Nature's Rx

Party sounds float up from a swimming pool in Washington, D.C. Twenty children shout and splash, toss balls, and snack on sandwiches, cookies, chips, and sodas. The guest of honor is nine-year-old Audra Shapiro, who has just finished two years of chemotherapy and whose leukemia is in complete remission. Her recovery from this cancer depended on a plant that originated halfway around the world.

Until the early 1960s Audra's disease would have meant sure death. Now the long-term survival rate for childhood leukemia is above 90 percent, thanks in part to vincristine, a chemotherapeutic drug made from the Madagascar rosy periwinkle. Vinblastine, another drug made from the same plant, helps cure most cases of Hodgkin's disease.

Plants like the periwinkle have contributed to the development of 25 to 50 percent of all prescription drugs used in the United States, either directly or by providing biochemical models, or templates, used to make synthetic compounds. Digitalis, which is used to treat chronic heart failure, comes from the leaves of the foxglove plant, and ephedrine, a component of many commonly prescribed respiratory medicines, is derived from a chemical formula from the ephedra plant. But overall, in the past 40 years there has been little development of new plant-based pharmaceuticals. During that period the U.S Food and Drug Administration (FDA) approved fewer than a dozen drugs derived from plants.

Part of the reason is simply bottom line. The development of a new FDA-approved drug costs as much as 500 million dollars. Manufacturers have found the route from plant to safe, reliable pill difficult and unpredictable, so there is limited incentive to base drug development on plants. Still, almost two-thirds of the Earth's 6.1 billion people rely on the healing power of plants; for them nothing else is affordable or available. And even in industrialized countries where scientifically formulated drugs are readily available—Americans spent 103 billion dollars on retail prescription drugs in 1998—use of nonprescription botanical drugs is rising dramatically. In 1990, 2.5 percent of Americans purchased herbal remedies; in 1997, 12.1 percent spend roughly five billion dollars on them.

What part of that money was spent wisely is a matter of some debate. While many plants have been the subject of extensive study and their effects well documented, data on others are inconclusive. Scientists are often unable to determine which chemical or combination of chemicals within a plant is responsible for relieving pain or stimulating blood flow or creating a feeling of increased wellbeing. Trying to find the part of a plant that has a specific effect can be like disassembling a radio to search for the one part that makes the sound.

Certain claims—"Guaranteed Better Health: only $5.00!"—in a proliferating number of special interest publications may well be false. No one knows, furthermore, to what extent the placebo effect is at play: Sometimes people want natural remedies to make them feel better whether or not the substance had any effect.

Nonetheless, that plants contain bioactive chemicals, many with beneficial medicinal effects, is undeniable. Arnold Relman, editor in chief emeritus of the New England Journal of Medicine, who has attacked various forms of alternative medicine for being based on "irrational or fanciful thinking" or on theories that "violate basic scientific principles," says that therapy based on botanical products need not be in fundamental conflict with mainstream medicine. "Many plant-derived materials," says Relman, "have been proved to have important biological effects."

Relman insists on scientific testing before he'll believe in an herbal remedy, but people use hundreds of plants, not all of which have been tested by science, to combat ailments ranging from cancer to colds. Echinacea, an herb taken in tablet or liquid form, activates phagocytes—white blood cells that ingest bacteria and viruses. It can be effective in fighting flu, herpes, and yeast infections. Garlic contains allicin, a chemical that has antibiotic and antifungal effects, as well as compounds that can lower cholesterol and combat hypertension. Ginger contains at least ten antiviral compounds, and studies have shown that it reduces vertigo and motion sickness. Chemicals in goldenseal, an herb of the buttercup family, kill certain bacteria, fungi, and protozoans.

Rosy periwinkle, the plant so important in Audra's leukemia treatments, is one of more than 10,000 known plant species in Madagascar, a Texas-size island off the coast of southeast Africa. Many of these species originally were found nowhere else in the world. A huge array of them, I discovered, is available for sale on any morning at the outdoor market in Antananarivo, Madagascar's capital.

I arrived at the market at 6:30 a.m. In an area roughly the size of two city blocks were hundreds of straw mats, on tables and on the ground, piled with sticks, leaves, grasses, bark, wood chips, oils, seeds, and nuts. White clay bowls held red, yellow, and orange berries for medicinal oils. Branches and stalks were tied in bundles. Vendors shaved sticks with hacksaws and wrapped the shavings in paper or banana leaves to sell.

My companion, Nat Quansah, an ethnobotanist from Ghana for nearly two decades, explained that the vendors in the marketplace represent the local population's main medical resource, functioning not only as salespeople but also as doctors and pharmacists. Their knowledge comes from experience, from trial and error with plant remedies, from methods passed down from generation to generation. Their advice—expert or not—might mean the difference between life and death. I learned from one that a plant used to correct hypertension becomes, in stronger dosages, a poison that people use to commit suicide.

