Protecting the Global Medicine Chest—and the biodiversity that produces it

As climate change shrinks rainforests, coral reefs, and other natural areas worldwide, the global medicine chest is vanishing as well. It is precisely biodiversity that has given rise to the many healing substances in the world around us, scientists say. In the last 25 years, just one drug out of 800-plus approved by the Food and Drug Administration was discovered by chemists working purely in a lab, says the former director of the National Cancer Institute. Here’s how to prevent the losses that imperil our own health, as well as that of the planet. [This information was correct in 2010, when this article was written for Prevention magazine.]

In the fall of 1973, a strapping 25-year-old was working at a job he enjoyed in a California sawmill, transforming trees into boards and training other workers. Until a fellow worker missed his hand signal to hold back the next log headed for the debarking machine. “The floor was covered with a thick layer of bark, so when the log rolled off the machine it knocked me down but didn’t kill me,” the worker recalls. Instead, it crushed two of the young man’s vertebrae, ruptured a disc, and produced excruciating, uncontrollable chronic pain that ruled every minute of his day and night.

“I couldn’t think about anything else,” he remembers. “The pain tore apart my marriage. I became estranged from my son. I had trouble holding down jobs.” Commonly prescribed opiate-derived remedies, such as Percoset, were effective for only a short time, because of the tolerance to them that patients inevitably develop. Eventually, no matter how much he took, he couldn’t escape the agony.

            Finally, in 1987 he realized he could stop the pain for good. He went into the backyard with a .357 Magnum, put the muzzle in his mouth, and pulled the trigger. The gun misfired, and he decided God was telling him there was another solution.

The answer was taking shape in a laboratory at the University of Utah, where a team headed by biology professor Baldamero M. Olivera, PhD, was analyzing the complicated mix of compounds in the venom that a marine snail uses to stun and kill its prey. Olivera knew about the vividly patterned, 1–5-inch snails from a boyhood hobby collecting seashells; though he’d never been stung, he also knew that so-called cone snails (example shown here) were powerful little critters, with some species squirting out poison that could kill a human. And he was aware that snake venom had been used to make drugs, notably Captopril, prescribed for hypertension, congestive heart failure, complications of diabetes, and more. That meant there was a good chance cone snails could be a source of cures, too. Olivera’s group published its first paper on potentially useful components of the venom—proteins called conopeptides—at about the time the young sawmill worker had his accident.

Olivera set about figuring out how the conopeptides worked, eventually discovering that one of them affected the nervous system’s communication system. Neuroscientist George Miljanich, PhD, began collaborating with Olivera in 1984 and, around when Quinton tried to take his life, realized that the conopeptide in question had a potential analgesic effect. Even better, its mechanism was unusual: stopping the nervous system from sending pain signals to the brain in a manner that bypassed the so-called opiate receptors, where drug tolerance builds up. That meant a medicine made from it would keep working, no matter how long a patient used it.

First under the aegis of the biotechnology firm Neurex, and later as medical director of Elan Pharmaceuticals, Miljanich would develop the conopeptide into the powerful new painkiller Prialt—but that was nearly 20 years away. The careful process of producing new pharmaceuticals—collecting raw materials, identifying potentially useful substances, discovering how they function, developing formulations that can be taken as medications, shepherding them through animal and human trials, and finally receiving FDA approval—can take many years and cost close to billion dollars, says Gordon Cragg, PhD, former chief of the Natural Products Branch of the National Cancer Institute (NCI) and one of the developers of paclitaxel, also known under the brand name Taxol, a breast and ovarian cancer drug originally derived from yew trees in the American Northwest.

Cragg, Olivera, and Miljanich are among the many leading scientists worldwide who explore natural substances for novel ways to conquer discomfort and disease. Nature has long been our source for therapies, including traditional herbal cures—still relied on by 85% of the world’s population and increasingly popular in the United States—and modern prescription medications. In the last 25 years, just one drug out of 800-plus approved by the Food and Drug Administration was discovered by chemists working purely in a lab, says Cragg.

RACE AGAINST TIME

Development, pollution, climate change, industrial activities such as mining and logging, and other processes are changing the planet quickly, though, and many regions are losing plants, animals, and microbes that may provide the next medical breakthrough, says Jeffrey Wise, director of the Pew Environment Group’s Global Conservation Initiative. Just in the Amazon and Indonesia, 120,000 square miles of richly diverse rainforest have been lost in last decade. Unless we move immediately to save these precious resources, we may miss out on new life-saving cures, Wise says.

