Historically Speaking: Aspirin, a Pioneering Wonder Drug

The winding, millennia-long route from bark to Bayer.

The Wall Street Journal

February 1, 2024

For ages the most reliable medical advice was also the most simple: Take two aspirin and call me in the morning. This cheap pain reliever, which also thins blood and reduces inflammation, has been a medicine cabinet staple ever since it became available over the counter nearly 110 years ago.

Willow bark, a distant ancestor of aspirin, was a popular ingredient in ancient remedies to relieve pain and treat skin problems. Hippocrates, the father of medicine, was a firm believer in willow’s curative powers. For women with gynecological troubles in the fourth century B.C., he advised burning the leaves “until the steam enters the womb.”

That willow bark could reduce fevers wasn’t discovered until the 18th century. Edward Stone, an English clergyman, noticed its extremely bitter taste was similar to that of the cinchona tree, the source of the costly malaria drug quinine. Stone dried the bark and dosed himself to treat a fever. When he felt better, he tested the powder on others suffering from “ague,” or malaria. When their fevers disappeared, he reported triumphantly to the Royal Society in 1763 that he had found another malaria cure. In fact, he had identified a way to treat its symptoms.

Willows contain salicin, a plant hormone with anti-inflammatory, fever-reducing and pain-relieving properties. Experiments with salicin, and its byproduct salicylic acid, began in earnest in Europe in the 1820s. In 1853 Charles Frédéric Gerhardt, a French chemist, discovered how to create acetylsalicylic acid, the active ingredient in aspirin, but then abandoned his research and died young.

There is some debate over how aspirin became a blockbuster drug for the German company Bayer. Its official history credits Felix Hoffmann, a Bayer chemist, with synthesizing acetylsalicylic acid in 1897 in the hopes of alleviating his father’s severe rheumatic pain. Bayer patented aspirin in 1899 and by 1918 it had become one of the most widely used drugs in the world.

ILLUSTRATION: THOMAS FUCHS

But did Hoffman work alone? Shortly before his death in 1949, Arthur Eichengrün, a Jewish chemist who had spent World War II in a concentration camp, published a paper claiming that Bayer had erased his contribution. In 2000 the BMJ published a study supporting Eichengrün’s claim. Bayer, which became part of the Nazi-backing conglomerate I.G. Farben in 1925, has denied that Eichengrün had a role in the breakthrough.

Aspirin shed its associations with the Third Reich after I.G. Farben sold off Bayer in the early 1950s, but the drug’s pain-relieving hegemony was fleeting. By 1956 Bayer’s British affiliate brought acetaminophen to the market. Ibuprofen became available in 1962.

The drug’s fortunes recovered after the New England Journal of Medicine published a study in 1989 that found the pill reduced the threat of a heart attack by 44%. Some public-health officials promptly encouraged anyone over 50 to take a daily aspirin as a preventive measure.

But as with the case with Rev. Stone, it seems the science is more complicated. In 2022 the U.S. Preventive Services Task Force officially advised against taking the drug prophylactically, given the risk of internal bleeding and the availability of other therapies. Aspirin may work wonders, but it can’t work miracles.

Historically Speaking: The Quest to Understand Skin Cancer

The 20th-century surgeon Frederic Mohs made a key breakthrough in treating a disease first described in ancient Greece.

The Wall Street Journal

June 30, 2022

July 1 marks the 20th anniversary of the death of Dr. Frederic Mohs, the Wisconsin surgeon who revolutionized the treatment of skin cancer, the most common form of cancer in the U.S. Before Mohs achieved his breakthrough in 1936, the best available treatment was drastic surgery without even the certainty of a cure.

Skin cancer is by no means a new illness or confined to one part of the world; paleopathologists have found evidence of it in the skeletons of 2,400- year-old Peruvian mummies. But it wasn’t recognized as a distinct cancer by ancient physicians. Hippocrates in the 5th century B.C. came the closest, noting the existence of deadly “black tumors (melas oma) with metastasis.” He was almost certainly describing malignant melanoma, a skin cancer that spreads quickly, as opposed to the other two main types, basal cell and squamous cell carcinoma.

