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Lemma with the berry

Profiting from Biodiversity Scientific American 96

THE BERRY AND THE PARASITE

A 30-year struggle to control schistosomiasis has revealed much about patents and profits. In 1964 Aklilu Lemma of Addis Ababa University traveled to Adwa, Ethiopia, to study schistosomiasis. This debilitating disease of the liver or bladder affects some 300 million people in Africa, Asia and Latin America. The Schistosoma parasite multiplies within snails that infest rivers and ponds; when humans use the water, the organism enters their skin. At one brook, Lemma saw women washing clothes with the sudsy extract from the local endod berry. Downstream, the snails were dead. Back in Addis Ababa, Lemma, who has a Ph.D. from Johns Hopkins University, instituted a program to study whether the endod berry could be safely used in controlling Schistosome-bearing snails. Although endod also kills mosquito larvae and fish, he found that it is harmless to rats; in humans, it is an emetic. "People grow it around their houses," Lemma reports. "They have tested it for safety and adopted it as a useful plant." The subsequent saga of the berry attests to the difficulties that developing countries experience in benefiting from their own biodiversity. Each observer attributes endod's travails to a different stumbling block, but one moral seems to be clear: it takes a determined, politically savvy proponent to ensure that the promise of a product is realized for its own local community. Lemma's results attracted scientists from the National Research Development Corporation in London, who offered to collaborate. "They took sackfuls of berries," Lemma relates, and he says he heard no more from them. Returning to Adwa, he and his colleagues started a test to see if endod could halt schistosomiasis. If the disease was not transmitted for five years, they theorized, children between one to six years of age should be free from it. In 1970 Lemma left for a sabbatical at the Stanford Research Institute (SRI), stopping in London to check on his C4 collaborators." The tests had been so encouraging, he was informed, that the scientists had patented rather than published. Lemma did not appear on the patent, which was for an extraction process for endod. At SRI, he worked with Robert M. Parkhurst, who isolated the active ingredient in endod, naming it "lemmatoxin. " Along with chemist Wilfred A. Skinner, the researchers obtained a patent on a different method. But Lemma convinced his colleagues that because endod was "poor man's medicine for a poor man's disease," it was unseemly to profit from it. Accordingly, SRI donated its patent to a nonprofit foundation that Lemma hoped to establish in Ethiopia. "I felt we should get the farmers to grow it and use it locally," Lemma explains. He challenged the British scientists to donate theirs as well. The affair became diplomatically embarrassing; the scientists capitulated. In 1974 the results from Adwa came out: among 3,500 children between one and six years in age, the prevalence of schistosomiasis had fallen from 50 to 7 percent. Yet to become widely adopted, endod needed the blessing of the World Health Organization. That was not forthcoming. Ken E. Mott, who heads the WEO's schistosomiasis project, says the problem was Lemma's patents: "It was uncertain how endod should be developed, because somebody had a personal [and financial] agenda in this." The @O instead recommended a chemical molluscicide marketed by Bayer at $27,000 a ton in hard currency. (Endod sells for about $1,000 a ton.) The VMO questioned the safety of the berry, requiring that it pass tests costing millions of dollars. But the VVTHO would not help fund such tests, and in 1987 Mott advised the Italian goveniment not to provide research grants for endod. The endod patents then belonged to the Ethiopian Science Foundation, which was eventually subsumed by the Ethiopian government. Lemma attributes the VMO's animosity to a difficulty believing that good science can emanate from developing nations. "The things done in Africa did not hold any weight in the U.S. or Canada," Parkhurst agrees. In 1976 Lemma joined the United Nations, serving on the Science and Technology Commission. He convened two endod conferences; funding started to trickle in from foreign-aid agencies and private organizations. The Intemational Development Research Center (IDRC) in Ottawa offered to conduct the toxicity tests required by the VMO-provided the Ethiopian government renounced the endod patents. The test results, published in 1990, surprised no one. "It's as harmless as soap," states the IDRCs Don de Savigny. Along with a colleague, Lemma received the Right Livelihood Award from the Swedish parliament in 1989 and was finally able to establish the nonprofit Endod Foundation. In 1990 the University of Toledo in Ohio granted Lemma an honorary degree. After Lemma's acceptance speech, his host, Harold Lee, asked if endod might be effective against zebra mussels. These mussels choke submerged pipes in the Great Lakes, racking up billions of dollars in damage. Lemma demonstrated how to apply the berries: the mussels died. In 1993 and 1994 the university obtained patents on this use of endod, with Lemma as an investigator. The university agreed to donate 1 0 percent of its earnings to the Endod Foundation. Last year Lemma requested that the University of Toledo donate the patents to the foundation, which would make them freely available to African ventures. The university responded with an offer to either sell the patents for $125,000 or license them for a $50,000 fee, plus 2.5 percent royalties and $ 1 0,000 in legal expenses, reserving the right to withdraw the license if net sales were less than $ 1 0 million in five years. Such terms, Lemma says, are impossible. "It is not university policy to give things away," Lee retorts. "Lenuna can develop endod for another use and get [his own] patent." But no one is benefiting from these patents: lemmatoxin is too costly to synthesize, and no African country will sell endod to the Toledo group. Meanwhile work on schistosomiasis goes on. The IDRC is conducting a field test to ensure that endod is efficacious in checking the disease. The Agronomic Institute in Florence is encouraging farmers to grow endod on wastelands. The University of Oslo is working with Addis Ababa University to check whether simply using endod as a soap can control the disease. "Endod," Mott says, "has ended up not benefiting anybody except a few personalities who have extended their careers by presenting themselves as advocates for the Third World." Diverse reasons are offered for endod's tortuous history. Parkhurst opines that "bureaucracy is what killed it more than anything," along with a distrust of Third World science. De Savigny points out that endod is not an expensive cure backed by the biomedical industry: "Something you pick off a bush doesn't have that kind of support." Lee charges that Lemma does not work hard enough: "Why do you think I spent two years and got a patent, and he spent 30 years and got nothing?" Lemma counters that endod may yet end up benefiting rural Africans: "That is my wish and my dream." -Madhusree Mukerjee