As we walked from table to table, I always inquired about rosy periwinkle. The vendors suggested a wide range of uses. Quansah explained that pharmaceutical researchers first became interested in it because people in the Philippines and the Caribbean use a home-brewed periwinkle tea to treat diabetes. Like many plants, it can lower blood sugar. But its strong anticancer properties came as a surprise to researchers.

In the Madagascan countryside people who need medication consult an ombiasy, or healer, with a special connection to plants and knowledge of sacred artifacts used to invoke their healing power. We visited the home of one such healer, four small rooms with dirt floors. Seated on wooden benches in the waiting area, we watched patient after patient leave with hands full of plants—one with the greenish Jateorhiza palmata vine to deaden pain, another with the leaves and bark of Harungana madagascariensis, which stimulate gastric juice secretion, useful in the treatment of digestive disorders. Scientists have documented the effects of both these plants.

I asked the healer where her medicines came from, expecting her to say that a lack of money prevented her from buying all the necessary medicinal plants. Instead she waved her hand in a sweeping motion. Quansah explained: "She just walks out of her house and picks whatever plants she needs."

How much longer will she able to do that, I wondered as we continued our drive across the island. Along the road that connects east and west Madagascar—potholed and in some places washed away—we encountered mile after mile of broken, smoldering trees, where slash and burn farming, fueled by population pressures, has left much of the land bare. Streams flowed dark red with soil runoff. Of Madagascar's thousands of plant species, Quansah said, a great number are in danger of extinction. "What once was rain forest is now a rain desert," one local man told me. "This place was very beautiful when I was a child. It was a forest filled with lemurs."

"Stop the car!" I shouted. Thinking of all the potential cures for cancer and other diseases being lost, I traced an "X" in the middle of the road and asked Quansah to stand on it. Not hiding that I was upset, I asked him to stand there until he could see a medicinal plant that grows only in Madagascar.

He examined the bushes and scrub trees on either side of the road and pointed to a vine hanging 20 feet (6 meters) away: "That purple flower there."

As we walked toward it, he began to show me other medicinal plants we passed along the way. We hadn't left the road when he stopped and touched a tall leafless stem that, crushed and brewed into a tea, acts as an anesthetic. Chemicals in the leaves of another bush, he said, kill a certain virus. More than an hour later we still hadn't reached the purple flowers. Every step of the way, Quansah showed me more medicinal plants.

In Romeo and Juliet William Shakespeare describes "the powerful grace that lies in herbs." It was becoming clear to me that plants' powerful arsenal of bioactive substances—compounds that affect living cells—can be of significant value in waging war against human ailments.

My growing faith in plant power was soon tested. Traveling with Quansah and me in Madagascar was Gerry Bodeker, founder of the Global Initiative For Traditional Systems of Health, based at Oxford University. "I think I'm getting sick," Bodeker said one morning.

He had a high fever, and I offered antibiotics. Bodeker refused, insisting that Quansah and I get what the local healer recommended. Preparing a batch of leaves according to her instructions, we gave Bodeker a tea to sip, then boiled another brew and bent him over the pot with a towel draped over his head so he could inhale the steam.

The next morning Bodeker was fine. Whether the herbs did any good was impossible to know. On our trip I also saw plenty of people whose high fevers did not respond to plant treatments. In one rural hospital most of the beds, dirty foam mattresses on wood frames, were occupied by children with malaria, a disease that afflicts at least 300 million people worldwide and kills more than a million each year. Staring at the ceiling, the children endured fever, headache, vomiting, and stomach pain. Many would eventually suffer convulsions, unconsciousness, coma, and, finally, death.

"We give chloroquine until our supply runs out, then we can do little for them," the hospital's only doctor told me. "The parasite takes over the red blood cells." He explained that synthetically manufactured chloroquine, the only antimalarial drug the doctor had, is often useless because the parasite can develop resistance to it.

A two-minute drive from the hospital brought us to a source of such resistance. To kill parasites that are sensitive to chloroquine, a patient must take 15 pills over three days. Yet vendors at roadside stands were selling chloroquine pills one at a time—no doctors or prescriptions involved—at a price equal to much of what a manual laborer would make in a day. Many people favor the pills over traditional remedies because their effect can be quick and dramatic. But after only a few doses most people either run out of money or feel better, and stop. After the pattern repeats a few times, their bodies become factories for drug resistant parasites.

"Despite the popularity of Western medicines, rural people throughout Africa and Asia still rely on plant remedies to combat malaria," said Philippe Rasoanaivo, chief scientist at the Institut Malgache de Recherches Appliuées back in Antananarivo. His research has isolated several plants that combat parasites. Some interfere with the parasite's DNA; others stimulate the oxygen-burning action of cells, releasing oxidants that can kill the parasites.

