The Smell of Disease: 5 Questions About Using Dogs to Detect Disease

Editor’s note: As COVID-19 spreads around the world, scientists are analyzing new ways to track it. A promising approach is to train dogs to recognize people infected with smelling samples of human urine or sweat. Glen Golden, a researcher who trained dogs and ferrets to detect avian flu in birds, explains why certain animals are good at detecting diseases.

1. What types have a nose for diseases?

Some animals have a highly developed sense of smell. These include rodents; Dogs and their wild relatives such as wolves and coyotes; and mustelids – carnivorous mammals such as weasels, otters, and ferrets. The brain of this species has three or more times more functional olfactory receptor neurons – nerve cells that respond to smell – than species with less olfactory abilities, including humans and other primates.

These neurons are responsible for detecting and identifying volatile olfactory compounds that send meaningful signals, like smoke from a fire or the aroma of fresh meat. A substance is volatile if it changes easily from liquid to gas at low temperatures, like acetone, which gives nail polish remover its fruity smell. Once it vaporizes, it can quickly spread through the air.

When any of these animals smell a significant smell, the chemical signal is converted into messages and carried through the brain. The messages go simultaneously to the olfactory cortex, which is responsible for identifying, localizing and remembering smells, as well as to other brain regions responsible for decision-making and emotion. This allows these animals to pick up many chemical signals over great distances and to make quick and accurate mental associations about them.

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2. How do researchers choose a target fragrance?

In most of the studies that used dogs to detect cancer, the dogs identified physical specimens, such as skin, urine, or breath, from patients who were either diagnosed with cancer or who were undiagnosed at an early stage. Scientists don’t know what smell dogs use or if it varies depending on the type of cancer.

The U.S. Department of Agriculture’s National Wildlife Research Center in Colorado and the Monell Chemical Senses Center in Pennsylvania have trained mice to detect avian influenza in stool samples from infected ducks. Avian flu is difficult to detect in wild herds and can spread to humans. Therefore, this work is intended to help wildlife biologists monitor outbreaks.

The Kimball Laboratory in Monell taught the mice to be rewarded for smelling a confirmed positive sample from an infected animal. For example, mice were given a drink of water when they walked down the arm of a Y-shaped maze containing the feces of a duck infected with the avian influenza virus.

While chemically analyzing the stool samples, the researchers found that the concentration of volatile chemical compounds in them changed when a duck was infected with avian flu. They concluded that this altered odor profile was what the mice recognized.

Members of the mustelid family such as ferrets, badgers, and otters have highly developed senses of smell. Here a wolverine is sniffing frozen meat buried deep in the snow.

Building on this work, we trained ferrets and dogs to detect avian influenza in poultry such as wild ducks and domestic chickens in a joint study between Colorado State University and the National Wildlife Research Center, which is currently under review for publication.

For ferrets, we first trained them to alert them or signal that they recognized the target odor by scratching a box that contained high ratios of these volatile compounds and ignoring boxes that contained low ratios. Next we showed the ferret fecal samples from both infected and uninfected ducks, and the ferrets immediately began drawing attention to the box containing the fecal sample from an infected duck.

This approach is similar to the way dogs are trained to detect known volatile odors in explosives or illegal drugs. However, sometimes we need to let the detector animal determine the odor profile to which it will respond.

3. Can animals be trained to recognize more than one target?

Yes. To avoid confusion about what a trained animal recognizes, we can teach it a different behavioral response for each target odor.

For example, in the U.S. Department of Agriculture’s Wildlife Services Canine Disease Detection Program, dogs respond with an aggressive alarm like scratching when they discover a sample of a duck infected with avian flu. If they discover a sample of a white-tailed deer that is infected with the prion and causing a chronic illness, they respond with a passive alarm like sitting.

Research at the University of Auburn has shown that dogs can remember and react to 72 smells during an olfactory memory task. The only limitation is how many ways a dog can communicate through different smell characteristics.

Photo courtesy of the U.S. Air National Guard. Photography by Senior Airman Sean Madden. Spc. Amber Freeman, of Kingston, NY, was assigned to the New York Army National Guard with Sophie, a Labrador Retriever service dog.

4. What factors can complicate this process?

First, any organization that trains animals to recognize disease needs the right type of laboratory and equipment. This may include personal protective equipment and air filtration, depending on the illness.

Another problem is whether the pathogen could infect the detection animals. If this poses a risk, researchers may need to inactivate the samples before exposing the animals. Then they need to see if this process has altered the volatile components that they teach animals to associate with infections.

Finally, handlers need to think about how to enhance the desired response from detection animals in the field. If they work in a population of mostly uninfected people – for example in an airport – and an animal has no chance of receiving a reward, it can lose interest and stop working. We look for animals that have a strong urge to work without stopping, but working long periods of time with no reward can be challenging even for the most motivated animal.

5. Why not build a machine that can do that?

At the moment we don’t have any devices as sensitive as animals with well-developed olfactory senses. For example, a dog’s sense of smell is at least 1000 times more sensitive than any mechanical device. This could explain why dogs discovered cancer in tissue samples that were medically classified as non-cancerous

We also know that ferrets can detect bird flu infection in stool samples before and after laboratory analysis shows the virus is no longer excreted. This suggests that some pathogens may have volatile changes in infected but asymptomatic individuals.

When scientists learn more about how mammals’ sense of smell works, they have a better chance of developing devices that are just as sensitive and reliable at detecting diseases.

The conversation


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