Although the oceans cover 70 percent of the planet's surface, much of their biomedical potential has gone largely unexplored. Until now.
A group of researchers at Scripps Institution of Oceanography at the University of California, San Diego, has for the first time shown that sediments in the deep ocean are a significant biomedical resource for microbes that produce antibiotic molecules.
In a series of two papers, a group led by William Fenical, director of the Center for Marine Biotechnology and Biomedicine (CMBB) at Scripps Institution, has reported the discovery of a novel group of bacteria found to produce molecules with potential in the treatment of infectious diseases and cancer.
"The average person thinks of the bottom of the ocean as a dark, cold, and nasty place that is irrelevant, but we've shown that this environment may be a huge resource for new antibiotics and drugs for the treatment of cancer," said Fenical.
The first paper, published in the October 2002 issue of Applied and Environmental Microbiology, highlights the discovery of new bacteria, called actinomycetes, from ocean sediments. For more than 45 years, terrestrial actinomycetes were the foundation of the pharmaceutical industry because of their ability to produce natural antibiotics, including important drugs such as streptomycin, actinomycin, and vancomycin. The data from this paper provide the first conclusive evidence of the widespread occurrence of indigenous actinomycete populations in marine sediments.
The second paper, published in the Jan. 20, 2003, issue of the international edition of the chemistry journal Angewandte Chemie, identifies the structure of a new natural product, which Fenical's group has named Salinosporamide A, from this new bacterial resource. The new compound is a potent inhibitor of cancer growth, including human colon carcinoma, non-small cell lung cancer, and, most effectively, breast cancer. January's report cracks the door open for a line of similar discoveries from the recently discovered Salinospora genus.
"The second paper shows the potential for the production of materials that are highly biologically active and very chemically unique. This is likely to be the tip of the iceberg of diverse chemical formulas that are out there," said Fenical.
Although more than 100 drugs today exist from terrestrial microorganisms, including penicillin, arguably the most important drug in medicine, the potential from land-based microbial sources began dwindling nearly 10 years ago. Pharmaceutical investigators searched high and low around the globe for new terrestrial, drug-producing microbes, but with diminishing payback. According to Fenical, when considering the ever-increasing resistance of bacteria to existing antibiotics, the need to make new discoveries becomes essential.
Surprisingly, the oceans, with some of the most diverse ecosystems on the planet, were largely ignored as a potential source for actinomycete bacteria. Given this omission, it was natural for Fenical's group at the Scripps CMBB to initiate studies of marine environments for new microorganisms important in pharmaceutical discovery.
His group developed new methods and tools for obtaining a variety of ocean sediments, including a miniaturized sampling device that efficiently captures samples from the deep ocean. They derived bottom muds from more than 1,000 meters deep from the Atlantic and Pacific Oceans, the Red Sea, and the Gulf of California. They also developed new methods for sifting through these samples (which contain roughly one billion microorganisms per cubic centimeter), culturing the microorganisms, identifying them by genetic methods, and screening their metabolic products for anticancer and antibiotic properties.
By genetic and culture analysis, Fenical's group discovered the new genus Salinospora, a type of actinomycete bacteria found in tropical and subtropical oceans, but never seen before on land.
The results from their biomedical studies were extraordinarily positive. Of 100 strains of these organisms tested, 80 percent produced molecules that inhibit cancer cell growth. Roughly 35 percent revealed the ability to kill pathogenic bacteria and fungi. Based on the worldwide distribution of Salinospora, Fenical estimates that many thousands of strains will be available.
"I would even go as far as to say that never before has this level of biological activity been observed within a single group of organisms," said Fenical.
These discoveries have been patented by the University of California and licensed to Nereus Pharmaceuticals Inc. for subsequent development. Nereus is a four-year-old biotech company in San Diego, Calif. dedicated to the development of new drugs from this new source for drug discovery.
"These extraordinary marine discoveries by Scripps Institution, coupled with their industrialization by Nereus Pharmaceuticals, could provide the next great source of drug discovery for the pharmaceutical industry," said Kobi Sethna, president and CEO of Nereus Pharmaceuticals.
"These discoveries speak to the future of antibiotic discovery," said Fenical. "They point to the fact that the ocean is an incredibly exciting new microbial resource. They indicate how little we know, and they demonstrate how much we need to invest in further exploration of the oceans."
In addition to Fenical, coauthors on the papers include Tracy Mincer, Paul Jensen, Christopher Kauffman, Robert Feling, and Greg Buchanan.
Funding for the studies was provided by the National Science Foundation; the National Cancer Institute of the National Institutes of Health; the University of California BioSTAR project; and the Khaled Bin Sultan Living Oceans Foundation.