Friedrich Sertürner — Morphine, the Opium Poppy and the First Alkaloid

Friedrich Sertürner: Life and Career (1783–1841)

A surveyor’s son from Schloss Neuhaus, apprentice at the Paderborn court pharmacy, pharmacist in Einbeck under Napoleonic law and later in Hameln, his honours from Jena to Paris, and his speculative work on galvanism and cholera.

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

Opium of unpredictable strength, the search for an “opium acid” that turned up a base, the 1805 and 1817 papers, the self-experiment told as history, and the debates over priority, dating and purity.

The Opium Poppy and the Chemistry of Morphine

Papaver somniferum from the ancient world to theriac and laudanum, what opium contains and why batches differ, how the poppy builds morphine, Robinson’s structure, Gates’s synthesis and engineered yeast.

The Alkaloid Revolution and Morphine in Medicine

Quinine, codeine and the cascade of plant alkaloids, factory production, the hypodermic syringe, addiction findings and the first narcotics laws, heroin, opioid receptors and the modern evidence on long-term use.

1. Who Friedrich Sertürner Was

Friedrich Wilhelm Adam Sertürner was born on 19 June 1783 at Schloss Neuhaus, the residence of the prince-bishops of Paderborn in Westphalia, now part of the city of Paderborn in Germany. According to the German national biography (Neue Deutsche Biographie), his father, Simon Joseph Sertürner, was a surveyor, map-maker and architect in the prince-bishop’s service. After his father’s death in 1798, the boy began an apprenticeship in 1799 at the Paderborn court pharmacy, and in 1803 he passed his examination as a pharmacist’s assistant.

In 1805 or 1806 (the sources differ) he moved to Einbeck to work in the town council’s pharmacy. Qualified as a pharmacist in 1809, he was able, under the Napoleonic law of the French-ruled Kingdom of Westphalia, to open a pharmacy of his own there; after Napoleon’s defeat that concession lapsed and the shop closed. From 1821 he ran the council pharmacy (Ratsapotheke) in Hameln, and that same year he married Eleonore von Rettberg; they had three sons and four daughters. He was never a professor. Honours came from the University of Jena, which gave him a doctorate in 1817, from learned societies in Germany, Russia and Portugal, and from the Institut de France, which awarded him its Prix Montyon in 1831.

His interests reached far beyond opium: galvanism, firearms, a “system of chemical physics” in the spirit of Romantic natural philosophy, and in 1831 a proposal, as the historian Jurna describes it, that cholera is caused by a poisonous, living, self-reproducing being — a speculation that pointed toward the later germ theory. Jurna writes that in his last years he felt his work was not properly esteemed and that his health declined. He died in Hameln on 20 February 1841 and was buried in Einbeck. The full story is in Friedrich Sertürner: Life and Career.

2. The Discovery on One Page

Opium was one of the most important drugs in any early nineteenth-century pharmacy, yet nobody knew which substance inside it did the work. The Neue Deutsche Biographie relates that, as an apprentice, Sertürner noticed that carefully made opium preparations still varied in strength; Klockgether-Radke notes that because opium’s constituents were unknown, exact dosing was almost impossible. Influenced by the Swedish chemist Carl Wilhelm Scheele, who had isolated a series of acids from plants, Sertürner at first expected opium’s active principle to be an acid.

Instead, around 1804 he obtained a crystalline substance with an alkaline character. He reported it in 1805 in a letter to Trommsdorff’s Journal der Pharmacie and described it further in a second paper there, but Goerig and Schulte am Esch write that this first report went unnoticed. After years of repeated work he published the decisive paper in 1817 in the Annalen der Physik: “On morphium, a new salt-forming base, and meconic acid, as the main constituents of opium.” The title states both claims — that morphium was a base able to form salts, and that meconic acid was opium’s other main constituent. Klockgether-Radke states that he proved in animals and in humans that the compound was opium’s principium somniferum, its sleep-making principle.

