What do giant salvinia, fire ants and Chinese tallow have in common? A fatally toxic compound, specific only to them, that could control their invasive spread.
In fact, Dr. Shiyou Li, director of SFA’s National Center for Pharmaceutical Crops, and his team of researchers believe the same could be true for every plant and insect in the world.
The primary goal of Li’s research during the past 30 years has been, and continues to be, the pursuit and discovery of anti-cancer agents. Li and his team have successfully isolated dozens of plant compounds, several of which show promise in reducing or destroying cancer cells without injuring normal cells. Most recently, they were granted a U.S. patent for anti-cancer Salviniol, a compound extracted from the floating fern giant salvinia — one of Texas’ most invasive aquatic plants.
In the process of conducting his research, Li made a shocking discovery that could significantly impact the battle against invasive species. He calls the concept endocides, or endogenous biocides.
“In our research, we involved hundreds, even up to 1,000 species of organisms, and we found a very interesting pattern,” Li said, seated in the conference room of his on-campus laboratory. Pausing on a slide in his PowerPoint presentation filled with various photos of flora and animals, he explained, “All the chemical compounds we are working with are called secondary metabolites. These are small molecules that some people think may involve defense for the producing organism but don’t involve its normal reproduction or development. We found that is not entirely true.”
Li and his team set about extracting these secondary metabolites first from dozens of different plants and later from various insects. They reintroduced the molecule, whose purpose Li believes is to regulate growth, back into the host organism either by direct spray or via the roots. In every single case studied by Li’s team thus far, this method killed the host without significantly harming any other surrounding organisms.
The discovery’s potential is thrilling to wildlife professionals fighting a relentless war against the spread of certain biological invasions, including giant salvinia.
“One of the drawbacks of using herbicides to manage salvinia, or any plant, is that the herbicides will affect other non-target plants,” said Thomas Decker, an invasive species biologist with the Texas Parks and Wildlife Department. “In large mats of salvinia, this isn’t usually a concern, but when salvinia is mixed in with other species, a manager has to weigh the benefits of treating the salvinia against the damage to other plants. Having a compound that selectively kills salvinia could allow more aggressive and thorough management of salvinia in conjunction with the conventional herbicides and biological control currently in use.”
Putting down scientific roots
In 1984, Li began botany research in China where he successfully identified nine new plant species or varieties, one of which was a new species within the Camptotheca genus. At that time, camptothecins, or CPTs, comprised the main compound in cancer-fighting drugs and received FDA approval for use with ovarian, lung and colorectal cancers.
Li’s first book on Camptotheca and camptothecins was prefaced and endorsed by Dr. Monroe Eliot Wall, an American chemist who co-discovered with Dr. Mansukh C. Wani anti-cancer compounds camptothecins and paclitaxel — two cancer drugs that comprised more than 25 percent of the world’s chemotherapy supply.
“Before we did the research, only one species, Camptotheca acuminata, was being used worldwide for cancer drug production,” Li said. “I was able to discover a second species within the same genus, but it was morphologically different.”
Li’s early research in the Camptotheca field involved experiments aimed at shortening the plant’s evolution process and, in turn, shortening the length of time needed to cultivate the plant for CPT production. To say he was successful is an understatement.
Several different Camptotheca cultivars were produced in Li’s lab with the same leaves and seeds as the parent plant but in a smaller, more condensed shrub version. As the cultivars grew smaller, the CPT yield grew much larger, meaning even a shrub-like version of what was once a tree contained at least the same amount of cancer-fighting compounds.
By applying endocides, Li also has developed several other dwarf cultivars of trees and herbaceous plants.
Li’s research did not go unnoticed. His discoveries caught the attention of Norman Borlaug, a man whose name is considered synonymous with the Green Revolution for his agricultural work. Borlaug received a Nobel Peace Prize in 1970 for his contributions to increasing the world food supply.
Li’s method of hastening the evolutionary process of plant growth excited Borlaug, so much so that Borlaug personally contacted the Rockefeller Foundation and told them to support Li’s work.
“He spoke to the director there, and the director of the Rockefeller Foundation then called me and said, ‘Well, Norman just called me and asked us to fund your research. He said he found it tremendously interesting,’” Li said. “However, he also said, ‘because we concentrate (our funding) on food production, we don’t support medical research.”’
