Felix Hoffmann

German scientist Felix Hoffmann (1868-1946) is credited as the inventor of aspirin, the first massproduced and mass-marketed consumer drug product. Hoffmann was a young chemist working for Bayer, the German chemical company, when he came up with a synthesized form of the chemical found in extract of willow-tree bark, which had been known for centuries as a pain reliever. Aspirin is notable as “the world's first truly synthetic drug,” according to an article in the Economist commemorating the centenary of Hoffmann's discovery, which was a product that “paved the way for the modern pharmaceuticals industry.”

Hoffmann was born on January 21, 1868, in Ludwigsburg, Germany, a city near Stuttgart. He was the son of Jakob, an industrialist, and went on to earn a science degree—magna cum laude—from the University of Munich in 1891. In 1893 he completed work on his doctorate, also awarded with magna cum laude honors, after writing a dissertation on the properties of dihydroanthracene, a source of hydrogen that could be used in industrial chemical applications such as hydrogenation. A year later Hoffmann joined the staff of Bayer, a manufacturer of dyes that had been founded in the northern city of Wuppertal, Germany, in 1863.

Began Researching Pain Relievers

Bayer was named after one of its two founders, Friedrich Bayer (1825-1880), a dye salesperson. Its first products were synthetic forms of chemical dyes whose mass-scale industrial production methods had only recently been discovered, and which proved much cheaper than the production of dyes made from natural sources. By the time Hoffmann began working for Bayer, it had expanded into other areas, and he was assigned to the company's state-ofthe-art research facility in Elberfeld, a city near Wuppertal, to work in its pharmaceutical research division.

Hoffmann's father was plagued by severe arthritis, and there were few pain relievers on the market that did not also have unpleasant or even adverse effects. Like many arthritis sufferers, Jakob Hoffmann disliked the taste of artificial salicylic acid, the most reliable remedy at the time and known as sodium salicylate. A chemical whose discovery had been made at Germany's University of Marburg in 1859, sodium salicylate was by the 1870s being mass-produced in the city of Dresden by the Heyden Company, but it had a terrible taste and could irritate the stomach lining to the point of causing ulcers. Scientists at Bayer and elsewhere were searching for a way to replicate the original salicylic acid in a more stable chemical form that would reduce its irritant properties.

Salicylic acid is derived from the bark and leaves of the willow tree, and this plant had been known for centuries as having analgesic, or pain-relieving, properties. It was depicted in clay tablets made by the ancient Sumerians, whose Mesopotamian settlements in the years between 5000 B.C.E. and 4000 B.C.E. are the first evidence of human civilization. Centuries later, the Greek physician Hippocrates (c. 460 B.C.E.-c. 370 B.C.E.) recommended chewing the bark or leaves of the white willow tree for pain relief.

Formulated Heroin in Bayer Lab

Hoffmann's breakthrough came on August 10, 1897, in the Elberfeld laboratory after he investigated the records and notes that had been written by a French chemist, Charles Frédéric Gerhardt (1816-1856). In 1853 Gerhardt mixed acetyl chloride—a corrosive liquid used by chemists as a reagent which gave off a white smoke—with sodium salicylate, but it was an unstable compound that to him did not seem to have much practical use. Hoffmann studied scientific notes on these experiments, and managed to come up with a variant by using two slightly different ingredients: he mixed a different form of salicylic acid derived from spirea alba—the Latin name for meadowsweet, a perennial herb—with acetic anhydride instead of acetyl chloride. This resulted in a far more stable form that could be used for medicine, and Hoffmann named it acetylsalicylic acid (ASA).

Bayer reportedly tested the compound on animals, then conducted a study on patients—said to be one of the first pharmaceutical trials involving human subjects—at Deaconess Hospital in Halle an der Saale, a town in the German state of Saxony-Anhalt. Executives at Bayer came up with the trade name Aspirin, with “a” referring to acetyl, plus “spir” for the spirea plant, and began distributing it in powder form to doctors as a pain reliever and fever reducer in 1899. The first water-soluble tablets were introduced a year later, and became the first medicine ever sold in tablet form. For the first several years of its existence, aspirin was available only through doctors, but it became an over-thecounter drug in 1915.

Oddly, the second major breakthrough of Hoffmann's career came just 11 days after the discovery that led to aspirin: heroin. This was the brand name that Bayer marketing executives gave the drug, and it was sold as a cough suppressant and even as a cure for morphine addicts from 1898 to 1910. Again, he was replicating the work of an earlier chemist, in this case C.S. Alder Wright at St. Mary's Hospital in London, England, in 1874. Heroin's addictive properties and harmful nature soon became apparent, and in contrast to the success of aspirin, this proved to be a major public relations embarrassment for the Bayer company.