Like many people, you may think of environmental changes as abstractions—perhaps changing a remote island or influencing the numbers on a scientist’s chart—but not affecting your life. Not so, according to Sara Howard, communications director for Congressman Russ Carnahan, who is putting together legislation to protect areas that supply a large portion of the world’s medicine chest. Places like tropical rainforests may seem far away, but what happens there impinges on you and your health, says Howard: “Conservation is a public health issue. Every one of us knows someone who relies on treatments for cancer, diabetes, and other serious illnesses—many of which supplied by the natural world. Without these remedies, our quality of life would be greatly affected.”

The losses in the tropics are already underway, reports Charles Wichman, director and CEO of the National Tropical Botanical Garden, in Hawaii. “One in every 4,000 tropical plants tested has healing potential, yet one-third overall are currently threatened with extinction,” says Wichman, whose organization sends teams to catalog mainly Pacific-region plants and save their DNA for future research. “Even worse, plants are often keystone species, providing shelter and food for many other organisms. As they die off, we may face a catastrophic biological collapse.”

            Miljanich, whoses many colleagues who search the globe for medicinal materials, sees the same pattern. “They all report increasing scarcity of numerous species, which reduces the variety of materials available for new medications,” he says.

Coral reefs (example shown here) are among the areas already affected. Because of their biodiversity, these structures have been dubbed the “rainforests of the ocean,” according to Cragg. However, climate change means rising ocean temperatures, and that in turn causes higher-than-normal levels of atmospheric carbon dioxide to dissolve in the water, bringing about the disintegration of the reefs and the death of creatures that live in and around them. “Coral reefs tend to be near coastlines, so are damaged by industrial pollution as well,” adds Cragg. “And fishermen cause yet more destruction when they use explosives to stun tropical fish that they then collect and sell to aquariums.”

As a result, some of the organisms that the reefs shelter, including cone snails, are disappearing. In 2003, an article in Lancet suggested a worldwide inventory and possible protection for the snails, which are a potential source of numerous additional drugs, including, says Olivera, stroke and epilepsy medications and yet more painkillers.

Supplies for existing drugs can also be at risk. The basis of Irinotecan comes from Camptotheca trees in China. Drought and unchecked logging have endangered them, though, and scientists are racing to find substitutes, including new cultivars of the tree that may be able to be cultivated as a crop in the United States and synthetic forms of the drug. One scientist described the difficulty of reproducing the complex natural compound in the laboratory as “hand-to-hand combat.”

New and existing pharmaceuticals aren’t the only threatened medications. Herbal remedies are also vanishing. Development and industrial activity mean loss of medicinal plants that thrive in specific ecological niches, such as prairies, bogs, deserts, and mountainsides. “Most of our country’s midsection has been plowed under for giant commercial farms growing single crops over vast areas,” says Linda LeMole, MNSci, executive director of United Plant Savers (UPS), a nonprofit that preserves healing plants in the US and Canada. In contrast, the old-time family farms grew multiple crops and included many wild areas—ditches, streams, woodlands, pasture edges, and more. “This means that the original wild populations of echinacea, pleurisy root, and other important healing plants of the prairie are at risk.”

Herbs may also disappear when so-called mountaintop mining removes most of a mountain and dumps it in a nearby stream, or when a bulldozer clears land for a mall or housing development, says Michael McGuffin, UPS board member and president of the American Herbal Products Association, a trade group. “It isn’t just the land that is lost. All its plants are gone, too.

As a result of these transformations here and abroad, many organisms are gone before we know what disease-fighting substances or mechanisms they contain, says Julie Sherman, manager of the Pew initiative. Even worse, she adds, many endangered areas are in developing nations that can’t afford to protect them. To help solve this problem, the conservation group assembled a coalition of major organizations, including World Wildlife Fund, Nature Conservancy, Wildlife Conservation Society, and Conservation International, to push for legislation that would help save these places.

As a member of the House Foreign Relations Committee, Russ Carnahan (D.-Missouri) is sponsoring legislation that would redirect a small amount of current foreign-aid expenditures to conservation efforts in developing nations. “The US spends $30–$40 billion to develop new drugs, but a tenth of that to protect the natural resources that go into them,” says Sherman. “Supporting conservation with a modest redirection of existing expenditures would go a long way to improving public health.”

MOTHER NATURE, TOP CHEMIST

Biodiversity itself is the source of the many complex and potentially useful substances in the world around us, according to Miljanich, now CEO of Airmid, a firm that develops drugs from natural products, including sea anemones and the herb rue (scientific name Ruta graveolens). “It’s a chemical war out there between predators and prey,” Miljanich says. “Predators such as cone snails, poisonous snakes, and the like diversify their toxins so they can attack many kinds of prey. The prey animals, in turn, have to produce antidotes, chemicals that are repellent to predators, and other ways to protect themselves. The most successful creatures have evolved a broad arsenal.”

