Travels with the war goddess: embedded journalism in a Samoan drug-discovery expedition.

DEC. 20, 2003 Huh? I stare at the e-mail on how not to offend Samoans who live in traditional villages. It would be polite to wear a lavalava all the time, whether going to church or going swimming? I'm planning to tag along with a botany expedition to a Samoan island and am reading up on the place. But what in the world could a lavalava be? Do the Samoans, whom I've just learned are strongly religious, somehow wear bathing suits to church? Although I obviously know little about Samoa, I have received an invitation that one doesn't get every day: to travel there with Nafanua, a legendary Samoan war goddess.

I've interviewed and taken classes from Nafanua's alternative, male manifestation as botanist Paul Cox of the National Tropical Botanical Garden in Kalaheo, Hawaii. At first sight, he is--with respect--too much of a family man with five children and too clearly a field biologist in glasses and running shoes to fit my expectations of a goddess.

Neither does he come across as warlike in an ax-wielding kind of way. I can very much imagine him winning a war, but by talking enemies into cooperating or by outmaneuvering them. (He once got a major airline to honor an overdue lost-luggage claim by obtaining a legal order that would have allowed seizure and auctioning of one of its planes.)

Cox received the goddess title--not a religious but a social one in the chiefly hierarchy--during a sojourn with Samoan healers in his search for plants useful for Western medicine. Pharmaceutical companies in the past decade have generally turned away from this approach, but Cox persists.

DEC. 21 I now know that a lavalava is a wide length of cloth that Samoans wrap around their lower bodies to form a sort of skirt. Both women and men wear them. Yes, even while swimming.

I'm reading Cox's Nafanua (1997, Freeman), the lively tale of his 1985 botanical research in Samoa. He describes how his mother's death from breast cancer focused his interests on searching for new medicines and inspired him to take his wife and their young children to live in a traditional village on a beach in rural Samoa. The memoir traces how a scientist, originally intending to cause as little impact as possible, gets caught up in the village's struggle against a foreign logging conglomerate to such an extent that at one dramatic point he prepared to mortgage his U.S. house to raise money for the effort. By the end, I'm not surprised the Samoans insisted that Cox accept the Nafanua title.

His search for breast-cancer drugs proved unsuccessful, but with natural-products chemists at the National Institutes of Health in Bethesda, Md., he began looking for plants that might show activity against HIV. Two healers had mentioned to Cox that a preparation from the bark of a tree called Homolanthus nutans controlled a disease that sounded to him like yellow fever or hepatitis. Perhaps there was some antiviral activity there.

In the late 1980s, a compound in the extract, since then dubbed prostratin, looked promising in the lab tests for activity against viruses. Recently, the AIDS ReSearch Alliance in West Hollywood, Calif., agreed to sponsor the first two rounds of clinical trials of prostratin.

Cox has already brokered an agreement that 20 percent of any of the alliance's profits will return to Samoa, but he's urging his team to think of ways that the Samoans might start some kind of industry if prostratin ever gets commercialized. Could they farm the trees? Make a rough extract? He's looking for new ideas.

DEC. 22 E-mails from veteran Pacific traveler and breadfruit horticulturalist Diane Ragone have clarified that contrary to the stereotypes of skimpy bikinis on the beaches of the Pacific, Samoan traditions demand a lot of covering up. In a village, tank tops and shorts would be unacceptable, and even jeans (on women or men) wouldn't be polite. After all, pants reveal two thighs.

APRIL 19, 2004 Our plane bumps down on the runway around 9 p.m. in Pago Pago, American Samoa. I'm seven time zones west of Washington, D.C.

