Stephen F. Austin State University

Patent is pending for process to produce shikimic acid from domestic sources.

NACOGDOCHES, TEXAS – No one knows for certain whether avian influenza, or bird flu, will become an international pandemic. The only thing experts agree on is that the supply of drugs to treat the illness is woefully inadequate. Scientists at Stephen F. Austin State University believe they have partially solved the problem, and the solution they have found is commonly located in many East Texas backyards.

A Switzerland-based pharmaceutical company, Roche, has exclusive rights to produce Tamiflu, one of three drugs known to be effective in fighting avian flu. While Tamiflu's success rate is not 100 percent, it is almost always effective and Dr. Shiyou Li, SFA research professor and director of the National Center for Pharmaceutical Crops, calls it "the best of the three."

Tamiflu is produced from shikimic acid, a compound first isolated from the Japanese shikimino-ki tree and found in higher concentrations in a commonly used cooking spice called star anise produced in China.

"Shikimic acid is a bottleneck in the production of Tamiflu," Li said. "It is a compound in many, many plants but the concentrations are usually very low and commercial extraction is not feasible. Star anise has been the best option, but I have read that it takes 30 kilos of star anise to produce one kilo of shikimic acid."

Countries around the world are currently in a race against the clock and each other to stockpile enough of the drug to treat their citizens in the event of an outbreak of the virus, and the price for shikimic acid has increased ten-fold in the process. Because the supply of shikimic acid is very small, the U.S. currently has stockpiled only enough of the drug to treat 1 percent of the population, Li said.

According to Li, having a shikimic acid supply available within the United States is vital to national security. It is also part of the National Strategy for Pandemic Influenza, which can be viewed at www.whitehouse.gov.

"Anytime our relations with other countries become strained, the U.S. is faced with losing our supply of resources used to produce drugs – whether it is Tamiflu or cancer drugs," Li explained. "We really need to concentrate on reducing our dependency on other countries."

Li's concerns for national security received support from the U.S. government to the tune of almost $1 million in grant funds. Through efforts led by U.S. Sen. Kay Bailey Hutchison, R-Texas, Li established the National Center for Pharmaceutical Crops at SFA in collaboration with the University of Mississippi. The center focuses on identifying and developing antiviral and anticancer drugs and securing strategic pharmaceuticals for the country. The support from Hutchison placed some additional pressure on Li to find a solution to the avian influenza vaccine problem.

"I started a center to protect our national security, and I felt it was my duty to produce something that would accomplish that goal," he said.

In fall 2005, Li and his team began studying plant samples to determine their viability as alternative shikimic acid sources. They studied thousands of plant samples from 32 families of plants, ranging from ferns and bamboo to hardwoods and conifers.

"We checked everything that was available," he said. "We were looking for a shikimic acid source that was easily produced and available in large quantities in the United States."

In addition to identifying suitable plants as shikimic acid sources, or specific parts of plants in some cases, Dr. Li's team developed new processes for extracting the shikimic acid in ways that are commercially viable, cost effective and environmentally friendly.

The university has applied to patent the new processes developed by Li's team. Although they are not ready to release specific details regarding which sources provided significant amounts of shikimic acid, David G. Henry, professor of patent and trademark at Baylor University School of Law, said the work of Dr. Li and his team represents a major breakthrough in satisfying a dire societal need and is a classic example of the type of innovation for which patent protection is intended.

"Based on our present understanding of the scientific landscape in this area, I believe that the present efforts will produce patent protection with far-reaching, positive effects for the university, its researchers and the surrounding communities," Henry said. "The technology itself will, I believe, have global implications."

Like the World Health Organization, Li believes the threat of an avian influenza pandemic is credible. According to the organization's Web site, three cases of avian influenza in humans were reported in 2003, all in Vietnam. In 2004, 46 cases were reported – some in Vietnam and some in Thailand. By 2005, human cases were reported in Cambodia, China, Indonesia, Thailand, Turkey and Vietnam, and the number of cases increased to 95.

"When people first heard of AIDS, it was isolated in one country," he stated. "Now it's everywhere. I believe that avian influenza may be the same and that it is likely to become transmissible from human to human, even though it is not now. Either way, it is better that we be prepared for this possibility."

Dr. Scott R. Beasley, dean of SFA's Arthur Temple College of Forestry and Agriculture, said an avian influenza pandemic could be reminiscent of the influenza outbreak at the end of World War I.

"If this happens, the world would need a supply of Tamiflu that greatly exceeds the amount now available," Beasley said. "Dr. Li's discovery may help us to develop the stockpile needed to confront such a disaster."

Even though Li and his team began their shikimic acid research in the fall, university researchers have 12 years of research experience in antiviral and antitumor properties of several plants, including Camptotheca, a cancer-fighting compound. Despite their success, it hasn't been all smooth sailing for the research team.

"On our initial screenings, everything was coming back negative. We'd been through so many samples but quickly realized there was a problem with our method," Li said. "We made some changes and then began to get some positive results."

Li credits the team with sticking to their work, even when the results were not favorable.

"I've never worked with a team that was so collaborative and supportive of each other," he said. "I could not have asked for a better team. When someone comes up with an idea, it doesn't matter whose idea it is, everyone tries very hard to make it work."

According to Li, the research required team members to work some very long hours.

"I was working on New Year's Eve when my wife called me," Li said. "I answered my phone and she said, 'Happy New Year.' I realized it was midnight and just said, 'Happy New Year.'"

It will be a happy new year for the Lis when partnerships are formed to commercialize the technologies Li and his team have discovered and the world is supplied with an ample supply of Tamiflu.

In addition to Sen. Hutchison, Li credits Dr. Tito Guerrero, SFA president, and Dr. Scott Beasley, dean of SFA's Arthur Temple College of Forestry and Agriculture, for the foresight and willingness to support the efforts of the pharmaceutical center.

"We have had help from so many people to make this possible," Li said. " Dr. David Creech with the SFA Mast Arboretum helped obtain some samples for us from nurseries and universities across the country. Also, I don't know how much progress we would have made without the help of our local leaders, especially Judy McDonald with the Nacogdoches Economic Development Corp., County Judge Sue Kennedy and state Rep. Roy Blake."