Kaua‘i garden’s research leads to deal to develop anti-AIDS drug from plant

Research done in part at the National Tropical Botanical Garden at Lawa‘i Kai and Kalaheo on Kaua‘i’s Southshore has led to discovery of an anti-AIDS medicine that could lead to a cure for the disease.

Dr. Paul Alan Cox, NTBG director and chief executive officer who now has an office in Provo, Utah, did plant-extraction work at the NTBG laboratory in Kalaheo when he was here on the Samoan rainforest tree which is also used by Samoan traditional-medicine healers to treat hepatitis, said Dr. Gaugau Tavana, director of education at NTBG.

The anti-AIDS drug prostratin comes from a gene in the mamala tree (Homalanthus nutans), and Cox, also with NTBG’s Institute on Ethnobotany, played a major role in the discovery of the drug, and helped broker an agreement announced recently, in Samoa, between representatives of the government of Samoa and the University of California at Berkeley, to equally share royalties from any sales of the drug, Tavana explained.

“It’s a landmark for all of us. There’s a lot of research work going on here,” said Tavana, adding that clinical trials are going on now to see if prostratin can be a remedy for HIV/AIDS by drawing out the virus in human bodies so that other medicines and treatment regimens can attack and kill it.

The work at NTBG in preserving endangered native plants is important because one of those rare plants could hold the key to curing any number of diseases, he said. “We’ll never know if it’s extinct.”

There is one mamala tree growing well at NTBG, and scientists there are waiting for it to produce seeds so that it can be planted more widely, Tavana continued.

Cox worked with traditional healers in Samoa, where the discovery was made. “I had a lot of help in this work from Kaua‘i,” Cox said via e-mail from London where he announced the agreement at the Natural History Museum. “The chairman of the NTBG Board of Trustees, Douglas McBryde Kinney, granted me sabbatical from my position as executive director of the NTBG so I can pursue this research as well as my studies on plant neurotoxins and neurological disease.

“Chipper Wichman, grandson of Juliet Wichman (who founded the Limahuli Gardens) agreed to serve as acting director,” Cox said. “The research has gone so well, Chairman Kinney asked me to continue doing full-time research by creating a new Institute for Ethnomedicine which will be affiliated with the NTBG. So on Jan. 1, 2005, Chipper will become executive director.

“In the prostratin work, I have been greatly assisted by Kaua‘i resident Dr. Gaugau Tavana, education director at the NTBG, who is a Samoan chief, and who has offered expert advice on Samoan culture and customs, and NTBG Research Associate Dr. Steven King, who is an expert on plant pharmaceuticals,” Cox said.

“Dr. Patricia Stewart, a NTBG research associate and physician, has greatly assisted in field work and interviews. NTBG Research Associates Dr. Sandra Banack and Dr. Susan Murch have helped me analyze mamala extracts in our Kaua‘i lab for prostratin,” Cox continued.

“Together we have developed HPLC techniques to determine which mamala plants are producing the most prostratin. This information will not only help the Samoan government in selecting the right plants for cultivation, but will help guide the University of California team in isolating the prostratin genes,” said Cox.

“NTBG volunteers have also helped, particularly Dr. Jim Douglass, who helped design the Kaua‘i lab, and Dr. John Bartelt, a retired head of Hughs lab, who helped implement our massively parallel super computer at the garden.

“And I am particularly grateful to NTBG Trustee Judy Webb and the Acacia Foundation, which built the plant-medicine laboratory at the gardens, where we conduct our work on discovering new plant medicines.

“Most of all, I am grateful to my wife Barbara, who together with our children lived with me in a thatched fale in remote Falealupo village for an entire year while I did the ethnobotanical field work that led to the discovery of prostratin,” Cox said.

“Although there was no electricity or running water in the village, and although we slept every night on woven pandanus mats, she never complained, and always helped me with my field collections and interviews. She is a remarkable woman who demonstrated unique sensitivity to people of different cultures.”

“This is an important event for the scientific research work carried out at the National Tropical Botanical Garden, for the island of Kaua‘i, the state of Hawai‘i, and for the discovery of new medicine from plants found in the islands,” said Tavana.

Ethnobotany is the study of plants and how they have been used by indigenous communities.

