For most of us, the name "Brazil" conjures up images of dense Amazon forests, idyllic beaches, and Carnival parties. But if a group of scientists working in the southeastern city of Porto Alegre have their way, in years to come the name will also bring to mind images of sophisticated drug-development laboratories and novel anticancer therapies.

At the South American Office for Anticancer Drug Development (SOAD), researchers screen terrestrial plants and marine life for new therapeutic compounds that can block cancer cell growth. And while they don't yet have any drugs for sale or in clinical trials, they do have a series of compounds that look promising.

Screening plant extracts for medically useful compounds is certainly not a new approach, even in the context of modern pharmaceutical research, but the existence of a center like SOAD in South or Central America is. Gilberto Schwartsmann, who established SOAD in 1993, modeled it after the drug development officies at the National Cancer Institute in Washington, D.C. and the European Organisation for Research and Treatment of Cancer (EORTC), where he had spent several years working in Amsterdam. As Schwartsmann explained in a recent telephone interview, "I wanted to return to Brazil, but I didn't want to reinvent the wheel." Therefore, he set up a clinical trials program that conforms to European and U.S. standards, and set up the natural products screening program with protocols, cell lines, and methods used at the larger, more established centers.

The basic plan behind the screening program is straightforward. Native plants are collected from various regions in Brazil, including the Amazon region to the north and the drier region near Porto Alegre in the south. Researchers dry the samples and mince them in either an aqueous or an organic solution, then add the extracts to rapidly growing cancer cells in culture. If an extract blocks cell growth or kills the cells outright, the researchers consider it interesting and will test it further against other cell lines. According to Noel Monks, who leads the screening group, if an extract looks good after a series of such tests at SOAD, they'll send it off to NCI's Natural Products Branch, where scientists will test it against 50 different cancer cell lines.

Depending on the results of the screen, the SOAD researchers then try to purify the active compound from the complex plant extract and begin to determine its mechanism of action and its effectiveness in mouse models. If the results still look promising, and there is evidence of either a new mechanism of action or increased effectiveness relative to existing drugs, then NCI will step in and help shepherd the compound along the drug development pipeline.

Gordon Cragg, director of NCI's Natural Products Branch, feels this sort of collaboration is profitable for everyone. The collection and initial screening process is labor-intensive, and NCI already has its hands full with extracts from other regions. On the other hand, the later stages of drug development can be very expensive, and NCI has financial resources that labs in countries such as Brazil lack. But, Cragg points out, this assistance from NCI benefits everyone, including the U.S. taxpayers who foot the bill, because it means more new anticancer drugs will ultimately become available.

Also - and this is not a trivial point, say both Cragg and Monks - if a compound is initially identified and characterized in Brazil, the Brazilian organization owns the patent rights to any subsequent commercial product. That means that the profits, or at least a percentage of them, return to the country where the plant naturally grows. And in a world where wealth and resources are so unevenly divided between industrialized nations and developing ones, and between the northern and southern hemispheres, questions about who owns the rights to natural resources and products developed from them are increasingly important, from both the political and practical standpoints.

Monks says that one of the ways that SOAD researchers identify likely plants to test is by asking native people about their traditional medicine. Because of this, retaining patent rights is not just about protecting Brazilian biodiversity, but also about ensuring that some of the money goes back to the native peoples. "It is very important to return some of [the benefits and profits] to the peoples who helped us find it," said Monks. "After all, they gave us secret information about their medicines."

In addition to testing plants that have an ethnomedical history, the researchers also tend to work with plant families that have already yielded interesting drug candidates. But, Monks says, they do some random testing as well. And Cragg points out that although some people look unfavorably on such random screening as "a fishing expedition," valuable compounds - most notably taxol - have already come from such efforts. "At the moment, mass screening is probably the best way to identify new compounds," says Cragg. As more information becomes available about malignant processes, designing drugs may become more reasonable, "but at this stage, it is very much screen as much as you can and see what looks effective."

Monks also occasionally takes advantage of the odd bit of information he comes across in the literature. For example, he said recently that after reading that extracts from some ferns have DNA-damaging activity, he and the botanist he works with have decided to collect native ferns to test. Though the extract "is causing trouble, [these data] might hint that there is an interesting compound."

As if the abundant and varied choices of terrestrial plants weren't enough, the SOAD screening group has recently expanded its search into the marine environment, and is collaborating with researchers at the Fundação Zoobotânica do Rio Grande do Sul to collect sponges from the Brazilian coast. "Marine organisms have fantastic chemistry that you don't see in terrestrial organisms, structures that are difficult to synthesize," said Monks. He hopes that this new venture will lead to compounds with novel mechanisms of action. Furthermore, because marine compounds need to act quickly before they are dispersed into the vast surrounding water, they tend to be very potent.

When SOAD was first established, it was unique in its scope and goals, but there is now a relatively large number of groups mining the natural resources of Brazil in search of novel therapeutics, according to both Monks and Cragg. But even today, SOAD is probably the largest screening program; and, says Schwartsmann, SOAD's clinical trials program is the only one of its kind in South America.