Scripps Scientist Looks to Ocean for Cures, LA Times, 05/18/06
By John Balzar
Source: Los Angeles Times
LA JOLLA, CA — You might never hear of Bill Fenical again. In the years ahead, though, you could owe him some of your good health. Perhaps your life.
Fenical probably won't join the ranks of those Communications Age nobles who transform convenience gadgetry and technological gewgaws into inconceivable wealth. Yet this chemist is hot on the trail of discoveries far more tantalizing.
William — "call me Bill" — Fenical, PhD, is out to cure cancer. Maybe prevent cancer.
Bill Fenical is a pioneer in an effort to beat other diseases that are rapidly — alarmingly — developing resistance to everything in the world's antibiotic medicine chest.
He is out to crack other maladies for which there are no cures at all.
And if Fenical, 64, doesn't achieve these things during his remaining years as a chief research scientist at Scripps Institution of Oceanography, he has blazed a trail that hundreds of others are rushing to follow. He's trained many of them himself. In this age when science is more corroborative and incremental than ever, Fenical is a pathfinder in the promising hunt for 21st century medicines from that vast, mysterious birthplace of life itself: the oceans.
It's a simple proposition: A medicine is merely a compound that repels or kills or somehow interferes with the organisms and processes of disease. In short, it is chemistry. Medicines from aspirin to penicillin are natural chemicals harnessed for the benefit of countless millions of humans.
The problem is that the terrestrial world has been scoured so thoroughly that science is running out of places to look and breakthroughs to count on. No significant new antibiotic, for instance, has been discovered in a generation. Bacteria, meanwhile, have been busy developing immunity to known antibiotics.
What makes Fenical's work promising is that there is so much chemistry at work in the undersea about which science knows so little.
"It's like opening a chest of new and exciting ideas," he says at his oceanfront laboratory overlooking the Scripps Pier. "This is, without question, going to lead to significant discoveries of drugs."
The oceans are not only the largest features of the planet; they are also the most bio-diverse. If you recall your high school biology, "genus" is the taxonomic group under which species of organisms are categorized.
Fenical and his team of researchers at Scripps have discovered and identified 15 genera of organisms never before known, thousands upon thousands of potential species. At that, Fenical says, they've barely started.
His lab has isolated and tested two compounds derived from marine organisms that are now undergoing human clinical trials as anti-cancer drugs. One of them, called SalA, is produced from previously unknown bacteria found in the mud of the deep sea. It is being tested on volunteer cancer patients for its potential to combat malignancy of the blood and bone.
The other, known as NPI-0058, is derived from a marine fungus that lives on seaweed. It is being administered to patients who have not responded to other treatments for its potential to counter aggressive tumors, such as those of the lung, breast and pancreas.
At least 13 compounds isolated by other laboratories are also in anti-cancer trials — a process that can sometimes take just months to show promise but often years to perfect.
"We will look back and talk about the sea as the bountiful resource that saves human lives," said Bill Gerwick, a former student of Fenical's who has returned to UC San Diego's Scripps Institution to join his old mentor here at the recently expanded Center for Marine Biotechnology and Biomedicine.
With Fenical as director, the center draws from the work of 30 research laboratories at the schools of medicine and pharmacology as well as from marine scientists at Scripps. It represents a significant bid by the university to maintain its place as a global powerhouse in the field.
A stocky, avuncular man with a noble paunch, a cowboy mustache and a taste for aloha shirts, Fenical long ago realized that most people don't give much thought to medicines beyond the costs and side effects.
For this reason, Fenical tries to simplify the explanation behind his growing excitement about the undersea.
Consider the colorful and delicate creatures on a coral reef. Many are so brilliant they cannot help but call attention to themselves. Yet they survive. Some utilize thorns or shells for defense. Many rely on chemistry alone — the same kind of natural warfare that the fungus Penicillium notatum uses to kill infectious bacteria, or, more crudely, that the skunk uses to fend off the coyote.
Those kinds of active chemicals form the basis for Fenical's research.
Collected during periodic expeditions, the chemicals are isolated, identified and tested against human pathogens: cancer cells, viruses, bacteria, fungi.
Those that show the capacity to kill harmful organisms are screened for side effects. Do they also kill healthy cells? Do they interfere with any of the many complex chemical processes of animal life?
Oh, the tests. Each step is intricate and maddeningly time-consuming. Entire buildings on the Scripps campus are filled with glass beakers and petri dishes and banks of machines that separate the living world into its microscopic components. Rooms heated to stifling temperatures are used to grow jars full of fresh organisms; nitrogen freezers hold libraries of the 14,000 or so substances Fenical's lab has collected over the years. The musty odors of organic chemistry are strong in the air.
At any given time, Fenical and other scientists at the center are testing several compounds that have them holding their breath. You can look into petri dishes in temperature-controlled rooms and see cancer cells dying in the face of chemical attack — perhaps the exact dish holding the very compound that will someday mark the dawn of a new era in medicine.
"Sometimes people think we sit around and dream up stuff and wait for a lightbulb to go off," Fenical says. "Wouldn't that be easy? But it doesn't work that way. Science edges ahead at infinitesimally small units. Discoveries are few and far between."
Whenever Fenical makes a speech, publishes a paper or winds up in the news, Scripps awaits the calls. Cancer victims and their families plead for word that the future is not so far off.
