If you were to ask Dr. Patty Pesavento 10 years ago whether cancer was a major concern in wildlife health, her answer would have been a flat “no.” But that was before she, a pathologist with the UC Davis School of Veterinary Medicine, began working with raccoons in Northern California.
Beginning in late 2012, wildlife rehabilitation centers and the California Animal Health and Food Safety Laboratory at UC Davis diagnosed multiple raccoons with serious tumors, all in the same area of the brain. Pesavento’s team got involved, and discovered that every tumor contained a newly described virus called raccoon polyomavirus. As the tumors grew, they generated intense pressure, often times spanning from the brain into the nasal cavity. The pressure on the brain led to aimless zombie-like behavior and, ultimately, death.
Many of the problems in these animals have been recognized by very vigilant wildlife rehabilitation centers. In particular, Melanie Piazza at Wildcare in Marin County has been an active collaborator with the veterinary school, with the goal of keeping track of changes and emerging diseases in all wildlife species.
So why now? If cancer was not a problem for raccoons in the past, what has changed? The answer could have to do with the environment, the virus or the raccoons themselves. Pesavento and her team are on the case.
The world’s first planned suburb was the city of Levittown, New York. Shortly after construction began in 1947, Levitttown-style developments swept the nation, dramatically reshaping the American housing landscape. In doing so, raccoons, which had previously either navigated the chaos of the city or scraped by on what they could forage in the forest, were gifted a smorgasbord of food waste without having to deal with the densely packed city streets.
Nowadays, in suburban neighborhoods, there can be the same number of raccoons on a suburban block as there are people. They spend the daylight hours up high in trees or down below in storm drains, only meddling at ground level in the silence of the night. While many wild animals retreat from human territory, raccoons thrive.
Scientists have tracked the movement of raccoons and learned that they often have routines that revolve around the schedules of nearby humans and pets. A raccoon may rummage through a trash can at one home shortly after the lights go out before strolling over to an outdoor cat bowl at a neighbor’s place once the kitty is let inside. Our routines, and their routes repeat from night to night, keeping them strategically out of the human sight.
As raccoons wander nightly in suburbia, they repeatedly engage with the products (and germs) of humans, domestic animals and other mesopredators that live at this human:animal interface. Each interaction with a cat bowl or a discarded piece of food represents a potential chance to share viruses with humans and their pets.
“Urban wildlife can be important sentinels of what’s happening in urban and rural areas,” said Deana Clifford, a Veterinarian for the California Department of Fish and Wildlife and an affiliated faculty member of the Karen C. Drayer Wildlife Health Center. “It’s our responsibility to investigate unusual mortalities in wildlife to keep tabs on what’s happening in those populations and facilitate the research that’s being done.”
Studies of raccoon genetics are very limited, but it is possible that suburbia has also hindered their genetic diversity. The bounty of food and the architecture of the streets gives them little reason to venture beyond a few-block radius, which could bias the local gene pool. Similar to what happens with endangered species, a lack of genetic diversity leaves animals more vulnerable to certain diseases and can hinder their immune response.
Which brings us to the tumors.
In humans, 20 percent of all cancers are caused by pathogens, most of which are viruses. In many cases we live with these persistent viruses for our entire lives, but they rarely cause tumors because they live with our immune systems. But if a person becomes immunosuppressed due to illness or medication, the virus is free to manipulate our own cells, sometimes resulting in cancer.
An example is human papillomavirus (HPV), which can cause cervical cancer. Many women who carry the virus don’t ever get cancer, but some women do. Cervical cancer caused by HPV is common enough that girls are now preemptively vaccinated to avoid that potential fate.
The virus Pesavento and her team discovered in the raccoon tumors is called Raccoon polyomavirus, which is in a family of viruses that are related to HPV. Raccoon polyomavirus has been found in high concentrations in all of the raccoon tumors and in lower concentrations in other tissues in the raccoons. But many raccoons in California that are tumor-free have been infected with the virus as well.
Dr. Molly Church, a graduate student and veterinarian, has demonstrated that 70 percent of the raccoons in California have been exposed to the virus, although a fewer number are actively infected. The numbers are lower in other parts of the US, and might help to explain why brain tumors in raccoons have so far only been found on the West Coast.
So why do the tumors develop in some raccoons but not others?
To answer this question, Pesavento and her graduate student Terza Brostoff compared raccoon polyomavirus to a rare but devastating human skin cancer called Merkel cell polyomavirus. As is the case with the raccoons, many humans have polyomavirus on their skin, but very few ever develop cancer.
Studying natural disease in raccoons is an opportunity to ask some long standing questions about cancer causing viruses
“We know the virus lives and replicates in tumor cells, but what cells are first infected?” asks Pesavento. “And in which cells do these viruses persist?”
So far, Pesavento and her team have found the raccoon virus in urine, on hair and in skin on raccoons, but it’s shed in much lower numbers than in the tumor. The goal moving forward is to understand how the virus behaves in those cells and how it is spread, not only between raccoons, but possibly among other wild and domestic animals.
Pesavento’s laboratory, along with collaborator and oncologist Dr. Kevin Woolard and a few close (and tolerant) friends, have logged thousands of miles chasing sick raccoons and roadkill in California.
On one Friday afternoon in 2014, her lab picked up two adult raccoons that had been euthanized for untreatable neurologic disease, and she brought them back to the lab at UC Davis for study.
One of them had a tumor and the other did not, which Pesavento called an “unbelievable opportunity.” She and Dr. Rachel Pollard, of the Veterinary Medicine Teaching Hospital Radiology team, did an MRI and a CT scan on both animals.
As you can see in the embedded video, the nasal cavity of the normal raccoon is separated from the brain by a sieve-like bone called the cribriform plate. The plate supports the olfactory tract, which extends from the back of the nasal cavity into the frontal lobe of the brain. Neuronal stem cells in this region are target of the Raccoon Polyomavirus.
The second raccoon, which had shown suspiciously docile behavior, had a brain tumor. The tumor compressed the brainstem, broke into the nasal cavity, had caused complete loss of the cribriform plate and had partially dissolved the frontal bone.
“The pressure of the growing tumor remodeled the regional bones” said Pesavento. “That entire hollow area you see on the CT scan was just filled with tumor. Absolutely filled. All of that nice, complicated cribriform bone and nasal turbinate was gone.”
The sick raccoons that Pesavento has studied were trapped because they were out wandering during the day. What had been intelligent nocturnal mesopredators had devolved into aimlessly wandering zombies with little regard for day or night, all because of the tumors.
“When we get a raccoon with a tumor, we’re usually months or even a year beyond when they were first exposed to the virus” said Pesavento. “How it gets into their brains, we have no idea.”
The target brain cell, however, has been uncovered.
Pesavento said there was some heated controversy in the beginning about the type of tumor caused by the virus. Drs. Woolard and Church later proved that the virus transforms a neural “stem cell” in the olfactory tract, which made total sense in retrospect, because it’s normal for these cells to differentiate into multiple different types.
“Left unchecked in growth,” began Pesavento, “Voila! Complicated, multi-lineage tumors!”
Now the team is focusing on studying the virus in its natural state. They have demonstrated causation between raccoon polyomavirus and the tumors, so the next step is to understand as much as they can about the polyomavirus itself. How does it spread from one animal to another? How and when is it shed? How does it live in those cells without being detected by an animal’s inflammatory system?