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MEDICINES THAT CHANGED THE WORLD

Steven R. King, Ph.D., Shaman Pharmaceuticals, Inc., South S.F., CA
Adapted from Pacific Discovery, Vol.45, No. 1, pp.23-31, Winter, 1992.

Highland Andean girl in Quito, Ecuador, selling medicinal plants.
Photo by Steven R. King, 1996.

By the time the first European explorers arrived, the native people of the Americas had developed complex medical systems complete with diagnosis and treatment of physical as well as spiritual illnesses. Indigenous peoples derived medicines and poisons from thousands of plants. Over the last 500 years, others, including those of us in North America, have profited from the medicinal knowledge and healing plants of this vast region. And yet, the Americas still contain an untapped wealth of healing gifts. Let's look at some of the plants that originated from Central and South America and how they affected history.

A MEDICINE FOR MALARIA

Drawing by David Wood,
Genentech Graphics Department
In the early 1500's, Indian fever bark was one of the first medicinal plants to find appreciative consumers in Europe. Taken from the cinchona tree (Cinchona officinalis), the bark was used as an infusion by native people of the Andes and Amazon highlands to treat fevers. Jesuit missionaries brought the bark back to Europe. By the early sixteenth century, this medicine was known as "Jesuit fever bark," quite a transformation.

The effectiveness of the bark's active ingredient, the alkaloid quinine, in treating malaria and other fever-inducing diseases made it worth nearly its weight in gold. Cinchona provides the first case of a medicinal plant that was needed too much and too quickly. Cinchona bark sewn in leather bundles was shipped in huge quantities from ports in Peru and Ecuador. As European powers established colonies in Africa and Asia, the demand for cinchona bark only increased to combat the scourge of malaria. For three centuries the global demand for cinchona bark grew constantly, threatening the tree's survival.

In 1923 the standard malaria treatment in the U.S.A.
An illegal act in the mid-nineteenth century ultimately saved the cinchona. In 1865, Charles Ledger smuggled a small collection of seedlings from South America. Since the British had commissioned their own team of smugglers, they declined to purchase Ledger's seedlings. However, the Dutch, eager to develop a supply for their colonies, bought some seeds. Within ten years, cinchona trees grew in Java. By 1930, Java produced more then 95 percent of the world's supply. The outbreak of World War II cut off the bark supply to all but the Japanese and their allies. Ironically, Southeast Asian seeds were then returned to Central America to establish plantations. Today, as a result of widespread drug resistance to some of its synthetic versions, cinchona's active ingredient, quinine, has reemerged as the medicine of choice to fight the most deadly form of malaria, caused by the parasite Plasmodium falciparum.

THE WONDERS OF THE COCA PLANT

Coca leaves.
Photo by Steven R. King, 1996.
The name coca (Erythroxylum coca) comes from an Aymara word meaning simply "tree." In Andean cultures, the leaves of the coca tree have been primarily chewed to obtain the benefits. From ancient times, indigenous people have added an alkaline such as crushed seashells or burnt plant ashes to the leaves in order to activate the pharmacologically part of coca. Literally dozens of different plant species have been utilized by different groups; the coqueros (coca users) were wise not only in how to use the plants, but in how to combine them in order to facilitate the release of active principles.

Coca is used as a folk medicine for ailments as diverse as toothache and altitude sickness. Coca has been and continues to be of importance not only for social and medicinal purposes, but the coca leaves themselves also show significant amounts of nutrients, including more iron and calcium than many of the food crops grown in the Andes. There is the belief among some Peruvian scientists that the low incidence of osteoporosis among Andean Indians is due in part to the high level of calcium in the leaves.

Scientists in Europe took little interest in coca until 1859, when an Italian neurologist, Paolo Mantegazza, wrote about the hygienic and medicinal virtues of the leaves. In 1860, a year later, a German chemist isolated the chemical responsible for the plant's power, cocaine. Carl Koler found cocaine could act as a local anesthetic in eye surgery. As the years passed, scientists found cocaine paralyzed nerve endings responsible for transmitting pain. As a local anesthetic, it revolutionized several surgical and dental procedures.

Poster advertising Vin Mariana, a wine containing coca. Photo by Steven R. King, 1996.
In the 1860's, a variety of ailments began to be treated with products derived from both coca and cocaine. A number of coca tonics became available, including a red Bordeaux wine combined with an extract of select coca leaves, called Vin Tonique Mariani. Manufactured in Paris, this elixir became the most popular prescription remedy in the world and was used by many celebrities, perhaps the most noted being Pope Leo XIII, who awarded the wine a Vatican gold medal and carried it around in a hip flask.

Cocaine, coca's derivative, has found many uses in developed countries, some positive and some quite detrimental. Today in medicine, coca has given us the chemical blueprint for a number of man-made substances that have local anesthetic properties of cocaine without the side effects. But in politics world-wide coca has become controversial due to the illegal use of its cocaine derivative. Many would like to see coca eliminated completely. Andrew Weil, an ethnobotanist and medical doctor, wrote, "Washington wants to eradicate coca. But Andean Indians contend that is a mistake to demonize the plant they hold sacred, and a surprising new coalition of scientists and politicians agrees."