Fenical's business card reads: professor at the University of California. But "entrepreneur" would be a more accurate description. Fenical's work thrives or not solely on his ability to win outside grants, chiefly from the federal and state governments. A research scientist must first be a salesman for his vision.
"I am completely a private enterprise," he says with a shrug.
His career began with an unsatisfying year as a chemist for an oil company. Then he turned to academia and oceanographic research, approaching Scripps in 1973 when hardly anyone was giving much thought to the chemical interactions of marine organisms. He was not regarded seriously, except by one man. The director of the institution gave Fenical nine months to find financial backing to start a research project.
With no office, no staff, no lab except for open space on a bench, Fenical survived the nine-month probation, but it took until 1977 before he could open his own laboratory. By then, he was traveling the warm-water oceans of the world, scuba diving to collect and identify marine plants.
Those were exciting years, a time of pure discovery.
Incrementally, he began to ponder the practical possibilities of those mysterious new organisms. In 1983, he discovered a sea fan off the Bahamas. From it, he isolated an agent that acted as an anti-inflammatory in humans. The substance, known as pseudopterosin, was patented by the university, and the cosmetic rights were sold to Estee Lauder for use in skin-care products. In fiscal 1994-95, the compound was among the UC system's top 10 patent royalty earners, bringing in $680,000. It was no small breakthrough. "Here, for the first time, was a scientifically proven marine product," Fenical says.
Pseudopterosin remains under study by a UC Santa Barbara research team as a promising treatment for wounds — countering the body's natural immune reactions such as swelling and inflammation, thus allowing faster healing.
After about 15 years, Fenical and his growing team of research scientists turned from plants to animals, in particular soft corals.
In 2001, his lab's energies were redirected again.
Fenical recalls the "eureka" moment. His team was analyzing the DNA of bacteria found in an early sampling of mud from the sea floor. The results were compared with a computerized inventory of all known life. No match. "Nada," Fenical says.
"Hello? We realized in a moment of discovery that we were working on microbes that had never been seen by science," he says. "We also realized that the bottom of the ocean could be the great source for pharmaceutical discovery."
The arc of his career has led him from organic chemistry to biology to microbiology to molecular biology, from pharmacology to engineering to genetics to bio-testing — a remarkable interdisciplinary journey in this era of hyper-specialization in science.
His peers recently recognized him as the innovative force who laid the foundation for the field known as marine chemical ecology. Professional chemists of the American Chemical Society likewise honored his "pioneering studies of biologically active, natural products." He has published more than 300 scientific papers, helped found Nereus Pharmaceuticals — a private company licensed through UC San Diego to bring marine medical discoveries to market in the future — and trained 113 doctoral and postdoctoral scientists.
Not all the work of science occurs in the laboratory, of course. Sometimes studying the ocean means you have to get wet.
Fenical berths his 42-foot trawler, Osprey, at La Paz, Mexico. As a teacher, coach, counselor and exemplar for the students his lab attracts from around the world, he leads them whenever he can out from under the fluorescent lights and into the ocean they love.
In 2000, this writer accompanied Fenical and five members of his lab on a research cruise into the sheltered clear-water bays of the Sea of Cortez in search of the ocean's chemical mysteries.
Fenical has been a diver since scuba diving was dangerous and experimental. Aboard the Osprey, diving is both essential endeavor and pleasurable pastime. Twice a day on this trip, his students splashed into the subtropical sea, filling baggies with sediment and thumbnail-size pieces of plant life.
Fenical set his sights on retrieving something else. He swam with tree-trunk legs among the eels, wrasses, jacks, parrotfish and triggerfish to bring back dinner. The professor is justifiably famous for his finger fish tacos, the key to which is a freshly speared grouper.
An advanced degree in oceanography requires vastly more classroom time and scholarly effort than an MBA, with the promise of financial rewards laughably less. True, under UC's system of incentives, researchers receive a 30% or so share of royalties on any discovery that is patented and sold. But rewards apart from money brought the Osprey to life at 6:30 in the morning and kept researchers organizing, logging and stowing their samples until far past midnight.
Perhaps part of it came from the relaxing interlude after the grouper vanished, when the margaritas were mixed in the muggy night air and the fantail lights attracted schools of cornetfish and scientists cannonballed into the water to join them.
The expedition ended up gathering 1,120 organisms. It was plenty to keep the lab busy for months.
"I'm not a dreamer," says Fenical.
Of course he's a dreamer.
In the years since the 2000 La Paz trip, Fenical's dreams and optimism have grown. Bringing his two most promising discoveries, SalA and NPI-0058, into clinical trials has finally quieted the last of the doubters. He has since joined a team of scientists from around the nation attacking cancer from the other end: trying to find a preventive drug.
To walk through his lab is to meet researchers, one after another, who feel they are closing in on something.
The chemical combat between the ocean's organisms, perfected over hundreds of millions of years of natural selection, is evermore a source of wonder to the scientists closest to it.
Much of the work of Fenical's lab, as well as of others, is a quest for incremental advances in medicine. One deep-sea compound under study, for instance, shows tantalizing promise in breaking down the resistance of Streptococci bacteria to standard antibiotics — in particular, the Strep-B infections that plague children.
Still, the chance of a breakthrough wonder drug, tomorrow's penicillin, hangs in the air. To this man who knows best, it's not "if" but "when."