Quinine

wild_quinine_bloom

Wild Quinine Bloom

Malaria has been known to Europeans since the beginning of recorded history. Indeed, there is some archaeological evidence from human remains that malaria was a problem during Neolithic times. Until the modern era, the disease was widespread in the Mediterranean area and greatly feared throughout Europe. Malaria is caused by a protozoan, a microbe larger than most bacteria. The microbe is transmitted by the bite of the female Anopheles mosquito. Standing water must be available for the mosquito to complete its life cycle. The female lays her egg masses in bodies of water that later support the hatchlings as they mature. Therefore, any wet, swampy area can be home to the Anopheles mosquito. Europeans probably first learned of quinine in 1638. At that time, the wife of the Spanish viceroy (the royal governor),

Countess Chinchón, was dying of malaria in Lima, Peru. In desperation, the royal physician recommended the use of a native cure—a powdered tree bark that the natives called quinquina. The powder was brought 500 miles (800 km) from the village of Loja in present-day Ecuador. The native treatment was successful. When the countess returned to Spain a few years later, she took along a supply of the powdered bark. The countess retained some of the medicine for herself, but she had another use for the rest. The poorly maintained family estate—about 25 miles (40 km) south of Madrid—was low-lying and badly drained.

The peasant population was constantly sickened by malarial fevers. The powdered bark cured their fevers, and the workers soon restored the land to its former productivity. There is no clear historical evidence that the story is true. Nevertheless, European botanists named the tree that supplies the medicinal bark after the Chinchón family. The medicine was called quinine, a European form of the native word quinquina. South American Indians have used quinine to cure fever-producing illnesses for untold centuries. However, malaria was unknown to South America before the Spanish conquest in 1520. Spanish soldiers who already had the disease brought it to the New World. Jesuit missionaries, sent to convert the natives to Christianity, were the first Europeans to see quinine as a potential treatment for malaria. The missionaries lived among the native peoples in remote areas where few Europeans dared to travel. The Jesuits probably observed the natives use quinine to treat many kinds of fevers. The Jesuits sent the powder back to Spain and to Rome, the headquarters of the Catholic Church. At first, physicians were highly suspicious of quinine and the use of the drug was confined to the clergy. A high church official, Cardinal John de Lugo, promoted the use of quinine by both his malaria-ridden parishioners and his clergy. At that time, priests rather than doctors administered quinine.

In England, opposition came not only from the medical establishment but also from the strong Protestant majority. They disliked and distrusted the Catholic Church and could not tolerate the idea that anything good could come from the Jesuits. Strangely, the man who popularized the use of quinine in England was a self-proclaimed physician—a quack by the name of Robert Talbor. Talbor had attended Cambridge University for a brief period of time. He had some training in pharmacy and had served as an apothecary’s apprentice. Talbor, a bright but unscrupulous man, recognized that the bark was quite effective. He also recognized that it could not be sold under its popular name, Jesuit Powder.

Talbor simply changed the name of the powder, masked the quinine’s bitter taste by adding it to wine, and set up a pharmacy in Essex—a malaria-ridden area south of London. He advertised that he had a secret formula that did not contain Jesuit Powder. Talbor also advertised that Jesuit Powder had dangerous side effects that his medicine did not produce. Because the “secret” formula worked well, and many malaria patients were relieved of their symptoms, Talbor’s reputation spread rapidly. He traveled to London at the request of wealthy malaria victims and soon grew rich. The English king Charles II became one of his supporters, in spite of the opposition of the Royal College of Physicians. The king suffered from malaria and Talbor’s remedy improved his health. In gratitude, Charles gave Talbor a knighthood. The quack became Sir Robert. Louis XIV, the king of France, became his next royal patron. Both the king and his son were victims of malaria. Their recovery was hailed throughout Europe, and Sir Robert went on to repeat his successes in Vienna and Madrid. When he returned to Paris, he was hailed as a genius. King Louis gave him an aristocratic French name, and Sir Robert Talbor became Sir Robert Talbot. When Sir Robert expressed the wish to return to England, Louis became upset. The king did not want the secret formula to slip away. Because quinine neither prevents nor cures malaria, the king was correct in thinking his family might require further doses. (Quinine helps suppress the multiplication of the malaria microbe and thereby prevents the severe fevers associated with the body’s response to the microbe.) King Louis proposed a deal. Sir Robert wrote the formula on a piece of paper, placed the paper in an envelope, and sealed the envelope. The formula was locked away—not to be opened until after Sir Robert died. In return, the king gave Sir Robert a handsome gift of money and a life pension. Talbor died in 1681, shortly after his return to England. When the envelope was opened, the royal personages, wealthy patrons, and physicians were embarrassed to discover that the secret ingredient had been the hated Jesuit Powder. The crafty Talbor had suspended the powdered bark of the cinchona tree in white wine where it made a bitter but acceptable elixir. People began to revise their attitude toward Jesuit Powder.