            Even plants protect themselves. If you have a garden, you may have noticed that deer generally don’t eat the most aromatic plants, such as sage and rosemary. The strong scents are anathema to grazing herbivores. “If you observe something that just sits there looking defenseless, such as a plant or a marine slug, yet survives in its ecological niche, you can bet it has good ways of protecting itself, in addition to methods of reproducing itself,” says Cragg.

Traditional herbal remedies come from the plants that have the most varied and powerful compounds, says LeMole. (Herb garden closeup shown here.) “These are called the ‘higher plants.’ If you look at their constituents with an instrument called a chromatograph, you find that they are much more complex than, say, houseplants. The medicinal ones are full of substances that healers have found useful for millennia.”

These potent substances—whether in plants or animals—attract the attention of developers of modern drugs as well as village healers, according to ethnobotanist Paul Cox, PhD, executive director of the Institute for Ethnobotany, in Jackson Hole, Wyoming. “It’s a place where the concerns of traditional people and scientists converge,” Cox says. One scientific organization that has focused on exploring the natural world is the National Cancer Institute. In 1960, it began an ambitious collection program in cooperation with the US Department of Agriculture. Since then, the institute has amassed a library of hundreds of thousands of extracts of leaves, bark, venom, and more, to be analyzed primarily for cancer drugs and other medications.

Collections like NCI’s, or the one at the National Tropical Botanical Garden, are essential because it is nearly impossible for chemists to dream up nature’s complex structures on their own, according to Cragg. “At Squibb,” he recalls, “scientists trying to produce a wider-spectrum antibiotic synthesized one million possibilities, to no avail. Then, in the river behind their New Jersey plant, they found bacteria that were exactly what they needed to make an antibiotic that was effective against more microbes.”

Cragg’s conclusion? “Nature is the supreme molecular architect.”

NEW IDEAS, NEW CURES

Mother Nature is not just a virtuoso chemist, she’s a prolific one. In seeking novel ways to attack disease, Miljanich and his colleagues at Airmid looked to history for inspiration. After finding reports as far back as ancient times that a tea made from the plant rue could be used for what we now know are autoimmune disorders, they used a molecule derived from the plant to explore treatments for diseases in which the immune system attacks healthy tissues, including multiple sclerosis, rheumatoid arthritis, and psoriasis.

The knowledge of healers in remote villages fascinates Cox, one of many ethnobotanists who travel the world to consult with today’s practitioners of ancient knowledge. The healers’ expertise is profound, Cox says: “When talking to them, I’m accessing a medical ‘database’ that goes back thousands of years.”

            He points to snakeroot, shown here, a plant long used in India to lower blood pressure and thereby allay anxiety and insomnia. The herbal remedy acts on the brain, researchers determined; they subsequently used this idea to create the blood pressure medicine Reserpine. “Before Reserpine, we dealt with hypertension by means of vasodilators, which widen blood vessels, thereby lowering pressure,” Cox explains. “Snakeroot taught us that there was another way: we could talk to the brain to solve the problem. Though Reserpine has been replaced by other hypertension drugs, we wouldn’t have any of them without that breakthrough concept.”

A specialist in the islands of the Pacific and Southeast Asia, Cox has often been awed by local skills. “Once, I was walking through a Samoan village with a healer and my teenage son, who was stung by a wasp,” he recalls. “The healer quickly took some bark from a tree, mashed it into a poultice, and applied to the fast-swelling site of the sting.” The intense pain and redness subsided in less than a minute. Back in the United States, a lab test confirmed the action of the bark of this particular tree against inflammation. Further studies suggest that it works against antibiotic-resistant Staphylococcus aureus and cancer. “The whole experience knocked my socks off,” Cox says.

While in Samoa, local practitioners showed Cox a tree-bark potion that could cure hepatitis with just one or two doses. When Cox took the brew to Cragg and others at NCI, the institute’s scientists found that it wasn’t useful against cancer, their main research concern; however, the potion did attack AIDS in novel ways—by flushing out the hidden virus reservoirs that build up in sufferers, so other drugs could get at the microbes and kill them.

“Because this treatment, eventually developed into the medication Prostratin, goes after the reservoirs, it has become an entirely new class of AIDS drug,” says Stephen Brown, MD, medical director of the AIDS Research Alliance, in San Francisco. The alliance supported further research and is moving toward about five years’ worth of human trials, likely to begin in early 2012.

