Researchers hack locust brains to help diagnose cancer by smelling them

• Cancer cells emit chemicals that are "different" from healthy cells.
• These can be sniffed out by locusts.
• The researchers intend to use the biological components of the locust needed to sense volatile compounds.

In their quest to find a technology that can "sniff" out cancer, researchers at Michigan State University have revealed that locusts can not only "smell" the difference between cancer cells and healthy cells, but they can also distinguish between different cancer cell lines.

"Noses are still state of the art," said Debajit Saha, an assistant professor of biomedical engineering at MSU. "There's really nothing like them when it comes to gas sensing. People have been working on 'electronic noses' for more than 15 years, but they're still not close to achieving what biology can do seamlessly."

The lack of gas-sensing devices creates a great opportunity when it comes to the early detection and intervention of diseases like cancer. When it is caught in its first stage, patients have an 80 percent to 90 percent chance of survival. But if it's detected much later, until stage 4, the numbers drop to 10 percent to 20 percent.

Cancer cells create different compounds as they work and grow, differently than healthy cells. If these chemicals make it to a patient's lungs or airways, then the compounds can be detected in exhaled breath.

"Theoretically, you could breathe into a device, and it would be able to detect and differentiate multiple cancer types and even which stage the disease is in. However, such a device isn't yet close to being used in a clinical setting," Saha said.

So Saha and his team are developing a new approach.

The research, which is yet to be peer-reviewed, has been published on BioRxiv.

Locusts have served the scientific community for decades

But, the researchers didn't want to engineer something that worked exactly like biology. Instead, they considered starting with the solutions biology has built after years of evolution, and then engineering them accordingly. According to Saha, the team is "hacking" the insect brain to use it for disease diagnosis.

"This is a new frontier that's almost unexplored," he said.

Saha and his team chose to work with locusts as their biological component. The insects have served the scientific community as model organisms for decades. Researchers already have an understanding of their olfactory sensors and corresponding neural circuits. This allowed the MSU researchers to easily attach electrodes to locust brains. The scientists then recorded the insects' responses to gas samples produced by healthy cells and cancer cells and then used those signals to create chemical profiles of the different cells.

Previously, Saha led research that detected explosives with locusts. This work factored into an MSU search committee recruiting Saha, said Christopher Contag, the director of IQ.

"I told him, 'When you come here, we'll detect cancer. I'm sure your locusts can do it,'" said Contag, the inaugural James and Kathleen Cornelius Chair, who is also a professor in the Department of Biomedical Engineering and the Department of Microbiology and Molecular Genetics.

One of Contag's research focuses on understanding why cells from mouth cancers looked different under his team's microscopes and optical tools. His lab found different metabolites that were volatile, meaning they could become airborne and sniffed out. "The cells looked very different metabolically, and they looked different optically," Contag said. "We thought it made a lot of sense to look at them from a volatiles perspective."

Early detection is key

Saha's locust sensors provided the perfect platform to test that. The two groups collaborated to investigate how well the locusts could differentiate healthy cells from cancer cells using three different oral cancer cell lines.

"We expected that the cancer cells would appear different than the normal cells," Contag said. "But when the bugs could distinguish three different cancers from each other, that was amazing."

The researchers believe their system would work with any cancer that introduces volatile metabolites into breath, which is likely most cancer types. The team is starting a collaboration with Steven Chang, director of the Henry Ford Head and Neck Cancer program, to test its detection system with human breath.

People needn't fret about seeing swarms of insects in their physicians' offices. The researchers intend to develop a closed and portable sensor without an insect, just the biological components needed to sense and analyze volatile compounds.

"Early detection is so important, and we should use every possible tool to get there, whether it's engineered or provided to us by millions of years of natural selection," Contag said. "If we're successful, cancer will be a treatable disease."

Abstract:

There is overwhelming evidence that metabolic processes are altered in cancer cells, and these changes are manifested in the volatile organic compound (VOC) composition of exhaled breath. Here, we take a novel approach of an insect olfactory neural circuit-based VOC sensor for cancer detection. We combined an in vivo antennae-attached insect brain with an electrophysiology platform and employed biological neural computation rules of antennal lobe circuitry for data analysis to achieve our goals. Our results demonstrate that three different human oral cancers can be robustly distinguished from each other and a non-cancer oral cell line by analyzing individual cell culture VOC composition-evoked olfactory neural responses in the insect antennal lobe. By evaluating cancer vs. non-cancer VOC-evoked population neural responses, we show that olfactory neurons’ response-based classification of oral cancer is sensitive and reliable. Moreover, this brain-based cancer detection approach is very fast (detection time ~ 250 ms). We also demonstrate that this cancer detection technique is effective across changing chemical environments mimicking natural conditions. Our brain-based cancer detection system comprises a novel VOC sensing methodology that will spur the development of more forward engineering technologies for the noninvasive detection of cancer.