In the shouting airport throng of Samoans, five obvious foreigners--half the expedition--easily find each other. Two are friendly graduate students who studied ethnobotany with Cox and are now working on a project together, Samantha Gerlach of Tulane University in New Orleans and Holly Johnson of the University of Illinois, at Chicago. Kevin Clyde will do satellite mapping, and the trip's physician is Patricia Stewart, a dermatologist from Santa Barbara, Calif. In the evening, discovering that I've never been to Samoa, Stewart says, "let's start with how to sit down; turning her toes outward and gracefully sliding cross-legged to the floor. "The most important thing is not to point your feet at anyone."

Of all the things I had worried about, insulting toe orientation had not occurred to me.

APRIL 20 Today's trip has been short in distance but dramatic in worldview. From Pago Pago, with its McDonald's, the five of us flew in a small plane to the main island of independent Samoa and then took a ferry to the far island of Savai'i.

We're among the very few foreigners who emerge from the ferry into the crush of passengers dashing for the half-dozen cabs or crowding onto buses. In the center of a two-lane road stands a man who I assume is a policeman. He's wearing a formal looking tunic with big buttons and what looks like a skirt. I'm not yet used to lavalavas on men.

We negotiate for two cabs and begin a dreamlike jaunt that has the rhythm of riding through an old American suburb with low houses, ample lawns, trees in the yards, and flowerbeds. However, many of these homes are of the traditional Samoan style, with no walls, and the yard tree is often a breadfruit, near gardens of bananas, taro, and cacao. I will later see a Weedwacker or two.

At Saipipi village, the cab pulls into the Tavana-family compound. A walled house sits among open-walled structures, or fales. There's a great confusion, with flocks of wide-eyed children in shorts and T-shirts materializing out of the shrubbery, a mountain of gear accreting on the lawn, a browsing chicken, and a fair amount of conversation--considering that none of us speaks Samoan.

Chief Tiumalu Paulo greets us in English, and we find out that the expedition hadn't been expected until the next afternoon. Regardless, in less than 2 hours, the Samoans redo the walled house, moving eight Western-style beds into the big main room and creating a women's and a men's sleeping area by draping flowered fabrics in lavenders, reds, blues, and greens.

APRIL 21 In the afternoon, a rented van lurches into the yard, and the rest of the expedition climbs out in a cacophony of arrival. Gaugau Tavana leads a dual life as both a high-ranking orator in this village and the director of education at the National Tropical Botanical Garden.

Globe-trotting biochemist Susan Murch, also of the botanic garden, has arrived, as has ethnobiologist Steven King, of PS Pharmaceuticals. And Cox--or should I say Nafanua?--is here at last. The Samoans often use Cox's war-goddess rifle, and I'm startled by how easily we fall into it, too. "Where's Nafanua?" one of them will ask. "Oh, he went back to the van for the camera," one of us will answer.

That evening, Nafanua calls together the expedition in our dormitory for an orientation meeting and--I am not making this up--a PowerPoint introduction. (The building does have electricity.) He's giving the presentation to a group of government ministers later that week, and Chief Malaya Vi'iga, orator Tavana's brother-in-law and a government official, critiques it.

APRIL 22 The day starts with two kava ceremonies. The kava shrub, a relative of black pepper, grows throughout Polynesia, and many people brew a drink from the root.

The first ceremony proceeds with speeches from the hosts and then from the guests. Faleasi, the taupou, or village virgin, mixes the dried root of kava with water in a wooden bowl on a dozen short legs. Then a man serves a coconut shell-full to each person in turn, alternating visitors and hosts paired by rank. The drink's color resembles cafe au lait, but the taste is rooty. My lips tingle and my tongue goes slightly numb. The Samoans say that the beverage calms anxieties, a benefit when a village has to sort out a difficult issue.

Some of the men have removed their shirts to reveal great arcs of tattoos sweeping up their sides, and the oratory sounds formal and ancient. After much speaking in Samoan, Cox suddenly mutters to us, "I'm going into the informed consent script."

