The Isolation of Morphine: Sertürner's Experiments, 1804–1817

Table of Contents

1. Opium Preparations of Unpredictable Strength
2. Looking for an Acid, Finding a Base
3. The Letter to Trommsdorff’s Journal, 1805
4. Years of Silence and Repeated Experiments
5. The 1817 Paper: Morphium and Meconic Acid
6. A Plant Alkali: Why Chemists Were Surprised
7. The Self-Experiment with Three Young Men
8. Gay-Lussac and the French Translation
9. Who Was First? Derosne, Seguin and the Dating Debate
10. Was Sertürner’s Morphine Pure?
11. Key Research Papers
12. Connections
13. Featured Videos

1. Opium Preparations of Unpredictable Strength

Opium is the air-dried latex — the milky sap — that seeps from cuts in the unripe seed capsule of the opium poppy, Papaver somniferum. By 1800 it had been used in medicine since antiquity, and every European pharmacy stocked it in several forms: the raw dried gum, powders, pills, extracts and alcoholic tinctures. Pharmacists made these preparations by hand, following the recipes in the official pharmacopoeias, and physicians prescribed them for pain, coughs, diarrhoea and sleeplessness.

The trouble was that nobody could say how strong any given batch would be. According to the German national biography (Neue Deutsche Biographie), Sertürner noticed as a young pharmacy apprentice that opium preparations made with great care, by the same method, still differed in their narcotic strength. The historian Klockgether-Radke puts the problem plainly: before the nineteenth century the individual compounds in opium were unknown, which made exact dosing almost impossible. Brook, Bennett and Desai, in their chemical history of morphine, make the same point — until the active substance was identified, the potency of an opium preparation could be neither predicted nor controlled.

The reason, as later chemistry would show, is that opium is a natural mixture. Its make-up depends on the plant, the soil, the weather, the harvest and the way the latex was dried and stored, and the active substances can make up a larger or smaller share of the gum from one lot to the next. A pharmacist weighing out a fixed amount of opium was therefore weighing out an unknown amount of whatever actually did the work. The story of how that “whatever” became a named, weighable substance is the story of this page. (What opium contains, and why it varies, is explained in more detail on The Opium Poppy and the Chemistry of Morphine.)

Sertürner’s question was simple to state and hard to answer: is there one particular substance inside opium that is responsible for its effect, and can it be separated out? If it could, a physician would no longer be prescribing an unpredictable plant product, but a single defined compound.

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2. Looking for an Acid, Finding a Base

Sertürner did not go looking for an alkaloid, because nobody yet knew that such a thing existed. The chemistry of plants at the turn of the nineteenth century was dominated by acids. The Swedish pharmacist-chemist Carl Wilhelm Scheele had, in the later eighteenth century, isolated a series of organic acids from plants and fruits, and his work showed that a plant’s character could depend on a particular acid it contained. According to the Neue Deutsche Biographie, Sertürner was influenced by Scheele’s plant-acid work and at first expected the active principle of opium to be an acid too — an “opium acid.”

He did find an acid in opium. But in the course of separating opium into its parts he also obtained something else: a crystalline substance with the opposite chemical character. Klockgether-Radke dates the isolation of this crystalline material to 1803/04. Where an acid turns certain plant dyes one colour and neutralises alkalis, this substance behaved like an alkali — it neutralised acids and combined with them to form salts, in the way that familiar mineral alkalis such as ammonia or potash do.

To understand why that mattered, it helps to recall the two great families of the chemistry of the time:

• Acids — sour substances such as vinegar or the acids Scheele had found in lemons, apples and sorrel; already well known in plants.
• Bases (alkalis) — substances such as lye, potash, lime and ammonia, which neutralise acids; until then regarded as belonging to the mineral world, not to living plants.

When an acid and a base meet, they neutralise each other and form a salt. Sertürner’s crystals behaved like the second family. That was the unexpected part of the discovery, and it took him, and the chemists who read him, more than a decade to accept fully what it meant.

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3. The Letter to Trommsdorff’s Journal, 1805

Sertürner’s first report appeared in 1805, not in a chemistry journal but in the leading German pharmacy journal of the day, the Journal der Pharmacie für Ärzte und Apotheker, edited by Johann Bartholomäus Trommsdorff. Jurna and Papini both describe it as a letter to the editor, printed in volume 13 of the journal (pages 229–243), in which Sertürner described a substance obtained from opium that had an alkaline character.