SOWING WHERE YOU REAP

Profits from biodiversity are neither easy to pinpoint nor to protect

That biodiversity is valuable enough to pay for itself has long been recognized as a selfevident truth. Roughly half the drugs in clinical use are estimated to derive from nature. The Biodiversity Convention, adopted in 1992 at the United Nations Conference on Environment and Development, tried to ensure that profits from such goods return to the place of origin to aid conservation and local communities. Despite some success, that goal remains elusive. Although bioprospectors-those who seek potential products in biota-number in the hundreds, the returns they promise to peoples in developing countries appear highly variable. "I've seen genuine outrage in parts of the world," attests Daniel M. Putterman, a consultant who helps developing countries negotiate deals with industry. The anger is cutting off parts of the world to bioprospectors. In Thailand, public ire has forced a British foundation to stop seeking the medicinal secrets of Karen tribes. In India, thousands of insects found in the luggage of two German 44 tourists" have prompted legislation regulating gene transfer; the Philippines recently passed just such a law. Even when they agree to the transfer of such resources, some Third World representatives remain uneasy about the power balance with their First World partners. "If you are a small fish swimming with a shark," says Maurice M. lwu of the Bioresources Development and Conservation Program in Cameroon, "it makes no difference if the shark has good intentions." These problems center on that special attribute of biological materials: they reproduce. Thus, a handful of seeds or micrograms of microbes might be enough to carry a genetic resource out of a country. Technological advances allow tiny amounts of material to be screened, so a drug developer may never have to return to the source country. 'The trick right now is monitoring the flow of material," explains Walter V. Reid of the World Resources Institute. When a benefit-sharing agreement is signed, local institutions must often rely on the integrity of the foreign partner in sharing information. "You have no way of knowing" what happened to a sample, notes Berhanu M. Abegaz of the University of Botswana. On occasion, a drug developer may offer to cultivate a plant in the source country, Abegaz says. Nevertheless, he adds, this arrangement can have a double edge: the firm that holds the patent can also control the price paid to farmers, and the producers are kept at a subsistence level.

The more land brought under cultivation, the greater may be the threat to biodiversity. And if collected from the wild, the plant itself may become endangered. That happened with the Pacific yew, which yields the anticancer agent taxol. If a drug can be synthesized in the laboratory, the pressure on biodiversity is eased (again, as with the yew), but then it can become hard to ensure that some proceeds return. Roger Kennedy, director of the National Park Service, has proposed that royalties from finds-such as the bacterium Thermus aquaticus, which was discovered in Yellowstone National Park and used in the enormously profitable polymerase chain reaction-be used to protect the parks. This idea is disputed by some pharmaceutical companies and by other observers, who point out the differences between property and intellectual property. In the case of T aquaticus, the counterargument goes, scientists discovered PCR-the technique is the product of their effort and thought. Thus, their intellectual work and financial investment deserve to be protected. Many experts feel that the Blodiversity Convention (which the U.S. has still not ratified) does not adequately protect patents or intellectual property. At the same time that developing countries are demanding a share of the royalties from drug discovery, many bioprospectors argue that the promise of such revenue is overblown. One profitable drug is developed, after 10 or 15 years, from some 1 0,000 to 1 00,000 substances that are screened. "The royalties may never come," points out Ana Sittenfeld of INBlo, a Costa Rican organization that supplies extracts to several pharmaceutical firms, including Merck. For instance, the National Cancer Institute (NCI) screened nearly 80,000 biological materials between t986 and 1991only one major lead has emerged so far. Small biotech companies have, however, discovered how to make money not just from the end product-the drugbut also from the steps that lead to it. Some rent out samples to pharmaceutical companies for screening; others do the screening and provide leads to substances. The industry assigns well-defined trade values to each step: extracts sell for $10 to $100, leads sell for $100 to $1,000, and a drug candidate with animal toxicology data sells for $1,000 to $10,000. "Those countries that had access to this market information have negotiated the best deals," Putterman notes. The most valuable benefit, Sittenfeld states, is technological training. INBio, often cited as an example for future Third World institutions, functions much like a biotech company, with attendant profits. In contrast, Abegaz laments a "failure to build capacity in Africa." Among the bioprospectors in Africa is the NCI, which has been criticized for providing minimal up-front benefits and no guarantee of royalties. INBio puts 10 percent of its research budget into conservation and trains local parataxonomists, who might otherwise have been using the forests in nonsustainable ways. The Intemational Cooperative Biodiversity Groups Program, set up by three U.S. agencies-the National Institutes of Health, the National Science Foundation and the Agency for International Development-also tries to build local capacity while bioprospecting. Joshua P. Rosenthal, who heads the program for the NIH, comments that such training helps local scientists in identifying areas rich in biodiversity. A handful of other bioprospectors have set up trust funds that promise returns if royalties ever start to flow. But ensuring that biodiversity survives its value to humanity remains a climb up a slippery slope. -Madhusree Mukerjee