Found to Prevent Blood Clots

For reasons still unclear, Hoffmann left his research position at Bayer and moved to an executive post in the company's marketing division not long after these breakthroughs. He remained there until he retired in 1928, and spent his final years in Switzerland. Never married, he died on February 8, 1946. Bayer went on to become a major international pharmaceutical corporation thanks to the success of aspirin, though its American aspirin franchise was seized by the U.S. government during World War I and deemed “enemy property.” The franchise was later sold at auction, and in 1920 Sterling Drug paid $5.3 million for the franchise to sell Bayer aspirin in the United States.

For the first several decades of the twentieth century, Bayer aspirin dominated the analgesic market. Its main competitors were sold under the brand names Excedrin, Anacin, and Bufferin, all of which used aspirin as the main ingredient, but Excedrin and Anacin also contained caffeine. Paracetamol, also known as acetaminophen, became part of a new class of pain relievers in the 1950s that were first sold in the United States under the brand name Tylenol. Ibuprofen, marketed as Advil, followed in the 1980s, along with naproxyn, which was introduced as the over-thecounter (non-prescription) remedy Aleve in 1994. The companies that introduced these pain relievers were Bayer's biggest competitors in the consumer drug market, and included Johnson & Johnson and Procter & Gamble.

With the newly crowded field of pain relievers, aspirin's share of the over-the-counter market declined precipitously until the late 1980s, when medical studies began to appear that showed its remarkable effectiveness in preventing the risk of heart attacks. Further research proved it could serve as a blood-thinning agent that could reduce the risk of a deadly blood clot immediately following a heart attack or stroke. At the turn of the twenty-first century, aspirin was the most widely studied drug in the history of medicine, with scientists investigating its other uses, including its possibilities as a cancer preventative, in more than 3,000 research studies that appeared annually.

Scientific Dispute over Credit

Bayer, which eventually regained the rights to its U.S. aspirin franchise, celebrated aspirin's hundredth anniversary in 1997. Two years later, a scientist at Strathclyde University in Scotland, Walter Sneader, presented a paper at the Royal Society of Chemistry's annual conference, in which he claimed that Bayer had been falsely attributing the discovery of aspirin to Hoffmann, when it was actually Hoffmann's lab colleague, Arthur Eichengrün (1867-1949), who deserved the credit. In the paper, which was published in the British Medical Journal in December of 2000, Sneader asserted that there were no company documents or records prior to 1934 that linked Hoffmann to aspirin's discovery, and instead the earliest records seemed to hint that Heinrich Dreser, head of the pharmaceutical research division at Elberfeld, had made some initial tests. “In a paper published in Pharmazie in 1949, Eichengrün claimed that he had instructed Hoffmann to synthesise acetylsalicylic acid and that the latter had done so without knowing the purpose of the work,” Sneader wrote. Another supervisor of Hoffmann and Eichengrün's disagreed over its potential, and so “Eichengrün tested it on himself, experiencing no ill effects. He stated that he then surreptitiously gave a supply of it to his colleague Dr. Felix Goldmann, who then recruited physicians to evaluate the drug in strict secrecy. Their reports were most encouraging.”

Sneader pointed out that Eichengrün had left Bayer in 1908 and founded his own successful chemical company which made flame-retardant materials. He was also Jewish, which put both him and his thriving Berlin factory in danger once Adolf Hitler (1889-1945) and the Nazi Party came to power in Germany in 1933 and began enacting anti-Semitic laws. Sneader asserted that the first mention of Hoffmann as aspirin's discoverer did not appear until a year after this, in 1934. “I believe the whole story was concocted so the Germans did not learn the most successful drug in history was discovered by a Jew,” Sneader told Rosemary Free, a journalist with the Herald of Glasgow, Scotland.

At the age of 76, Eichengrün had been deported to the Theresienstadt concentration camp in the present-day Czech Republic, but survived his 14-month internment. He died in December of 1949, the same month his article in the journal Pharmazie appeared. Both Bayer and other scientists disputed Sneader's claims, including Axel Helmstädter, the general secretary of the International Society for the History of Pharmacy, who sent a letter to the British Medical Journal stating, “There is no actual need for a reappraisal of Aspirin history. There are at least two sources earlier than Sneader's article reporting the development precisely,” one that discusses Eichengrün's claims, and one that “relies on a laboratory journal written and signed by Hoffmann in 1897,” according to Helmstädter.

Periodicals

American Medical News, October 20, 1997.

British Medical Journal, December 23, 2000.

Economist, February 21, 1998; August 9, 1997.

Herald (Glasgow, Scotland), September 2, 1999.

New York Times, August 9, 1997.

People, September 15, 1997.

Online

“Felix Hoffmann,” Bayer, http://www.bayer.com/en/Felix-Hoffmann.aspx (January 11, 2008).

“Felix Hoffmann,” The Great Idea Finder, http://www.ideafinder.com/history/inventors/hoffmann.htm (January 11, 2008).

“Rapid Responses to History: Walter Sneader, The Discovery of Aspirin: A Reappraisal,” British Medical Journal, http://www.bmj.com/cgi/eletters/321/7276/1591#12342 (January 10, 2008).