Rasonaivo, who almost died of malaria at 13, has developed a tea that shows great promise. "It has dried stem barks of Strychnos myrtoides," he said, handing me some chloroquine pills. "Patients take these pills and drink the infusion of the tea bag. The bark enhances the action of chloroquine against resistant parasites."

When we met, Rasonaivo was in the process of planning clinical trials that he hoped would persuade a Western pharmaceutical company to test and manufacture chloroquine combined with the resistance-fighting plant he had put into his tea bag. But he knew the implementation of his plan would not be simple. He told me a story that made clear why it was so difficult to turn Madagascan plants into Western pharmaceuticals.

Several years earlier a local healer in southern Madagascar had given Rasoanaivo an unnamed plant that subsequently showed strong anticancer effects in laboratory tests. He went back for more of the plant, but the new batch demonstrated no anticancer activity. "Some plant species have several subspecies or varieties, many of which we haven't yet identified," Rasoanaivo explained. "In addition, for the plant parts you pick to have the same chemical composition, you have to know exactly when to pick them. Chemical composition can vary from morning to night. Also, is the plant old or young? What is growing nearby?

"A typical plant, furthermore, has a large number of active molecules," Rasoanaivo continued. "Chemicals act and react with each other, sometimes augmenting, sometimes decreasing the impact on human cells. Modern scientists, to make a medicine, need a single active compound. They need to know exactly what is active in the medicine so it can be standardized, measured, and checked for toxicity."

In India, a healing system known as Ayurveda goes back several thousand years. Practitioners of Ayurveda employ nearly 2,000 cultivated and wild plant species from throughout the Indian subcontinent. The system does not focus on medicines that kill disease-causing microbes but rather operates according to the view that good health results from "maintaining the body's equilibrium," said Vijay Kinra, medical director at the Khosla Hospital, an Ayurvedic facility in Delhi. "Most natural is not to fight disease but to maintain health and prevent illness," he said. I asked him how he fights malaria, which is endemic in India.

"The treatment does not kill the parasite," he replied. "The treatment seeks to restore the body's balance."

This seemed crazy to me. Malaria protozoans take over a person's red blood cells. Why wouldn't you try to kill them?

In fact, although many children die of malaria in India, many adults live with the disease, developing an immunity and becoming sick only periodically. "In Western medicine you attack the parasite," said Kinra. "But we build our approach on the knowledge that lots of potentially harmful things live in the human body all the time. Lots of people are exposed to malaria and never get sick. We use plants to make the body strong and to boost its ability to live with the malaria parasite."

Remembering the children dying of malaria in Madagascar, I still wanted to kill the parasite. But I could see that other possibilities exist.

"You've only seen the beginning," Darshan Shankar told me. He's the founder and director of the Foundation for Revitalization of Local Health Traditions, a program striving to conserve medicinal plants and related cultural traditions in India.

I went with Shankar through the herb garden in the village of Jodagette, near Bangalore, where local healers rely on unwritten folk knowledge. We met three healers, all specialists—one treated burns, another snakebites, another skin conditions. The last healer broke open a plant stem and smeared the sticky white sap, which has an antibiotic effect, on my forearm. "We must honor this plant as we honor a blood bank," he said.

"Valuing and preserving the knowledge of these healers is as important as valuing and preserving the plants," Shankar told me. "The world has realized it should be concerned about saving biodiversity. But cultural knowledge is just as important. Destroy the local knowledge system and thousands of years of time-tested data are gone."

In Jodagette many villagers encounter deadly snakes, particularly during the monsoon season, when rice is sown. G. Swami Rao, who treats the villagers' snakebites, showed me how he grinds his plants into a paste. It's the only treatment for cobra bites available here. Antivenom, made with horse antibodies, is too expensive for the village to keep on hand, and it must be administered as soon as possible. The nearest hospital is about three hours away by car, and no one in Jodagette has a car.

Villager after villager told me how swallowing Rao's remedy after a snakebite had saved a friend or family member. Although they may have survived without any treatment, it is possible that molecules in Rao's plants chemically interact with components of the snake venom, or they may stimulate a helpful reaction such as an immune response or a rise in blood pressure.

When I visited Calcutta, I asked Antony Gomes, a Western-trained professor of physiology at the University of Calcutta, about Rao's plants. Why couldn't such a treatment be recorded and standardized? His answer reminded me of what Philippe Rasoanaivo had said about the plant in Madagascar that had shown anticancer effects.

Gomes told me how, a year earlier, he had visited a healer in rural West Bengal whose plant successfully countered cobra and viper poison. The healer's recipe had come from his grandfather to his father to him.

