Stone · 1763
Edward Stone and the willow bark
On the twenty-fifth of April 1763, in the rectory at Chipping Norton in north Oxfordshire, the Reverend Edward Stone, sixty-one years old, the vicar of Chipping Norton since 1745, completed a five-page letter to the Royal Society of London titled *An Account of the Success of the Bark of the Willow in the Cure of Agues*. The letter reported Stone's six-year clinical-empirical study of about fifty Chipping-Norton-and-surrounding-parishes patients suffering from the ague (the eighteenth-century term for malaria, then endemic in the fenland country and the Oxfordshire valley parishes) to whom Stone had administered dried-and-powdered bark of the white willow (*Salix alba*) in twenty-grain doses three times a day. About forty of the fifty patients reported significant fever-reduction and recovery within five-to-fourteen-days; ten reported no effect. Stone had been led to the willow-bark trial by the late-mediaeval doctrine of signatures (the folk-pharmaceutical convention that plants growing in marshy fever-country must, by Providence, contain the cure for the fevers of that country). The Royal Society published Stone's letter in the Philosophical Transactions of 1763. The active ingredient (salicylic acid in the bark, later salicin in the 1828 Munich-laboratory isolation by Johann Andreas Buchner) was the foundational substance of the 1897 Bayer-laboratory synthesis of acetylsalicylic acid, marketed as Aspirin from 1899. Aspirin is, by every careful judgment of the twentieth-century pharmaceutical historians, the most-consumed manufactured drug in human history.
It is twenty past three on the afternoon of Monday the twenty-fifth of April 1763, in the upstairs study of the Chipping Norton rectory on Church Street in north Oxfordshire, in pale spring light through the south casement. He is sixty-one years old. He is the Reverend Edward Stone, born at Princes Risborough in Buckinghamshire in 1702, schooled at the Eton King's Scholars' Foundation 1717–22 and Wadham College Oxford 1722–26 (BA 1726, MA 1729), ordained deacon in the Church of England in 1726, vicar of Chipping Norton in the Oxfordshire diocese since 1745.
On the writing-desk in front of him is the finished letter to the Royal Society, five pages of fine-clerk's-hand on quarto paper, in the standard formal-address of the Society's Philosophical Transactions. The letter is addressed to George Parker, second Earl of Macclesfield, the President of the Royal Society 1752–64. The letter summarises Stone's six-year clinical study of the anti-pyretic effect of dried-and-powdered white-willow bark in the treatment of the ague of the Cotswold-valley parishes.
He thinks: the six-year study is, by my clinical-empirical observation, sound. About forty of the fifty patients I have given the willow-bark powder to have shown significant fever-reduction within five-to-fourteen days. The ague had been, on the Cotswold-valley parish-record of the 1750s, a major annual cause of rural mortality.
He thinks: the doctrine-of-signatures hypothesis that led me to the willow (the folk-pharmaceutical convention that plants growing in marshy fever-country must, by Providence, contain the cure for the fevers of that country) is, on the rational scientific test, mostly mistaken. The willow-bark works on the fever because of some chemical principle in the bark; the Providential argument is the cultural-folk-medicine framing that led me to the test, not the explanation of why the bark works.
He thinks: the Royal Society will publish the letter. The Society's Philosophical Transactions are the only scientific journal in English of the 1760s. The publication will put the willow-bark observation in front of the British and Continental medical-chemical research-community for the following century.
Stone signed the letter, folded it, and sent it to the Royal Society offices at Crane Court off Fleet Street in the Wednesday morning post. The Royal Society read the letter at the meeting of the second of June 1763 (Stone himself was not present) and published it in the Philosophical Transactions Volume 53, pages 195–200, under the title An Account of the Success of the Bark of the Willow in the Cure of Agues, by the Rev. Mr Edward Stone, of Chipping-Norton in Oxfordshire.
The willow-bark observation entered the late-eighteenth-and-early-nineteenth-century pharmacology literature. The active anti-pyretic ingredient (salicin) was isolated from willow bark by the Munich pharmacist Johann Andreas Buchner in 1828. The Italian chemist Raffaele Piria isolated salicylic acid from salicin in 1838. The Bayer-pharmaceutical-laboratory chemist Felix Hoffmann synthesised the acetylated form (acetylsalicylic acid) in 1897 on the Bayer commercial-pharmaceutical research-and-development programme. Bayer launched the acetylsalicylic-acid product under the brand-name Aspirin (a- for the acetyl, -spirin for the Spiraea ulmaria meadowsweet plant from which Bayer's original salicylic-acid synthesis used the related-source-material) in 1899.
Aspirin is, by every careful judgment of twentieth-century pharmaceutical historians (Diarmuid Jeffreys, Aspirin: The Remarkable Story of a Wonder Drug, 2004), the most-consumed manufactured drug in human history. About a hundred and twenty billion aspirin tablets were consumed worldwide in the year 2024. Edward Stone died at Chipping Norton on the twenty-sixth of November 1768, sixty-six years old. He is buried at the Chipping Norton parish church of St Mary the Virgin. The rectory is now a small private house. The Bayer-AG-aspirin company in 2003 placed a bronze plaque on the Chipping Norton parish-church porch, in English: the Reverend Edward Stone, vicar of this parish 1745–1768, discoverer of the anti-pyretic properties of willow bark, 1763. The Chipping Norton willows on the Glyme stream below the parish-church are, by the parish-tradition, descended from the original Stone-trial trees of the 1750s.