The 1897 Synthesis of Aspirin and the Eichengrün Question

On 10 August 1897 a young chemist in the pharmaceutical laboratory of the Farbenfabriken Bayer at Elberfeld, Felix Hoffmann, wrote up a laboratory report on a substance he had made from salicylic acid and acetic anhydride: acetylsalicylic acid, in a pure form suitable for medical use. Within two years the substance had been tested in the company’s pharmacology laboratory, written up in a German physiology journal and put on sale under a new name, Aspirin. It went on to become one of the most widely used medicines in history. The plant story behind the molecule — willow bark, meadowsweet and salicin — is told on a companion page; this page is about the chemistry and the paperwork of 1897–1900.

It is also about a question that historians have argued over since 1949: who deserves the credit. Hoffmann’s colleague Arthur Eichengrün, a Jewish chemist who survived a Nazi camp, later wrote that he had directed the work and organised the first clinical trials. In 2000 the historian of pharmacology Walter Sneader re-examined the record in the BMJ and argued that Eichengrün’s account deserves to be taken seriously. What follows sets out the chemistry first and then the competing accounts, each attributed to the historian who gave it.

Table of Contents

  1. The Problem with Sodium Salicylate
  2. What Acetylation Does to Salicylic Acid
  3. Gerhardt’s 1853 Compound and Why It Was Not Enough
  4. The Laboratory Report of 10 August 1897
  5. Heinrich Dreser’s Tests and the 1899 Paper
  6. Naming Aspirin: Acetyl and Spiraea
  7. Patents in Germany and the United States
  8. Diacetylmorphine: The Other Acetylation of 1897
  9. Arthur Eichengrün’s Account and Sneader’s Reappraisal
  10. The 1934 Footnote and the Nazi-Era Silence
  11. Key Research Papers
  12. Connections
  13. Featured Videos

1. The Problem with Sodium Salicylate

By the time Hoffmann arrived at Elberfeld in 1894, salicylates were already established medicines. The molecule had first been met in plants — the bitter glycoside salicin from willow bark, and salicylic acid itself from meadowsweet — and had then been made in the laboratory. Hedner and Everts, in their history of salicylates in rheumatology, credit a German chemist named Gerland with a first synthesis of salicylic acid in 1852, and Hermann Kolbe published his own synthesis, “Ueber Synthese der Salicylsäure”, in 1860. Chemistry, rather than bark collecting, could now supply the drug.

The clinical breakthrough came in 1876. In March of that year the Dundee physician Thomas Maclagan reported in the Lancet on salicin in acute rheumatism, and in the same year, according to Hedner and Everts, the German physicians Stricker and Reiss published the first reports of salicylic acid in rheumatic disorders. Salicylic acid and its sodium salt, sodium salicylate, became standard treatments for rheumatic fever, joint pain and fever.

They came with a cost. Hedner and Everts record that gastrointestinal intolerance and bleeding with salicylates were reported early, although these reports were largely neglected until the 1950s. The biographical entry on Hoffmann in the Neue Deutsche Biographie (1972) sums up what the new compound was measured against: acetylsalicylic acid proved superior to sodium salicylate because it had fewer side effects. That comparison — the same useful salicylate action with less trouble for the patient — is the problem the 1897 work set out to solve.

The willow and meadowsweet chapters of this story, from Edward Stone’s 1763 letter to the Royal Society through the isolation of salicin, are told on the companion page Willow Bark, Meadowsweet and the Natural Salicylates Behind Aspirin.

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2. What Acetylation Does to Salicylic Acid

Salicylic acid is a small molecule built on a benzene ring that carries two working groups side by side: a carboxylic acid group (–COOH), which makes it an acid, and a phenolic hydroxyl group (–OH), the same kind of group found in carbolic acid. Both groups matter to how it behaves in the body and on the tissues it touches.

“Acetylation” means attaching an acetyl group — the two-carbon fragment of acetic acid, the acid of vinegar — to a molecule. When salicylic acid is acetylated, the hydrogen of the phenolic –OH is replaced by an acetyl group, and the hydroxyl becomes an ester. The result is acetylsalicylic acid. Hoffmann’s US patent describes the reagent that does this: acetic anhydride, a reactive form of acetic acid. The same reagent could acetylate other natural substances that carry hydroxyl groups, as section 8 shows.