“The hope is that Prostratin will clear people of the virus,” says Cox. So far, all materials for the tests have come from Samoan mamala trees (whose scientific name is Homolanthus nutans), though researchers are looking for the active ingredient in other plants and devising ways to synthesize it in order to take the pressure off that source, says Brown.

Once the drug is on the market, the people of Samoa will share in profits from it. “I made sure their intellectual property rights were protected,” says Cox, who notes that giving them a fair share helps them preserve their valuable knowledge, while encouraging them to share their cures with the rest of us.

Cox finds that village practitioners are pleased that he notates their remedies. “Cultural change means medicine men and women are as endangered as their plants,” he says. “One older lady I interviewed called her grandchildren around her and admonished them for being less interested in her cures than I was—a visitor from far away. But kids want to wear jeans and listen to hip hop. We are right to worry that biodiversity is being lost, but we should also be concerned that traditional medicine—a valuable part of our global cultural diversity—may not last much longer either.”

GIVING NATURE A BREAK

There are many efforts underway to make sure we don’t run out of ideas for new medicines and information about old ones. Traditional herbalists worldwide typically harvest their cures sustainably. “It makes sense,” says ethnobotanist Linda Different Cloud, PhD, who lives and works on the Standing Rock Sioux Reservation in North and South Dakota, shown here. “We don’t deplete your ‘pharmacy.’ In fact, we manage it—replanting to replace what we harvest—so we find more in years to come.” It’s counterintuitive, but important to recognize, she says, that populations of Native medicinals like camas and sweetgrass have declined now that American Indians don’t have the opportunity to tend them as widely as they once did.

Though local practitioners used to be the primary source of medicines for Americans of all ethnicities—not just Native Americans—by the mid-20^th century, most of us had turned to large pharmaceutical firms and makers of commercial herbal supplements for our remedies. These companies, which use huge amounts of raw materials to make medications that serve national or international clienteles, have also sought to take the pressure off natural sources. Collecting in the wild is very expensive, explains Cragg. Further, acquiring perhaps tons of bark or leaves in order to extract enough of the active ingredients needed for many courses of a modern medication can wipe out the very organism the drug depends on, he says.

In some cases, big drug and herbal-supplement firms have turned to farms that produce the raw materials they need. The materials for popular supplements such as echinacea, black cohosh, goldenseal, and ginseng are cultivated as well as collected in the wild, says McGuffin, of AHPA. According to Cox, conventional pharmaceutical preparations with farmed supplies include the heart medicine digitalis, much of which comes from fields of foxgloves in Spain; malaria drugs from the plant artemisia, grown in countries including China and Vietnam; and the cancer drug Vincristine, made from Madagascar periwinkle grown in warm regions, including the American South. Taxol also has an agricultural basis nowadays. “The medication was originally made from the bark of yew trees,” says Cragg. “But stripping the bark from a tree kills it, so a way was found to use the needles, which grow back after harvesting. Now, one major source is yew plantations in Italy.”

There are also attempts underway to produce Taxol’s active ingredient in the lab, another money- and nature-saving strategy. In the case of the recently approved diabetes drug Byetta, the material it uses to signal the pancreas to make more insulin is based on a compound from the saliva of Gila monsters, an endangered reptile of the American Southwest (shown here). “Now, the active ingredient is synthesized,” says Byetta user Virginia Valentine, a diabetes sufferer and proprietor of Diabetes Network, a counseling service in Albuquerque, New Mexico. “I tell my clients, ‘Don’t worry, you’re not taking Gila monster spit!’”

Despite these efforts, however, the forces overwhelming the environment and destroying habitats worldwide nowadays are chipping away at nature’s bounty and the promise of new cures. “The escalating losses are alarming,” says Sherman of the Pew Global Conservation Initiative. “Two-thirds of the 10 million species with which we share this planet could be lost by the end of the century—a loss comparable to what occurred during the mass extinction that killed off the dinosaurs. We are losing resources before we even know what cures they might offer.”

HAPPY ENDINGS
In 2007, Harvard Foundation named Baldomera Olivera Scientist of the Year for his research. His work not only produced the materials that would become Prialt, but also inspired thousands of spin-off studies by other scientists, who used the powerful conopeptide Olivera had identified to discover more about how the nervous system works.

That same year, the sawmill worker—now in his 60s—got welcome news, when his doctor referred him to a specialist to see if he could get some relief from Prialt, which had recently been FDA-approved for pain that couldn’t be treated any other way. The medication doesn’t work properly if it goes through the digestive system, so a pump had to be installed in his abdomen to send tiny amounts of Prialt directly into his bloodstream on a regular basis. “Determining the correct dose was the hard part,” he recalls. “Too little and it doesn’t deal with the pain, but too much and you can have side effects including dizziness or even hallucinations.”