ILLUSTRATION: THOMAS FUCHS

After Hippocrates, nearly 2,000 years elapsed before earnest discussions about black metastasizing tumors began to appear in medical writings. The first surgical removal of a melanoma took place in London in 1787. The surgeon involved, a Scotsman named John Hunter, was mystified by the large squishy thing he had removed from his patient’s jaw, calling it a “cancerous fungus excrescence.”

The “fungoid disease,” as some referred to skin cancer, yielded up its secrets by slow degrees. In 1806 René Laënnec, the inventor of the stethoscope, published a paper in France on the metastatic properties of “La Melanose.” Two decades later, Arthur Jacob in Ireland identified basal cell carcinoma, which was initially referred to as “rodent ulcer” because the ragged edges of the tumors looked as though they had been gnawed by a mouse.

By the beginning of the 20th century, doctors had become increasingly adept at identifying skin cancers in animals as well as humans, making the lack of treatment options all the more frustrating. In 1933, Mohs was a 23-year-old medical student assisting on cancer research in rats when he noticed the destructive effect of zinc chloride on malignant tissue. Excited by its potential, within three years he had developed a zinc chloride paste and a technique for using it on cancerous lesions.

He initially described it as “chemosurgery” since the cancer was removed layer by layer. The results for his patients, all of whom were either inmates of the local prison or the mental health hospital, were astounding. Even so, his method was so novel that the Dane County Medical Association in Wisconsin accused him of quackery and tried to revoke his medical license.

Mohs continued to encounter stiff resistance until the early 1940s, when the Quislings, a prominent Wisconsin family, turned to him out of sheer desperation. Their son, Abe, had a lemon-sized tumor on his neck which other doctors had declared to be inoperable and fatal. His recovery silenced Mohs’s critics, although the doubters remained an obstacle for several more decades. Nowadays, a modern version of ”Mohs surgery,” using a scalpel instead of a paste, is the gold standard for treating many forms of skin cancer.

WSJ Historically Speaking: In Epidemics, Leaders Play a Crucial Role

ILLUSTRATION: JON KRAUSE

Lessons in heroism and horror as a famed flu pandemic hits a milestone

A century ago this week, an army cook named Albert Gitchell at Fort Riley, Kansas, paid a visit to the camp infirmary, complaining of a severe cold. It’s now thought that he was America’s patient zero in the Spanish Flu pandemic of 1918.

The disease killed more than 40 million people world-wide, including 675,000 Americans. In this case, as in so many others throughout history, the pace of the pandemic’s deadly progress depended on the actions of public officials.

Spain had allowed unrestricted reporting about the flu, so people mistakenly believed it originated there. Other countries, including the U.S., squandered thousands of lives by suppressing news and delaying health measures. Chicago kept its schools open, citing a state commission that had declared the epidemic at a “standstill,” while the city’s public health commissioner said, “It is our duty to keep the people from fear. Worry kills more people than the epidemic.”

Worry had indeed sown chaos, misery and violence in many previous outbreaks, such as the Black Plague. The disease, probably caused by bacteria-infected fleas living on rodents, swept through Asia and Europe during the 1340s, killing up to a quarter of the world’s population. In Europe, where over 50 million died, a search for scapegoats led to widespread pogroms against Jews. In 1349, the city of Strasbourg in France, already somewhat affected by the plague, put to death hundreds of Jews and expelled the rest.

But not all authorities lost their heads at the first sign of contagion. Pope Clement VI (1291-1352), one of a series of popes who ruled from the southern French city of Avignon, declared that the Jews had not caused the plague and issued two papal bulls against their persecution.

In Italy, Venetian authorities took the practical approach: They didn’t allow ships from infected ports to dock and subjected all travelers to a period of isolation. The term quarantine comes from the Italian quaranta giorni, meaning “40 days”—the official length of time until the Venetians granted foreign ships the right of entry.

Less exalted rulers could also show prudence and compassion in the face of a pandemic. After the Black Plague struck the village of Eyam in England, the vicar William Mompesson persuaded its several hundred inhabitants not to flee, to prevent the disease from spreading to other villages. The biggest landowner in the county, the earl of Devonshire, ensured a regular supply of food and necessities to the stricken community. Some 260 villagers died during their self-imposed quarantine, but their decision likely saved thousands of lives.