In the body, much of an aspirin dose is broken back down to salicylic acid, which carries on the familiar salicylate effects. But the acetyl group turned out to have a job of its own. Decades later, in 1975, Gerald Roth and Philip Majerus showed that aspirin permanently attaches its acetyl group to a single protein in human blood platelets, most likely the enzyme cyclo-oxygenase, and that the change lasts for the life of the platelet. John Vane and Regina Botting later summarised how this enzyme, which makes prostaglandins, explains aspirin’s actions. None of this was known in 1897; the chemists of Elberfeld were looking for a better-tolerated salicylate, and the acetyl group’s own pharmacology was a discovery of the 1970s. That later story is told on How Aspirin Works and on the wing for John Vane.

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3. Gerhardt’s 1853 Compound and Why It Was Not Enough

Acetylsalicylic acid was not a new molecule in 1897, and nobody involved claimed that it was. In 1853 the French chemist Charles Gerhardt published a long study of the acid anhydrides, “Untersuchungen über die wasserfreien organischen Säuren” (“Investigations into the anhydrous organic acids”), in the Annalen der Chemie. In the course of that general work on anhydrides he produced an acetylated form of salicylic acid. Wood (2015) and Hedner and Everts (1998) both point to Gerhardt’s 1853 compound as the first appearance of the substance.

Gerhardt’s interest was chemical classification, not medicine, and his product was not a pure, stable drug. The Science History Institute’s profile of Hoffmann makes the distinction that matters: the compound had been made before, but not in a pure and stable form. The Neue Deutsche Biographie likewise credits Hoffmann with obtaining acetylsalicylic acid “in pure, stable form” in 1897.

A second earlier preparation also appears in the record. Hoffmann’s US patent of 1900 explicitly contrasts his product with an earlier compound described by the chemist Kraut, setting out how the substance made with acetic anhydride differed from it. In other words, Hoffmann’s contribution as the documents present it was not discovering a new molecule, but producing a known one in a form clean and stable enough to be a medicine — and that difference became the centre of the patent arguments described below.

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4. The Laboratory Report of 10 August 1897

The central document is Hoffmann’s laboratory report dated 10 August 1897. Both Wood (2015) and Sneader (2000) describe it as recording acetylsalicylic acid in a pure form suitable for medical use. It is the earliest dated piece of paper tying Hoffmann’s name to the substance, and it is the basis of the long-standing account that credits him with the discovery.

Sneader draws attention to the report’s last sentence, which notes that the substance was being examined for its usefulness. He reads this as consistent with testing already being under way at the time Hoffmann wrote — a detail that becomes important when Eichengrün’s later claim about his own early trials is weighed.

The report itself says nothing about motive. The popular story of why Hoffmann made the compound — to relieve his father’s rheumatism, because his father could not tolerate sodium salicylate — does not come from the report. As Sneader showed, that story first appeared in print in 1934, almost four decades later (see section 10). On this page it is treated as a later account, not as established fact.

For Hoffmann’s own life before and after the report — his pharmacy training, his doctorate in Munich and his later move to the commercial side of the business — see Felix Hoffmann: Life and Career.

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5. Heinrich Dreser’s Tests and the 1899 Paper

A new substance made in the chemistry laboratory went next to the pharmacology laboratory. At Elberfeld that laboratory was headed by Heinrich Dreser, and the Science History Institute records that Dreser tested acetylsalicylic acid there. His results appeared in 1899 in Pflügers Archiv für die gesammte Physiologie, under the title “Pharmakologisches über Aspirin (Acetylsalicylsäure)” — “Pharmacological notes on Aspirin (acetylsalicylic acid)”. The paper, published in June 1899 and running to thirteen pages, was the scientific introduction of the drug to the medical world, and its title already uses the new trade name.

The Neue Deutsche Biographie gives 1899 as the year the substance was marketed as Aspirin. Dreser’s paper carried his name alone. Hoffmann, the chemist who made the compound, did not appear as an author — one reason the question of who did what in 1897–1899 was left to later recollection rather than settled in print.

Dreser’s role is also part of the dispute. Arthur Eichengrün later wrote that the drug reached the market despite Dreser’s opposition, after Eichengrün arranged clinical trials of his own; Sneader’s reappraisal takes this account seriously (section 9). The surviving publication, however, is Dreser’s, and it is the paper through which the medical world first read about aspirin’s pharmacology.

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6. Naming Aspirin: Acetyl and Spiraea

The name chosen in 1899 records the plant history of the molecule. The “A” stands for acetyl. The “spir” recalls Spiraea, the old botanical name of meadowsweet, from which salicylic acid had been obtained in the nineteenth century and named Spirsäure (“spiraea acid”). Wood (2015) explains the name as acetyl plus Spirsäure; the Science History Institute describes it as “A” plus “spirin” from Spirea. The two wordings differ in detail, but both trace the name to meadowsweet.