The sources do not agree on how clearly Sertürner understood what he had found at this stage. The Neue Deutsche Biographie describes the first 1805 article as concerning an “opium acid” (Opiumsäure) and records that this acid did not have sleep-inducing properties. In other words, the first report was framed around the acid he had been looking for, while the alkaline substance that would become morphine appeared within it.

A second, longer paper followed in the same journal, volume 14 (pages 47–93). Its title — Darstellung der reinen Mohnsäure (Opiumsäure) nebst einer chemischen Untersuchung des Opiums mit vorzüglicher Hinsicht auf einen darin neu entdeckten Stoff — translates roughly as “Preparation of pure poppy acid (opium acid), together with a chemical investigation of opium with particular regard to a newly discovered substance in it.” The Neue Deutsche Biographie dates this paper to 1805; Papini dates it to 1806. In it Sertürner described the alkaline, base-like properties of the newly discovered substance.

Goerig and Schulte am Esch note that the hypnotic (sleep-inducing) and pain-relieving properties of the substance were already known to Sertürner from animal tests before his later trial on people. The “poppy acid” of the title is the substance he would later rename meconic acid, from the Greek word for poppy.

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4. Years of Silence and Repeated Experiments

The 1805 reports made almost no impression. Goerig and Schulte am Esch write simply that Sertürner’s first report “remained unnoticed.” The historians do not give a single cause, but the circumstances recorded in the biographies help explain the silence:

• Who he was. In 1805 Sertürner was in his early twenties, a pharmacist’s assistant with no university post, who had passed his assistant’s examination only in 1803.
• Where it appeared. The reports were printed in a pharmacy journal, read mainly by apothecaries, rather than in the journals followed by the leading chemists of Paris, London and the German universities.
• How it was framed. As the Neue Deutsche Biographie describes it, the first article was presented around an “opium acid”; the alkaline substance was the surprise inside the report, not its headline.
• What chemists believed. Hosztafi, in his history of the discovery of alkaloids, describes the chemistry of the period as dogmatically denying that bases could be formed by plants at all — so a claim of a plant alkali ran against the expectations of its readers (see section 6).

Sertürner’s own life was also unsettled. In 1805 or 1806 (the sources differ) he moved from Paderborn to Einbeck to work as an assistant at the town council’s pharmacy, and from 1809 he ran a pharmacy of his own there, opened under the laws of the French-ruled Kingdom of Westphalia. These were the years of the Napoleonic wars, and his professional energy went into keeping a business alive. That story is told on the Life and Career page.

He did not abandon opium. According to the Neue Deutsche Biographie, Trommsdorff encouraged him to repeat his experiments on a larger scale, and Sertürner returned to the work over the following years, refining his separation of the substance and confirming its properties. Goerig and Schulte am Esch describe the 1817 publication as the product of this repeated work: it was there that he set out the findings again, more fully, and gave the substance its name.

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5. The 1817 Paper: Morphium and Meconic Acid

In 1817 Sertürner published the paper that made his reputation, this time in Ludwig Wilhelm Gilbert’s Annalen der Physik, a widely read scientific journal that carried chemistry as well as physics. Its title states the two central claims directly:

Ueber das Morphium, eine neue salzfähige Grundlage, und die Mekonsäure, als Hauptbestandtheile des Opiums — “On morphium, a new salt-forming base, and meconic acid, as main constituents of opium.”

The paper ran to more than thirty pages (volume 55, pages 56–89). Its two claims were these:

1. Morphium is a base. The crystalline substance was a salzfähige Grundlage — literally a “salt-capable foundation”, a base that combines with acids to form salts. This was the chemically revolutionary claim.
2. Opium’s main constituents are a base and an acid. In the raw drug, morphium occurs alongside meconic acid, the “poppy acid” of his earlier papers.

Jurna and Goerig both identify the 1817 paper as the place where Sertürner first used the name Morphium. The name comes from Morpheus, the Greek god of sleep and dreams — a choice that announced what the substance did. Klockgether-Radke describes the achievement as showing that this compound was the principium somniferum, the “sleep-making principle”, of opium: the long-sought single substance responsible for the drug’s best-known effect.

