboratory assistant. His medical thesis of 1843 was on gastric juice.

The discoveries came quickly. In 1848 he showed that pancreatic juice digests fat, and with the chemist Barreswil reported that the liver contains sugar; in 1857 he isolated glycogen, the “animal starch” the liver stores and releases. He found that cutting a sympathetic nerve in the neck made one side of the face flush and warm, opening up the study of the nerves that widen and narrow blood vessels. He became Magendie’s deputy at the Collège de France in 1847 and succeeded him as professor in 1855, later holding chairs at the Sorbonne and the Muséum national d’Histoire naturelle. He was elected to the Académie française in 1868 and received the Royal Society’s Copley Medal in 1876. He died in Paris on 10 February 1878 and was the first French scientist to be given a state funeral.

His experiments were performed on living animals, as was the practice of his day; his wife, Fanny Martin, whom he married in 1845 and from whom he separated in 1869, opposed vivisection, as did their daughters. The full story is in Claude Bernard: Life and Career.

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2. Curare: The Discovery on One Page

In his 1865 book Bernard wrote that “In 1845, Monsieur Pelouze gave me a toxic substance, called curare, which had been brought to him from America. We then knew nothing about the physiological action of this substance.” Other accounts date his first experiments to 1844 or 1846, so the safest statement is that the work began in the mid-1840s. What was known came from travellers such as Alexander von Humboldt: the poison was complicated to make and, introduced under the skin, it killed an animal very quickly.

His method was what he called a physiological autopsy. In his own words: “First, I put curare under the skin of a frog: it died after a few minutes; I opened it at once, and in this physiological autopsy I studied in succession what had become of the known physiological properties of its various tissues.” He found that “the heart maintained its movements”, the muscles “kept their normal contractility”, but “when the motor nerves were stimulated directly, they no longer caused any contraction in the muscles.” The same result followed in mammals and birds. In limb experiments, a curarised muscle stopped answering its nerve yet still contracted when stimulated itself.

Bernard’s own conclusion was that “curare causes death by destroying all the motor nerves, without affecting the sensory nerves”. A 2006 review in the British Journal of Pharmacology sums up his place: the curares’ “site of action in producing neuromuscular block was determined by Claude Bernard in the mid-19th century”. His interpretation was later refined. The physiologist Alfred Vulpian proposed the motor end-plate — the specialised patch where nerve meets muscle — as the exact site, and historians describe some thirty years of debate at the Société de Biologie before Bernard was won over. The chemical explanation, acetylcholine, came only in the twentieth century. Details are in Curare and Carbon Monoxide: Claude Bernard’s Poison Experiments.

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3. Carbon Monoxide and the Scarlet Blood

“About 1846, I wished to make experiments on the cause of poisoning with carbon monoxide,” Bernard recalled. He poisoned a dog and found that “its blood was scarlet in all the vessels, in the veins as well as the arteries” — odd, because venous blood is normally dark. Rabbits, birds and frogs gave the same result. His first idea, that oxygen was somehow lingering in the venous blood, failed when he tried to release that oxygen with hydrogen. “My preconceived idea was therefore false,” he wrote, and he used the episode in his book as a lesson in how a failed hypothesis teaches.

Returning to the problem in his 1856 course at the Collège de France, he shook arterial blood with carbon monoxide over mercury and found the gas above it “remarkably enriched with oxygen”: there had been “an exchange, volume by volume, between the carbon monoxide and the oxygen of the blood”, and the carbon monoxide then “remained chemically combined in the blood and could no longer be displaced either by oxygen or by other gases.” Elsewhere in the same book he describes the gas as deadly “when uniting more firmly than oxygen with the hemoglobin”. In 1928 Otto Warburg credited him with the discovery of what is now called carboxyhaemoglobin. In 1895 the British physiologist John Scott Haldane published a study of the action of the gas on man, and in 1912 Douglas, Haldane and Haldane worked out the laws by which haemoglobin combines with carbon monoxide and oxygen.

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4. The Natural Source: Curare Vines of South America

Curare is not one substance but a family of arrow and dart poisons made by many peoples of the Amazon basin and the Guianas from the bark and stems of forest vines. Two plant families supply them: the moonseed family (Menispermaceae), above all the liana Chondrodendron, and the Loganiaceae, the family of Strychnos. European writers described poisoned arrows from the early sixteenth century, and Walter Raleigh mentioned them in his account of Guiana in 1596.

