9/29/2004

Landmark agreement between Samoa and UC Berkeley could help search for AIDS cure

UC Berkeley's Jay Keasling (left) and ethnobotanist Paul Alan Cox (right) sign agreement with village elders in Samoa, agreeing to share with them any royalties from sales of an anti-AIDS drug derived from the native mamala tree. (Photo courtesy Jay Keasling/UC Berkeley)

By Robert Sanders, UC Berkeley Media Relations

The University of California, Berkeley, has signed an agreement with the Samoan government to isolate from an 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, announced Thursday, September 30 in Apia, the capital of Samoa, supports Samoa 's assertion of national sovereignty over the gene sequence of Prostratin, a drug extracted from the bark of the mamala tree (Homalanthus nutans). 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 bark and stemwood of the mamala tree. Researchers in the laboratory of Jay Keasling, UC Berkeley professor of chemical engineering and QB3 faculty affiliate, plan to clone the genes from the tree that naturally produce Prostratin and insert them into bacteria to make microbial factories for the drug. 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 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 Samoan mamala tree, Homalanthus nutans, from which the promising anti-AIDS drug Prostratin was isolated. UC Berkeley researchers hope to extract from the tree the genes that make Prostratin, insert them into bacterial factories, and produce pure, inexpensive drugs for developing nations, sharing any profits with the Samoan people. (Photo by Paul Alan Cox and Patricia Stewart)

The agreement, signed by Prime Minister Tuila'epa Aiono Sailele Malielegaoi of Samoa and UC Berkeley's Vice Chancellor for Research Beth Burnside, gives Samoa and UC Berkeley equal shares in any commercial proceeds from the genes. Samoa 's 50 percent share will be allocated to the government, to villages, and to the families of healers who first taught ethnobotanist Paul Alan Cox how to use the plant. The agreement also states that UC Berkeley and Samoa 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, director of the Institute for Ethnobotany at the National Tropical Botanical Garden in Hawaii. "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 Samoa.

"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.

Samoan healer Ake Lilo prepares an anti-viral extract from the bark of the mamala tree. The extract has been used traditionally to treat hepatitis, but its primary ingredient, a chemical named Prostratin, has shown promise as an anti-AIDS drug. (Photo by Paul Alan Cox and Patricia Stewart)

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. Gaugau Tavana, a Samoan educator from the National Tropical Botanical Garden, 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 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 members of the class of chemical compounds called isoprenoids.