Even though Li’s research did not fall within the Rockefeller Foundation’s philanthropic purview, he continued to receive support from a number of individuals, including then-U.S. Sen. Kay Bailey Hutchison, U.S. Rep. Louie Gohmert and U.S. Sen. Ted Cruz, among many others.
In fact, several years ago, Hutchison contacted Li directly to ask that he try to identify a native U.S. resource that contains shikimic acid, a chemical used in the production of Tamiflu. The world supply of shikimic acid is derived from the Chinese spice star anise, but in years of flu epidemics, supply would run short.
“We probably spent a few months working day and night, even through the New Year holiday, to identify a plant with the same compound,” Li said. “I even remember going to the field at 1 a.m. collecting samples. We screened a lot of plant samples, and we finally found this.”
Moving aside compound diagrams and sifting through various plant matter on the table in front of him, Li held up a leaf from a sweetgum tree.
“I told Senator Hutchison it’s not an issue because the sweetgum tree supply in Nacogdoches was enough for the needs of the whole U.S.”
Li also is one of a team of 12 working for M.D. Anderson’s Center for Cancer Prevention by Dietary Botanicals investigating the curative effects of turmeric.
Claims to fame
In 1994, Li joined SFA, working explicitly with plants from East Texas and other regions. During the past two decades, his team has screened more than 1,300 species of plants and isolated more than 2,000 compounds from 52 of those species. Of those 2,000 compounds, 186 had never been discovered.
Currently, Li has two staff scientists working in the lab. Dr. Ping Wang has worked for SFA since 2005, and she is responsible for the isolation of 27 new compounds, including Salviniol and salvinisides. Dr. Zushang Su has worked with Li since 2011 and has isolated 43 new compounds.
Thirteen patents have been filed, a few of which are still pending, for a number of compounds Li and his team have discovered that show promise in fighting the spread of cancer.
The most recently granted patent was for the compound Salviniol, which Li’s team discovered in and extracted from giant salvinia. Lab trials conducted at the NCPC verify Salviniol can slow and, in some cases, completely inhibit the growth of a wide range of cancer cells, including pancreatic and lung cancer cells.
“Dr. Li and his team of researchers at the National Center for Pharmaceutical Crops are engaged in cutting-edge, basic research that is raising the national profile on the quality of research conducted at SFA,” said Dr. Hans Williams, dean of the SFA Arthur Temple College of Forestry and Agriculture. “We have been aggressive in promoting Dr. Li’s results in various outlets because it is critical for us to continue to highlight his research. Raising awareness of his important discoveries will assist Dr. Li in his efforts to find financial support to continue his work.”
Of course, while incredibly exciting, the discovery of Salviniol is the first step in a long and arduous process of clinical and other testing before the compound could be potentially used in the creation of a cancer-fighting drug.
“Right now, we are only in the early stages of discovery,” Li explained. “For this to become an available medicine you need human clinical trials, and you need FDA approval. All of that is the medical doctors’ job. We are just doing research. We don’t know how toxic this is to human systems yet. We don’t know the long-term impact on humans.”
Li’s hope is to use compounds like Salviniol in conjunction with the theoretical discoveries inherent to the endocide process to both target cancer cells and rebalance the body’s growth abilities. If endocides do, in fact, regulate an organism’s growth, Li hopes to harness those processes to better understand why cancer grows and to control it.
In the meantime, endocides have vast possibilities in the realm of invasive species management.
“Basically, the endocide is solving environmental cancer,” said Dr. Steve Bullard, SFA provost and vice president for academic affairs. “Invasive plants and insects are absolutely huge problems worldwide, so when you look at ecological health, these invasive species are like cancer. They take over, and soon you don’t have your native ecosystem anymore.”
Endocides show promise that invasive species can be effectively managed without polluting the environment or harming nearby, non-invasive plants. And maybe eventually they can be used to regulate invasive human cells, too.
For now, Li and his team of talented scientists continue to trek through East Texas landscapes, snipping leaves here and plucking weeds there, in the hopes that, one day, they’ll peer down through a microscope in the SFA National Center for Pharmaceutical Crops and realize the cure for cancer was hidden in the Texas wilderness all along.