I remember from our briefing that the team has received NIH funding that requires informed, written consent from Samoans who help with the scientific investigation. Orator Tavana has been translating the document into Samoan. However, Cox and King had planned an additional step that they see as rendering the spirit of the requirement into Samoan culture, where major decisions are made at a kava ceremony. As Cox translates for us in a scene I never imagined when reading about research regulations, the taupou looks on and the assembled chiefs give permission for research.

The ceremony ends with a sua, or gift-giving ceremony, in which waves of men and women stride into the fale with woven mats, leaf baskets of small roast pigs, and cans of corned beef. The guest party traditionally makes a gift also; I see a roll of bills handed to the hosts, and I am colossally glad that all I have to do in these complex interactions is keep my feet pointed to the side.

Local school officials arrive for the next kava ceremony to thank Cox and Tavana for donations of school-books and computers. This ceremony ends with another dizzying sua, this time including the butchered meat of a bull and its head presented to us on a litter that four men bring to the edge of the fale.

Next, we hike deeper into the family's property to see several young trees of H. nutans, which even some of the botanists had never encountered in the wild. Two H. nutans, or mamala as the Samoans call them, are growing near a wall. They're slim trees, perhaps 10 or 15 feet high, with somewhat heart-shaped leaves and dangling strings of pinhead-size, greenish flowers.

After expedition members spend a few minutes as botanical tourists, taking turns photographing the showiest branch, they start the serious research of the day. Some write notes on H. nutans' growth habits, while others take detailed photographs of its features or search for other plants to map.

I tag along with Gerlach and Johnson, for whom the Tavana family demonstrates the traditional way to extract starch from the manioc root. The Samoans and the botanists take turns grating the root on a strip of metal dotted with nail holes. The pulp gets kneaded with coconut leaflets and filtered through burlap. A ring of children watches.

APRIL 23 By this point, I'm realizing that documenting plant uses is tricky in more ways than I'd expected. The things I'd thought would be the hard parts have been smoothed over for this expedition. The family and their neighbors haven't seemed distrustful or nervous, but extraordinarily hospitable and helpful. However, there's been much disagreement. I've heard various local interviewees say that manioc starch gets used as famine food, that it gets used to prepare highly prized party dishes, that the white-stemmed plants have the prized yellow roots, that, no, it's the yellow-stemmed plants that have the yellow roots, that the plant we're looking at is typical of a yellow-rooted plant but is unusually pale, and so on. I ask Cox about the contradictions. "That's what gives it the ring of truth," he says. Eventually, field data make sense, he adds.

The researchers are also collecting voucher specimens to deposit at the Samoan Department of Agriculture. At one point, I hear someone looking for a knife and offer my pocketknife. There's general amazement. "How did you get it here?" several colleagues ask me in concert. "I put it my checked luggage,' I say, wondering how adults could not think of this. "You mean you checked luggage?" Murch answers, clearly wondering why an adult could do such a thing.

Concerns about homeland security have changed field botany, Murch says. She came to Samoa from Canada by way of Sweden and Australia, all with carry-on luggage. When the expedition reached Samoa, she had to shop for such contraband as ethanol, for preserving samples. The worst challenge confronted King, who is in charge of finding cardboard to be put between layers of plants in the drying press. When he reached Samoa, he had to shop for a box cutter. The whole expedition stops working for a moment to emphasize to hun, unnecessarily, the need to remember to take it out of his pack before he goes to the airport.

APRIL 25 We have traveled to Falealupo, at the end of the island. Ake Lilo, a daughter-in-law of one of two healers who originally told Cox about mamala, greets us in an open-air fale containing a ring of lime-green, wooden Adirondack chairs.

She brews an extract of the mamala bark in the traditional way, creating a bowl of pungent brown liquid that Cox pours into sample bottles for the Samoan government. Then Lilo demonstrates starch extraction from masoa, a plant that the researchers suspect is being replaced as a cooking ingredient on this island by manioc.

