Raiders of the Forest Cures
by John Tidwell
The Indians had found something. The bearded American
scientist stopped scribbling notes and moved quickly
through the riot of tropical foliage while shouts of
“Kokoe!” echoed ahead of him. Mist was spreading
over western Colombia’s mountainous Choc’o
region, one of the wettest places on earth and home
to mysterious creatures the indigenous Embera peoples
called Kokoe. The animals’ skin is so poisonous,
the Indians say that an arrowtip touched to it would
become deadly for months—excellent for hunting.
Donning a glove, the American biochemist from the National
Institutes of Health hustled up to the stream where
several muscular hunters were clustered. Scooping up
the source of the commotion—a bright orange, half-inch-long
frog that regarded him with black, unblinking eyes,
John Daly smiled beneath the broad brim of his hat.
Phyllobates terribilis, he mused, perhaps the
deadliest animal on earth, as well as a potential treasure
to medical science!
The natural world is the origin of most of our medicines and remains alluring to scientists and to pharmaceutical companies alike, each seeking new and unknown drug sources. It’s tantalizing to think that the cure for AIDS or cancer could be out there, in the biochemical bouquet of a rainforest flower or the venomous sting of a reef snail in the sea.
Or maybe the next pharmaceutical bestseller might be sloshing in the calabash of some obscure village shaman. The wilderness that was once considered useless is now seen as a vast genetic frontier, chock-full of species with a nearly infinite variety of biochemical weaponry, hammered into unique forms over the millennia by the forge of natural selection. Smithsonian entomologist Terry Erwin has estimated that there may be greater than ten quintillion different insect species on Earth, more than anyone could catalogue in a lifetime.
Today, with a global pharmaceutical market worth hundreds of billions of dollars, it has become clear to drug companies, large and small, that natural products from remote places may lead to fortune and glory. According to a study by Scotland’s University for Drug Research, nine of the 20 top-selling pharmaceuticals worldwide are derived from natural products, with profits reaching beyond $16.5 billion in 2001. Taxol, discovered in 1967 in the bark of the Pacific Yew tree (Taxus brevifolia), has not only become the number one treatment for breast and ovarian cancer, but has generated close to $2 billion dollars in sales last year.
The quest for medicinals from animal and plant species has mushroomed since the 1960s and over a hundred major drug companies are now “bioprospecting.” Some companies, like California’s Shaman Pharmaceuticals, have focused entirely on seeking cures in the folk remedies of indigenous peoples, convinced that the “Philosopher’s Stones” of medicine could be found in their dying arts. Today, hunting for new medicines has proven to be more scientifically frustrating and politically volatile than most bioprospectors ever envisioned when they first ventured out into the wild.
Prospecting and Piracy
When Steven Speilberg brought Indiana Jones to the screen
in the 1981 film Raiders of the Lost Ark, he
gave name and identity to the archetypal scientist-explorer.
Later films, like Medicine Man (1992) and The
Serpent and the Rainbow (1987) that were based
on the real-life bioprospecting adventures of ethnobotanist
Wade Davis, reinforced the image of the swashbuckling
American adventurer. But seen through the eyes of the
indigenous peoples whose temple he has just raided,
the heroic Indiana suddenly looks like a thief.
Like the cinematic Dr. Jones, scientists have long thought they had the right to take animal or plant samples from the field for study. In fact, recording folk traditions or bringing back a dollop or two of a shaman’s magical concoctions was not only considered good science, it was (and still is) absolutely necessary to understanding the culture. Back in the 1970s when John Daly wanted to learn how poison-dart frogs made their toxins, he didn’t hesitate to collect scores of them from many different South American countries, boxing them up and mailing them back to his lab in Bethesda, Maryland. This was how scientific work was done, and most countries had no laws against the export of plants or animals for scientific purposes. Everyone assumed the indigenous peoples didn’t care. Big profits from these samples were also not part of the equation back then because scientists couldn’t modify complex toxin molecules or produce mass quantities of a drug from a small field sample.
