Kingston leads exploration of Suriname's medicine chest
by Su Clauson-Wicker
The dark, humid canopies of the South American rainforests are "the lungs for the world," Virginia Tech chemist David Kingston says, as they convert global gases like carbon dioxide into life-sustaining oxygen. Kingston suspects the rainforests may be the medicine chest of the world as well. But he and other medicinal chemists may never know the extent of this medicinal arsenal. Hundreds of the forests' unexamined species become extinct every year, their potential for curing the world's ills lost forever as loggers level the jungle. A year ago, Kingston began an ambitious project to both save the rainforest and examine jungle plants as potential cures for human diseases. Under a $2.3-million grant from the National Institutes of Health, he is directing a research and development team working in the murky rainforests. He hopes to discover new medicinal drugs and help the native people preserve rainforest biodiversity. He is collaborating with Bristol-Myers Squibb, the Missouri Botanical Garden, and Conservation International, a nonprofit conservation group. Kingston is principal investigator of a five-year research project that will seek out biologically active natural products from Suriname to produce antibiotic and anti-cancer compounds and other pharmaceuticals. Suriname is a small, fairly stable country on the northeastern coast of South America. The government recently has sold an Indonesian firm the logging rights to large tracts of rainforest near the Guyana border.
Biodiversity project benefits
indigenous people "I've been involved in another project to examine potential medicines from the rainforest, but this is one of the first in the world to work with and share economic benefits with indigenous people," Kingston says. The researchers will test plants identified by local medicine men, and information on healing plants will be documented for use by future medicine people. In accordance with the project's ground rules, a Surinamese company has been equipped and funded to do the initial extractions. Native technicians were trained, and testing began last summer. So far nothing particularly active against cancer has been found, but Kingston is optimistic that useful chemicals will emerge from the rainforest. If a cancer treatment is found, Suriname (and Virginia Tech) will receive royalties. This will be true even if the original plant is so rare that the drug must be duplicated synthetically in the lab.
Patience--a chemist's virtue
"It takes about two years to know if you have something good or not," Kingston says. "And a lot more to determine if you have something worth marketing." Patience is a virtue a chemist learns to develop. Kingston began doing unsponsored research on the cancer-fighting drug, taxol, back in 1979. Three years passed before he received even modest funding for the project and five more elapsed before he and graduate student Zhiyang Zhao were able to patent their water-soluble derivative of taxol. "It took 12 years from discovery of taxol until clinical trials were run," Kingston says. "Taxol comes from a relatively rare Pacific yew, so it had to show some very exciting anticancer activity to be worth looking at. In phase I testing (on terminally ill volunteer patients), researchers ran into a toxicity problem that very nearly killed taxol as a drug. Luckily, it was an allergic reaction to the emulsifying agent, so taxol was still in the running." Kingston's particular contribution to taxol research was to bypass the emulsion by creating a water-soluble taxol derivative. In addition, he found an analog of taxol that has proven significantly more effective than taxol in preliminary testing.
Gathering and testing underway
In the Suriname project, native healers and scientists from the Missouri Botanical Garden gather samples of jungle plants. They use technology from a global positioning satellite system, so that the precise location of each plant is identified. Samples are sent to BGVS, the local firm doing extractions, and then on to Bristol-Myers Squibb (BMS) pharmaceutical company, in the United States. At BMS, the samples are tested for anticancer activity, and active samples are relayed on to Virginia Tech. "Our work at Virginia Tech consists of isolating, then identifying the active compound," Kingston says. "The plant is like a little factory, making everything it needs to grow--maybe a thousand different compounds. Some of these compounds--maybe the ones for defense from predators, maybe ones we don't understand yet--inhibit the growth of cancer cells. "When you try to find these compounds, you don't know what you're looking for--you're working in the dark. Your flashlight is the biological assay. That's what we're doing in the Virginia Tech laboratory. As we run more purification steps, we filter out inactive compounds so we have a compound that is purer. The more steps we run, the more active our final product becomes." Virginia Tech researchers, often graduate students, will also identify the active agent with a powerful imaging tool called nuclear magnetic resonance. This will give them the chemical structure of the molecule--something the FDA requires before human testing can begin. Then the sample is sent back to Bristol-Myers for extensive biological testing on animals. If the drug tests well and shows no unusual toxicity, it is tested on diseased human volunteers, both alone and in combination with other medicines. "Finding a chemical compound in a plant that becomes a medicine is like hitting the jackpot," says Jim Miller, assistant curator of the Missouri Botanical Garden. "But there are lesser yields; more likely we will find a chemical that has a certain biological activity and design something from that." "We will find new drugs in the rainforest," Kingston asserts. "But whether we find them in Suriname, I can't predict. Suriname will benefit, economically, in tangible ways. And protecting the rainforest--our lungs--is in the best interest of all of us."
Virginia Tech Magazine Volume 17, Number 2 Winter 1995