As a 2005 history in the Journal of the Royal College of Physicians of Edinburgh puts it, “Like quinine, at first came the extract but no plant, and later the plant but no chemical compound.” In the early nineteenth century Benjamin Brodie found that small curarised animals survived if their lungs were inflated with bellows, and Charles Waterton kept a curarised donkey alive by artificial breathing — proof that the poison kills by stopping the breathing muscles. In 1935 the chemist Harold King isolated the active alkaloid tubocurarine from a museum sample, and in 1936 Henry Dale, Wilhelm Feldberg and Marthe Vogt showed that motor nerve endings release acetylcholine, the messenger curare blocks. Tubocurarine sits on the muscle’s acetylcholine receptors without switching them on, so the nerve’s signal no longer reaches the muscle. In 1938 an expedition led by Richard Gill brought back more than 11 kg of curare, and Chondrodendron tomentosum was identified as a plant source — though Gill himself disputed that curare comes from that one plant alone. The full story is in Curare: The Arrow Poison, Its Plants and Its Science.

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5. Timeline at a Glance

• 1813 — Born 12 July at Saint-Julien, near Villefranche, Rhône.
• 1834–1843 — Medical studies in Paris.
• 1841 — Becomes François Magendie’s laboratory assistant at the Collège de France.
• 1843 — Medical thesis on gastric juice.
• Mid-1840s — First curare experiments (1845 in his own later account).
• About 1846 — First carbon monoxide experiments: scarlet blood in the veins.
• 1847 — Magendie’s deputy at the Collège de France.
• 1848 — Fat digestion by pancreatic juice; sugar in the liver.
• 1855 — Succeeds Magendie as professor at the Collège de France.
• 1856 — Note to the Académie des sciences analysing muscle and nerve with curare; carbon monoxide shown to displace oxygen from the blood.
• 1857 — Isolates glycogen; publishes his lectures on toxic and medicinal substances.
• 1864 — Popular essay “Du curare”; a whole Collège de France course devoted to curare (1864–65).
• 1865 — Introduction à l’étude de la médecine expérimentale.
• 1868 — Elected to the Académie française.
• 1876 — Copley Medal of the Royal Society.
• 1878 — Dies in Paris on 10 February; state funeral.
• 1929 — Walter Cannon builds on the milieu intérieur in “Organization for physiological homeostasis”.
• 1935–1936 — King isolates tubocurarine; Dale, Feldberg and Vogt show acetylcholine release at motor nerve endings.
• 1942 — 23 January, Montreal: Harold Griffith and Enid Johnson give curare during surgery.
• 1947 — Daniel Bovet’s gallamine, the first synthetic neuromuscular blocker used clinically.

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6. Later Significance: Inner Environment, Method and the Operating Room

Bernard’s most famous idea grew out of all this work. Living things, he argued, survive in a changing world because they keep their own inner surroundings — the blood and fluids that bathe the cells — remarkably steady; in his words, the constancy of the internal environment is the condition of free and independent life. The word for this, homeostasis, was coined later by the American physiologist Walter Cannon, whose 1929 review built directly on Bernard. The physiologist Denis Noble has called Bernard “the first systems biologist” because the idea implies control processes working together across the whole organism.

His 1865 Introduction to the Study of Experimental Medicine argued for a medicine resting on experiment rather than on authority or ready-made systems. Historians note that he insisted researchers explain why their results varied instead of hiding the variation in averages, and that he favoured comparing treated with untreated patients. He also held a unified view of how anaesthetics act, which one historian of anaesthesia places a quarter-century ahead of the better-known Meyer–Overton theory.

Curare itself went from arrow poison to operating-room drug. On 23 January 1942 in Montreal, the anaesthetist Harold Griffith and his resident Enid Johnson gave curare to a young man having his appendix removed, and published the result that year; muscle relaxants became established in surgery after 1943. In 1947 Daniel Bovet synthesised gallamine, the first synthetic blocker used in patients, and he received the Nobel Prize in 1957. Carbon monoxide, meanwhile, remains a major cause of poisoning; it is the subject of a 2009 clinical review in the New England Journal of Medicine. The full account is in Claude Bernard’s Legacy.

