Biomarkers or chemical concentrations linked to lung cancer in human breath can be detected by honeybees that – amazingly – can also distinguish among different types of malignancy via only the “smell’ of the cell cultures.
Researchers at the Michigan State University’s College of Engineering and its Institute for Quantitative Health Science and Engineering said that the findings could be used as a model for developing new tests to diagnose lung cancer at an early stage.
Honeybees have a sensitive olfactory system designed to help them navigate complex environments encompassing foraging, reproduction, brood care, and defense, so they can be used to reliably detect a wide range of volatile chemicals – the ‘smell’ of objects – while also distinguishing among odor mixtures efficiently even at low concentrations.
“Insects have an amazing sense of smell the same way dogs do,” said Prof. Debajit Saha, who said that he and his team wanted to see if honeybees could distinguish among chemicals in human breath from that of a healthy person.
Biological “noses” like those in the honeybee antennae and olfactory brain are extremely sensitive, and the bees learn odor identity and perform complex olfactory behavioral tasks – similar to dog noses that have been successful in the detection of different volatile olfactory compounds.
The research was published in the Biosensors and Bioelectronics journal and titled “Precision detection of select human lung cancer biomarkers and cell lines using honeybee olfactory neural circuitry as a novel gas sensor.”
Lung cancer is the second most commonly diagnosed form of cancer worldwide and the leading cause of cancer-related death among both men and women. There are two main types – non-small cell lung cancer and small-cell lung cancer, each of which has different characteristics. Larger cells grow slower, while the smaller ones can proliferate and spread quickly.
Comparing healthy and synthetic breath mixtures
Elyssa Cox, Saha’s former lab manager, and Michael Parnas, a doctoral candidate working in Saha’s lab, developed a “recipe” for a synthetic breath mixture using different levels of six compounds such as trichloroethylene and 2-methylheptane to create the chemical makeup of the breath of someone with lung cancer and a synthetic healthy breath mixture.
“It took a steady hand to create the recipe,” said Cox. “We tested the synthetic lung cancer versus healthy human breath mixtures on about 20 bees.”
They helped design a customized, 3D-printed harness to hold a live honeybee while she attached a tiny electrode to its brain to measure any changes in the bee’s brain signals.
“We passed those odors on to the antenna of the honeybees and recorded the neural signals from their brain,” said Saha. “We saw a change in the honeybee’s neural firing response.”
The researchers also wanted to measure how much of the cancer-indicating compounds needed to be present in someone’s breath for the honeybee to detect cancer.
“They detected very small concentrations; it was a very strong result,” said Saha. “Bees can differentiate between minute changes in the chemical concentrations of the breath mixture that is in the parts-per-six-billion range.”
Parnas analyzed the neural data and saw the spikes in the bees’ brain signals.
“We can see differences in how the honeybees are smelling,” said Parnas. “We detected several different neurons firing in the honeybees’ brains that clearly differentiated between the synthetic lung cancer breath and healthy breath.”
“What’s amazing is the honeybee's ability to not only detect cancer cells but also distinguish among cell lines of various types,” said Autumn McLane-Svoboda. “The future implications for this are huge as our sensor could allow for patients to receive specific cancer diagnoses quickly, which is imperative for correct treatment routes.”
Saha envisions this work will open the door for more biological and smell-based disease detection technologies. In the future, Saha’s team plans to develop a noninvasive test requiring patients only to breathe into a device; the sensor inside, based on honeybee brains, would analyze the breath and wirelessly report back in real-time if cancer chemicals are present.