Later the same year Sertürner published a supplement in the same journal (volume 57, pages 183–202) under the title Ueber eins der fürchterlichsten Gifte der Pflanzenwelt — “On one of the most terrible poisons of the plant world” — described as an addition to his treatise on meconic acid and morphium, with remarks on the acidic extractive matter of opium and its compounds. The title alone shows that Sertürner understood the substance he had isolated to be not only a sleep-bringer but a powerful poison.

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6. A Plant Alkali: Why Chemists Were Surprised

Isolating a pure substance from a plant was not new in 1817; Scheele and others had already isolated plant acids, and sugars and other plant materials were known. What was new was the kind of substance. Hosztafi, reviewing the discovery of alkaloids, describes morphine as a plant alkali that forms salts with acids, and describes the chemistry of the period as having dogmatically denied that such bases could exist in plants. Alkalis belonged, in the thinking of the time, to the mineral world.

Sertürner’s substance broke that rule. It was made by a living plant, it contained nitrogen, and it behaved as a base — neutralising acids and forming crystalline salts. Once chemists accepted that one plant could make such a substance, they had a reason to look for others in every medicinal plant whose active principle was still unknown. This new class of plant bases came to be called alkaloids (“alkali-like”), and a run of them was isolated from medicinal plants in the decades that followed; that story is told on The Alkaloid Revolution and Morphine in Medicine.

The historians of medicine place Sertürner’s discovery at a turning point:

• Goerig and Schulte am Esch call him a co-founder of alkaloid chemistry, and see the discovery as part of pharmacy’s move from alchemy to science.
• Klockgether-Radke describes morphine as laying the foundation for the alkaloids, and as the first pure opioid available for pain treatment with a single defined compound.
• Hosztafi treats morphine as the first plant base recognised as such, the starting point of alkaloid chemistry.

The practical meaning was just as large as the theoretical one. A base forms salts, and salts can be crystallised, purified, weighed and dissolved in known amounts. For the first time a physician could, in principle, work with a defined quantity of the active substance of a medicinal plant rather than an unknown share of a variable natural gum. The same logic would later be applied to quinine from cinchona bark, to the active substances of other medicinal plants, and eventually to modern drug standardisation.

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7. The Self-Experiment with Three Young Men

Chemistry could show that the crystals were a base. It could not show that they were the part of opium that acted on the human body. Sertürner had already seen the effects in animals: Goerig and Schulte am Esch write that the hypnotic and pain-relieving properties were known to him from animal tests, and Klockgether-Radke states that he proved in animals and in humans that the compound was opium’s sleep principle.

The human test is the most dramatic episode in the story, and it is told here as history only. Papini, drawing on Sertürner’s own description, recounts that Sertürner took the dissolved substance himself, together with three young men. The trial nearly ended in disaster. According to Papini’s account, the participants suffered pain in the stomach region, exhaustion and a severe narcosis that brought them close to fainting, and Sertürner described these effects in detail.

Several things about this episode stand out to modern readers:

• It demonstrated potency. The severity of the reaction to a single purified substance was itself evidence that the crystals were the concentrated active principle of opium, far stronger by weight than the raw drug.
• It showed the danger. The experience is consistent with the title of his supplementary paper of the same year, which called the substance one of the most terrible poisons of the plant world.
• It belonged to its time. Self-experiment was a common way for pharmacists and physicians of the early nineteenth century to test new substances. There were no ethics committees, consent procedures or controlled clinical trials; the young participants’ involvement would be judged very differently by the research-ethics standards that developed in the twentieth century.

Popular accounts of the experiment often add further details, including specific amounts and the remedies used afterwards. This page reports no amounts or methods: morphine is covered here as history and pharmacology only, and some figures in circulation are not supported by the scholarly sources consulted.

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8. Gay-Lussac and the French Translation

This time the work was noticed. In the same year, 1817, Franz Anton Choulant published a paper in the Annalen der Physik (volume 56, pages 337–354) titled Bestätigung und Wichtigkeit der Entdeckung eines neuen Alkali (des Morphium), welches Herr Sertürner in dem Opium aufgefunden hat — “Confirmation and importance of the discovery of a new alkali (morphium), which Herr Sertürner has found in opium.” The title itself records two things: that another investigator had confirmed the finding, and that he regarded morphium as a new alkali of real importance.

