The fever-bark tree, quinine (Cinchona spp.)

RUBIACEAE, Madder Family

Malaria has probably killed more people than all the wars and all the plagues combined, including the Black Death. Today there are still 100-200 million victims of malaria every year (statistics are difficult to verify), most within reach of medication, but it still kills a couple million people every year. Perhaps soon it will be eclipsed by fatal viral diseases, such as AIDS and the ever-threatening Ebola virus, but malaria has shaped the course of history for millenia. Kings, popes, and military leaders were struck down in their prime by malaria. Alexander the Great was a young victim. This deadly disease was at one time commonplace in London, Paris, Washington D.C., and even New York City, and during the American Civil War, malaria was a major killer of troops. Nowadays, malaria is mostly confined to the tropics, and so is not widely understood or feared in temperate North America and Europe.

The name means "bad air," because people originally thought that the disease came from bad swamp air. Emperor Nero drained the swamps near ancient Rome, in order to rid the city of that bad-air disease. It was not until 1880 that the French army doctor Charles Laveren discovered a protozoan destroying red blood cells in the blood of malaria victims, and the British doctor Ronald Ross found that mosquitoes were carriers of the protozoans. Both men received the Nobel Prize. The protozoan is a species of Plasmodium, a flagellated one-celled organism with a complex life cycle. Many other vertebrate species have their own, deadly species of Plasmodium as well.

Cinchona was originally used by Indians in tropical forests of northwestern South America for centuries, and around 1630 Spanish Jesuits learned about the bark of this tree. The Jesuit priests got natives to harvest the bark, and also to practice ecology--for every tree they cut down, the worker had to replant five trees, arranged in the shape of a cross. By 1645, quinine bark had been carried to Rome, for use at the Vatican. However, in Europe Roman Catholics and Protestants were bitter enemies, so Protestants refused to use the bark, considering it to be an evil papal plot; as a consequence of that bigotry, Oliver Cromwell died of malaria in 1658, and so changed the history of England, one supposes. Eventually "quinine" was accepted as a cure for malaria in Europe after heads of state were cured by a young and upstart apothecary's assistant named Robert Talbor, who treated Charles II of England and Louis XIV of France with quinine. After Talbor's death, the formula of his famous "wine," purchased by Louis XIV, was published, and malaria became a critical part of European medicine. This drug replaced primitive "cures," such as limb amputation, blood-letting, and skull operations.

Seeds of quinine plants were smuggled out of South America by Charles Ledger in 1865, for a fee of about 20 dollars (about the cost of Manhattan Island!), and some of these seeds eventually established quinine plantations in Java. This action obviously destroyed the South American monopoly on quinine and established a new Dutch monopoly. The native who helped Ledger, Manuel Incra Mamani, was jailed, beaten, and eventually starved to death for his participation in the scheme.

Quinine, an alkaloid, was isolated in 1820 by French chemists Pelletier and Caventou, and there is a monument in Paris commemorating this achievement. More than 30 alkaloids are known from the bark of this genus. In 1823, Dr. John Sappington of Philadelphia acquired several pounds of quinine and issued "Dr. Sappington's Fever Pills." He persuaded ministers in the Mississippi River Valley to ring the church bells every evening to alert people to take the pills, and through that enterprise, Sappington became a very wealthy man. Quinine and the temporary control of mosquitoes by DDT allowed the United States to build the Panama Canal, because malaria was checked.

The world supply of cultivated quinine trees in Asia (especially in Indonesia and Java) was captured by Japan in 1942, and Germany captured the quinine reserves in Amsterdam, so Allied forces had to use emergency measures during World War II. Before the fall of the Philippines, the U.S. managed to escape with four million seeds, which were germinated back in Maryland and then transplanted in Costa Rica and other Latin American countries, but initial hopes were low that any of this would be in time for the war effort. Roughly 60,000 U.S. troops died in Africa and the South Pacific from malaria. This stimulated the development of synthetic but unpleasant substitutes (Paludrin, Maloprim, Fansidar, and Aralen) in 1944 for use by Allied troops in tropical climates, although a Smithsonian botanist named Raymond Fosberg was able to secure millions of pounds of Cinchona bark in 1943 and 1944 for the Allies from forests and plantations in northern South America.

Quinine is a powerful antipyretic, i.e., it effectively lowers body temperature. During malaria, the victim goes through 3- or 4-day bouts of extreme chills and then burning fever that can reach 107 degrees F, brought about by the episodes of reproduction in and synchronous rupture of red blood cells by the malaria pathogens. Most human fatalities result when body temperature is too extreme, and quinine thereby permits the victim to pass through critical stages of lethal body temperature. The alkaloids also help to slow down the infection and reproduction of the protozoan.

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