The first 3500 years of aspirin history from its roots – A concise summary

doi:10.1016/j.vph.2018.10.008

Vascular Pharmacology

Volume 113, February 2019, Pages 1-8

https://doi.org/10.1016/j.vph.2018.10.008 Get rights and content

Abstract

Aspirin is currently the most widely used drug worldwide, and has been clearly one of the most important pharmacological achievements of the twentieth century. Historians of medicine have traced its birth in 1897, but the fascinating history of aspirin actually dates back >3500 years, when willow bark was used as a painkiller and antipyretic by Sumerians and Egyptians, and then by great physicians from ancient Greece and Rome. The modern history of aspirin precursors, salicylates, began in 1763 with Reverend Stone – who first described their antipyretic effects – and continued in the 19th century with many researchers involved in their extraction and chemical synthesis. Bayer chemist Felix Hoffmann synthesized aspirin in 1897, and 70 years later the pharmacologist John Vane elucidated its mechanism of action in inhibiting prostaglandin production. Originally used as an antipyretic and anti-inflammatory drug, aspirin then became, for its antiplatelet properties, a milestone in preventing cardiovascular and cerebrovascular diseases. The aspirin story continues today with the growing evidence of its chemopreventive effect against colorectal and other types of cancer, now awaiting the results of ongoing primary prevention trials in this setting. This concise review revisits the history of aspirin with a focus on its most remote origins.

Graphical abstract

Section snippets

Aspirin – a miracle drug

Aspirin is today the most widely used drug all over the world, and in 2017, with some dispute about its real birth date, has celebrated its 120th birthday. Aspirin use in preventing cardiovascular and cerebrovascular diseases has been one of the biggest pharmaceutical achievements of the twentieth century. While most recent developments in secondary and primary cardiovascular prevention, and now in cancer chemoprevention, are still currently in the spotlight of the medical literature, the more

The ancient history of salicylates: willow bark

The charming story of the world's best-known drug began over 3500 years ago. Salicyline – a glycoside contained in the bark of willow trees belonging to the family of Salicaceae, genus Salix, such as Salix alba, Salix fragilis – is indeed probably the oldest remedy still currently in use [11]. The use of willow leaves for the treatment of inflammatory rheumatic diseases was already known by the Sumerians (Table 1). The ancient Egyptians used extracts of myrtle and willow leaves to soothe joint

Salicin

In 1758, the Reverend Edward Stone (1702–1768), from Chipping Norton, Oxfordshire, England, studied the healing properties of willow, looking for a valid and cheaper remedy than the expensive cinchona bark for treating “the agues” (i.e., malarial symptoms) [6]. He administered aqueous extract of Salix alba bark to 50 patients with fever, and discovered that the administration of these extracts every 4 h had a marked antipyretic action. Stone presented this study to the Royal Society of London

The 20th century: from mechanism of action to indications in cardiovascular disease

After its commercialization, aspirin use spread rapidly throughout the world, and became so famous as to be cited by several writers, including Franz Kafka, Thomas Mann, Henry Miller, José Ortega y Gasset and Gabriel Garcìa Marquez in their literary works. It was soon also used by illustrious personalities, from the son of Tsar Nicholas II (inappropriately, because he was hemophiliac) to Winston Churchill after his first stroke. In 1950, aspirin entered the Guinness World Records for being the

Aspirin today

Although the benefit of aspirin treatment, beyond its analgesic, antipyretic and anti-inflammatory effects, is now clear for acute coronary syndromes and for secondary cardiovascular prevention, the evidence in patients without prior cardiovascular disease (primary prevention) remains less clear [54,66,67]. Evidence-based guidelines recommend aspirin patients at cardiovascular risk, defined as ≥1–2 major cardiovascular events (death, myocardial infarction, or stroke) per 100 person-years, who

Conclusion

The charming history of aspirin goes thus back to Egyptian healers who used the willow bark to cure joint pain. Synthesized as it is today in 1897 and marketed in 1899 as an analgesic, antipyretic and anti-inflammatory agent, aspirin continues to attract research and debate related to its antiplatelet properties. It is now the most commonly used drug worldwide and has proved to be lifesaving in the prevention of cardiovascular disease. Its future, possibly for the entire millennium, still seems

Disclaimer

Aspirin, as shown here, has many fathers. As any short summary of such an immense story, the authors have been obliged to make a selection of what appeared to them most relevant. As a result, they did not cite a huge number of very relevant contributions and contributors especially in modern times, when claims have not yet withstood the test of time. They ask for understanding and forgiveness in such – in their opinion not unreasonable – choices.

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ReviewThe first 3500 years of aspirin history from its roots – A concise summary

Abstract

Graphical abstract

Section snippets

Aspirin – a miracle drug

The ancient history of salicylates: willow bark

Salicin

The 20th century: from mechanism of action to indications in cardiovascular disease

Aspirin today

Conclusion

Disclaimer

Lancet

Hematol. Oncol. Clin. North Am.

J. Biol. Chem.

J. Biol. Chem.

Lancet

Am. J. Med.

Am. J. Cardiol.

J. Am. Coll. Cardiol.

Prostaglandins Other Lipid Mediat

Eur. J. Pharmacol.

J. Am. Coll. Cardiol.

J. Am. Coll. Cardiol.

Lancet

J. Am. Coll. Cardiol.

Lancet

Am. J. Obstet. Gynecol.

Lancet

Handb. Clin. Neurol.

J. Am. Coll. Cardiol.

Lancet Oncol.

Aspirin: The Remarkable Story of a Wonder Drug

Acetylsalicylic Acid

The discovery of aspirin: a reappraisal

BMJ

The role of aspirin in the prevention of cardiovascular disease

Clin. Med. Res.

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. Ser. B Biol. Sci.

Aspirin for prevention of preeclampsia

Drugs

The aspirin story - from willow to wonder drug

Br. J. Haematol.

Effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials

BMC Cancer

Murder, Magic and Medicine

The Papyrus Ebers

An account of the success of the bark of the willow in the cure of agues

Phil Trans

The Italian contributions to the history of salicylates

Reumatismo

La salicina, principio medicamentoso del salice bianco (Salix alba. o base vegetale salificabile). Giornale di Farmacia-Chimica e Scienze Accessorie o sia Raccolta delle scoperte, ritrovati e miglioramenti fatti in Farmacia ed in Chimica

Sostituto indigeno del solfato di chinina

Biblioteca Italiana o sia Giornale di Letteratura, Scienze ed Arti

Salino amarissimo antifebbrile

Giornale di Farmacia-Chimica e Scienze Accessorie o siano Annali Universali delle scoperte, ritrovati e miglioramenti fatti in Farmacia ed in Chimica

Aspirin and Other Salicylates

Découvert de la salicine

J de Chimie Medicale

Sulle alterazioni che alcuni acidi subiscono nell'organismo animale

Il Nuovo Cimento, Tipografia Pieraccini, Pisa

Untersuchungen über die wasserfreien organischen Säuren

Liebigs Ann.

Drug discovery - a history

Aus der Traubschen Klinik. Über die Resultate der Behandlung des Polyarthritis rheumatica mit Salicylsäure

Berl Klin Wochenschr

Nachtrag zur Anwendung der Salicylsäure bei dem akuten Gelenkrheumatismus

Berl Klin Wochenschr

Review
The first 3500 years of aspirin history from its roots – A concise summary