Felix Hoffmann — Aspirin, Willow Bark and the Salicylate Story

On 10 August 1897 a young chemist named Felix Hoffmann (1868–1946), working in a company laboratory in the German town of Elberfeld, wrote up a report describing acetylsalicylic acid in a pure form suitable for medical use. Two years later the substance went on sale as aspirin, and it became one of the most widely used medicines of the twentieth century. The molecule had a far older ancestry. For thousands of years people had chewed or brewed the bark of the willow tree for pain and fever; in the nineteenth century chemists drew out its bitter principle, salicin, turned it into salicylic acid, and then learned to make salicylic acid in a factory. Hoffmann’s contribution was the last step: a gentler, stable form of an old plant medicine.

This wing tells the story in four deep-dive articles: the man himself, the 1897 synthesis and the later dispute over who deserves the credit, the willow bark and meadowsweet lineage together with the salicylates found naturally in food, and how aspirin works and what the twentieth century learned about it. The overview below gives the whole story on one page. It is history and science for curious readers; the research figures are reported as findings, not as guidance.

Table of Contents

  1. Deep-Dive Articles
  2. 1. Who Felix Hoffmann Was
  3. 2. The Discovery on One Page
  4. 3. The Natural Source: Willow, Meadowsweet and Salicin
  5. 4. The Question of Credit
  6. 5. Timeline at a Glance
  7. 6. Later Significance
  8. Key Research Papers
  9. Connections
  10. Featured Videos

Deep-Dive Articles

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Felix Hoffmann: Life and Career (1868–1946)

A manufacturer’s son from Ludwigsburg, pharmacy apprentice in three cities, Munich chemist, Elberfeld laboratory chemist and later pharmaceutical manager, and how his reputation was built and later questioned.

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The 1897 Synthesis of Aspirin and the Eichengrün Question

Why sodium salicylate needed improving, what acetylation does, the report of 10 August 1897, Dreser’s tests, the name, the patents, and the credit dispute as historians tell it.

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Willow Bark, Meadowsweet and the Natural Salicylates Behind Aspirin

From ancient willow remedies and Edward Stone’s 1763 letter to salicin, salicylic acid as a plant hormone, and the salicylates in fruit, herbs, spices and tea.

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How Aspirin Works: From Vane’s Prostaglandins to the Heart and Cancer Trials

John Vane’s 1971 discovery, the two cyclooxygenases, why one dose affects platelets for life, and the heart-attack, Reye’s syndrome and cancer findings that followed.

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1. Who Felix Hoffmann Was

Felix Hoffmann was born on 21 January 1868 in Ludwigsburg, in the kingdom of Württemberg, the son of Reinhold Hoffmann, a local manufacturer. According to the German national biography (Neue Deutsche Biographie), he attended the Latin school in Ludwigsburg and then trained as a pharmacist through apprenticeships in Geneva, Hamburg and Neuveville between 1886 and 1889. He went on to study pharmacy and chemistry at the University of Munich, passed the pharmaceutical state examination in 1891, and in 1893 earned a doctorate under the chemist Eugen Bamberger with work on anthracene and quinoline derivatives.

In 1894, on the recommendation of his Munich professor Adolf von Baeyer, he joined the pharmaceutical laboratory of the dye and chemical firm Farbenfabriken Bayer at Elberfeld. After aspirin was introduced he moved from the bench to the commercial side of the pharmaceutical business, which he directed for many years. He retired in 1928, spent his later years pursuing an interest in art history in Italy and Switzerland, and died in Lausanne on 8 February 1946. The full story is in Felix Hoffmann: Life and Career.

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2. The Discovery on One Page

By the 1890s salicylic acid and its salt, sodium salicylate, were standard treatments for rheumatic fever and pain, but they were hard on the stomach and tasted unpleasant. The idea behind Hoffmann’s work was a simple piece of chemistry called acetylation: attaching a small acetyl group to the salicylic acid molecule, using acetic anhydride. The resulting compound, acetylsalicylic acid, was not itself new — the French chemist Charles Gerhardt had made an impure form of it in 1853 during his studies of acid anhydrides — but no one had produced it in a pure, stable form fit to be a medicine.

Hoffmann’s laboratory report of 10 August 1897 describes exactly that. The pharmacologist Heinrich Dreser, head of the company’s pharmacological laboratory, tested the substance and published “Pharmakologisches über Aspirin (Acetylsalicylsäure)” in 1899, the year the drug was launched. The name joined “A” for acetyl with “spir”, which historians trace to Spiraea, the old botanical name of meadowsweet, from which salicylic acid had once been obtained. A German patent was refused because the compound had been described before, but United States Patent 644,077, with Hoffmann named as inventor, was granted on 27 February 1900. In the same period Hoffmann also acetylated morphine, producing diacetylmorphine, a compound that had already been made in 1874. The chemistry is told in The 1897 Synthesis of Aspirin and the Eichengrün Question.

