Rudolf Buchheim & Oswald Schmiedeberg: The Founders of Experimental Pharmacology

For most of history, knowledge about medicines was a catalogue: lists of roots, barks, seeds, minerals and the virtues tradition claimed for them. That catalogue was called materia medica, and it was learned from books. In 1847 a 27-year-old Saxon physician named Rudolf Buchheim (1820–1879) arrived at the small university of Dorpat, on the eastern edge of the Russian Empire (today Tartu, in Estonia), and began asking a different question: what does a remedy actually do when it enters a living body? To answer it he set up a laboratory, which historians describe as beginning in his own house and at his own expense, and tested drugs by animal experiment and chemical analysis. Historians of the field regard it as the first laboratory devoted to experimental pharmacology anywhere in the world.

His pupil Oswald Schmiedeberg (1838–1921), a forester’s son from the Baltic province of Courland, wrote his doctoral thesis in that laboratory, took it over when Buchheim left, and in 1869 published with his colleague Koppe a book on muscarine, the poison of the red-and-white fly agaric mushroom. In 1872 Schmiedeberg moved to the new university of Strasbourg, co-founded the journal Archiv für experimentelle Pathologie und Pharmakologie in 1873, and over the next half-century trained about 120 pupils from some 20 countries, about 40 of whom went on to hold pharmacology chairs of their own — among them John Jacob Abel, the founder of American pharmacology. This wing tells their story, from the Dorpat laboratory to the plants and mushrooms they studied and the school that spread the new science around the world.

Table of Contents

  1. Deep-Dive Articles
  2. 1. Who Buchheim and Schmiedeberg Were
  3. 2. The Discovery on One Page: Dorpat, 1847
  4. 3. Muscarine and the Fly Agaric, 1869
  5. 4. The Natural Sources: Foxglove, Ergot, Pepper and Other Plant Drugs
  6. 5. Timeline at a Glance
  7. 6. Later Significance: The Strasbourg School and Modern Pharmacology
  8. Key Research Papers
  9. Connections

Deep-Dive Articles

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Rudolf Buchheim and Oswald Schmiedeberg: Two Lives from Dorpat to Strasbourg

A Bautzen physician’s son and a Courland forester’s son, teacher and pupil: Dorpat, Giessen, the 1872 Strasbourg chair, honours, Nobel nominations and the last years in Baden-Baden.

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Dorpat 1847: Buchheim’s Laboratory and the Birth of Experimental Pharmacology

How a house laboratory in a small Baltic university town turned materia medica into an experimental science, with pharmacological groups, some 80 to 90 dissertations and the 1876 debate over independent institutes.

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Muscarine, the Fly Agaric and the Plant Drugs of Buchheim and Schmiedeberg

The fly agaric and the 1869 muscarine book, the slowed frog heart and atropine, the road to acetylcholine, foxglove’s digitoxin and Buchheim’s studies of ergot, pepper, croton oil and kousso.

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The Strasbourg School: Schmiedeberg’s Students, the Archiv and the Legacy of Pharmacology

About 120 pupils and 40 chairs, John Jacob Abel and American pharmacology, the journal founded in 1873, hippuric and glucuronic acid, and how historians rank the two founders today.

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1. Who Buchheim and Schmiedeberg Were

Rudolf Richard Buchheim was born on 1 March 1820 in Bautzen, in the Kingdom of Saxony, the son of a town and district physician. He studied medicine at the medical-surgical academy in Dresden and at the University of Leipzig, where he did physiological-chemical work under Ernst Heinrich Weber, and took his medical degree in 1845. While still in Leipzig he translated Jonathan Pereira’s English textbook of materia medica into German, pruning remedies he judged useless and adding newer ones. In 1847 the Imperial University of Dorpat appointed him associate professor of pharmacology, dietetics, history of medicine and medical literature, and in 1849 full professor. He left Dorpat for the chair of pharmacology at Giessen in 1867 and died there on 25 December 1879.

Johann Ernst Oswald Schmiedeberg was born in autumn 1838 at Laidsen in Courland, then a Baltic province of the Russian Empire and today part of Latvia; the date is given as 29 September in the old Julian calendar used there, 11 October in the modern one. His father was a forester. He went to school in Dorpat, studied medicine there from 1860 to 1866, and wrote his doctoral thesis under Buchheim on measuring chloroform in the blood. He became Buchheim’s assistant, took over the Dorpat institute after Buchheim left in 1867, and was made full professor in 1871. In 1872 he accepted the chair of pharmacology at the newly founded university in Strasbourg, where he remained until 1918, when Germans had to leave Alsace after the First World War. He died in Baden-Baden on 12 July 1921. The full parallel story is told in Two Lives from Dorpat to Strasbourg.

