Brown Goo and the Avian Flu

by Kristina Brooks

If someone had told Margaret Scheuermann ’08 that her scientific research at Scripps College would include climbing ladders, picking prickly sweetgum balls off campus trees, and holding a blow dryer on a dripping solution for half an hour, she wouldn’t have batted an eye. She says she’s always wanted to be a scientist, and such work comes with the territory.

Margaret has recently been caught off guard, however, by widespread media attention on her research. Working with Thomas Poon, associate professor of chemistry in the Joint Science Department, Margaret has devised a better method of extracting shikimic acid—a key ingredient in the manufacture of an antiviral drug that combats the avian flu virus—from the crunchy, unlovable sweetgum balls that litter The Claremont Colleges’ campuses.

Poon first discovered that shikimic acid, a substance that makes drugs more soluble, could be extracted from sweetgum seed pods while working with a team of students at Randolph Macon College, in 1998. At that time, Poon and his students collected the gumballs from Liquidambar trees and collected the seeds. However, their extraction process yielded only minute amounts of shikimic acid.

Fast forward to the fall of 2005, when CMC student Michael Fujinaka, studying abroad in Hong Kong, e-mailed Poon about an article he had read on the shrinking supply of shikimic acid. The primary source for shikimic acid, star anise, is found mainly in China, and its scarcity was creating a shortage of Tamiflu, the world’s primary anti-avian flu drug. Knowing of Poon’s earlier work on sweetgum balls, Fujinaka suggested that Poon return to the lab.

Then, Margaret’s physics professor sang her praises to Tom Poon, who, recalls Margaret,”gave me a ‘quick project’ on drug solubilization before even meeting me.”

Once they had collected the sweetgum balls, Poon’s research team of Fujinaka and Scheuermann hit the lab. One of Margaret’s first discoveries was that the shikimic acid was turning into a solid, brown goo. Realizing that “when something doesn’t work, asking ‘why?’ rather than getting frustrated” would be the key to success, Margaret set about trying other organic purification techniques in different orders.

In the Joint Science Department, a chemist is never far from a biologist (or a physicist), and this interdisciplinary neighborliness led Poon’s team to a key discovery. Biology professor Emily Wiley suggested that the goo was undissolved DNA.

Margaret explains: “In the process of taking compounds out of the seeds, you take all sorts of compounds, including the plant’s DNA. When you try to remove the solvent, the DNA and shikimic acid react with each other and make this useless, brown crud, which is why we couldn’t get high yields [of shikimic acid].”

The team realized that heating the sample would cause more of the shikimic acid to dissolve but would not have much effect on the DNA.

“Margaret ended up standing with a heat gun for a half hour while the compounds were filtering through,” says Poon. “We do a lot of jury-rigging and improvising in the lab. We actually use a hair dryer quite a lot.”

While the team’s yield of shikimic acid from the seeds is only 1.3%, compared to 3.7% from star anise, the vastly greater supply of sweetgum seed pods makes this a significant discovery. Indeed, when Margaret presented the team’s findings at the American Chemical Society’s annual meeting in March, she was thrust into a session with graduate students, post-doctoral fellows, and professors. She drew the attention of many interested scientists, including a representative of Gilead Sciences, owner of the Tamiflu patent.The team’s research has since been covered in the Atlanta Journal Constitution, as well as several local media outlets.

A fellow Scripps student, Liza Enrich ’07, will continue on this project with Poon, working to determine the optimal time in the seed pod’s life cycle to extract the shikimic acid. Margaret, meanwhile, is working this summer with an inorganic chemist at the University of Washington to find catalysts. She’s on to new classes and challenges at Scripps this fall.

“My favorite part of being a scientist,” Margaret emphasizes, “is being in the lab—no doubt about it.”