Discovering Diversity In The Tropics

By Mario C. Aguilera

William Gerwick is quite happy to tell you about his scientific expeditions to Fiji. He can expound on the amazing explorations his group has led to Madagascar, Papua New Guinea, and other destinations in search of exotic molecules that could one day lead to new treatments for human diseases.

But broach the subject of Panama and it’s time to get comfortable in your seat. The Scripps Institution of Oceanography at UC San Diego professor’s palpable enthusiasm is rooted in his laboratory’s multifaceted drug discovery and training program that ranges from the Central American country’s rain forest jungles to its underwater world.

Just mention a potential drug called “Coibamide” to uncork Gerwick’s excitement. The island of Coiba off Panama’s Pacific coast was free of human inhabitants for hundreds of years, save for the pirates that occasionally encamped there. A prison was housed in one section of the island for about a century until it closed in 2004. The rest of the island remained an undisturbed wilderness.

It was here, while exploring Coiba’s shallow waters in June 2004 that Kerry McPhail, then a postdoctoral scientist working with Gerwick, discovered a cyanobacterium, a primitive photosynthetic organism with features unlike any previously encountered by scientists. Laboratory analysis and testing revealed that the organism naturally produces a potent cancer-fighting compound.

“To the full extent that we can tell, the compound is working by a novel mechanism to kill cancer cells,” said Gerwick, a scientist with the Scripps Center for Marine Biotechnology and Biomedicine and the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences. “It has a very unusual molecular structure unlike any we’ve seen before.”

Undisturbed locations such as Coiba are rare and disappearing around the world. Gerwick’s research in Panama is helping to counteract that slide through a unique program that blends drug discovery from the natural world, the conservation of biodiverse sources, training for young scientists, and scientific as well as economic development in economically disadvantaged countries.

The International Cooperative Biodiversity Groups (ICBG) program, the brainchild of Josh Rosenthal and others at the Bethesda, Maryland-based Fogarty International Center, oversees a handful of programs around the world and regards Gerwick’s Panamanian research center as a model of success.

“Through ICBG, we are involved in an integrative program of joint discovery that engages the host country, not only in the final rewards of drug discovery, but in the rewards that come from being engaged in the process,” said Gerwick.

HIDDEN CURES AWAIT

When the Panamanian government began moving prisoners off Coiba in 2004 with the idea of closing the prison facility, the picturesque island was initially slated for development as a tourist attraction because of its undisturbed beauty. Gerwick’s group and others led counterefforts aimed at preserving the island’s rich diversity. Their push helped lead to Coiba’s designation as a Panamanian national park and UNESCO (United Nations Educational, Scientific, and Cultural Organization) World Heritage Site, protected by law from commercial development.

Panama’s location as a bridge between North and South America and a natural thoroughfare for a diverse assortment of migratory land and water species gives it a unique appeal to scientists. Flora and fauna on the Caribbean side of the isthmus are vastly different from the Pacific side.

“Despite the fact that we all know Panama because of its famous canal, I have been struck by how remote and primitive and relatively unspoiled large stretches of Panama remain today,” said Gerwick.

Lena Gerwick, a biologist and fellow Scripps researcher, believes that in addition to cancer, the Panamanian environment could be holding biomedically promising sources for treating malaria and tropical diseases such as Chagas’ disease, leishmaniasis, and dengue fever. Such diseases have been labeled as “neglected” afflictions because they impact millions of people but have been largely forgotten by the developed world and pharmaceutical companies due to the anticipation of poor returns, and thus few resources are made available to find new treatments for these diseases.

“If you have a lot of diverse organisms, as you find in the tropics, they produce a large diversity of natural products,” said Lena Gerwick, a co-principal investigator for the Gerwick lab’s ICBG-sponsored program. “There is high competition for every species to carve out its own niche and survive. With that you find a lot of compounds used in defense and other diverse activities. Within this biodiversity might be the next cure for malaria or the next cure for tuberculosis, so there is a great need to conserve it.”

Marcy Balunas, a joint Scripps postdoctoral researcher and Smithsonian Tropical Research Institute (STRI) postdoctoral fellow, attributes the country’s rich diversity of organisms to its wealth of geological features, including flatlands, mountainous regions, and distinct coastlines.

“It’s one of the biodiversity hotspots in the world,” said Balunas, who was born and raised in the United States but is now a full-time resident of Panama City. “It’s amazing.”

