San Francisco Chronicle - Monday, August 24, 1992

The compound, prostratin, has been tested only in the test tube against the AIDS virus. It will be years before it can be tested on people.

Nonetheless, Paul Cox, the Brigham Young University professor who saved the forest from bulldozers, is excited, as are National Cancer Institute researchers studying the drug.

"Everything we do seems to look better and better," said Cox, 38, an ethnobotanist and tropical rain forest biologist. Ethnobotany studies the way indigenous peoples use plants for medicine.

PROMISING RESULTS

The institute's research has yielded two promising results.

First, human lymphocytic cells were coated with prostratin and doused with HIV-1. Not only did the prostratin keep those cells from succumbing to the virus, which causes AIDS, it protected cells when added as much as 24 hours after infection.

Researchers also found that prostratin inhibits the growth of tumors. That was a big surprise because prostratin is part of a group of organic compounds known to cause tumors. Cancer researchers can use this clue to better understand the compounds.

For Cox, the results are a hint that a dream might come true, a dream that began as a nightmare.

His mother, a wildlife biologist, died of cancer in November 1984. "I felt so terribly helpless. I wondered what I could do with my life to help people," Cox recalled.

EMBRACING ETHNOBOTANY

He embraced ethnobotany, a topic of his dissertation at Harvard University, and traveled with his wife and four children to the Samoan islands in search of native healers. They spent parts of eight years in the islands, located in the Pacific Ocean about 2,200 miles southwest of Hawaii.

"We just had our mats and a little grass hut on the beach," he said.

One day in 1987, weeping islanders ran into the village saying bulldozers were destroying the forest. Village leaders had sold the forest to raise money to build a school ordered by the government.

"I said, 'What if I could pay for your school, would you stop?' " Cox recalled. "One of the chiefs ran eight miles and stood in front of the bulldozer."

RAISING FUNDS

Cox and his wife were prepared to sell their home and car in Utah to pay the $85,000 mortgage for the school, but donations from family, friends and students made that unnecessary.

Within a year, the Samoans turned their 30,000-acre forest into the Falealupo Rain Forest Preserve -- and made Cox a chief.

He continued to research tips from native healers and to collect plants and trees.

One such tip led him to Homolanthus nutans, a tree with shiny green leaves, pale flowers, and the compound known as prostratin in its trunk. Samoan healers use it to treat yellow fever, a viral disease spread by mosquitoes.

ANALYZING PROSTRATIN

Cox sent a sample to the National Cancer Institute in the late 1980s. The results of work by chemists there were published in the Journal of Medicinal Chemistry this summer.

Gordon Cragg, director of the institute's natural products branch, cautions that prostratin could take a decade to develop as a drug safe for humans, by Western definition. "The exciting thing is they've isolated this active compound," said Suraiya Rasheed, director of the viral oncology and AIDS research laboratory at the University of Southern California.

However, she said more study is needed into prostratin's effects on inhibiting the AIDS virus in normal lymphocytic cells from human blood.

TUMOR CELLS

The best results found by the cancer institute were in tumor cells, which are particularly hardy and not as susceptible to viral attack. On normal cells, prostratin inhibited the virus, but only at high doses. And the cells were made static, essentially worthless, in the process.

With new technology, researchers can synthetically create the compound, then manipulate molecules in search of a more perfect compound that kills the virus but not the cell, Rasheed said.

Thomas Evans, director of AIDS research at the University of Utah, notes that dozens of potential HIV-fighting drugs are identified each year.

"There are a lot of different compounds that inhibit HIV in the test tube that don't pan out, either because they're toxic or because when they're used in animals or humans they just don't work," he said.

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