Antibiotic resistance causes problems not only in hospitals but in the general community as well. Researchers at the University of California, San Diego (UCSD) Medical Center, the Scripps Institution of Oceanography and Skaggs School of Pharmacy realize the gravity of this problem and are striving to solve it by harvesting new antibiotic candidates and bacteria from the ocean.
Dr. William Fenical, professor of oceanography and director of the Center for Marine Biotechnology and Biomedicine at UCSD, spearheaded the project many years ago through his scuba expeditions to the bottom of the ocean. William Gerwick, one of his Ph.D. students from 1981, recently joined the Scripps faculty to continue the work he started with Fenical in the 1970s.
“This initiative is incredibly exciting,” Gerwick said.
The research encompasses the goal of not only finding new antibiotics but also changing the strategy of antibiotic therapy to avoid the resistance problem. Aside from scientists like Gerwick and Fenical who study marine organisms, this goal includes the expertise of pharmacologists, medical doctors and immunologists/disease experts.
Victor Nizet, associate professor of pediatrics in the UCSD School of Medicine, runs an infectious disease research lab in collaboration with this project.
“The ultimate goal is to take a compound that was discovered from the ocean and bring it all the way into a phase I clinical trial,” Nizet said.
Approximately 20 researchers in his lab study how bacteria cause disease and how the human immune system works to fight these diseases.
“Another thing that we’re trying to do through this program is to think of whether there are innovative, completely new strategies for antibiotic therapy that might be less prone to this problem of drug resistance,” Nizet said. “We are using molecular techniques to discover how bacteria produce disease.”
He further explained that by identifying a bacterial gene that causes disease, researchers can design, screen and identify antibiotics that fight the infectious gene. However, this type of research requires new sources of bacteria and antibiotics. These new sources are found at the bottom of the ocean during expeditions by marine scientists like Gerwick and Fenical.
Terrestrial sources of bacteria and antibiotics were exhausted around 1970. Although scientists are able to chemically modify existing bacteria to improve their effectiveness, these minor changes do not create new classes of antibiotics. The modified forms basically work through a traditional mechanism. Unfortunately, that mechanism builds up resistance to bacteria over time.
“Here in the ocean, which covers about 70 percent of the earth’s surface, ecologists estimate there may be as many as 10 million new species of bacteria that have yet to be discovered,” Nizet said.
Fenical, Gerwick and others tap these resources by scuba-diving and sending down a probe to the ocean floor, sometimes as deep as 5-, 6- or 7,000 feet.
“We particularly focus in on something known as blue-green algae, or cyanobacteria,” Gerwick said.
These cyanobacteria, better known as “pond scum” to those outside the science community, are amazing molecules in terms of their complex structures and biological activity. Gerwick takes trips all over the world to collect samples of these algae. Recently, he collected samples with a team in Papua New Guinea and Panama.
“It’s kind of electric when you see some new chemistry,” he said of his algae collection.
New kinds of chemistry in antibiotic research are needed because the National Institutes of Health (NIH) and drug companies do not pursue this type of research. Financially, it is more profitable for them to develop medicines that treat chronic conditions than medicines that treat a single infection. Nizet said he hopes that academia can provide potential antibiotic candidates, adding that the antibiotic development team at UCSD hopes to partner with a philanthropic organization, pharmaceutical company or other funding organization to propel the project into full productivity.
“We’re not really interested in licensing out one chemical here and one chemical there,” he said. “We want to create a comprehensive program that can yield benefits not just this year but for many years to come.”