The human test is told as history only. Papini, drawing on Sertürner’s own description, recounts that he took the dissolved substance himself together with three young men, and that the trial nearly ended in disaster, with stomach pain, exhaustion and a severe narcosis close to fainting. The French chemist Gay-Lussac arranged a French translation of the 1817 paper, which brought the discovery to wide attention, and Franz Anton Choulant published a confirmation of the new alkali. The French pharmacists Derosne and Seguin also obtained crystalline material from opium in those years; historians such as Hosztafi review the priority claims, and the literature credits Sertürner as the first to recognise and describe a plant base. The year of the discovery is itself debated, with sources giving dates from 1803 to 1806. The whole account is in The Isolation of Morphine.

3. The Natural Source: The Opium Poppy

Opium is the air-dried latex of the seed capsule of the opium poppy, Papaver somniferum — the “sleep-bearing” poppy. Brook and colleagues date human use of opium back to the sixth millennium BCE. Norn and co-authors trace its written history from a Sumerian clay tablet of about 2100 BCE, which some scholars believe refers to the poppy, through Theophrastus, Dioscorides, Celsus, Galen and Avicenna, to theriac, the famous compound remedy in which opium was one of dozens of ingredients. Seventeenth-century physicians knew it as laudanum, an opium tincture; the site’s Sydenham’s Laudanum page tells that chapter.

Opium is a variable mixture of several alkaloids — morphine, codeine, thebaine, papaverine and noscapine among them — and their proportions differ from one batch to the next, which is exactly the problem Sertürner set out to solve. Chemically, morphine is a benzylisoquinoline alkaloid, a family the poppy assembles step by step from the amino acid tyrosine and which also includes berberine. Beaudoin and Facchini note that the opium poppy remains the only commercial source of morphine and codeine and of the semisynthetic drugs made from them. Sir Robert Robinson worked out morphine’s structure in the 1920s and Gates and Tschudi reported its first total synthesis in 1952, yet Brook and colleagues write that chemical synthesis still cannot compete with extraction from the plant. The plant side of the story is in The Opium Poppy and the Chemistry of Morphine.

4. The Alkaloid Revolution

Before morphine, chemists widely held that plants could not contain bases. Hosztafi’s history of the discovery of alkaloids describes how the recognition of a nitrogen-containing plant “alkali” that neutralised acids to form salts overturned that view, and opened a search for the active principles of other medicinal plants. Within two decades a run of alkaloids followed. In 1820 the Paris pharmacists Pierre Joseph Pelletier and Joseph Caventou isolated quinine from cinchona bark, the traditional fever remedy for malaria, and in 1832 Pierre-Jean Robiquet isolated codeine, a second opium alkaloid.

The Neue Deutsche Biographie describes Sertürner’s discovery as a starting point for the rise of the chemical-pharmaceutical factories, and Papini records morphine being prepared on a commercial scale by 1833. Goerig and Schulte am Esch count Sertürner among the co-founders of alkaloid chemistry, and see his work as part of pharmacy’s move from alchemy to science: for the first time a plant medicine could be given as one defined, weighable compound instead of a mixture of unknown strength. That chain, from medicinal plant to purified molecule, runs through much of modern pharmacology. It is told in The Alkaloid Revolution and Morphine in Medicine.