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3. The Natural Source: Willow, Meadowsweet and Salicin

Historians of aspirin trace its roots back some 3,500 years: willow preparations for pain and fever appear in the records of the Sumerians and Egyptians, and reviewers of the history report that Greek physicians in the Hippocratic tradition knew willow bark for inflammatory pain. The modern scientific story begins in 1763, when the Reverend Edward Stone of Chipping Norton in Oxfordshire wrote to the President of the Royal Society describing how dried, powdered willow bark had relieved the “agues”, or fevers, of about fifty people over five years.

In the late 1820s chemists including Johann Andreas Buchner and Henri Leroux extracted the bark’s bitter active principle, salicin. Salicin was later converted to salicylic acid, which had also been obtained from meadowsweet (then Spiraea ulmaria, now Filipendula ulmaria), and in 1860 Hermann Kolbe published a chemical synthesis of salicylic acid that eventually allowed it to be made in quantity. In 1876 the Scottish physician Thomas Maclagan reported giving salicin in acute rheumatism, and German physicians reported on salicylic acid in rheumatic disease the same year.

Salicylic acid is not only a drug. Plants make it as a defence hormone against infection and stress, and an analysis of 333 foods found it in most fruits (especially berries and dried fruits), in smaller amounts in vegetables, and at high levels in some herbs and spices such as curry powder, paprika, thyme and rosemary, with tea also a notable source. A small Scottish study found higher serum salicylic acid in vegetarians than in non-vegetarians, with some overlap with people taking low-dose aspirin. The plant side of the story is in Willow Bark, Meadowsweet and the Natural Salicylates Behind Aspirin, and the site’s herb pages cover Willow Bark and Meadowsweet.

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4. The Question of Credit

For decades Hoffmann was presented as the sole inventor of aspirin, and a popular story held that he made it to ease his father’s rheumatism. In a 2000 reappraisal in the BMJ, the pharmaceutical historian Walter Sneader showed that this story first appeared in 1934, as a footnote in a history of chemical engineering, and argued that it is not a reliable source.

Sneader examined the claim of Arthur Eichengrün, a chemist at the same company, who stated in 1949 that he had directed Hoffmann to make acetylsalicylic acid and had arranged early clinical testing of it. Eichengrün was Jewish; he was persecuted under the Nazi regime, was held at Theresienstadt during the war, and had said nothing publicly for some fifteen years after 1934. Sneader pointed to the last sentence of Hoffmann’s own 1897 report, which says the substance was being examined for its usefulness, as consistent with testing already being under way, and argued in support of Eichengrün’s account. The historian Elisabeth Vaupel published a biography of Eichengrün in 2005, and the Science History Institute notes that evidence has surfaced indicating he played a significant role. The credit remains disputed; the full account is in The 1897 Synthesis of Aspirin and the Eichengrün Question.

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5. Timeline at a Glance

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6. Later Significance

For seventy years after 1897 nobody knew how aspirin worked. In 1971 the British pharmacologist John Vane showed that aspirin and similar drugs block the production of prostaglandins, hormone-like substances involved in pain, fever and inflammation; the enzyme they inhibit, cyclooxygenase, was later found to come in two forms, COX-1 and COX-2. Vane shared the 1982 Nobel Prize for the work, told in the site’s John Vane wing. In 1975 Gerald Roth and Philip Majerus showed that aspirin permanently acetylates a single protein in blood platelets, which explains why its effect on clotting lasts for the platelet’s whole lifespan.

That discovery turned a pain reliever into a heart medicine. In the 1950s a California general practitioner, Lawrence Craven, had reported daily aspirin in connection with fewer heart attacks, but his observations drew little notice. In 1988 the ISIS-2 trial of 17,187 people with suspected heart attack found that aspirin given for a month reduced five-week vascular deaths from 11.8% to 9.4%. Later findings followed: a fall in Reye’s syndrome in American children after the link with salicylates was reported around 1980, and a 2011 analysis of eight long-term trials that found fewer cancer deaths among people assigned daily aspirin, with the difference appearing after about five years. Researchers also report that serious stomach bleeding with salicylates was noticed early but largely neglected until the 1950s. The later story is told in How Aspirin Works, and the medicine itself on the site’s Aspirin page.

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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. Stone E. An account of the success of the bark of the willow in the cure of agues. Philosophical Transactions of the Royal Society of London. 1763;53:195-200. DOI: 10.1098/rstl.1763.0033
  5. Hedner T, Everts B. The early clinical history of salicylates in rheumatology and pain. Clin Rheumatol. 1998;17(1):17-25. PubMed PMID: 9586674
  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. 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
  8. Desborough MJR, Keeling DM. The aspirin story - from willow to wonder drug. Br J Haematol. 2017;177(5):674-683. PubMed PMID: 28106908
  9. Swain AR, Dutton SP, Truswell AS. Salicylates in foods. J Am Diet Assoc. 1985;85(8):950-60. PubMed PMID: 4019987
  10. Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5-6):255-8. PubMed PMID: 14592543
  11. 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
  12. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988;2(8607):349-60. PubMed PMID: 2899772

PubMed Topic Searches

  1. PubMed: aspirin history
  2. PubMed: salicylates willow bark
  3. PubMed: dietary salicylates
  4. PubMed: aspirin cyclooxygenase mechanism

Further Reading

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Connections

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