More Chemistry

In 1820, two young Frenchmen working in Paris, Joseph Pelletier and Joseph Caventou succeeded in isolating the key ingredient in quinine. They found it to be a very complicated enzyme molecule called an alkaloid. This molecule is composed of three carbon rings. Two of the rings have one atom of nitrogen and two of carbon as attachments. The third ring is unusual because the attached carbon atoms connect to a structure with an oxygen and hydrogen atom at its end. The identification of the curative ingredient in quinine was important for three reasons. First, raw bark could be tested for its quinine content, and payment could be based on the amount of that ingredient. Second, because the active ingredient could be weighed, doctors could prescribe the exact amount needed for proper treatment. The tendency to overdose patients was greatly reduced. The third advantage concerned the new, easier way in which quinine could be administered. The pure alkaloid could be extracted from the raw bark and formed into small pills. The bark’s bitter taste was no longer a problem.

Breaking the Monopoly

The first half of the 1800s was a time of political unrest in much of Latin America. The people were fighting for their independence from European rule, and governmental authority was often lacking. Bandit groups and armed militias controlled many parts of the countryside, and this confusion interfered with the availability of quinine. Major land owners controlled the harvesting of the wild cinchona trees and the world market depended on such supplies. The number of wild trees was rapidly decreasing because stripping away the quinine-rich bark killed the tree. Also, the transportation routes from the forests to the ports were often interrupted by local warfare. The price of cinchona bark rose as it became a scarce commodity. The Dutch had grave problems with malaria among the colonists and native workers in the Dutch-owned East Indies, present-day Indonesia. They hoped to solve that problem and make a handsome profit by cultivating cinchona trees on Java, an island in their colony. The Dutch government sent a botanist, J. C. Hasskarl, to collect seeds and seedlings in Peru and Bolivia. Dutch diplomats in Peru were told to make similar collections. The plant material was placed on a Dutch warship headed for present-day Jakarta, the capital of Indonesia. The voyage took a long time and few seeds or seedlings survived. Those that did produced bark with a low quinine content and the project was an economic failure. In 1859, Clement Markham, an Englishman, persuadedhis government to develop plantations of cinchona trees in India. Richard Spruce, the noted South American explorer and botanist, was assigned to collect the seeds. Although a million trees were planned for southern India and Ceylon (now Sri Lanka), the planting was poorly organized and the trees did not prosper. Charles Ledger, a British citizen who lived in Bolivia, was the next to threaten the South American monopoly on quinine. Ledger was a professional bark dealer who employed natives to locate wild cinchona trees and harvest their bark. He assigned one of the workers to collect seeds from very productive trees. Ledger hoped to sell the seeds to the British government and thus reawaken their interest in cultivating cinchona trees. Ledger sent 14 pounds (6.3 kg) of seeds to his brother, George, who offered them for sale. The government officials had bad memories about Clement Markham’s plan and declined to do business with the Ledger brothers. George Ledger then asked the Dutch if they were interested in the seeds. Their officials were cautious but agreed to purchase a pound at a very low price. The other 13 pounds (5.9 kg) were sold to a British planter on his way to India. The planter traded them for different seeds as soon as he arrived at his destination. The 13 pounds (5.9 kg) of cinchona seeds were mishandled by the seed traders and never germinated. The pound of seeds purchased by the Dutch was handled far more carefully. The cinchona seeds were shipped to Java, where growing conditions matched those in Peru and Bolivia. The quinine content of the healthy young plants tested three to four times higher than those from the prior plantings. The Dutch, through their greater botanical skill, had broken the South American monopoly and now controlled the most productive source of quinine. The unfortunate native who had gathered the seeds in Bolivia was thrown into jail for violating the Bolivian prohibition against collecting cinchona seeds. Undoubtedly, the poor man was unaware that he was responsible for assuring a steady supply of one of the world’s most important medicines. Atabrine, the first synthetic medicine for malaria, was not developed until 1926. This synthetic drug helped break the Dutch dominance of the quinine market.

Potent Natural Medicines: Mother Nature’s Pharmacy

Copyright © 2006, 1998 by J. S. Kidd and Renee A. Kidd

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One response to “Quinine

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