A new study from Michigan State University (MSU) researchers reveals that honeybees can detect lung cancer biomarkers in a person’s breath. The insects can also distinguish between healthy and lung cancer cells just by smelling a cell culture.

Unlike humans, honeybees don’t have a nose. They smell with their antennae, which function similarly to vertebrate noses. Molecules in the air enter tiny pores in their antennae and interact with receptors on olfactory neurons. These neurons are sensitive to very small concentrations and a broad range of different molecules. 

“When a honeybee smells anything the neurons within the antennal lobe start to respond. We can see these responses as an electrical pattern, known as spikes, which is basically how neurons communicate with each other,” Michael Parnas, first author of the study and a Ph.D. candidate at MSU, told ZME Science.

The pattern of spikes changes depending on what the honeybee smells. So, for instance, when a honeybee smells lung cancer cells, its neurons will form spikes different than those when it smells healthy cells.  

Honeybees can sniff out the slightest sign of cancer

According to the researchers, human body cells release a variety of molecules as part of their normal functions and in response to different stimuli. These molecules serve various purposes, including metabolic processes, signaling, and communication. 

Since the metabolism and micro-environment of cancer cells differ from those of normal cells, the molecules they release also have distinct odors. The researchers performed a series of experiments to know whether honeybees could detect this difference. 

They immobilized a living honeybee in a small 3D-printed harness such that only its antennal lobe was exposed to the external environment. Next, they attached tiny electrodes to the insect’s brain to record the activity of its neurons in real-time. They then wafted different mixtures of air over the antennae.

First, they introduced the honeybee to a synthetic breath mixture mimicking the breath of a healthy person. In the next round, they exposed the bee to a synthetic mixture smelling the same as the breath of a person with lung cancer. When they studied how honeybee’s neurons responded in both cases, they noticed several differences. 

For instance, the lung cancer breath mixture had nine biomarkers (decane, trichloroethylene, undecane, etc.) associated with the disease. The brain activity (spikes) showed that the neurons associated with the antennae responded to all nine lung cancer biomarkers. It seems that the honeybees detected all these chemicals. 

No such spikes were observed in the case of a healthy breath mixture. 

Moreover, “The honeybee could detect individual biomarkers even at very low concentrations (from parts-per-billion to parts-per-trillion), similar to the concentrations that would be found in real breath. There is no current medical technique that can tell the difference in the breath of healthy people and those with lung cancer in such a way,” Parnas said.

Smelling lung cancer in cell culture

The study authors performed another experiment to see whether honeybees could detect lung cancer in cell cultures. They exposed the insects to different cell cultures, some with healthy cells and others with varying types of lung cancer.

Surprisingly, their neuron activity showed that the bees were able to distinguish not only between cancer cells and healthy cells but also between different types of cancer cells. For instance, the neurons responded differently to small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) samples.

“In our final experiment, we showed that the honeybees could not only detect lung cancer cells but also differentiate between different lung cancer cell lines. This is important from a diagnostic perspective as different types of lung cancer need different treatment regimes,” Parnas told ZME Science.

Excited by these results, the researchers now plan to conduct a study where they might detect lung cancer in real breath. They believe that, one day, devices based on honeybee brains could tell whether a person has lung cancer just by smelling their breath. Such a device would make lung cancer diagnosis easier and more accessible than ever.

The study is published in the journal Biosensors and Bioelectronics.