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SAN JUAN, Puerto Rico — Many of the drugs in our medicine cabinets, from companies like AstraZeneca, Pfizer, and GlaxoSmithKline, began life in Puerto Rico. In the 1960s and 70s, lured by specialized tax incentives, most of the world's leading pharmaceutical companies set up shop on this Caribbean island. The Commonwealth now produces 16 of the 20 top-selling drugs in the United States.
Today, with a faltering local economy and an awareness of global trends, leaders in the island's academic, business, and policy circles are working to turn Puerto Rico and the Caribbean into a hub for biotechnology, including drug discovery and development as well as manufacturing. At the recent annual meeting of the AAAS Caribbean Division, it was clear that a key place to begin is with region's natural resources.
Featuring presentations on natural products from Caribbean plants, algae as biofuel, fungal contributions to industrial microbiology, and the San Juan Bay Estuary, much of the 20 September meeting at the University of Turabo reflected the sentiments expressed the day before by José Lasalde, vice president for research and technology at the University of Puerto Rico.
"The question is right now, how can we bring R&D to Puerto Rico? The whole economy here will depend on how we bring more investment in our science and technology," Lasalde said.
From Bioprospecting to Biotech
Cympolia barbata, also known as tufted joint algae | Flickr/danybotica
The Caribbean region's abundant biodiversity makes it a hotspot for pharmaceutical knowledge. For example, the little green pompoms and segmented stems of a seaweed called Cympolia barbata are a common sight in shallow Caribbean waters. When biochemist Simone Badal McCreath and her colleagues at the University of the West Indies in Kingston, Jamaica isolated the plant's compounds and tested them in human cells, they found that two of the compounds blocked cancer-causing pathways in colon cancer cells.
C. barbata is one of six plants endemic to the Caribbean whose compounds have recently shown promise as anticancer agents, Badal McCreath reported in her keynote address at the AAAS meeting. At least one U.S. patent is now pending, and Badal McCreath plans studies in animal models and clinical trials to further investigate whether these compounds could be the basis for safe and effective new cancer drugs.
She also continues to screen compounds from the many Jamaican plants that researchers have not studied yet. Despite the abundance of natural compounds to investigate, the odds that any one of them will make it to market as a commercial drug are small. Fewer than 10 approved drugs are based on compounds from natural marine products, and 12 are in the development pipeline, according to Néstor Carballeira, a biochemist at the University of Puerto Rico who studies new compounds from marine organisms.
Simone Badal McCreath | AAAS
"One of the key issues is to convince major pharmaceutical companies to take over and to create enough interest in the compound [after it is discovered]," he said during a panel discussion with Badal McCreath. "It takes millions of dollars to get a compound through to market, so you have to convince the right company to carry on the research."
Although the ultimate goal for Badal McCreath's research is product development, "knowledge is power," she said. Even if a natural product does not make it to market, "accumulating as much data as you can and publishing these in peer reviewed journals contributes significantly to future research."
Natural products research in the Caribbean faces logistical difficulties too. Both speakers agreed that simply having enough material to run experiments on is a major challenge. When compounds are extracted, care must be taken not to deplete endemic or endangered stocks, and the availability of the machines and other resources for synthesizing compounds is often limited in Jamaica, Badal McCreath said.
Fungi are also of great interest for their anti-cancer activity and other pharmaceutical properties. Michelle Martínez Montemayor of the Central University of the Caribbean in Bayamon, Puerto Rico described the potential therapeutic use of the reishi mushroom Ganoderma lucidum against inflammatory breast cancer. Her research using cancer cells and mouse models has shown that reishi suppresses protein synthesis and tumor growth by affecting survival and growth signaling pathways that act on gene translation. Martínez presented her work in a session organized by the Puerto Rico Society of Microbiology (PRSM), which is the local branch of the American Society for Microbiology. The PRSM Student Chapter at the University of Turabo collaborated in hosting the AAAS event.
Sharon Cantrell of the University of Turabo, a researcher in fungal biodiversity, also shared strategies for fungal isolation and characterization. She noted that the 1000 Fungal Genomes Project will strengthen genome-based phylogenies to resolve characterization uncertainties.
A Hunger for Innovation and Partnership
Natural products research is not alone in needing the right resources and tools in order to flourish. Recognizing that many areas of biotechnology research require state-of-the-art facilities, the University of Puerto Rico has built a $72 million, 153,000 square-foot, eight-story Molecular Sciences Building designed to attract and support academic-industry partnerships and to incubate new high-tech startups. Research centers on drug discovery, materials characterization, and HIV vaccine research are already operational; a neuroscience center and a facility that houses research animals are expected to be up and running in the next two years. The HIV vaccine project will be led by former AAAS Caribbean Division president Abel Baerga Ortiz, who is an associate professor in the Department of Biochemistry at the University of Puerto Rico School of Medicine.