5. Timeline at a Glance

1783 — Sertürner is born at Schloss Neuhaus near Paderborn on 19 June.
1799 — Apprenticeship begins at the Paderborn court pharmacy.
1803 — Examination as a pharmacist’s assistant.
Around 1804 — Isolation of a crystalline substance from opium (sources give dates from 1803 to 1806).
1805 — First report, a letter to Trommsdorff’s Journal der Pharmacie.
1805 or 1806 — Move to the council pharmacy in Einbeck.
1809 — Qualifies as a pharmacist and opens his own pharmacy in Einbeck under Westphalian law.
1817 — The Annalen der Physik paper names morphium as a salt-forming base; doctorate from Jena.
1820 — Pelletier and Caventou isolate quinine from cinchona bark.
1821 — Takes over the Ratsapotheke in Hameln; marries Eleonore von Rettberg.
1831 — Prix Montyon of the Institut de France; his cholera hypothesis.
1832 — Robiquet isolates codeine from opium.
1841 — Sertürner dies in Hameln on 20 February.
1855 — Alexander Wood of Edinburgh publishes his method of injecting opiates at painful points.
1914 — The US Harrison Narcotics Act is passed, taking effect in 1915.
1952 — Gates and Tschudi report the first total synthesis of morphine.
1973 — Pert and Snyder demonstrate the opiate receptor in nervous tissue.
1975 — Hughes, Kosterlitz and colleagues identify the enkephalins, the body’s own opioids.

6. Later Significance: Morphine in Medicine and the Addiction Findings

Klockgether-Radke describes morphine as the first pure opioid that allowed pain to be treated with a single defined compound. Hamilton and Baskett write that its use became widespread only after the hypodermic needle and syringe arrived, nearly fifty years after its isolation; the Edinburgh physician Alexander Wood published his method of injecting opiates directly at painful points in 1855. In the decades that followed, injected morphine spread through military and civilian medicine, and so did dependence on it. Papini traces the first US federal controls, the Smoking Opium Exclusion Act of 1909 and the Harrison Narcotics Act of 1914, and the story of heroin, diacetylmorphine, sold from 1898 as a supposedly non-addictive substitute for morphine before its own addictiveness was recognised.

A century and a half after Sertürner, scientists found out why morphine acts on the body at all. In 1973 Candace Pert and Solomon Snyder demonstrated a specific opiate receptor in nervous tissue, and in 1975 John Hughes, Hans Kosterlitz and colleagues identified the enkephalins, short peptides the brain makes itself that act on the same receptors. Hamilton and Baskett described morphine in 2000 as still the most widely used analgesic and the standard against which new opioids for pain after surgery are compared. The modern evidence on long-term use is sobering: a 2015 systematic review for a US National Institutes of Health workshop by Chou and colleagues found the evidence insufficient to determine whether long-term opioid therapy improves chronic pain and function, while finding a dose-dependent risk of serious harms including overdose, opioid abuse, fractures and heart attack. Norn and co-authors note that the long search for a non-addictive opiate has not succeeded. The site covers these risks on its Opioid Overdose and Opioids for Chronic Non-Cancer Pain pages.

Key Research Papers

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
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
Jurna I. [Sertürner and morphine--a historical vignette]. Schmerz. 2003;17(4):280-3. PubMed PMID: 12923678
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
Hosztafi S. The discovery of alkaloids. Pharmazie. 1997;52(7):546-50. PubMed PMID: 9266593
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
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
Norn S, Kruse PR, Kruse E. [History of opium poppy and morphine]. Dan Medicinhist Arbog. 2005;33:171-84. PubMed PMID: 17152761
Beaudoin GA, Facchini PJ. Benzylisoquinoline alkaloid biosynthesis in opium poppy. Planta. 2014;240(1):19-32. PubMed PMID: 24671624
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
Pert CB, Snyder SH. Opiate receptor: demonstration in nervous tissue. Science. 1973;179(4077):1011-4. PubMed PMID: 4687585
Hughes J, Smith TW, Kosterlitz HW, Fothergill LA, Morgan BA, Morris HR. Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature. 1975;258(5536):577-80. PubMed PMID: 1207728
Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, Dana T, Bougatsos C, Deyo RA. The effectiveness and risks of long-term opioid therapy for chronic pain: a systematic review for a National Institutes of Health Pathways to Prevention Workshop. Ann Intern Med. 2015;162(4):276-86. PubMed PMID: 25581257

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