This is how dogs, mice and ferrets are used to 'sniff' and detect diseases

By Glen J. Golden - The Conversation

Editor's Note

1. What species have a nose for disease?

Some animals have highly developed senses of smell.

They include rodents;

dogs and their wild relatives, such as wolves and coyotes;

and mustelids: carnivorous mammals such as weasels, otters and ferrets.

The brains of these species have three or more times as many functional olfactory receptor neurons (nerve cells that respond to odors) than species with less acute olfactory abilities, including humans and other primates.

These neurons are responsible for detecting and identifying volatile olfactory compounds that send significant signals, such as smoke from a fire or the aroma of fresh meat.

A substance is volatile if it changes easily from a liquid to a gas at low temperatures, such as acetone that gives nail polish remover its fruity smell.

Once it vaporizes, it can quickly spread through the air.

When one of these animals detects a significant scent, the chemical signal is translated into messages and carried throughout its brain.

A dog's sense of smell is at least 1,000 times more sensitive than any mechanical device.Getty Images

The messages go simultaneously to the olfactory cortex, which is responsible for identifying, locating and remembering the smell, and to other brain regions responsible for decision-making and emotion.

So these animals can detect many chemical signals at great distances and can make quick and accurate mental associations about them.

2. How do researchers choose a target scent?

In most studies that have used dogs to detect cancer, the dogs have identified physical samples, such as skin, urine, or breath, from patients who have been diagnosed with cancer or who have undiagnosed cancer at an early stage.

Scientists don't know what scent cue dogs use or if it varies by cancer type.

The US Department of Agriculture's National Wildlife Research Center in Colorado and the Monell Center for Chemical Senses in Pennsylvania have trained mice to detect avian influenza in fecal samples from infected ducks.

Avian flu is difficult to detect in wild flocks and can spread to humans, so this work is designed to help wildlife biologists monitor outbreaks.

Kimball's lab at Monell taught mice to get a reward when they smelled a confirmed positive sample from an infected animal.

For example, mice were able to drink water when they traveled down the arm of a Y-shaped maze containing feces from a duck infected with the avian influenza virus.

By chemically analyzing the fecal samples, the researchers found that the concentration of volatile chemical compounds in them changed when a duck became infected with bird flu.

They then inferred that this altered odor profile was what the mice recognized.

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

With the ferrets, we began by training them to alert, or signal that they had detected the target odor, by scratching a box that contained high proportions of those volatile compounds and ignoring boxes that contained low proportions.

Next, we showed the ferrets fecal samples from infected and uninfected ducks, and the ferrets immediately became alert 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.

Sometimes, however, we have to let the sensing animal determine the scent profile it will respond to.

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

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

For example, dogs in the US Department of Agriculture's Wildlife Services Canine Disease Detection Program respond with an aggressive alert, such as scratching, when they detect a sample from a duck infected with bird flu.

When they detect a sample from a white-tailed deer infected with the prion that causes chronic wasting, they respond with passive alertness, such as sitting up.

Research at Auburn University has shown that dogs can remember and respond to 72 odors during an odor memory task.

The only limitation is the number of ways a dog can communicate about different scent cues.

4. What kinds of factors can complicate this process?

First, any organization that trains animals to detect disease needs the right kind of laboratory and equipment.

Depending on the illness, that could include personal protective equipment and air filtering.

Another concern is whether the pathogen could infect detection animals.

Two coronavirus sniffer dogs named Valo (left) and ET stand with their handlers at Helsinki airport in Vantaa, Finland, where they are trained to detect COVID-19 from arriving passengers, on September 22, 2020.Getty Images

If that poses a risk, researchers may need to inactivate samples before exposing animals.

They then need to see if that process has altered the elements that they are teaching the animals to associate with infection.

Finally, trainers need to think about how to reinforce the desired response of detection animals in the field.

If they work in a population of mostly uninfected people, say at an airport, and an animal doesn't get a chance to earn a reward, it may lose interest and stop functioning.

We look for animals that have a strong drive to work without stopping, but working for a long time without reward can be a challenge for even the most motivated animal.

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

Right now we don't have devices that are as sensitive as animals with well-developed senses of smell.

For example, a dog's sense of smell is at least 1,000 times more sensitive than any mechanical device.

This could explain why dogs have detected cancer in tissue samples that have been medically cleared as non-cancerous.

We also know that ferrets can detect avian influenza infection in fecal samples before and after laboratory tests show that the virus has stopped shedding.

This suggests that for some pathogens, there may be volatile changes in individuals who are infected but asymptomatic.

As scientists learn more about how the mammalian sense of smell works, they will have a better chance of creating devices that are as sensitive and reliable in detecting disease.

Glen J. Golden is a research scientist and professor at Colorado State University, United States.