But by the end of the 1970s, the biological revolution was rolling, and together with rapid advances in computer science and instrumentation, scientists had the tools not only to “see” molecules more clearly, but to change their chemical structure, making them more or less potent as needed. The routine modification of small molecules, such as the alkaloids found in poison-dart frogs, and of organisms, by introducing new or modified DNA, has since followed. By June 1980, the Supreme Court had ruled that genetically engineered living creatures could be patented and owned. Not only was this a major step for science, it changed all the rules of medicine hunting. Suddenly, there was a much greater potential to profit from “wild” drugs and collected genetic diversity. What was once a fairly arcane field of science became the high-stakes game of bioprospecting.
At about the same time, conservation groups and nongovernment organizations (NGOs) began a serious campaign to save the rainforests of the world from logging and strip-mining. They began to promote rainforest products that could only exist if the jungle was left alive and healthy. While some groups made efforts to sell Brazil nuts and shade-grown coffee, ethnobotanists like Mark Plotkin began promoting the Amazon and other rainforests as a vast pharmaceutical cornucopia. In Tales of a Shaman’s Apprentice, Plotkin made the case that the rainforest might be home to thousands of as-yet-undiscovered plant and animal species that produce chemicals key to defeating disease. The campaign was popular, especially among pharmaceutical companies. During the 1980s and ‘90s, every major drug company from AstraZeneca to Roche began bioprospecting projects in the Amazon and around the world, racing each other to be the first to stake a claim on the next Taxol. And not all the players were as principled as Plotkin and other conservationist.
Illicit Prospecting
It wasn’t long before rumors emerged of secret
exports avoiding customs, of scientists planning to
arrive in remote villages aboard armed military helicopters,
and of companies making millions from herbs swiped from
shamen. Some Brazilian scientists claimed more than
20,000 plants were being taken out of the country by
foreigners every year, with no efforts to compensate
the indigenous peoples or the Brazilian government.
Many accounts were unsubstantiated, but surely many
were legitimate.
In 1974, an American pharmacology grad-student named Loren Miller brought a medicinal Ayahuasca vine (Banisteriopsis caapi) home from Ecuador and began cultivating it in Hawaii. In 1986, he got a U.S. patent and created the International Plant Medicine Corporation to market it. The hallucinogenic Ayahuasca is one of the most sacred plants for many Ecuadorian Indian tribes, one that shamans have used for centuries for healing and divination. When the tribes found out about Miller’s patent in 1994, they were outraged, declaring Miller an “enemy of indigenous people” and threatening to kill him if he returned. Most of the developed world said this wasn’t theft, it was business—unsavory perhaps—but business. Molecules and genes in plants and animals down to the smallest microbe were now patentable. But as more cases of hardball-capitalist bioprospectors emerged, indigenous peoples joined forces with human-rights NGOs to mount a legal bulwark against what they called biopiracy.
The movement culminated in 1992 with the United Nation’s Convention on Biodiversity (CBD), an agreement signed by 144 countries at the Earth Summit in Rio de Janeiro. Simply put, the CBD gave nations sovereignty over their genetic and biological resources and entitled them to “fair and equitable sharing of benefits” from their exploitation. It also recognized the rights of indigenous peoples to their traditional knowledge, and that any use of that knowledge should require their permission. Most of the developing nations of the world ratified the treaty. Most of the developed nations, including the United States, did not, stating that they were concerned it would harm the biotech industry. But while the CBD was an inspirational gesture that provided a legal framework upon which countries like Ecuador or the Philippines could build laws against ruthless bioprospecting, it was grandly ignored by both the scientific community and the developed world. Nevertheless, a political line in the sand had been drawn—nothing would be the same again.
Biopiracy Exposed
In the late 1990s, a British biochemist named Conrad
Gorinsky was studying the folk cures of the Wapishana
Indians, who live on the border of Brazil and Guyana.
