Worms Detect Cancer by Scent

By Iva Fedorka

You may have read stories about cats and dogs that seem to sense when someone is sick. Now, scientists are studying whether small worms can use chemosensation to detect early disease processes.

If small worms could “smell” lung cancer cells, perhaps a device incorporating them could help provide an easy and painless way to screen for disease. A team from Seoul, Korea, introduced its “worm-on-a-chip” in March 2022 at a meeting of the American Chemical Society held in San Diego, California.

Choosing an Animal Model

The most likely candidate for this model is the common roundworm, Caenorhabditis elegans. Because they’re about a millimeter in length, multiple worms could easily fit in a small space.

Although C. elegans cannot see or hear, their sense of smell is good. In fact, the worms have roughly the same number of genes for chemical sensing as dogs, mice, and other mammals known for their sense of smell.

Shin Sik Choi, a biotechnologist who helped develop the system at Myongji University in Seoul, South Korea, thinks scent is the likely source of the worms’ attraction to cancer cells. This is because the diseased cells release odor molecules. “In nature,” he explained to Science News for Students, “a rotten apple on the ground is the best place where we are able to find the worms.”

The Sense of Smell

Which scents stimulate C. elegans nerve cells? Choi and his team tested some volatile organic compounds or VOCs produced by cancer cells and identified floral-scented 2-ethyl-1-hexanol as a prime candidate.

The human brain has about 86 billion nerve cells or neurons, but C. elegans has only 302 nerve cells in total. Since the worm bodies are transparent, scientists can actually determine the specific nerve cell that reacts to cancer cell aromas by having it fluoresce when stimulated.

To test their hypothesis, the team used a special strain of genetically modified C. elegans with no 2-ethyl-1-hexanol receptors. While the unmodified worms preferred cancer cells over healthy ones, the modified worms did not, which may mean that 2-ethyl-1-hexanol has a role in attracting the worms to diseased cells.

Making the Screening Device

The researchers created a microscope slide-like construct with three large indentations or wells. Healthy human cells were placed in a well at one end and lung cancer cells added to a well at the other. Approximately 50 worms were put in the middle well where they could smell the cells at either end.

“About 70 percent of the worms move toward the cancer,” says Choi. He also believes that percentage could be increased with training.

Choi also wants to test whether the worms can still detect cancer without being directly exposed to diseased cells. A recent study by another researcher (Scientific Reports, August 24, 2021) showed that C. elegans preferred the urine of patients with breast cancer over samples from healthy subjects.

Noninvasive screening tests that use a patient’s blood, urine, or saliva may one day help detect cancer in its early stages, which would help speed diagnosis and treatment.