Unlocking periwinkle’s potent secrets

Vonny Salim ’07

by Gayle Boss
Fall 2012

When she was a child and had a cold, Vonny Salim ’07 wasn’t dosed with medicine from a bottle. Instead her mother fed her garlic, “which is nasty, but works,” Salim said. “And she made a drink from the leaves of a plant to treat my dad’s high blood pressure. She taught me the power of nature to heal.”

Salim wondered why plants could heal. What was going on inside them to make such medicine?

“I was quite a biology nerd,” she admitted.

Her questions took her from her native Indonesia to Seattle to study biology and chemistry.

“In Seattle my host family had two members suffering from cancer. That made me sad, and it focused my study. I thought, ‘Couldn’t we find something from plants to cure cancer?’”

The question lodged deeply. When she transferred to Calvin, Salim learned from biology professor David Koetje the principles of plant biotechnology, and, in the lab with professor John Beebe, she saw how those principles played out in the breeding of hostas.

For her graduate work, she was eager to hone in on plant-based cures for cancer. Where and how to do that? An Internet search suggested: Madagascar periwinkle, Vincenzo De Luca. In September 2008 she began research in De Luca’s lab at Brock University in St. Catharines, Ontario.

Chemists have long known that a chemical compound called vinblastine, produced by the Madagascar periwinkle, inhibits the out-of-control cell growth that characterizes cancer and so is an effective chemotherapy treatment. The problem is that each periwinkle makes only a very small amount of vinblastine. Extracting and purifying these small yields makes vinblastine an expensive drug. If, however, scientists could identify the precise step-by-step pathway along which enzymes catalyze chemical reactions to form vinblastine, then the drug could be synthesized outside periwinkles. Identifying that pathway has been the decades-long work of De Luca’s lab, the work Salim joined.

Salim and her research partner discovered the reason periwinkles produce such small amounts of vinblastine. In the last step of the chemical pathway that forms the drug, two compounds, catharanthine and vindoline, join. But the plant keeps these compounds largely separated. Salim went on to discover that the reason the plant keeps catharanthine on its leaf surfaces is that the compound is toxic to fungi and larvae that eat the leaves.

The bulk of Salim’s research now is to identify the genes that control the pathway of enzymatic reactions that produce catharanthine and vindoline.

“There are multiple genes in the pathway of each compound that we haven’t identified,” she explained. “Those are the genes I’m looking for. If we know the specific genes that control every single step of the pathway, then we can transfer those genes into a yeast that will release the drug in one step. That will make the drug much more affordable. But I’m afraid that’s still a long way off.”

The past four years of research have made clear to Salim how long a road it is to her dream of identifying a new plant-based cure for cancer.

“The first year was rough,” she said. “I learned to pray, asking God for direction. Because these systems are complex, and without God’s direction, you’re looking for a needle in a haystack. Now it’s not a burden. I wake up in the morning and say, ‘What’s new today, God?’ Research isn’t just an occupation for me. It’s walking with God.”