He then took out patents on bioactive compounds found
in two of the Indian’s traditional medicines:
Tipir (which he renamed Rupununine), an antibiotic from
the seeds of the endangered greenheart tree (Ocotea
rodiaei), and a polyacetylene compound that he
dubbed Cunaniol, from the leaves of the barbasco bush
(Clibadium sylvestre), which apparently was
a powerful neuromuscular stimulant. By the time the
Wapishana found out what Gorinsky had done, he had already
formed a partnership with a Canadian venture capital
company to market “his” new drugs.
When the Indians tried to sue the 55-year-old scientist, they discovered that his actions were all perfectly legal. “I don’t owe them anything,” Gorinsky said. “I made all the intellectual effort and spent thousands of dollars out of my own pocket. Would the Indians ever invest in this?” he announced in the Brazilian press. This kind of denial of wrongdoing was a defiant stance that scientists and drug companies had used with some success many times in the past. But in the years since the CBD was formed, the legal and political landscape had changed, with countries, NGOs, and indigenous peoples challenging bioprospecting claims as never before.
With help from local and U.S. NGOs, the Wapishana mounted a legal protest that grew into political arm wrestling between England and Guyana. In the end, the British Patent Office dropped Gorinsky’s claim to Cunaniol (officially they said it lacked novelty). Accused of biopiracy by four other countries where he had worked, Gorinsky now stands to lose his other patent, as well as his reputation as a scientist. Similarly, in 1999, Ecuadorian tribal leaders and representatives of more than 400 other South American tribes came to Washington, D.C., in full traditional dress to demand the U.S. drop Loren Miller’s patent on Ayahuasca. The political theatrics worked, and the U.S. Patent & Trademark Office revoked what it called Miller’s “flawed patent.”
Prospecting Backlash
Over the past five years, such NGOs as Action Aid, GRAIN
(Genetic Resources Action International), and ETC (Erosion
Technology and Concentration group, formerly RAFI) have
begun a concerted campaign against bioprospecting of
any kind. Wherever they perceive biopiracy has occurred,
these organizations assume the role of advocate for
indigenous peoples, accusing the corporations of “illegal,
immoral, and unethical” practices, threatening
them with product boycotts back home and scuttling deals
that have often taken years and millions of dollars
to arrange. For these true believers, there is no difference
between bioprospecting and biopiracy. “Bioprospecting
is like waking up in the night to find robbers in your
home with a bag full of your possessions,” explains
Alejandro Argumedo, head of the Indigenous People’s
Biodiversity Network, “And when you ask them what’s
going on, they reply, ‘Don’t worry, we have
a proposal for benefit-sharing!’”
Developing countries have also begun to put legal muscle behind the CBD’s moral commandments. A few years after the Rio Convention, the Philippines was the first country to create laws that required bioprospectors to collaborate with local scientists, get the consent of indigenous peoples, and provide compensation to the government. In 1997, Brazil enacted similar laws, and shortly thereafter arrested scientists from Switzerland and Germany who tried to take field notes and samples out of the country without official permission. Today most South and Central American countries have erected such legal barricades and tend to view every scientist or drug company as Cortez in disguise.
Scientists have been understandably upset. While most favor sharing drug profits with local governments and peoples, many biochemists blame the CBD and its resultant fears of biopiracy for a chilling effect on field research. “When the world mentality was that natural resources were common ownership, there was a fertile utilization of natural resources for drug discovery,” said William Fenical, director of University of California, San Diego’s Center for Biotechnology and Biomedicine in a 1999 New York Times article. The Rio Convention destroyed that, he says. It took Fenical four years to get the Philippines to give him permits to hunt for a species of bioactive coral, and when he arrived, they revoked the permits and charged his partner, Bristol-Meyers Squibb, $600,000 in penalties—because, they said, Fenical did not “go through the whole process.”