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Key Research Papers

1. Black J. Claude bernard on the action of curare. BMJ. 1999;319(7210):622. PubMed PMID: 10473481
2. Breathnach CS. Claude Bernard and his revelations in physiology. Ir J Med Sci. 2014;183(1):139-46. PubMed PMID: 24297053
3. Jensen J, Puissant C. Claude Bernard’s route to the isolation of glycogen: the journey that changed scientific views on the physiological role of the liver and animal metabolism. Eur J Appl Physiol. 2026;126(2):629-647. PubMed PMID: 41417056
4. Bowman WC. Neuromuscular block. Br J Pharmacol. 2006;147 Suppl 1(Suppl 1):S277-86. PubMed PMID: 16402115
5. Cousin MT. Vulpian and not Claude Bernard first proposed the hypothesis of the motor end-plate as the site of action of curare. Anesthesiology. 2002;97(2):527-8. PubMed PMID: 12151956
6. Sternbach GL, Varon J. The Resuscitation greats. Claude Bernard: on the origin of carbon monoxide poisoning. Resuscitation. 2003;58(2):127-30. PubMed PMID: 12909373
7. Douglas CG, Haldane JS, Haldane JB. The laws of combination of haemoglobin with carbon monoxide and oxygen. J Physiol. 1912;44(4):275-304. PubMed PMID: 16993128
8. Lee MR. Curare: the South American arrow poison. J R Coll Physicians Edinb. 2005;35(1):83-92. PubMed PMID: 15825249
9. Raghavendra T. Neuromuscular blocking drugs: discovery and development. J R Soc Med. 2002;95(7):363-7. PubMed PMID: 12091515
10. King H. Curare alkaloids. Part I. Tubocurarine. J Chem Soc. 1935:1381. DOI: 10.1039/jr9350001381
11. Dale HH, Feldberg W, Vogt M. Release of acetylcholine at voluntary motor nerve endings. J Physiol. 1936;86(4):353-80. PubMed PMID: 16994763
12. Elsherbini N, Backman SB. The connection between Dr. Harold Griffith and Richard Gill: new insights into the history of curare use in anesthesia from previously unknown correspondence. Can J Anaesth. 2024;71(12):1664-1671. PubMed PMID: 38653929
13. Griffith HR, Johnson GE. The use of curare in general anesthesia. Anesthesiology. 1942;3(4):418-420. DOI: 10.1097/00000542-194207000-00006
14. Cannon WB. Organization for physiological homeostasis. Physiol Rev. 1929;9(3):399-431. DOI: 10.1152/physrev.1929.9.3.399
15. Noble D. Claude Bernard, the first systems biologist, and the future of physiology. Exp Physiol. 2008;93(1):16-26. PubMed PMID: 17951329
16. Morabia A. Claude Bernard, statistics and comparative trials. J R Soc Med. 2018;111(9):335-336. PubMed PMID: 30226095
17. Perouansky M. The quest for a unified model of anesthetic action: a century in Claude Bernard’s shadow. Anesthesiology. 2012;117(3):465-74. PubMed PMID: 22801051
18. Weaver LK. Clinical practice. Carbon monoxide poisoning. N Engl J Med. 2009;360(12):1217-25. PubMed PMID: 19297574

PubMed Topic Searches

1. PubMed: Claude Bernard history
2. PubMed: curare history
3. PubMed: milieu intérieur homeostasis
4. PubMed: carbon monoxide carboxyhemoglobin history

Further Reading

• Bernard C. An Introduction to the Study of Experimental Medicine, translated by H. C. Greene (1927; Dover reprint 1957). Internet Archive
• Bernard C. Leçons sur les effets des substances toxiques et médicamenteuses. Paris: Baillière, 1857.
• Bernard C. “Du curare.” Revue des Deux Mondes, 1 September 1864.

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Connections

• Pharmacology
• Claude Bernard: Life and Career
• Curare and Carbon Monoxide: Claude Bernard’s Poison Experiments
• Curare: The Arrow Poison, Its Plants and Its Science
• Claude Bernard’s Legacy: Milieu Intérieur, Experimental Medicine and Curare in Anaesthesia
• Daniel Bovet: Antihistamines, Curare, and Blocking the Body’s Own Signals
• Otto Loewi & Henry Dale: Acetylcholine and the Chemistry of Nerve Signals
• Paracelsus: The Dose Makes the Poison and the Birth of Chemical Medicine
• The Neuromuscular Junction: How a Nerve Commands a Muscle
• Carbon Monoxide
• Carbon Monoxide Poisoning
• Hemoglobin & the Oxygen Dissociation Curve

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