The response to more recent pandemics has not always met that same high standard. When viral severe acute respiratory syndrome (SARS) began in China in November 2002, the government’s refusal to acknowledge the outbreak allowed the disease to spread to Hong Kong, a hub for the West and much of Asia, thus creating a world problem. On a more hopeful note, when Ebola was spreading uncontrollably through West Africa in 2014, the Ugandans leapt into action, saturating their media with warnings and enabling quick reporting of suspected cases, and successfully contained their outbreak.

Pandemics always create a sense of crisis. History shows that public leadership is the most powerful weapon in keeping them from becoming full-blown tragedies.

WSJ Historically Speaking: The Quest for Unconsciousness: A Brief History of Anesthesia

The ancient Greeks used alcohol and opium. Patients in the 12th century got a ‘soporific sponge.’ A look at anesthetics over the centuries

ILLUSTRATION: ELLEN WEINSTEIN

Every year, some 21 million Americans undergo a general anesthetic. During recent minor surgery, I became one of the roughly 26,000 Americans a year who experience “anesthetic awareness” during sedation: I woke up. I still can’t say what was more disturbing: being conscious or seeing the horrified faces of the doctors and nurses.

The best explanation my doctors could give was that not all brains react in the same way to a general anesthetic. Redheads, for example, seem to require higher dosages than brunettes. While not exactly reassuring, this explanation does highlight one of the many mysteries behind the science of anesthesia.

Although being asleep and being unconscious might look the same, they are very different states. Until the mid-19th century, a medically induced deep unconsciousness was beyond the reach of science. Healers had no reliable way to control, let alone eliminate, a patient’s awareness or pain during surgery, though not for lack of trying.

The ancient Greeks generally relied on alcohol, poppy opium or mandrake root to sedate patients. Evidence from the “Sushruta Samhita,” an ancient Sanskrit medical text, suggests that Indian healers used cannabis incense. The Chinese developed acupuncture at some point before 100 B.C., and in Central and South America, shamans used the spit from chewed coca leaves as a numbing balm.

Little changed over the centuries. In the 12th century, Nicholas of Salerno recorded in a treatise the recipe for a “soporific sponge” with ingredients that hadn’t advanced much beyond the medicines used by the Greeks: a mixture of opium, mulberry juice, lettuce seed, mandrake, ivy and hemlock.

Discoveries came but weren’t exploited. In 1540, the German alchemist and astrologer Paracelsus (aka Theophrastus Bombastus von Hohenheim) noted that liquid ether could induce sleep in animals. In 1772, the English chemist Joseph Priestley discovered nitrous oxide gas (laughing gas). Using it became the thing to do at parties—in 1799, the poet Coleridge described trying the gas—but no one apparently tried using ether or nitrous oxide for medicinal purposes.

In 1811, the novelist Fanny Burney had no recourse when she went under the knife for suspected breast cancer. She wrote later, “O Heaven!—I then felt the Knife rackling against the breast bone—scraping it!”

Despite the ordeal, Burney lived into her 80s, dying in 1840—just before everything changed. Ether, nitrous oxide and later chloroform soon became common in operating theaters. On Oct. 16, 1846, a young dentist from Boston named William Morton made history by performing surgery on a patient anesthetized with ether. It was such a success that, a few months later, Frances Appleton Longfellow, wife of Henry Wadsworth Longfellow, became the first American to receive anesthesia during childbirth.

But these wonder drugs were lethal if not administered properly. A German study compiled in 1934 estimated that the number of chloroform-related deaths was as high as 1 in 3,000 operations. The drive for safer drugs produced such breakthroughs as halothane in 1955, which could be inhaled by patients.

Yet for all the continuous advances in anesthesia, scientists still don’t entirely understand how it works. A study published in the December 2017 issue of Annals of Botany reveals that anesthetics can also stop motion in plants like the Venus flytrap—which, as far as we know, doesn’t have a brain. Clearly, we still have a lot to learn about consciousness in every form.