In Apia, Samoa, the landmark agreement was announced between officials of the government of Samoa and those at the University of California, Berkeley, in which Samoan leaders extended their national sovereignty to the gene sequence for the anti-AIDS drug prostratin, derived from a rainforest tree also used to treat hepatitis in traditional medicine.

Officials with UC-Berkeley and the Samoan government signed the agreement to isolate from the indigenous tree the gene for a promising anti-AIDS drug, and to share any royalties from sale of a gene-derived drug with the people of Samoa.

The agreement supports Samoan officials’ assertion of national sovereignty over the gene sequence of prostratin, a drug extracted from the bark and stem wood of the mamala tree.

The drug currently is being studied by scientists around the world because of its potential to force the AIDS virus out of hibernation in the body’s immune cells and into the line of fire of anti-AIDS drugs now in use.

“Prostratin is Samoa’s gift to the world,” explained Samoan Minister of Trade Joseph Keil. “We are pleased to accept the University of California as a full partner in the effort to isolate the prostratin genes.”

Despite prostratin’s promise as an anti-AIDS drug, its supply is limited by the fact that the drug has to be extracted from the mamala tree bark and stem wood. Researchers in the laboratory of Jay Keasling, UC Berkeley professor of chemical engineering, plan to clone the genes from the tree that naturally produces prostratin, and insert them into bacteria to make microbial factories for prostratin. A similar technology is currently being explored to produce the anti-malarial drug artemisinin.

“A microbial source for prostratin will ensure a plentiful, high-quality supply if it is approved as an anti-AIDS drug,” said Keasling, who also is a faculty affiliate with the California Institute for Quantitative Biomedical Research (QB3) and head of the Synthetic Biology Department at Lawrence Berkeley National Laboratory.

“We consider the actual gene sequences as part of Samoa’s sovereignty, and every effort will be made to reflect this fact.”

The agreement, signed by Prime Minister Tuila’epa Aiono Sailele Malielegaoi of Samoa and UC Berkeley’s Vice Chancellor for Research Beth Burnside, gives Samoan and UC-Berkeley officials equal shares in any commercial proceeds from the genes. Samoa’s 50-percent share is to be allocated to the government, to villages, and to the families of healers who first taught ethnobotanist Cox how to use the plant.

The agreement also states that officials at UC-Berkeley and with the Samoan government will negotiate the distribution of the drug in developing nations at a minimal profit if Keasling is successful.

“This may be the first time that indigenous people have extended their national sovereignty over a gene sequence,” said Cox.

“It is appropriate, since the discovery of the anti-viral properties of prostratin was based on traditional Samoan plant medicine.”

The National Cancer Institute, which patented prostratin’s use as an anti-HIV drug, requires any commercial developer of prostratin to first negotiate an equitable benefit-sharing agreement with the Samoan government.

“I think that UC-Berkeley could set a precedent both for biodiversity conservation and genetic research by including indigenous peoples as full partners in royalties for new gene discoveries that result from their ancient medicines,” Keasling said.

Keasling and a team of scientists led by Cox traveled to Samoa in early August to meet with leaders in three Samoan villages where the tree grows.

They obtained the prior informed consent of the chief’s council from each village to assist in the research in return for a share of the prostratin gene proceeds. Tavana, a Samoan educator at NTBG, presented a Samoan-language PowerPoint presentation on genetic engineering in each village.

A previous royalty agreement on prostratin was signed in 2001 by the prime minister of Samoa and officials with the AIDS ReSearch Alliance, which is sponsoring clinical trials of prostratin as an anti-AIDS therapy. That agreement would return 20 percent of any commercial profits arising from the plant-derived compound to the people of Samoa.

Keasling and his Samoan collaborators will freeze living cells from the mamala tree in liquid nitrogen, so that extraction of the perishable RNA can be conducted in the laboratory.

Then begins the process of tracking down the enzymes that actually build the molecule prostratin.

Once Keasling has pinpointed the key enzymes and cloned their genes, he plans to insert the genes into a strain of E. coli bacteria that he has created to produce isoprenoid compounds like prostratin.

The product of more than 10 years of genetic engineering, the bacterial factories have already proven useful in producing precursors of the anti-malarial drug artemisinin, which he hopes to produce inexpensively for people in the developing world. The process also can be used to produce flavors and fragrances, many of which also are isoprenoids.

Paul C. Curtis, associate editor, may be reached at 245-3681 (ext. 224) or pcurtis@pulitzer.net.