On May 11, 1838, the Vicksburg Register in Mississippi carried an ad for a miracle drug to fight a disease ravaging the country. The potion worked safely without purging the bowels or upsetting the stomach. And it would break a fever within 48 hours.
It was simply Sappington’s Anti-Fever pill, for the Maryland-born John S. Sappington, a physician who marketed its use for symptoms of malaria.
Once known as the Jesuits’ Powder, and the “English remedy” after its early promoters, the drug’s key ingredient was quinine.
Now President Trump is promoting a synthetic form of quinine — hydroxychloroquine — as a treatment for covid-19, the disease caused by the novel coronavirus.
The drug still is used to combat malaria and has been found to work on other ailments. But there’s scant evidence it can fight covid-19. And on Friday the Food and Drug Administration warned that people should not take it for the virus outside of a hospital or clinical trial.
Quinine, too, was thought to cure many things: typhoid fever, yellow fever, measles, gout, toothaches and sore feet.
It also was used by Nazi doctors in human malaria experiments in the Dachau concentration camp during World War II.
German scientist Claus Schilling, an expert in tropical diseases, infected hundreds of patients with malaria by exposing them to parasite-carrying mosquitoes.
He then treated them with quinine and other drugs to see how they reacted.
“Thirty or forty died from the malaria itself,” Franz Blaha, a physician and Czech inmate at Dachau, testified after the war. “Three hundred to four hundred died later … because of the physical condition resulting from the malaria attacks. In addition there were deaths resulting from poisoning due to overdoses.”
Schilling was hanged as a war criminal in 1946.
Quinine, or the lack of it, has played a critical role in warfare for generations, as doctors tried to fight off the impact of malaria, which could decimate an army with fevers and chills.
(The term "malaria,” — literally, bad air — goes back to the Italian physician Francesco Torti, who first used it in 1711, according to Marie Louise Duran-Reynals’s 1946 book, “The Fever Bark Tree.”)
During World War II, an American hospital official wrote during the battle for the Philippines: “If we do not secure a sufficient supply of quinine … all other supplies we may get, with the exception of rations, will be of little or no value,” said historian Karen M. Masterson.
“The early battles in the Pacific boiled down to which side had the means to replace fever-stricken troops,” she wrote in her 2014 book, “The Malaria Project.”
Lt. Gen. Robert L. Eichelberger recalled: “Disease was … more deadly peril to us than enemy marksmanship. We had to whip the Japanese before the malarial mosquito whipped us.”
At that time, malaria was mostly treated with the quinine-like synthetic Atabrine, a medicine designed by German chemists in the early 1930s.
But Atabrine, like quinine, had side effects, including gastritis, hallucinations and psychosis, Masterson wrote. Plus, it turned the skin of GIs and Marines yellow.
“The most hair-raising [side effects] were rashes that … progressed grotesquely, with skin falling off in sheets, creating open sores that attracted flies,” Masterson wrote. Other side effects included “erratic mood swings, violent anger, and deep depression …[along with] the standard diarrhea, vomiting, and cramps.”
Then came the rumor the drug caused impotence.
During the fight for the Pacific island of Guadalcanal, Marines rejected Atabrine. Their officers had to watch them take the pills and make sure the pills were swallowed. But the Marines would later spit them out.
Thousands got sick. “For every battle casualty, ten men lay sick with malaria,” Masterson wrote.
The Defense Department ordered everyone to take the pills or risk court-martial. (Atabrine was succeeded by less toxic chloroquine in 1943, and then hydroxychloroquine in 1955, according to the Cleveland Clinic Journal of Medicine.)
In days of old — when the sick were bled, purged, blistered and poisoned by their doctors — people were not so resistant to an effective substance that would stave off malaria.
Other bizarre remedies hadn’t worked, Duran-Reynals, the quinine historian, reported.
One ancient cure went: “Take the urine of the patient and mix it with some flour to make … seventy-seven small cakes … Proceed before sunrise to an anthill and throw the cakes therein. As soon as the insects have devoured the cakes the fever vanishes.”
Another approach was to cut the ear of a cat, “let three drops of the blood fall in some brandy, [add] a little pepper … and [give] it to the patient to drink.”
Thus, when quinine finally was accepted, it was hailed as a miracle.
What came to be called quinine had been found in remote sections of what was then Peru, in the bark of a leafy evergreen tree. The first mention of it came from an Augustinian monk and anthropologist, Antonio de la Calancha, in 1639, according to Duran-Reynals.
“A tree grows which they call ‘the fever tree’ … whose bark, of the color of cinnamon, made into powder … and given as a beverage, cures the fevers … it has produced miraculous results,” he reported.
“Thus … did Father Calancha announce to the world that a cure had been found for the most widespread disease of the time,” Duran-Reynals wrote.
Over the next few centuries, the wondrous essence of cinchona bark was caught up in the religious, political and scientific turmoil of the times. (The tree was named for the countess of Chinchon, wife of the viceroy of Peru, who erroneously was said to have been cured by the bark.)
It was praised by those it helped and condemned by the blood-letters and stomach-purgers of the medical establishment.
Protestants saw it as Catholic medicine. To the French it was an English cure. But those who figured out how to use it knew they were on to something.
In the 1670s, despite the hidebound medical establishment, a young English pharmacist, Robert Talbor, became an expert in treating fevers. He had moved to the southeast coast of England, where fevers were “epidemical."
By trial and error, he came up with a secret formula — “my particular … medicine,” he called it. He would reveal only that it was “a preparation of four vegetables,” and he warned people about using the “Jesuits’ Powder.”
In unskilled hands, “I have seen most dangerous effects,” he wrote.
Yet it was the key ingredient in his remedy, and in his hands it worked.
One patient was a high-ranking French army officer who remembered the medicine years later.
“It was a powder steeped in a large glass of white wine, the whole of which [Talbor] ordered me to drink three times in 24 hours,” the unnamed officer wrote, according to a 1961 account by medical historians Rudolph E. Siegel and F.N.L. Poynter.
The officer got better and took Talbor to see the English King Charles II, then visiting the port city of Sheerness. The king was impressed, made Talbor a knight and later was cured of a fever by Talbor’s mysterious remedy.
It was only after Talbor’s death in 1681 that his secret was revealed. “It was very surprising to find that it was nothing but [quinine] well disguised,” the French officer recalled.
A century and a half later, malaria — or ague, as it was called — was rampant in the United States, especially on the frontier.
In 1819, in Arrow Rock, Mo., a village overlooking a bend in the Missouri River, Maryland’s own Sappington set up a practice in a region called Booneslick.
Experimenting with quinine from imported cinchona tree bark, he came up with his famous “fever pill” in 1832, according to the State Historical Society of Missouri.
Sappington thought it acted by “correcting the bile, giving tone and energy to the stomach and bowels.” (It actually attacked the mosquito-borne parasites that cause malaria.)
At any rate, it worked. Demand skyrocketed. He became wealthy.
Like Talbor, he kept his formula secret.
In 1844, he wrote a book in which he finally revealed the ingredients: licorice, myrrh, sassafras oil and quinine.
He admitted: “The whole virtue of the pills consisted in the quinine alone.”
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