Probing for Poisons

Is it a common cold or pesticide exposure?

Chuck Thompson’s first love was poisons.

Like many young boys, he was fascinated with the silver screen depiction of danger and suspense that was toxicology. A spy might barely escape drinking poison that was cleverly slipped into his glass, or a dart shot from the darkness could cause instant paralysis. It’s the sort of exhilaration that makes for great fiction, and people are drawn to it.

That thrill even drew Thompson to study psychology in college. Poisons cause a chemical reaction in the brain, and psychology is the study of the brain, right?
UM chemist Chuck Thompson poses with a protein biomarker he uses in his research. The red indicates an attached insecticide.

"Luckily, early on I was counseled to focus on the molecular level of what was happening in the brain," Thompson says.

Realizing the silver-screen intrigue he desired lay in chemistry, Thompson turned away from the study of psychological demons and focused instead on real-world poisons.

Now, The University of Montana professor studies chemical toxicology and neurochemistry. With his long hair tied in a ponytail, an acoustic guitar leaned in the corner of his office and dressed in a tie-dyed lab coat, he conducts research on the effects on the human body of poisons we interact with daily: pesticides.

The toxins — used on agricultural crops and other vegetation to protect plants from hungry insects — eventually end up digested, breathed or handled by humans in crop fields, at grocery stores or on our dinner plates.

The pesticides Thompson studies work like nerve gas. They shut down the nervous system of insects when they snack on treated plants. The same thing happens to humans, but because we’re so much larger, the effects are small and often go unnoticed.

It’s difficult to know what exactly the effects of pesticides on humans are, since many people don’t understand when they have been exposed. A family picking apples in an orchard may breathe pesticides that were sprayed recently. When one apple-picker develops a headache later in the day or feels nauseous, they may attribute it to stress, dehydration or working too hard. Though that may be the case, they also could have experienced pesticide exposure and are having an acute or mild reaction to the poison.

The trick, Thompson says, is to be able to tell the difference between an insecticide exposure event and the common cold.

"Wouldn’t it be great if everyone had a little cotton swab and they tested their saliva to see if they’re having an exposure event or if instead they are experiencing headache or nausea?" he says.

That convenience is exactly what Thompson and his business and research partner Jon Nagy are trying to develop through their company, ATERIS Technologies.

ATERIS isn’t part of Thompson’s research at UM, but you can see how the science inspired the innovation.

Thompson and Nagy are working to develop a simple, inexpensive field test that can help people determine if they are experiencing a reaction to pesticide exposure.

The two scientists know each other from working together as lab partners in 1984 at the University of California, Berkeley. Nagy, who now lives in Bozeman, works with nanoparticles, microscopic objects that can be designed to change color or light up when they encounter a certain substance.

"We know pesticides attack proteins," Thompson says. "What if we put that protein on a nanoparticle? If the pesticide reacted to it, the nanoparticle would report back and let us know this is not a headache caused by stress. This is an exposure."

The practical applications of such a test could help people seek speedy medical attention to address an exposure and also help Thompson and other researchers find out more about how pesticides affect human physiology over time.

"My research at the University is based on understanding the real, heartfelt effects of pesticide exposure that are rooted in chemistry," he says. "We use every instrument and tool we have to figure out if there’s a way to determine how these work and how they shut the nervous system down."

But there is a bigger problem than the mild, acute reaction. Long-term exposure and clusters of exposure over a lifetime could be related to neurological disorders people develop in middle age or later, such as Parkinson’s or Alzheimer’s diseases.

"Epidemiological studies can find clusters, but there isn’t good biochemical evidence to determine that a certain insecticide is attacking a particular group of cells," Thompson says.

The answer is better reporting of exposure events — particularly better self-reporting. Right now, researchers depend on physicians and epidemiologists saying they’ve come across a number of patients who all have experienced the same thing, and those patients all work in the same factory or field.

This is where ATERIS comes in. The company has received three Small Business Innovation Research grants through the National Institutes of Health, and recently the research entered the proof-of-principle stage. It looks like the technology will work, but now Thompson and Nagy will explore if it’s possible to manufacture the device that can detect what they’re looking for, as well as provide a test kit for easy self-reporting.

"There’s plenty of tests that detect pesticides, and plenty that detect dead proteins," Thompson says. "But we need to develop a test to find that interaction."

The company, based both in Missoula and Bozeman, brings research and technology jobs to Montana. Teams of up to 15 people have worked on ATERIS projects, and UM students have the opportunity to launch a research career in a state traditionally known for tourism and natural resource development.

"UM put a mission before me in 2003 to look at economic development and independent companies," Thompson said. "My research at UM is not directly related to ATERIS, but it still contributes to the larger economic outlook."

If ATERIS can develop the test — ideally small enough to fit in a shirt pocket and only costing about $5 — a positive exposure result would only be the first step for a patient.

Thompson uses a mass spectrometer to analyze a pesticide sample in UM’s Skaggs Building.After a general exposure event is confirmed, follow-up exams at a hospital, and perhaps more detailed tests developed later by ATERIS, could determine what the specific ill-effects of the insecticide are.

It’s scary to think that your dinner salad could send you to the hospital, but for years people have endured exposure to pesticides without dropping dead like the insects the poisons are design to kill. The key is dilution.

Most pesticides were developed in the 1950s and ’60s, and they all are off patent now, allowing a multitude of these compounds on the market. Thompson says the companies that originally developed pesticides hoped to protect of crops and intended to keep humans and large mammals safe through dilution of the poison. You would have to eat large amounts of the chemicals to experience a deadly reaction like an insect, and there was no understanding of the small, incremental damage that could be caused.

It was believed these pesticides all acted in a general way such as "kills bugs, doesn’t kill people." But pesticides behave in individual ways, specifically targeting different protein panels.

Proteins are the movers and shakers of the human body. They catalyze reactions. If a pesticide stops a protein, it stops a million things from happening. And although dead or damaged protein can be discarded and regenerated, those reactions and development are permanently disrupted.

"They didn’t know, I think, at the time that they were developing something that would target different proteins," Thompson says of the scientists who worked to bring stability to agriculture by developing pesticides. "They didn’t have the tools or understanding."

But the fact remains that poisons people interact with daily halt the communications in their bodies, and the long-term effects of that are unknown.

"When we think about the effect of memory, learning and plasticity, maybe these pesticides are attacking proteins that may be important in child development," Thompson says. "Infants and children exposed to the same amount of toxins would experience a greater affect because they are smaller. You have to ask, ‘Are women during pregnancy or nursing putting themselves or their infants at risk?’"

One of the first large-scale studies of pesticide exposure currently is under way. It will determine if people are at risk just by purchasing produce, both domestically and internationally grown. It’s impossible to avoid exposure, and even Thompson — while he advocates washing your produce — doesn’t eat strictly organic food. He’s a data point in the study of these toxins, just like the rest of us.

"As a scientist I just like being one of those dots and someone willing to make a few connections between these dots," he says.

— By Bess Pallares

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