Pitzer in the News 2005-2006 Academic Year

Can this seed help stop bird flu?
Claremont researchers find building blocks for Tamiflu in pods

By Caroline An, Staff Writer
Inland Valley Daily Bulletin, April 10, 2006

CLAREMONT - Researchers at the Claremont Colleges may have found a solution in the fight against the avian flu virus in an unlikely location --on the lawns and in the trees of their own campuses. They have determined that sweetgum balls -- the round, prickly seed pods and a fruit of the sweetgum tree -- are rich in shikimic acid.

That's the starting material needed to manufacture the compound Tamiflu -- a drug used in the defense against the H5N1 avian flu virus and to fight different strains of the flu, said Dr. Thomas Poon, associate professor of chemistry in the joint science departments of Claremont, Pitzer and Scripps colleges.

Poon and two undergraduate students presented findings of their two-months-long study of the sweetgum tree at an American Chemical Society's meeting in Atlanta in late March.

The primary source today of shikimic acid is the spice star anise, a licorice-flavored ingredient of the five-spice powder of traditional Chinese cooking.

With the threat of bird flu -- a case was confirmed in Scotland last week -- the world's supply of the spice is rapidly dwindling. Purchases by drug companies have tightened the supply and hoarding by individuals who erroneously believe the star anise seed itself will protect them against the flu has also contributed to the shortage.

Roche Pharmaceuticals, manufacturer of Tamiflu since 1996, made 55 million doses of the drug in 2005 and aims to produce 400 million doses by the end of this year.

While the numbers have increased, Gilead Sciences, owner of the Tamiflu patent, served Roche with a termination notice in 2005. The two sides settled shortly after, and Gilead now has a more visible role in the drug's marketing and manufacturing, said Erin Edgley, Gilead spokeswoman.

Poon believes the sweetgum tree might be an answer to the shortage of star anise for the production of the drug.

Using a kitchen blender, conventional oven and methanol to extract shikimic acid from the seeds, the Claremont team squeezed about two-tenths of an ounce from a pound of sweetgum seeds. A pound of star anise seeds usually provides a half-ounce to one ounce of shikimic acid.

Poon acknowledges that the yield from the sweetgum seed is much less than from star anise, but the U.S. is dotted with these trees -- from Connecticut to central Florida and parts of California, including several on the campuses of the Claremont Colleges.

The three shopping bags of seeds used in the team's research were picked from trees on campus. Star anise is mostly found in China.

‘‘The trees can be in someone's yard or along the road,'' he said. ‘‘There are a lot of sweetgum trees in the U.S.''

The U.S. Forest Service estimates that one bushel of sweetgum balls contains an average of 82,000 seeds. The trees produce seeds beginning at age 20 and can reproduce until they are 150 years old.

The Claremont team began research last fall after Michael Fujinaka, a junior at Claremont McKenna College and one of the two undergraduates on the team, read reports about developing Tamiflu.

Poon had studied sweetgum trees when he was professor at Randolph-Macon College in Virginia in 1998, and Fujinaka suggested that he restart the research since shikimic acid was the building block to making Tamiflu.

Roche contends that the shortage of Tamiflu isn't related to quantity of star anise seeds. The company now uses a fermentation process which lessens the reliance on star anise for shikimic acid, said Terence Hurley, Roche spokesman, in an e-mail.

The research conducted at Claremont was performed with the company's fermentation process in mind, Poon said.

‘‘We know they have their source, and that's fine. All of these years, the star anise was Roche's primary source for shikimic acid,'' he added. ‘‘I'm just glad we found another source in the U.S.''

He warns that their work is still in the first stages; the team is seeking a method to extract more acid from the sweetgum balls.

Additionally, the new source could come in handy with other countries that are having difficulty finding enough of the acid for their own production. Last fall, the Taiwan government signed an agreement with a supplier to buy three metric tons of shikimic acid.

Roche is also working with manufacturing partners to increase production and granted sub-licenses to three companies in China and India to manufacture Tamiflu there, Hurley wrote.

Academics applauded the research in Claremont as another weapon in the fight against bird flu.

Dr. Michael Lai, distinguished professor of molecular microbiology and immunology at USC's Keck School of Medicine, said that with increased global competition for shikimic acid, having domestic sources for the material would be a great benefit.

‘‘Shikimic acid is running low, and it's good to know there are other sources in case we need to step up production,'' he said.

Lai blames the current shortage of the drug squarely on Roche because ‘‘there is only one company with the intellectual property rights,'' he said. ‘‘Other countries aren't allowed to manufacture without their consent.''