The link to meadowsweet is one of name and history. By the 1890s salicylic acid could be made by chemical synthesis, following the published work of Gerland and Kolbe, so the name is better read as a record of where chemists first met the acid than as a description of the raw material used at Elberfeld. Wood’s further statement that the 1897 product was made from meadowsweet-derived acid is not repeated here as fact.

Meadowsweet (today classified as Filipendula ulmaria) remains a herb in its own right, with a long history in European folk medicine for fevers and joint complaints. The site’s pages on Meadowsweet and its salicylates and the aspirin story cover the plant itself.

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7. Patents in Germany and the United States

Because acetylsalicylic acid had been made before, patent protection was not straightforward. According to the Science History Institute’s profile, the German patent application was rejected on the grounds that the compound had already been made, even though the earlier preparations were not pure and stable. In its home country, then, the drug was protected by its trade name rather than by a patent on the molecule.

The United States reached a different decision. US Patent 644,077, titled “Acetyl Salicylic Acid”, names Felix Hoffmann of Elberfeld as inventor, assignor to the Farbenfabriken of Elberfeld Company. The application was filed on 1 August 1898 and the patent was granted on 27 February 1900. Its text sets Hoffmann’s product, made with acetic anhydride, against the earlier compound described by Kraut, arguing that the two differed in their properties.

The patent is one of the few documents of the period that puts Hoffmann’s name formally on the invention, and it is often cited in support of his credit. It records who was named as inventor for legal purposes; it does not settle who directed the research, which is the question the later dispute turned on. The trademark itself had a further history after the First World War, when it was lost in several countries and “aspirin” became a common word there — a story told on How Aspirin Works and Its Legacy.

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8. Diacetylmorphine: The Other Acetylation of 1897

The same reaction that turned salicylic acid into acetylsalicylic acid could be applied to other natural products. The Science History Institute records that in the same period Hoffmann, at Dreser’s direction, acetylated morphine, the main alkaloid of the opium poppy. The product was diacetylmorphine, which the company marketed under the name heroin.

Diacetylmorphine was not new either. The Science History Institute notes that it had already been made in 1874 by an English chemist, so, like acetylsalicylic acid in Germany, it could not be patented. Diacetylmorphine is today known chiefly as a drug of addiction. The exact day sometimes given online for Hoffmann’s first preparation of it is not confirmed in the sources used for this page and is not repeated here.

Historians often set the two acetylations side by side, because they show the same chemical idea producing one of medicine’s most widely used drugs and one of its most harmful within a short span of time at the same laboratory. This page reports the episode as history and pharmacology only. The wider history of opium and morphine in pain medicine is covered on the history of chronic pain treatment.

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9. Arthur Eichengrün’s Account and Sneader’s Reappraisal

Arthur Eichengrün was a chemist at the same Elberfeld works. In 1949 he published his own account of the discovery. According to Sneader’s summary of that account, Eichengrün stated that he had instructed Hoffmann to synthesise acetylsalicylic acid, and that it was his own clinical trials, carried out in secret, that led to the drug being marketed despite Dreser’s opposition. On his account, Hoffmann was the chemist who carried out the synthesis under his direction, not the originator of the project.

In “The discovery of aspirin: a reappraisal” (BMJ, 2000), Walter Sneader examined Eichengrün’s claim against the surviving documents. He pointed to the last sentence of Hoffmann’s 10 August 1897 report, which says the substance was being examined for its usefulness, as consistent with testing already under way. He also argued that the best-known evidence for Hoffmann as sole originator — the story about his father’s rheumatism — came from a late and unreliable source (section 10). Sneader concluded that Eichengrün’s version deserved serious consideration.

Other historians have built on that reappraisal. Elisabeth Vaupel, a historian at the Deutsches Museum in Munich, published a full biography of Eichengrün in 2005 under the title “Arthur Eichengrün — tribute to a forgotten chemist, entrepreneur, and German Jew”, restoring him to the history of German chemistry. The Science History Institute’s biography of Hoffmann now states that “some evidence has surfaced that indicates that Arthur Eichengrün … played a significant role”, and suggests that he was left out of the official story because he was Jewish. Wood (2015) also reports that Sneader supports this view, while noting that the company’s own histories continued to credit Hoffmann.