The doctor soon got it right, and he had his life back. He had begun to write, and within days after starting Prialt, he was outlining a novel. “I always felt I had something to contribute — if only I could get rid of the pain,” he says.

This is a pivotal moment in history, according to Sherman. We can choose to take action and save natural resources, so more people have happy endings, she says. “This is about the health of all of us—you, me, and the planet.”

CURES AT RISK

In addition to the rainforests and coral reefs, many places and their medicinal resources are at risk worldwide.

Tropical mountains—Frogs from these areas have already provided important medications, including the basis for modern surgical anesthesia, according to Karen Lips, PhD, associate professor of biology and amphibian specialist at University of Maryland. Other frogs have promise for new antibiotics, analgesics, anesthetics, and more, says neurobiologist George Miljanich, PhD, CEO of drug development company Airmid. Though the situation is the worst in mountainous tropical zones, such as those in Borneo, Africa, and South America, frog populations are declining everywhere, according to Lips. “They are dying without our ever knowing what they could provide,” she says. “For example, we wanted to figure out how a certain species that gestated its young in its stomach turned off its digestive juices during that period. Understanding that mechanism could have provided ideas for new stomach-ulcer medicines. The frog is now extinct, and we’ll never have that information.”

Wetlands—These moist areas are important sources of microbes that scientists use to create new antibiotics, according to Miljanich. However, wetlands are disappearing in the United States and around the world, as they are polluted and/or paved over for development. “I live in the San Francisco Bay Area, where we have filled in almost all the wetlands,” he says. “We are turning resource-filled places into pharmaceutical wastelands.”

Appalachian forests—Mining, which cuts huge swaths out of the land, has killed off many southern Ohio and West Virginia forests and their medicinal plants, including American ginseng—the most important and potent type of this plant worldwide, according to Lynda LeMole, of United Plant Savers, which protects medicinal herbs. Over the last 4 decades, first local people, then her organization, replaced topsoil and replanted ginseng in a strip-mined tract in Rutland, Ohio. You can visit 1,200 acres of restored forest, prairie, rolling hills, and ponds; there’s an herb-themed walking trail. For information on this and 70+ other botanical sanctuaries the organization accredits nationwide, go to unitedplantsavers.org.

Oceans—Much of the work collecting promising material from the marine environment has been fairly recent, says Flora Katz, PhD, program officer of the NIH’s International Biodiversity Group Program. “However, we consider it our most promising source of new drugs,” she says. Some marine-sourced medicines have made it into commercial use, including AIDS drug AZT, from a sea sponge; cancer drug Trabectedin, from the Caribbean sea squirt; and pain drug Prialt, from cone snail venom (see main story). Other material from creatures such as sponges and new species of bacteria found only in the deep ocean may become antibiotics, anticoagulants, cancer drugs, and more. Climate change is transforming the world’s oceans quickly, though, Katz says, meaning that we are continually cutting down our chances of finding future life-saving medications from the sea. “When I look lists of drugs that are approved or in trials, I see that many of their sources are already endangered,” she says.

GET INVOLVED

You can help preserve nature’s gifts for future generations, says Richo Cech, medicinal-plant expert and owner of Horizon Herbs, an organic seed farm and nursery. The solutions are in your backyard:

Grow endangered medicinal plants. They’re beautiful, says Cech, and, should you wish to make your own remedies, you’ll have living plants on hand and won’t have to purchase the materials or gather them from the wild. “One important at-risk herb is echinacea, which you can grow easily in full sun in your home garden,” he says. “Two others are ginseng and black cohosh, which thrive under hardwood trees, such as maples or oaks. A word of advice, though: grow the original wild form of the plants, not hybrids from the garden center, which may have been bred for an unusual blossom color, for example, and lost some healing value.” For seeds and growing instructions tailored to your region, call Cech’s company at 541-846-6704; log onto horizonherbs.com; or obtain the printed mail-order catalog, which is as packed with useful information as any textbook.

Avoid over-harvesting in the wild. This has meant the disappearance of many superstar herbs, including echinacea and ginseng. Contact Cech’s company for beautiful, effectuve alternatives to cultivate in your area.

Make your own remedies. Excellent books for this purpose include The Way of Herbs, by Michael Tierra, and Rosemary Gladstar’s Herbal Recipes for Vibrant Health: 175 Teas, Tonics, Oils, Salves, Tinctures, and Other Natural Remedies for the Entire Family, by Rosemary Gladstar.

Volunteer. Ask your parks department about volunteer projects to protect your local environment. 

Text c. Stephanie Woodard; 2 photos c. Woodard, the rest courtesy Wikimedia Commons.