Once a medicine-hunting playground, the Philippines now has some of the toughest regulations, approving only two out of 37 bioprospecting proposals, according to a Columbia University study. Andes Pharmaceuticals was rejected by the Colombian government because their proposal was not specific enough about which plant species would be collected. British researchers at Portsmouth University had to return 120 bottles of marine fungus to Thailand because they were not collected with proper permission years before. It took John Daly three years to get Panama to approve his proposal to collect poison dart frogs, giving up altogether on Venezuela. Practically every major pharmaceutical company has been accused of biopiracy in recent years, as well as prominent scientists like Daly. In fact, the charge has been used so often and so indiscriminately, that intellectual property lawyer Michael Gollin says, “If you haven’t been called a biopirate at one time or another, you haven’t been active enough in the field.”
Pharmaceutical companies, always sensitive to public opinion, have reacted with a number of strategies to save face and keep prospecting, including targeting plants and animals that indigenous tribes don’t use, a practice that limits chances of success. The ETC says another approach big drug companies use is to let a smaller company make the deal with shaman. Then the big company buys promising compounds from the little one. NGOs claim that drug companies have also been covertly using middlemen in the field to obtain samples. In the past, the people on the ground have not necessarily been company employees, but intermediaries, says Hope Shand, Research Director for ETC group. Drug companies play governments against each other, or against their indigenous peoples, to get the best deal, especially if the desired organism occurs in more than one region. Shand points to one case in which a team from the National Institutes of Health wanted to do some bioprospecting in the Philippines but were denied. So they struck a deal with Vietnam and Laos instead. However, the question remains, is this biopiracy, as ETC claims, or just smart shopping?
In recent years, many pharmaceutical companies have made strident efforts to be as open and fair as possible, making deals that meet every government requirement, with benefit-sharing plans for those involved. This strategy worked beautifully for a medicine-hunting deal on the island of Fiji that included the local government, SmithKline-Beecham, and the University of the South Pacific. Gollin, who helped broker the agreement and says this, and a similar project on Samoa, stand out as shining examples of bioprospecting projects that are above-board and respectful of the rights of all parties.
Uncertain Prospects
Unfortunately, such successes have been few. Contrary
to the claims of both bioprospecting boosters and foes,
finding medicines in the wild is often neither simple
nor profitable. While there have been some stellar discoveries
like novocaine from the coca plant, aspirin from willow
bark, and cortisone from wild yams, comparatively few
drugs have resulted from bioprospecting in recent years.
Merck spent seven years and $1 million courting Costa
Rica to get access to its rainforest, and never found
anything worth developing.
Biochemists say that while NGOs roar about the lack of profit sharing when a company finds a spicy new compound, they fail to take account of the long and arduous process it will have to undergo before the drug makes it to the marketplace—if it ever does. A bioactive compound may show potential, but that is no assurance it will make it through clinical trials, much less become a pharmaceutical best-seller.
It can often take 15 years of analysis, refinement, and three levels of human trials before a new drug is approved in the U.S., and at that point it may bear only a slight resemblance to its natural form. Ziconotide, a treatment for severe epilepsy found in the toxin of Philippine cone snails (Conus spp.), was turned down last year by the FDA after going through the entire process, and must now go through further tests before being reviewed again. Many drug companies spend huge amounts of time and money on prospective drugs, only to discover that its molecule was the wrong size or just too costly to synthesize. This should not be too surprising; after all, these natural compounds evolved as defenses to specific ecological threats, not to suit human needs. Sometimes the molecule is too fragile or too big to be easily copied, or the venom is too powerful—or not powerful enough—to be used for humans. Botanist Robbins of the World Wildlife Fund says, “It’s basically a shot in the dark… pharmaceutical companies throw out a large net and try to pull in everything they can find.” In all, perhaps one out of 10,000 species proves to be commercially viable, Robbins estimates.