Taken together, the historians cited here describe the credit for aspirin as disputed rather than settled. Hoffmann’s name stands on the 1897 report and the US patent; Eichengrün’s claim rests on his own later account, which Sneader and Vaupel judge credible. None of the sources accuses Hoffmann of misconduct, and Hoffmann died in February 1946, three years before Eichengrün’s full account was published. Readers interested in Hoffmann’s side of the story will find the documented facts of his career on Life and Career.

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10. The 1934 Footnote and the Nazi-Era Silence

The familiar version of the discovery — Hoffmann, distressed by his father’s rheumatism and the side effects of sodium salicylate, set out to find a gentler salicylate — has been retold in textbooks, anniversary articles and company histories. Sneader traced it to its first appearance: a footnote in a 1934 history of chemical engineering by Albrecht Schmidt. Nothing earlier, he found, records the story, and he argued that the source is unreliable. On the evidence the historians present, the “father’s rheumatism” motive is a later account, first published thirty-seven years after the event.

The date matters. By 1934 the National Socialists had been in power for a year, and Jewish scientists were being pushed out of German public and professional life. Sneader records that Eichengrün, who was Jewish, remained silent for fifteen years after 1934 under that persecution. He noted that the Deutsches Museum in Munich displayed aspirin as a discovery credited only to Dreser and Hoffmann. During the Second World War he was imprisoned in the Theresienstadt camp, and Sneader reports that he wrote about the discovery from there in 1944. He survived the war and published his account in 1949.

Wood (2015) adds that Eichengrün claimed his contribution had been expunged from the archives during the Nazi period, and that Sneader supports this view. These are the historians’ findings and Eichengrün’s own claims, reported here as such. They place the most famous version of the aspirin story — the devoted son and his father’s rheumatism — at a moment when a Jewish colleague’s name could not be printed in Germany, which is why historians such as Sneader and Vaupel treat that version with caution.

What is not disputed is the chemistry: a pure, stable acetylsalicylic acid was produced in the Elberfeld laboratory in 1897, tested in 1899, and became the medicine whose mechanism John Vane would explain in 1971. The question that remains open in the historical literature is how the credit for that work is to be divided.

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Key Research Papers

  1. Sneader W. The discovery of aspirin: a reappraisal. BMJ. 2000;321(7276):1591-4. PubMed PMID: 11124191
  2. Vaupel E. Arthur Eichengrün--tribute to a forgotten chemist, entrepreneur, and German Jew. Angew Chem Int Ed Engl. 2005;44(22):3344-55. PubMed PMID: 15798983
  3. Wood JN. From plant extract to molecular panacea: a commentary on Stone (1763) 'An account of the success of the bark of the willow in the cure of the agues'. Philos Trans R Soc Lond B Biol Sci. 2015;370(1666):20140317. PubMed PMID: 25750237
  4. Hedner T, Everts B. The early clinical history of salicylates in rheumatology and pain. Clin Rheumatol. 1998;17(1):17-25. PubMed PMID: 9586674
  5. Gerhardt Ch. Untersuchungen über die wasserfreien organischen Säuren. Justus Liebigs Annalen der Chemie. 1853;87(1):57-84. DOI: 10.1002/jlac.18530870107
  6. Dreser H. Pharmakologisches über Aspirin (Acetylsalicylsäure). Pflüger, Archiv für die Gesammte Physiologie des Menschen und der Thiere. 1899;76(5-6):306-318. DOI: 10.1007/bf01662127
  7. Kolbe H. Ueber Synthese der Salicylsäure. Justus Liebigs Annalen der Chemie. 1860;113(1):125-127. DOI: 10.1002/jlac.18601130120
  8. Maclagan T. The treatment of acute rheumatism by salicin. The Lancet. 1876;107(2740):342-343. DOI: 10.1016/s0140-6736(02)46434-3
  9. Roth GJ, Majerus PW. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest. 1975;56(3):624-32. PubMed PMID: 1159076
  10. Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5-6):255-8. PubMed PMID: 14592543
  11. Montinari MR, Minelli S, De Caterina R. The first 3500 years of aspirin history from its roots - A concise summary. Vascul Pharmacol. 2019;113:1-8. PubMed PMID: 30391545
  12. Desborough MJR, Keeling DM. The aspirin story - from willow to wonder drug. Br J Haematol. 2017;177(5):674-683. PubMed PMID: 28106908

PubMed Topic Searches

  1. PubMed: aspirin history
  2. PubMed: Eichengrün and aspirin
  3. PubMed: acetylsalicylic acid discovery
  4. PubMed: salicylates, history and rheumatism

Further Reading

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Connections