Cox, who has been watching from the sidelines, now asks Lilo to try the starch procedure again, but this time on a little log of the mamala--the plant with the potentially antiviral bark She hesitates. He explains that he's wondering whether the Samoans could use some familiar local technology to make a crude mamala extract to sell to pharmaceutical manufacturers, thereby reaping more of the financial benefits.

Cox adds that analyses so far have found the active compound throughout the wood, not just in the bark. Lilo gamely gives it a try, scraping the length of wood across her grater. It sticks and jerks, and the grater quickly clogs with wood scrapings. One of our traveling companions, Gaugau from Saipipi, takes a turn. There's much debate and advising, but the venture doesn't appear to be working.

Then, there's a complex exchange in Samoan, and traditional equipment for making kava appears. Kava comes from a shrub, so the process for making an extract from woody plant parts is familiar. Helpers nick off chips of the wood and pack them into a metal cylinder on the ground. The men take turns lifting a heavy metal pole and thudding it down to soften and bruise the chips. Lilo then wraps the chips in a white cloth and dips them again and again into a bowl of warm water. My heart sinks when she raises the bundle. The water drips out almost clear, not brown as it was in the traditional preparation.

Cox, however, has been standing beside her and looking down into the bowl. The liquid there is actually brown. There may be hope after all. Lilo squeezes for several minutes, and then Cox packages a sample of this extract too. It will be months before chemical analysis can evaluate the success of the new extraction, but Cox is bouncing with excitement.

APRIL 27 Stuck in Pago Pago, I flip back through my notes of the week. There's botany in there, sure, but I'm struck by how much I've recorded about the local customs--how relationships have been built, how carefully investigators must frame questions, how visitors can avoid offending their hosts. Studying plants this way requires a whole lot about people.

It feels funny not to wear a lavalava now.

RELATED ARTICLE: Pharmaceutical odds.

Looking for ways to improve drug discovery

Most people have an unrealistic view of how easy it is to tap nature for pharmaceuticals, says David Newman of the National Cancer Institute (NCI) in Bethesda, Md. who nevertheless is an enthusiastic fan of natural chemistry. He's a researcher in the NCI branch that assists drug discovery and development from natural products. Yet be objects to popular myths about the endeavor. "There's been a lot of hype," he cautions.

Newman objects when enthusiasts call a rainforest green gold in honor of its potential for valuable pharmaceuticals. It's not just a matter of asking an indigenous healer what vine cures cancer, he says.

Medicinally useful compounds from whatever source require a lot of luck and work to find. Newman estimates that chemists screen hundreds of thousands of compounds to get 100 worth closer study. Of those 100, perhaps 10 make it through laboratory evaluation to tests on people. Of those 10 compounds, perhaps one or two end up on sale as drugs. Ethnobotanist Paul Cox of the National Tropical Botanical Garden in Hawaii suggests that studying indigenous peoples practices can improve those odds a bit.

Since the mid-1980s, drug companies have done less searching of rainforests, oceans, and other natural venues for drugs, instead, most pharmaceutical companies have taken advantage of improved computers and robotics to confine most of their work to laboratories. In an approach called combinatorial chemistry, they systematically design arrays of compounds as variations on a chemical theme. Then fast, automated screening systems search for particular kinds of biological activity.

Newman, however, argues that this approach hasn't lived up to its promise. The number of small molecules new to drug use and approved by the FDA or its equivalent worldwide for all diseases hit a 20-year low in 2001. He and his colleagues say in the July 2003 Journal of Natural Products that more than half of the 877 new drug compounds approved between 1981 and 2002 came from or where inspired by natural substances.

Newman adds that combinatorial chemistry has produced plenty of variations on known medicinal compounds. Yet in cancer drugs, he says only one compound in advanced clinical trials or already approved by the FDA came entirely from combinatorial chemistry. The approach does a great job of improving the utility of compounds a ready biologically active. But for original ideas in medicinal chemistry, Newman advises going back to nature.--S.M.