Gomes took the healer's plant to his laboratory to test on rats. He prepared a dosage of snake venom that he could predict would kill 50 percent of the animals. He administered it by injection, and 50 percent of the rats died. Next, he gave the same dosage to another group of rats, then fed them an extract of the roots. None of the rats died.

Gomes returned for more of the plants, but the healer had grown suspicious and refused to provide any more.

So Gomes had a botanist examine what remained of the first batch of plants. Together they went to rural West Bengal, collected the same plant, and again tried the experiment. The new plants did nothing to neutralize the venom. Just as Rasoanaivo had found in his work with anticancer medicines, the chemical composition of plants is complicated. Even with all their modern technology scientists do not know which plants to pick or when to pick them or whether traditional healers might have added other herbal or nonherbal ingredients to the cure.

Gomes's story was another illustration of why pharmaceutical companies spend an insignificant amount of their research money on natural products and why they focus most of their resources on genetic research and synthetic drug design: Understand the pathological process that causes disease, and design a molecule that fixes it.

This isn't to say that researchers have given up trying to produce effective pharmaceuticals from plants. In 1976 Baruch Blumviral won the Nobel Prize in medicine for his work on infectious viral diseases. Among his accomplishments was the discovery of an antigen, or a marker, on the surface of the hepatitis B virus cell. This discovery led to the development of a hepatitis vaccine.

Blumberg's vaccine is produced synthetically, but he and his team, hoping to treat people who had already contracted hepatitis B, later studied hundreds of plants used by traditional healers worldwide to fight jaundice, a symptom of the disease. They extracted chemicals from Phyllanthus amarus, a mainstay of India's Ayurvedic medicine. In laboratory and animal tests, these chemicals acted on the hepatitis B virus, disrupting its development—a result repeated in a clinical trial on patients in India.

When other researchers repeated the experiment, however, their findings were inconclusive. The plant's effectiveness varied, apparently, depending on where it grew and when it was picked. I asked Blumberg if he believed that it was impossible for modern medicine to develop reliable pharmaceuticals from plants.

"No," he replied. "The lesson is that we need a better way to deal with all the variables involved. We need a new way to listen to nature while maintaining all the advantages of science. Certainly science should be open to this. By definition science welcomes new evidence, new ways of thinking. It has no final truths. It is a continuous quest and exploration."

One of the world's leaders in the quest is Jim Duke, a botanist who recently retired from the U.S Department of Agriculture after three decades of studying medicinal plants. He's the author of The Green Pharmacy and Herbs of the Bible: 2000 Years of Plant Medicine.

In Duke's medicinal garden in rural Maryland hundreds of plants carpet a hillside sloping down to a creek. Some of the plants are more than ten feet (three meters) tall, others crawl along the ground; some are brightly colored, others drab. Bees and butterflies, along with the scents of apple, licorice, and mint, fill the air.

As Duke described the plants, I realized that untapped plant power abounds everywhere. Seeds of the milk thistle, a weed that grows in many backyards, contain silymarin, a compound that helps prevent toxins from entering the human liver.

"Come down to the catacomb," Duke said, leading me into his book filled-basement. "I wish we could get the spiritual connection to plants that shamans have," said Duke, "but in some ways we know a lot more. We have studies and evidence. Not romantic views of how nature works but hard facts."

As we flipped through his computerized data bank, Duke talked about how isoflavones in soybeans may fight breast cancer; how angelica contains compounds that cause smooth-muscle cell walls to relax, reducing chest pain, or angina, caused by atherosclerosis; and how the kava rhizome contains compounds used as numbing agents or as sedatives.

One of Duke's missions is to gather data to help overcome the resistance to plant remedies. I told him about a woman who suffers from severe arthritis. The medicine she takes for pain causes bleeding and shortness of breath. A friend suggested various botanicals, but the woman refused to try plant or herbs. "They're not scientific or medical," she said. She wanted a pill.

Duke pointed out that if a little white pill could significantly cut chances of developing cancer, having a heart attack, or suffering from a stroke, people would take it, especially if it had no side effects. In fact, he said, this "pill" already exists. It's called "eating fruits and vegetables every day." Scientists have started to identify the antioxidants, detoxifiers, hormone regulators, and other substances in food that cut the risk of various diseases.

"We can merge science with herbalism," Duke said. "This will give us better drugs than if we rely on manufactured drugs alone. We can use science to test plants, to find what works best. The issue is not nature versus science; rather it is how to use science to get the best medicine, be it natural or synthetic.

"My life's ambition," said Duke, "is to get the FDA to require drug companies to test their new synthetic drugs not only against inactive substances, or placebos, but also against any known or suspected herbal alternative. We can have what plants offer without leaving the scientific method."

Back in Duke's garden I spotted what appeared to be a common weed and bent to pull it up. "Please don't," Duke said. The plant was chicory, which contains chicoric acid—a chemical that shows promising activity against the virus associated with AIDS.

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