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2. The Discovery on One Page: Dorpat, 1847

Buchheim’s great discovery was not a single drug but a way of working. Before him, a remedy’s properties were mostly asserted from tradition and from bedside impressions. He replaced those claims with experiments: giving a substance to an animal and recording what happened, and using chemistry to find out what the substance was and what became of it in the body. Philippu and Seifert describe him founding “the first laboratory of pharmacology worldwide in the basement of his private house, having at hand only small financial resources but many gifted students”. Tartu historians have since revisited the details of where the laboratory stood; by 1860 it had purpose-built rooms in an annex to the university’s Old Anatomical Theatre.

Buchheim also brought order to the remedies themselves. He grouped drugs that shared many features into “pharmacological groups” named after their best-known member, and his own paper titles show the method at work: the group of croton oil (1857), the group of piperine (1876) and the group of atropine (1876). Over twenty years in Dorpat his laboratory produced some 80 to 90 doctoral dissertations and about a hundred experimental studies, depending on the historian counting. When the surgeon Theodor Billroth argued in 1876 against separate pharmacological institutes, Buchheim answered the same year with an essay on the tasks and place of pharmacology at the German universities. The story is told in full in Dorpat 1847: Buchheim’s Laboratory.

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3. Muscarine and the Fly Agaric, 1869

Schmiedeberg’s best-known early work came from a mushroom. The fly agaric (Amanita muscaria), the red-capped, white-spotted toadstool of fairy-tale pictures, has a common name that suggests an old use against flies, and Siberian shamans used it as an inebriant. In 1869 Schmiedeberg and his Dorpat colleague Koppe published a book on muscarine, which they described as the poisonous alkaloid of the fly agaric. In their experiments the mushroom’s extract slowed the beat of the frog heart and, in stronger doses, stopped it — an effect resembling stimulation of the vagus nerve, and one that atropine, the alkaloid of the belladonna plant, could block. Greim sums up the achievement as “the identification of muscarine as the stimulant of the nervus vagus and its antidote atropine”.

That pairing became one of pharmacology’s basic tools. Henry Dale’s 1914 study of choline esters and “their relation to muscarine”, and Otto Loewi’s 1921 experiment showing that the vagus nerve acts on the heart through a chemical messenger, led to acetylcholine — and the class of acetylcholine receptors that muscarine switches on is still called muscarinic. Later research also found that the fly agaric itself carries only traces of muscarine: its effects on the brain come mainly from ibotenic acid and muscimol, while real muscarine poisoning is linked to some small Inocybe and Clitocybe mushrooms, which Dörner and colleagues describe as a serious threat that can cause circulatory collapse or death. The muscarine story, the chemistry and the hazards are set out in Muscarine, the Fly Agaric and the Plant Drugs.

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4. The Natural Sources: Foxglove, Ergot, Pepper and Other Plant Drugs

Almost every medicine the two men studied came from a plant, a fungus or a food. Schmiedeberg’s study of the active constituents of foxglove (Digitalis purpurea), published in 1874–75, sorted the “digitalins” then sold into separate substances — digitonin, digitoxin, digitalin and digitalein — and King’s American Dispensatory of 1898 credited him with “a critical study of the more important digitalins of commerce”. Foxglove was the heart remedy William Withering had described a century earlier; Schmiedeberg’s chemistry helped turn the leaf into defined compounds.

Buchheim’s papers read like a tour of the old herbal: the purgative seed oil of Croton tiglium (1857), the active constituent of ergot, the fungus of rye (1874), cod liver oil (1874), the pungent principle of black pepper, piperine (1876), the belladonna alkaloid atropine (1876), and kosin, from kousso, a flower long used against tapeworm (1876). Schmiedeberg later wrote on the toxicological importance of solanine in potatoes (1895) and on caffeine, nicotine and theophylline. These titles show what they studied; the pages of this wing report their findings only where a historian has described them.

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5. Timeline at a Glance

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6. Later Significance: The Strasbourg School and Modern Pharmacology

Historians describe the division of labour simply: Buchheim introduced experimental methods, and Schmiedeberg developed them further and spread them. According to Greim, Schmiedeberg trained about 120 pupils from 20 countries, and about 40 of them held chairs of pharmacology; Philippu and Seifert write that he “trained most of the professors of his time” and that from Strasbourg the discipline spread to Germany, Austria, Switzerland, Italy, Norway, Britain and the United States. Hattori and colleagues trace the start of experimental pharmacology in Japan to Schmiedeberg’s Japanese disciples. Among his pupils were Hans Horst Meyer in Vienna, Arthur Cushny in Britain and the United States, Erich Harnack and Wolfgang Heubner, and John Jacob Abel, who spent the 1887–88 academic year with him, was professor of pharmacology at Johns Hopkins from 1893 to 1932, led the founding of the American Society for Pharmacology and Experimental Therapeutics in 1908, and prepared crystalline insulin in 1926.