FROM DART POISON TO MUSCLE RELAXANT

In the sixteenth century, a group of Spanish explorers traveled the Amazon River. During the voyage, one explorer was hit in the hand by an arrow and died soon after. The culprit was curare, used widely as an arrow poison by many Amazon Indian groups (as it is still used by a few today). The complex processes used to make curare were a guarded secret. Often 30 or more ingredients could be found in one recipe. Indigenous Amazonians often mixed plants of different genera to concoct their potent toxins; their skill and knowledge in safely preparing these poisons is a testimony to their incredible ingenuity. Amazonian curares are divided into two groups based upon the container the plant is stored in: pots or tubes. Pot curare in the East Amazon is predominately from the species Strychnos guianensis. Tube curare in the West Amazon is from Chrondrodendron tomentosum. (The curare in modern medicine is made from the latter species, therefore, its name: tubocurarine.)

For many centuries the exact content of curare remained a mystery to Western observers; not until 1800 did Alexander Von Humboldt witness and document the preparation of curare by the Indians from the Orinco River. In 1814, an explorer named Charles Waterton injected a donkey with curare. Within ten minutes, the donkey appeared dead. Waterton cut a small hole in her throat and inserted a pair of bellows, then pumped to inflate the lungs. The donkey held her head up and looked around. Waterton continued artificial respiration for two hours until the effects of curare had worn off. Curare was found to block the transmission of nerve impulses to muscle, including the diaphragm muscle, which controls breathing.

In 1939, the active ingredient of curare was isolated. In 1943, it was introduced successfully into anesthesiology. Curare provided adequate muscle relaxation without the depressant effect of deep anesthesia induced by ether or chloroform. Over the last 20 years, physicians have used curare to ease the stiffened muscles caused by polio and to treat such diverse conditions as lockjaw, epilepsy, and cholea (a nervous disorder characterized by uncontrollable muscle movements). Eventually more effective treatments were found for these illnesses, but the active ingredient of curare, d-tubocurarine, led to the skeletal muscle relaxant Intocostrin, used in surgery ever since. Synthetic analogs of d-tubocurarine are used tens of thousands of times per day in the operating room.

TREATMENT FOR AN EYE DISEASE

Pilocarpine is used to treat glaucoma.
Photo by Steven R. King, 1996.
If you hold the leaf of the jaborandi tree (Pilocarpus jaborandi) up to the light, you see translucent droplets on its surface. Each droplet is a gland that secretes an alkaloid-rich oil. Several substances are extracted from this aromatic oil, including the alkaloid pilocarpine, a weapon against the blinding disease glaucoma.

The shrub-like jaborandi tree is native to Northern Brazil. Brazilian folk medicine often uses a tea made from the leaves as a diuretic and sweat-inducer. Applied to the scalp, it is said to prevent baldness. An infusion of the powdered leaves has been used as a stimulant and expectorant in diabetes and asthma. It has been incorporated into the treatment of a number of diseases including pleurisy (inflammation of the lung tissue) and rheumatism (muscle and joint pain).

Pilocarpine assists in the transmission of impulses from the ends of autonomous nerves to the working muscles. These nerves trigger such functions as the beating of the heart and the focusing of the eye. When applied to the eye of a person suffering from early stages of glaucoma, pilocarpine stimulates the muscle that contracts the pupil to relieve eye pressure. Since the disease blinds by building up pressure until the eye can no longer function, pilocarpine can save eyesight.

Pilocarpine has found other medical applications as well. At present, for example, it is used in tablet form, under the name Salegen, to treat xerostoma, or dry mouth syndrome. Interestingly, in the Tupi Indian language, the name for the jaborandi is the "slobber-mouth plant," and its long-standing use in Brazil has been to induce salivation. Had we listened more closely to what the indigenous people of Brazil called their folk remedy and questioned its purposes in their medicinal storehouse of knowledge, the development of our dry-mouth syndrome product might have come years earlier.

THE MEDICINAL USES OF THE PINEAPPLE

In 1493, Columbus came across the pineapple (Ananas comosos) on the island of Guadeloupe. The natives who cultivated these fruits called them ananas and believed that they had been brought from the Amazon many generations earlier by the warlike Caribs. (This oral history may be true, as pineapple-shaped jars have been found in pre-Incan burial sites in Brazil.)

A few explorers had observed that Indians used pineapple poultices to reduce inflammation in wounds and other skin injuries. Native people also drank the juice to aid digestion and to cure stomach ache. In 1891 an enzyme that broke down proteins (bromelain) was isolated from the flesh of the pineapple, accounting for many of the pineapple's healing properties. It has been found that bromelain can also break down blood clots, which consist mainly of protein. Research continues. This enzyme may well play a major part in heart attack treatment in the near future, as well as in the treatment of burned tissue, abscesses, and ulcers.

WHAT DOES THE FUTURE HOLD?

In the early part of the century, plants were a vital source of raw material for medicines. Later, techniques were developed to produce synthetic replacements for many of the medicines that had been derived from the forest. But recently, problems with drug resistant microorganisms, side effects of modern drugs, and emerging diseases where no medicines are available, have encouraged an interest in plants once again as a significant source of new medicines. Modern-day researchers are coming to appreciate fully the vast medicinal knowledge of the indigenous people.

Companies from developed countries are now researching plants, some of which are known to have been used for medicinal purposes and others which offer potential. One South San Francisco company in particular, Shaman Pharmaceuticals, Inc., emphasizes a respectful collaboration with native and indigenous peoples as their primary method of drug discovery. With further research and exploration, doubtless many other medicines await discovery in the Americas.

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