The decisive step came from France. Jurna, Papini and Krishnamurti and Rao all relate that the French chemist Joseph Louis Gay-Lussac, one of the most influential chemists in Europe, took an interest in Sertürner’s work and arranged for a French translation. In their accounts, it was this translation that brought Sertürner’s scientific breakthrough: through it the discovery reached the Paris chemists, who were then the leading centre of the science. The French form of the name, morphine, is the one that passed into English and most other languages.

Recognition followed. The University of Jena awarded Sertürner a doctorate in 1817, and learned societies elected him to membership in the following years. In 1831 the Institut de France awarded him a Prix Montyon; Krishnamurti and Rao add that it came with the title “Benefactor of Humanity.” These honours are described more fully on the Life and Career page.

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9. Who Was First? Derosne, Seguin and the Dating Debate

As with many discoveries, the question of who was first has been argued over ever since. Two strands run through the debate.

Rival claims from France

Sertürner was not the only pharmacist working on opium in the first years of the nineteenth century. In France, the pharmacists Charles Louis Derosne and Seguin also obtained crystalline material from opium in the same years. Their claims have been put forward as competing with Sertürner’s. Hosztafi’s history of the discovery of alkaloids reviews these priority claims. The view reflected in the historical literature consulted for this page is that, whatever crystalline material others may have obtained, Sertürner was the first to recognise and describe a plant base — to understand that the substance was an alkali, that it formed salts, and that it was the sleep-making principle of opium. That recognition, set out in the 1817 paper, is why the discovery carries his name.

Which year?

The year of the discovery is also debated, and the sources give anything from 1803 to 1806:

• 1803/04 — Klockgether-Radke dates the isolation of the crystalline substance to these years; his 2002 paper marked “200 years of pain therapy with opioids.”
• 1804 — the year given by many general histories of morphine.
• 1805 — the date of the first publication, used by some historians, among them Hamilton and Baskett, as the date of the discovery.
• 1805 or 1806 — the date of the second paper in Trommsdorff’s journal, given as 1805 by the Neue Deutsche Biographie and as 1806 by Papini.

The question was important enough to the German history of pharmacy that in 1954 Coenen published a whole paper on the year in which Sertürner discovered morphine in Paderborn. Part of the difficulty is that “discovery” can mean different things here: the first time Sertürner obtained crystals, the first time he reported them in print, or the 1817 paper in which he fully understood and named the substance. Each choice gives a different date, which is why this page’s title spans 1804 to 1817.

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10. Was Sertürner’s Morphine Pure?

One more question hung over the discovery: was the substance Sertürner isolated actually pure morphine, or a mixture? The question is a fair one, because opium contains not one alkaloid but several. Later chemists isolated many of them; codeine, for example, was isolated from opium and characterised by the French pharmacist Pierre-Jean Robiquet in 1832, according to Papini. A crystalline product separated from opium by the methods of 1805 or 1817 could in principle have carried other alkaloids with it.

In 1957 Haussermann and Schecker took up the question directly in a paper titled, in translation, “Has Sertürner isolated pure morphine? Paper chromatographic purity tests for the alkaloid.” Paper chromatography, a technique developed in the 1940s, separates the components of a mixture as a solvent carries them at different speeds along a strip of filter paper, so that even small amounts of a second substance can show up as a separate spot. Applying a twentieth-century analytical tool to a question about early-nineteenth-century chemistry, the paper treated the purity of Sertürner’s product as something that could be tested rather than assumed. (No abstract of the paper is available in PubMed, so its detailed findings are not summarised here.)

Whatever the exact purity of his first crystals, the historians cited on this page agree on what Sertürner achieved: he showed that the effect of a medicinal plant could be traced to a single, separable chemical substance, and that this substance was a plant base. The structure of morphine itself would take more than a century more to work out, and its first laboratory synthesis came only in 1952 — a story told on The Opium Poppy and the Chemistry of Morphine. What followed in medicine — the hypodermic syringe, morphine’s spread, and the findings on addiction — is on The Alkaloid Revolution and Morphine in Medicine.