The new Molecular Sciences Building at the University of Puerto Rico | AAAS
Multiple pharmaceutical and biotech companies have signed or are negotiating agreements whereby they will collaborate with University of Puerto Rico scientists and take advantage of the high-end instruments in the building. José Lasalde, the vice president for research and technology at the university, sees this as an important stage in a broader attempt to change the university culture to one that more strongly values translational research.
"There is a new generation of scientists that are hungry for these kinds of activities. They want to be involved in those aspects of technology transfer and commercialization," he said. "The university is experiencing a reinvention of how we do science."
Prospects for Algae-Based Biofuel
A former marine shrimp farm in Dorado, Puerto Rico where redevelopment for aquaculture and microalgae culture is planned. The red circle marks a "shovel ready" pilot project. | Mario Velasco/Jorge Gaskins
Two other resources that the Caribbean has in abundance are sunlight and coastal waters. Some researchers and entrepreneurs therefore see a future for algae biofuel as a source of sustainable energy for the island, which currently gets only 1 percent of its energy from renewable sources, according to Jorge Gaskins, president of Bio-Lípidos de Puerto Rico Inc./Replenish Energy.
"Puerto Rico could produce a significant fraction of our total energy requirements using marine biomass if we make reasonable reductions in total energy consumption" and if regulatory hurdles can be overcome, said session organizer Gary Gervais, a research associate in the Department of Environmental Sciences at University of Puerto Rico Río Piedras campus.
One promising algae species is a microalgae called Botryococcus, which produces a combination of fatty acids similar to that in vegetable oils, according to Catalina Dávila, a post-doctoral student at the University of Puerto Rico. Oil extracted from this species could make a high-quality biofuel that could be converted into biodiesel. Dávila has also determined that the microalgae efficiently removes nutrients from water and may thus be useful in wastewater treatment.
Although many questions remain about the economics and regulatory issues of large-scale algae farming, Gaskins described a 320-acre pilot project that is "shovel ready" near Dorado, Puerto Rico. Once funding is secured, algae will be grown on land that was formerly a shrimp farm. The algae will be used for several purposes in addition to fuel production; for example, it will become food for cultured shrimp and tilapia. The animals' waste, in turn, will be used to fertilize the algae.
Puerto Rico's Most Important Resource
The AAAS Caribbean Division meeting also honored several notable scientists, educators, and students. Minnuette Rodríguez Harrison won the Lucy Gaspar Award for Excellence in Science Education, for her innovative environmental education programs at the Julián E. Blanco Ballet Specialized School in San Juan. A poster session showcased many talented students, including Francheska Delgado-Peraza, whose presentation, "β-arrestin signaling from the Cannabinoid Receptor," won the Robert I. Larus Award and a trip to the 2015 AAAS Annual Meeting in San Jose, CA.
The conference was dedicated to Graciela Candelas, Distinguished Professor at the University of Puerto Rico Río Piedras Campus, who has left a profound legacy at the university through her research on transfer RNA synthesis in the spider Nephila clavipes, her many contributions to the UPR RPC graduate biology curriculum, and her training of more than 100 students who went on to pursue careers in academia, medicine, and industry.
Graciela Candelas and some of her former students | AAAS
Gaskins and the other speakers in the session acknowledged that clarification from the Puerto Rican government on its biofuel policy is needed. And, there is little support from the environmental agencies, according to Gervais. "They say, we need to conserve all the [shoreline property] we have left for tourism, so we shouldn't do anything new. The idea of a marine farm is very hard to talk about," he said.
The conservation of another important body of water, the San Juan Bay Estuary, has been largely neglected, but researchers who spoke at another AAAS meeting session are changing that. Experts from the San Juan Bay Estuary Program explained that this estuarine system, which includes eight different bays and lagoons, has been dramatically impacted by development of the land, illegal sewage discharges, and aquatic debris. Eighty-eight percent of the people living in the highest density areas around the estuary live under poverty levels, and 90% of them are exposed to polluted waters through flooding and other types of contact.
A wide variety of living resources find food and shelter in this estuary system that provides habitat for over 160 bird species, 19 reptile and amphibian species, 124 fish species including 18 sport fish species, and approximately 300 wetland plant species, according to Jorge Bauzá Ortega, the science director of the San Juan Bay Estuary Program. The program administers a number of programs, many involving community volunteers, to clean up, monitor, and conserve the San Juan Bay Estuary.