Scientist of the Year Baldomero M. Olivera Discovers Poisonous Secrets

He was like a little boy scouring the beach in search of a prized find: a perfect shell, with the right shape and color, with no chips or cracks. In the Quezon City home of one of the foremost shell collectors in the world (requesting anonymity, this man has over 20 shells named after him, and holds the size record for over 30 others), amid dusty cabinets and cartons that must contain hundreds of thousands – maybe millions, from the tiniest specimens smaller than a baby’s fingernail to huge ones the size of wash basins – of shells, Dr. Baldomero “Toto” Olivera, Distinguished Professor of Biology at the University of Utah and Harvard Scientist of the Year, was happily picking shells, and he’s been at it for a good part of the morning.

“That’s quite a lot of shells,” we say, looking at the shells on a tray beside him, trying to get in a question every so often in what bears little resemblance to an interview.

He laughs, and says, “Yes, but you know, he (referring to the owner of the house and the shells) is going to take back most of them, so I better get a lot so I’ll at least be left with some.”

From somewhere behind a wall of cartons the owner registers vigorous agreement: “I’m going to confiscate them!”

“See?” Olivera laughs heartily, adding more shells to his tray. We don’t know how the subsequent haggling went and how many shells Olivera finally managed to take with him, since we took our leave when the discussion between the two old friends turned seriously shell.

Olivera was in Manila last month to speak at several forums, including the Ayala Foundation’s Innovation Forum, and lectures at the University of the Philippines and St. Luke’s Hospital. Last March he was honored by the Harvard Foundation as 2007 Scientist of the Year at their annual Albert Einstein Science Conference, a singular honor for a man who has done groundbreaking work in the field of neurotoxicology. He led a team that isolated the components of toxins found in venomous cone shells found in Philippine waters, enabling the development of a new type of painkiller that is more powerful than morphine but, unlike opiates, is non-addictive.

His discovery is the basis for the drug Prialt, with 2006 sales topping $12.5 million. It is used for cancer, AIDS and other pain patients for whom traditional drugs like morphine no longer offer enough relief. Unfortunately, Olivera doesn’t make a single cent on this, since he never bothered to patent his discovery, and simply “gave” this particular component – called a conopeptide – to a researcher in California back in 1985 who was then looking into how nerve cells release chemical signals.

Like a typical “pure” scientist, Olivera says he is thrilled to see his work go from theory to reality,  from pure research to actual medicine. He told Forbes Asia in a recent interview, “In many ways I feel like I am living every scientist’s dream.”

His dream began with a childhood fascination for seashells, not just to play with or collect, but to learn their scientific names and characteristics. He graduated with a Bachelor of Science degree in chemistry, summa cum laude, from the University of the Philippines in 1960, migrated to the U.S. the following year and got his PhD in biochemistry in 1966 from the California Institute of Technology, as well as a research fellowship. He then did post-doctoral work at Stanford University’s School of Medicine and was a fellow of the Damon Runyon Research Fund from 1966 to 1968.

Despite these early successes and the prospects of a very bright future in the scientific world in the U.S., Olivera returned to the Philippines and took on the position of research associate professor of biochemistry at the University of the Philippines College of Medicine, where he continued his pioneering work on DNA replication. He would not confirm it, but we were told by other sources that Olivera and his team were nominated for the Nobel Prize for their work on DNA ligase, the enzyme that enables genetic material to fuse, which in turn makes such processes as cloning possible.

Unfortunately, lack of funds and equipment at the research facilities here hobbled his work and he returned to the U.S. He took up a position as visiting research associate professor at the Kansas State University. In 1970, he joined the University of Utah as associate professor, became a full professor three years later and in 1992 was named Distinguished Professor of Biology. He is also director of the Olivera Lab. Last year, he was appointed a Howard Hughes Medical Institute Professor.

Olivera’s most outstanding work is on neurotoxins produced by venomous cone snails found in the tropical waters of the Philippines. These cone snails sting their prey – fish, mollusks and other marine creatures – with a harpoon-like device, delivering venom that can be so lethal a human would be dead within hours of just one sting.

With his researchers here in the Philippines, Olivera collected and isolated the components in the venom of one particular snail, Conus geographus, to find the toxin that causes paralysis in its victims. To their surprise, they found that the venom contained hundreds of different nerve toxins, which they subsequently found to be peptides, or small protein-like molecules. He noted that these were “potentially a pharmacological cornucopia.”

Despite the exciting potentials of the discovery, not much happened until several years later, when one of Olivera’s graduate students at the University of Utah injected the venom directly into the spine of lab mice. Each mouse reacted differently – falling asleep, shaking, convulsing, becoming sluggish – depending upon which conopeptide was injected.

Further research revealed how specific each conopeptide worked, honing in on just one type of molecule, usually channel proteins that control the flow of electrically charged particles such as calcium and sodium.

In the mid-1980s Olivera developed a component that blocked calcium channels. In 1985 he sent this to a researcher at the University of Southern California who was looking into how nerve cells release chemical signals. The researcher eventually left USC to work for biotech firm Neurex, which then focused its research on conopeptides. It developed a synthetic version of the peptide and began clinical trials in 1993.

Five years later, an Irish pharmaceutical bought Neurex for $700 million and took the drug through the necessary trials. In 2004, the U.S. Food and Drug Administration approved the drug, Ziconotide with trade name Prialt, for treatment of chronic pain. First year sales of Prialt hit $6.1 million, and sales last year doubled to $12.5 million.

Global sales for prescription pain medication reportedly totaled $25 billion last year, and are expected to hit $41.5 billion by 2010. While Olivera has not profited financially from this initial application of his research, the cone snail has a lot more to offer. There are about 700 species of cone snails, and with each possibly containing up to 200 conopeptides, the medicinal possibilities are myriad indeed, not just for pain management but for other nerve-related medical conditions as well, like Parkinson’s.

Olivera has founded a firm, Cognetix, a Utah-based biotech that is currently developing four conopeptide compounds, two for pain treatment that have been through early clinical trials. The two other compounds are for treatment of heart ailments (myocardial infarction). The group is seeking additional funding to proceed with the extremely expensive process of clinical testing.

In the meantime, Olivera continues to coax secrets out of the shells that have fascinated him since childhood. And he is also totally committed to a new role he has recently taken on – that of lolo to his first grandchild, a beautiful baby girl named Macy. In January next year, the entire Olivera family will visit the Philippines, and perhaps Lolo Toto can take little Macy to the shores where, many years ago, he searched the beach for shells, unaware that they would eventually share their secrets with him, for the good of mankind.