Fresh Evidence Points To Marine Bacteria As A Source Of Anti-Cancer Drug

The marine invertebrate Bugula neritina, a brown bryozoan animal with stringy tufts that look like algae, appears unremarkable and similar to a variety of moss-like sea creatures. In fact, bryozoans are widely known by boat operators, who consider them ordinary fouling organisms and often scrape them off their vessels’ hulls.

But their potential may be far from ordinary. Scientists previously discovered Bugula neritina to be the source of bryostatins, a family of chemical compounds currently being studied for their ability to treat a variety of cancers. The anti-cancer drug Bryostatin 1 can be extracted from colonies of Bugula neritina.

The new study provides evidence that bacteria that live inside Bugula neritina, and are passed in larvae from one generation to the next, are the likely source of the anti-cancer compound.

"This paper presents a whole series of experiments from a variety of different directions that provide evidence that this bacteria may indeed be the agent for producing the drug," said Margo Haygood, the senior author of the paper appearing in this month’s issue of Applied and Environmental Microbiology.

Through the experiments, Haygood and her co-authors identified a gene of the type that produces the compound. They also showed that the gene is expressed solely in the bacteria, called "Candidatus Endobugula sertula."

The findings pave the way for new studies in Haygood’s laboratory, research that addresses problems historically facing the development of drugs from the sea.

"Currently there really isn’t a practical way to produce enough bryostatin for people to use. Even if there were enough of the animals out there, collecting enough would be environmentally destructive. This is one of the biggest problems in the development of drugs from marine organisms," said Haygood, an associate professor in the Marine Biology Research Division and the Center for Marine Biotechnology and Biomedicine at Scripps.

"There are many cases of these very interesting and useful compounds that are found in marine invertebrates that are suspected to be made by bacterial symbionts (organisms living in symbiosis with another). This work is important because if we can use this experimental system to unlock the potential of these bryostatin drugs, it can serve as a model for many, many others."

Haygood’s new research is addressing two areas: Attempting to cultivate and grow the bacteria outside of its natural environment within Bugula neritina; and attempting to clone the genes that make the drug and deliver them into an organism that can be more practically produced in large quantities.

Most anti-cancer drugs act by killing any rapidly growing cells, inevitably interfering with the body’s normal processes. Bryostatin 1 "flips a switch" that controls how cells behave in the body. In the case of leukemia cells, for example, it seems to bring them to their senses and make them behave like normal blood cells. The drug is now in clinical trials for use in humans.

CalBioMarine Technologies Inc. of Carlsbad, Calif., has signed an exclusive agreement with UCSD to commercialize Haygood’s findings for the eventual commercial supply of bryostatin.

Co-authors of the paper include Seana Davidson, Scott Allen, Grace Lim, and Christine Anderson. Davidson is now at the University of Washington.

The study was supported by the California Sea Grant College Program, the National Sea Grant Technology Program, the National Cancer Institute, CalBioMarine Technologies Inc., and the Howard Hughes Medical Institute.

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Scripps Institution of Oceanography, at the University of California, San Diego, is one of the oldest, largest, and most important centers for global science research and graduate training in the world. The National Research Council has ranked Scripps first in faculty quality among oceanography programs nationwide. The scientific scope of the institution has grown since its founding in 1903 to include biological, physical, chemical, geological, geophysical, and atmospheric studies of the earth as a system. More than 300 research programs are under way today in a wide range of scientific areas. The institution has a staff of about 1,300, and annual expenditures of approximately $140 million from federal, state, and private sources. Scripps operates one of the largest U.S. academic fleets with four oceanographic research ships and one research platform for worldwide exploration.