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Key Research Papers

1. Sertuerner. Ueber das Morphium, eine neue salzfähige Grundlage, und die Mekonsäure, als Hauptbestandtheile des Opiums. Annalen der Physik. 1817;55(1):56-89. DOI: 10.1002/andp.18170550104
2. Sertuerner FW. Ueber eins der fürchterlichsten Gifte der Pflanzenwelt, als ein Nachtrag zu seiner Abhandlung über die Mekonsäure und das Morphium; mit Bemerkungen, den aciden Extractivstoff des Opiums und seine Verbindungen betreffend. Annalen der Physik. 1817;57(10):183-202. DOI: 10.1002/andp.18170571006
3. Choulant FA. Bestätigung und Wichtigkeit der Entdeckung eines neuen Alkali (des Morphium), welches Herr Sertürner in dem Opium aufgefunden hat. Annalen der Physik. 1817;56(8):337-354. DOI: 10.1002/andp.18170560802
4. Jurna I. [Sertürner and morphine--a historical vignette]. Schmerz. 2003;17(4):280-3. PubMed PMID: 12923678
5. Goerig M, Schulte am Esch J. [Friedrich Wilhelm Adam Sertürner--the discoverer of morphine]. Anasthesiol Intensivmed Notfallmed Schmerzther. 1991;26(8):492-8. PubMed PMID: 1786314
6. Klockgether-Radke AP. [F. W. Sertürner and the discovery of morphine. 200 years of pain therapy with opioids]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2002;37(5):244-9. PubMed PMID: 12015680
7. Krishnamurti C, Rao SC. The isolation of morphine by Serturner. Indian J Anaesth. 2016;60(11):861-862. PubMed PMID: 27942064
8. Schmitz R. Friedrich Wilhelm Sertürner and the discovery of morphine. Pharm Hist. 1985;27(2):61-74. PubMed PMID: 11611724
9. Coenen H. [On the year of morphine discovery in Paderborn by Sertürner]. Arch Pharm Ber Dtsch Pharm Ges. 1954;287(4):165-80. PubMed PMID: 13198184
10. Haussermann H, Schecker HJ. [Has Serturner isolated pure morphine? Paper chromatographic purity tests for the alkaloid]. Arch Pharm Ber Dtsch Pharm Ges. 1957;290/62(10):509-16. PubMed PMID: 13471017
11. Hosztafi S. The discovery of alkaloids. Pharmazie. 1997;52(7):546-50. PubMed PMID: 9266593
12. Papini AM. From morphine to endogenous opioid peptides, e.g., endorphins: the endless quest for the perfect painkiller. Substantia. 2018;2(2):81-91. DOI: 10.13128/substantia-63
13. Brook K, Bennett J, Desai SP. The Chemical History of Morphine: An 8000-year Journey, from Resin to de-novo Synthesis. J Anesth Hist. 2017;3(2):50-55. PubMed PMID: 28641826
14. Hamilton GR, Baskett TF. In the arms of Morpheus the development of morphine for postoperative pain relief. Can J Anaesth. 2000;47(4):367-74. PubMed PMID: 10764185

PubMed Topic Searches

1. Sertürner and morphine
2. History of morphine
3. History of alkaloid discovery
4. Opium in the history of pharmacy

Further Reading

• Friedrich C. “Sertürner, Friedrich Wilhelm.” Neue Deutsche Biographie 24 (2010), 271–273. deutsche-biographie.de
• Sertürner FW. Letter and paper on opium in Journal der Pharmacie für Ärzte und Apotheker 13 (1805) 229–243 and 14 (1805/1806) 47–93.
• Friedrich Wilhelm Sertürner, der Entdecker des Morphins: Lebensbild und Neudruck der Original-Morphium-Arbeiten. Springer, 1983 (reprint, foreword by A. Doenicke).

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Connections

• Friedrich Sertürner — Morphine, the Opium Poppy and the First Alkaloid
• Friedrich Sertürner: Life and Career (1783–1841)
• The Opium Poppy and the Chemistry of Morphine
• The Alkaloid Revolution and Morphine in Medicine
• Pharmacology
• Paracelsus: The Dose Makes the Poison and the Birth of Chemical Medicine
• Dioscorides: De Materia Medica and the Roots of Pharmacology
• Avicenna: The Canon of Medicine and the Rules for Testing Drugs
• William Withering: Foxglove and the Birth of Digitalis
• Felix Hoffmann — Aspirin, Willow Bark and the Salicylate Story
• Chronic Pain: History and Discovery
• Insomnia: History and Discovery

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