There is also the cost of developing a drug. A favorite biopiracy example cited by NGOs is that of vincristine and vinblastine, two anti- cancer drugs discovered in Mexico by Eli Lilly in 1954. The compounds were found in a plant that is common to most nurseries and backyards and originally came from Madagascar more than 100 years ago: the rosy periwinkle (Catharanthus roseus). While Lilly has made an estimated $100 million per year from these alkaloids, Madagascar was never given a dime in return. Proponents say those who cry foul don’t take into account the years and money Lilly invested in the development of these drugs. In the 1950s, it cost about $40 million to bring a single medicine to market. Today it’s close to $500 million. After 30 years and more than $200 million in investment capital, Shaman Pharmaceuticals, the “great white hope” of rainforest medicinals, only developed one drug, an anti-diarrheic. Last year, the company filed for bankruptcy because it couldn’t afford to put drugs through the FDA approval.
Scarlet Letter
The more one explores the issues of biopiracy, says
Gollin, the more it seems to be about politics rather
than economics. The brand of biopiracy now carries a
stigma of criminality that, true or not, is very hard
for companies to shake. Partners become skittish, investors
bail out, and the public begins to view the corporate
product with a suspicious eye. Sometimes the accusation
alone is enough to kill a pharmaceutical project or
halt a drug’s development. In 1998, a consortium
of U.S. and Mexican universities and government agencies
tried to launch a $2.5 million bioprospecting project
with the Maya from the southern Mexican state of Chiapas.
Brent Berlin, the project’s leader and a noted
anthropologist, and his colleagues went to great lengths
to address every concern, obtain every permit, and assuage
every fear in order to examine the folk medicine of
the Maya for possible development. But not all the Maya
were happy with the arrangement. ETC (then RAFI) took
up their cause and publicly leveled charges of biopiracy
at the project. The whole thing collapsed shortly thereafter.
Berlin remains bitter, not just because his project was halted before anything was even found, but because he feels ETC attacked the wrong bioprospectors. “Sure there are bad guys out there,” he says, “but who is the first target when these people start screaming ‘biopiracy’? We are…. It’s not the folks who are out there doing it surreptitiously…. It’s the folks who are trying to do it right.” John Daly agrees, pointing out that he has been accused of biopiracy and, after 40 years, neither he nor Abbott Labs, who is trying to develop a synthetic compound based on poison-dart-frog poison, have made a cent on these alkaloids. Conrad Gorinsky and Loren Miller have not either.
The very definition of biopiracy begins to unravel when put under the legal microscope. Despite admonishments by NGOs, their supporters, and even the CBD, bioprospecting and even what could be considered biopiracy, is not a crime in most parts of the world. “There is no legal term for biopiracy,” says Gollin. “So if a company’s actions don’t need to be illegal to be called ‘biopiracy’ then what is biopiracy? It begins to mean whatever you want it to mean,” he concludes. This is not to say, he explains, that taking natural resources out of a country, be they toxic frogs or raw diamonds, without official permission is legal definitely is not. But when bioprospecting is done with the permission of both governments, sabotaging it is not so much a legal issue as a political act.
The political agenda of ETC is the recognition and respect for the rights of indigenous peoples. Some NGOs have made the case that biopiracy is an intellectual property issue, and should be addressed by international law. But according to Robert Boherer, Professor of Law at California Western School of Law, national sovereignty ought to be enough to protect the natural resources of a country and its indigenous peoples the ruling government wants to do. From this perspective, charges of biopiracy have more to do with political powerplays than medicines and intellectual property. Sadly, the real victim in this drama may be science. What future bioprospecting has may be a question that no one can yet answer.
Life from the Dealdy
A
Very Special Toad
—John Tidwell is a freelance writer living in Silver Spring. He has written numerous articles on conservation issues for ZooGoer, as well as articles on history for American Heritage and American Legacy magazines.
ZooGoer 31(5) 2002.
Copyright 2002 Friends of the National Zoo.
All rights reserved.
