Unexplained disappearances, a baffling plague, an irreplaceable society crumbling: these are not the trappings of a musty history textbook or war coverage from across an ocean. They are essential pieces of a modern-day mystery that spans the globe.
This is the story of honeybees, their struggle to survive and the secret they may have to saving themselves. It’s the tale of three CFANS investigators and their team, who hope to learn the bees’ secret and use it to save humans, as well.
And it all began with a sore throat.
Once upon a time
About seven years ago, a researcher from the Ukraine working at the University of Minnesota medical school on lab trials to combat HIV came down with a cold. She, like countless people around the world, had always relied on a traditional treatment for such woes, a substance found in any honeybee hive: propolis.
Propolis, sometimes known as bee glue, is a thick, sticky resin that bees collect from tree buds and use to cement holes in the hive and defend it against invading parasites and diseases. Traditional healers from South America to China, Japan to Eastern Europe, have valued propolis as a remedy for such ailments as gum problems and dental health, skin issues and oral sores, as well as viruses and the common cold.
The researcher tracked down propolis at the Minneapolis farmers’ market and made herself a tincture to soothe her viral woes. Then she brought her cure to work with her and ran a test: propolis versus HIV. Propolis won.
Propolis demonstrated antiviral activity against HIV, prompting a study on propolis that paired the medical school with a team of researchers from CFANS. That project showed promising results, but propolis is an incredibly complex substance, and the mystery of precisely which elements are active remained unsolved. The researchers involved, though, didn’t stop considering the study’s implications.
Where the bees are
“I started thinking, ‘wait, if propolis is so good for humans, it’s got to also be good for bees,’” explains Marla Spivak, co-principal investigator in a new two-year project to identify the active compounds in honeybee propolis.
For the past several decades, bees have been stricken by parasites and viruses introduced by humans and global movement, to the point that wild or feral honeybees have become virtually extinct, explains Spivak, a professor in the Department of Entomology and bee expert. In the past year, entire colonies have mysteriously disappeared, an epidemic bee experts have named Colony Collapse Disorder (CCD), which has decimated some beekeepers’ bee populations.
Spivak speculates that CCD could be the cumulative effect of diseases and parasites that affect only honeybees, new systemic insecticides, crop specialization and destruction of native plant corridors, among other things. Whatever the cause, CCD threatens the pollinators of one-third of all U.S. food crops.
“Honeybees are a very ancient society. They’ve been closely associated with humans forever. As long as human history has been recorded, we’ve been beekeepers,” says Spivak, citing the innumerable food crops humans rely on bees to pollinate, as well as honey and other hive products. “Now bees are suffering, and they’re suffering for reasons mostly that we’ve created.”
She reasoned that a study could be designed to address both honeybee and human health. Testing chemical compounds against bee diseases can be done much quicker than any done with human subjects, and could produce results that can quickly be applied to combat bee diseases. Those same results could then be tested against HIV and other human viruses. She enlisted two of her colleagues from the university’s original propolis study to join her on the project, which is funded by a grant from CFANS: Jerry Cohen and Gary Gardner from theDepartment of Horticultural Science.
“I went to Jerry and said, what would be really cool would be to analyze the components of propolis and to use the bee as a screen to quickly test which are active against bee diseases and bee viruses,” Spivak explains. “So I came up with the idea to use the bees as a screen and they came up with the methods.”
According to the limited research available on the chemical makeup of propolis, it is composed of between 300 and 500 compounds. But these researchers are interested in things present in very small amounts that may be novel and active, Cohen said, so the number may be closer to 3,000 to 5,000. In order to purify a single compound, he says, the researchers have to be able to analyze literally thousands of compounds. The key to analyzing so many compounds, and fractions of those compounds, is to create a process that can run a large number of tests of many different chemical compounds very quickly. In similar tests, such assays have taken longer because there was no screen with which to score relative antibacterial or antiviral activity.
“One of the limitations of the original project we worked with was that we had no rapid assay for biological activity,” Cohen says. “It involved harvesting cells from patients, so it wasn’t trivial. What makes the bee part of this project very important is that quick screening system for bee pathogens, bacteria that cause the death of bees.”
Using propolis supplied by Spivak’s contacts from countries around the world, as well as from her own hives on the St. Paul campus, the study will identify any variations that arise from different plant sources in propolis from different locations, as well as any role the bees may have in altering its chemistry. The three professors collaborate with Lana Barkawi, a post-doctoral biochemist in Cohen’s lab, and toxicology Ph.D. student researcher Mike Wilson to create their new screening process.
The ultimate goal of the rapid assay will be to identify any new compounds—compounds that have not been identified or tested against HIV—that show anti-microbial activity, both toward bacteria and viruses using insect pathogens. Then the researchers will submit those compounds to an external service to do specific anti-HIV tests on enzymes unique to the virus.
“The danger with something like propolis, because it’s been looked at for literally millennia, is that you can move down the line, and discover something that’s already known,” says Gardner. “Our focus is on two key terms: active and novel.”
Barkawi, who participated in the original HIV study, says the bee pathogen screen is an entirely practical step, because contract labs aren’t interested in getting huge numbers of fractions to run through their assays. “It’s how many compounds, thousands? And we’re looking for the needle in the haystack. There has to be a selection somehow.”
“We might find something novel that’s never been evaluated on HIV, we might not,” Gardner says. “But we have this background in propolis and HIV expression, so it’s not like we’re saying we can cure AIDS because propolis is good.”
A broader forecast
“Of course, a long-term hope is that after testing propolis components on bee diseases and viruses, we can find components that would be really helpful to treat human viruses, and particularly an inexpensive treatment for HIV for developing nations,” Spivak says. But hopefully “within two years we’ll have identified fractions that are active against bee pathogens for sure, and hopefully bee viruses. Another application of this research is that beekeepers may be able to diversity their income by harvesting and selling propolis, so this can be lucrative for them.”
The researchers hope this study will have impacts beyond the initial identification of active compounds, like isolating other antimicrobial properties in the plant products, Cohen suggests. “Especially when you run into things like antibiotics with growing resistance. Most of our existing antibiotics come from fungal sources.”
They each credit the grant’s unique opportunity for interdisciplinary cooperation as the motivation for an investigation none of them would be able to perform on their own, and they foresee prospects of related inquiry. Gardner says he and Cohen would be interested in following the plant agents in propolis back to their sources in individual plant resins.
But Spivak reflects on the dangers to her bees, their colonies and beekeepers, and hopes for something different. “I really hope that bees change propolis when they collect it, because that leaves bees in the picture,” she says. “I want them to be indispensable, so that people maintain the bees, which are so important.”
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