Among her assortment of duties, Balunas coordinates field expeditions off remote islands and lush mangroves, and conducts analyses inside laboratories at Panama’s Institute of Advanced Scientific Investigations and High Technology Services (INDICASAT).

She also collaborates with other scientists in Panama such as botanist Alicia Ibañez, a STRI scientist and conservationist from Spain, who is developing a botanical guide to Coiba as well as working on a management plan for the island.

Balunas also spends much of her days in Panama mentoring students. On top of its environmental biodiversity efforts, William Gerwick’s group in Panama has added a component that fosters human diversity. Working through the CREO (Conservation, Research, and Educational Opportunities) program, ultimately funded through the National Institutes of Health (NIH), William Gerwick and Balunas have hosted a handful of American minority students at its Panamanian base, where they live and train alongside researchers such as Balunas, Ibañez, and other scientists.

“Panama is a great place to live and to work,” said Balunas. “It’s given me some really unique opportunities as a scientist but also as a person, living in another country, learning Spanish and becoming part of the Panamanian culture as a U.S. citizen abroad.”

Samples extracted from the wilderness are analyzed in Panamanian labs and sometimes shipped to Scripps Oceanography’s La Jolla campus for further analysis. Investigations include bioassays, a technique that determines a substance’s biological activity (for example, against cancer, malaria, and other diseases) and its potency, DNA analysis for taxonomic identification, and investigations using instruments such as mass and NMR (nuclear magnetic resonance) spectrometers, which can image the structure of organisms down to the molecular level.

Each field expedition yields numerous samples that produce hundreds of compounds that are examined and evaluated. Some candidate compounds have been seen before, while others are new but have nothing to offer for treating diseases. But every so often a candidate compound emerges such as Coibamide—now in preclinical evaluation—revealing a novel structure and amazing potency against a certain disease.

“Working in Panama is a great adventure,” said Balunas. “It’s an adventure every day. I have adventures in the city and I have them during hiking trips and during marine collection trips. We go to places that are amazingly wonderful—some of which have been protected by the Panamanian government and therefore have really stayed in a pristine condition—so it’s really an amazing experience.”

SCIENCE, STUDENTS, AND SOCIETY

Gerwick’s Panama program was recently awarded nearly $5 million by ICBG for its continuation. It is one of eight active ICBG initiatives based elsewhere in Costa Rica, Indonesia, Fiji, Madagascar, Vietnam, Papua New Guinea, and the Philippines.

ICBG was launched in 1992 with a mix of enthusiasm about naturally produced pharmaceutical drugs and a concern that access to many novel compounds would be rapidly disappearing as more and more organisms and habitats around the world fell to extinction. The program is funded by a mix of organizations, including the NIH, National Science Foundation, U.S. Department of Agriculture, Department of Energy, and administered through the Fogarty International Center of the NIH.

“There was a realization in the early ‘90s that we could combine research-capacity building and benefit sharing in developing countries with natural products drug discovery—and at the same time support conservation—for a win-win-win situation,” said Josh Rosenthal, ICBG’s program manager.

Cumulatively, researchers across the ICBG’s global network have identified more than 1,000 compounds of biological interest —about one-third new to science—and provided training for more than 4,000 scientists. The researchers have generated hundreds of scientific publications.

Beyond core scientific achievements, ICBG’s successes have been born in the partnerships forged with governments in developing countries and the resulting scientific infrastructures that have been shaped. The ICBG program not only facilitates short-term needs such as access to remote sites and permits for expedition collections, but also engenders an ongoing trust with the country’s scientific community. In Panama this is built upon a long-lasting partnership with STRI and affirmed with the successes of ICBG Panama.

Each newly discovered compound and drug candidate and each newly trained scientist and student pulls the science-government relationship further away from the days of yesteryear when so-called “pirate bioprospectors” would fly into a developing country, pillage its wilderness for biological sources of profitable drugs, and flee without involvement or benefit of the government or the host country’s research community.

“ICBG attempts to develop a structure for collaborative research and sharing the benefits of that research with developing country organizations,” said Rosenthal.

Rosenthal praises the Gerwicks for establishing a program that integrates all of ICBG’s main objectives.

“Most of the ICBG programs have had some success in helping national governments to conserve biological diversity and develop approaches to share that support science, laying the groundwork for future generations of scientists,” said Rosenthal, “but the Panama group put it all together in a very successful and innovative way, and demonstrated that this complicated program is compatible with first-class discovery science.”