The journal Schmiedeberg co-founded in 1873 is still published as Naunyn-Schmiedeberg’s Archives of Pharmacology, and his laboratory’s work on how the body changes drugs — the formation of hippuric acid in the kidney, studied with Gustav Bunge, and the camphor studies with Meyer that brought glucuronic acid into drug metabolism — became part of the basic science of drug handling. Holmstedt and Liljestrand, quoted by Greim, called Schmiedeberg “undoubtedly the most prominent pharmacologist of his time”; Pohar and Hansson count 18 nominations for the Nobel Prize in Physiology or Medicine, though he never received it. The full account is in The Strasbourg School and the Legacy of Pharmacology.

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Key Research Papers

  1. Toomsalu M. Rudolf Richard Buchheim, the founder of pharmacology. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(11):2793-2811. PubMed PMID: 37294428
  2. Philippu A, Seifert R. History of pharmacology: 1-the Department of Pharmacology of the University of Tartu (Dorpat): genealogy and biographies. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(1):5-17. PubMed PMID: 36413339
  3. Philippu A, Seifert R. History of pharmacology:2 - The Institute of Pharmacology of the University of Strasbourg: genealogy and biographies. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(1):19-33. PubMed PMID: 36520164
  4. Greim H. Oswald Schmiedeberg (1838-1921) : Ninth Pharmacologic‑Historical Forum, 2024, Munich, Germany. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(12):9591-9596. PubMed PMID: 39042158
  5. Scheindlin S. Our man in dorpat: Rudolf Buchheim and the birth of pharmacology. Mol Interv. 2010;10(6):331-5. PubMed PMID: 21263158
  6. Muscholl E. Second W.D.M. Paton Memorial Lecture. The evolution of experimental pharmacology as a biological science: the pioneering work of Buchheim and Schmiedeberg. Br J Pharmacol. 1995;116(4):2155-9. PubMed PMID: 8564242
  7. Lee MR, Dukan E, Milne I. Amanita muscaria (fly agaric): from a shamanistic hallucinogen to the search for acetylcholine. J R Coll Physicians Edinb. 2018;48(1):85-91. PubMed PMID: 29741535
  8. Michelot D, Melendez-Howell LM. Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. Mycol Res. 2003;107(Pt 2):131-46. PubMed PMID: 12747324
  9. Dörner S, Trottmann F, Jordan PM, Rogge K, Bartels B, Werz O, Hertweck C, Hoffmeister D. The Fatal Mushroom Neurotoxin Muscarine is Released from a Harmless Phosphorylated Precursor upon Cellular Injury. Angew Chem Int Ed Engl. 2024;63(52):e202417220. PubMed PMID: 39432715
  10. Pohar M, Hansson N. The "Nobel Population" in Pharmacology: Nobel Prize laureates, nominees and nominators 1901-1953 with a focus on B. Naunyn and O. Schmiedeberg. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(7):1173-1185. PubMed PMID: 31953675
  11. Hattori Y, Ishii K, Yanai K, Endoh M. The large part German medicine has played in the development of experimental pharmacology in Japan. Naunyn Schmiedebergs Arch Pharmacol. 2023;396(1):35-42. PubMed PMID: 36282300
  12. Schmiedeberg O. Rudolf Buchheim, sein Leben und seine Bedeutung für die Begründung der wissenschaftlichen Arzneimittellehre und Pharmakologie. Archiv für Experimentelle Pathologie und Pharmakologie. 1911;67(1):1-54. DOI: 10.1007/bf02012802
  13. Schmiedeberg O. Untersuchungen über die pharmakologisch wirksamen Bestandtheile der Digitalis purpurea L. Archiv für Experimentelle Pathologie und Pharmakologie. 1874;3(1):16-43. DOI: 10.1007/bf01958772
  14. Buchheim R. Ueber die Aufgaben und die Stellung der Pharmakologie an den deutschen Hochschulen. Archiv für Experimentelle Pathologie und Pharmakologie. 1876;5(4-5):261-278. DOI: 10.1007/bf01976918

PubMed Topic Searches

  1. PubMed: Rudolf Buchheim
  2. PubMed: Oswald Schmiedeberg
  3. PubMed: Dorpat pharmacology history
  4. PubMed: Amanita muscaria muscarine

Further Reading

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Connections

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