These Sick Animals Could Be Key to Understanding Cancer

Figuring out why California's sea lions, Canada's belugas, and Australia's Tasmanian Devils are so susceptible to cancer may help us unravel the mysteries of the disease.

SAUSALITO, California—The office door flies open and in rushes Alissa Deming, fresh from an ultrasound on a stranded sea lion. Deming wants a word with the boss, chief veterinarian Frances Gulland, who has monitored cancer in marine mammals for two decades.

“I think we’ve got a case,” says Deming, an animal virologist and fellow at the Marine Mammal Center, a nonprofit rescue and research institution perched on the Marin Headlands across the Golden Gate Bridge from San Francisco. “The uterus is dilated and the lining is thickened like endometriosis.”

Deming thinks the animal may be the latest victim of a scourge of genital cancers afflicting California’s sea lions.

Gulland, sun-bleached and trim after years of rescuing ocean animals, is skeptical. She comes from the look-first-for-the-normal school of diagnosis for wildlife. This sea lion, she suggests, may have been pregnant, aborted, and not yet returned to a normal size uterus. She promises, though, to examine the animal before she flies to Mexico to look at the corpses of two rare vaquita porpoises that washed up in the Gulf of California. Deming is appreciative, knowing further tests will reveal whether the animal’s tissue is cancerous. “Everybody wants to work with Frances,” says Deming. “Everybody.”

Sea lions have the highest known cancer rate in wildlife, which came to light when Gulland and others started cataloguing a disturbing number of urogenital cancers in the animals off the California coast. Twenty years ago, they found a strikingly high 18 percent (66 out of 370 animals) of sea lions examined since 1979 had signs of aggressive urinary and genital cancers. In more recent years, they’ve reported the same high rate. Soon after, they detected a stubborn virus in the dead animals.

This research with sea lions is critical to understanding cancers that plague wildlife—and, perhaps, human beings as well. These marine mammals may hold the key to understanding the complex interactions among genes, viruses, and the environment that trigger cancer—essentially getting to the bottom of why cancers attack living creatures.

So far, by comparing surviving sea lions that have escaped cancer with dead ones that have cancer, researchers have identified specific genes that appear to increase their susceptibility to the disease. Next, they are trying to discover what role the virus, called OtHV1, is playing. Is it causing the cancer? Or is it just a benign herpesvirus living in the sea lion’s reproductive tract?

The answers could have profound implications for human and animal health. If we can understand the mechanism by which the herpesvirus is using the sea lion’s own cells to cause cancer, scientists could develop ways to prevent a similar virus from taking control of human cells.

Cancer Seems Rare in Most Wildlife

Researchers generally suspect that wild animals of every species get cancer in some form, but not at rates as high as humans. Discovery of cancer-ridden animals in nature is happenstance, so comparing their rate of cancers to the rate of human cancers cannot be done with any accuracy.

“The incidence of cancer in the wildlife we examine for cause of death is very low—except for certain populations,” says Valerie Shearn-Bochsler, a veterinary pathologist at the National Wildlife Health Center run by the U.S. Geological Survey in Madison, Wisconsin.

Over 41 years the national center has examined 400,000 animals. At most 2 percent or less were diagnosed with neoplasia, or tumors.

Unless there is a crash in a population, or an unusually high number of cases turning up in well-studied protected species, deaths due to malignancies may go unnoticed, she says. For instance, the center looks at all carcasses of northern sea otters off the Pacific Northwest, North Carolina’s red wolves, and bald eagles nationwide. In these animals, cancer is not a significant cause of death.

“Most wild animals die unobserved. It’s almost a matter of luck for someone to stumble across one. We know they get cancer because we see the individual reports,” says Shearn-Bochsler. “For every solitary cancer case we come across, there may be 20 others, or there may be none, in the same area.

“Nevertheless,” she adds, “if cancer was causing significant decline in a wildlife species, it would likely eventually be detected and investigated, and the increase in cancer rates would become apparent.”

In one of the strangest cases, Australia’s once common marsupial, the Tasmanian devil, began to die in the mid-1990s from a transmissible facial cancer—to the point that it is now in danger of disappearing. Virus-plagued green turtles and other sea turtles living in polluted waters off Florida, Hawaii, and in the Caribbean carry malignant growths.

Veterinarian James Wellehan, Deming’s doctoral adviser at the University of Florida, says all living animals get cancer, typically as they age, due to assaults to their DNA. More is known about some species than others; the ones that aren’t “cute and pretty” often fail to win the money for much study at all, he says.

Animals, People Share Toxic Exposures, Viruses

Studying wildlife, particularly mammals, that share exposures to industrial chemicals, viruses, and other cell-damaging agents could shed light on what may be happening in people, too.

The failure of beluga whale populations to recover after the end of the hunt in the St. Lawrence estuary alerted Canadian researchers to investigate the region’s polluted waters, which then revealed a rash of cancers.

“Over the years we have seen an unusual number of cancers for a free-ranging population of sea mammals, higher than any other except for the California sea lion,” says veterinarian Dr. Stephane Lair, director of the Canadian Wildlife Health Cooperative, Quebec.

In the belugas, tumors start in various systems, including the lung, stomach, intestine, adrenal gland, bladder, and liver. This suggests that a virus is not the cause of their cancers.

Stricter regulation of some toxic chemicals that are polluting the estuary has helped. The belugas’ cancerous tumors have declined, Lair says. Nevertheless, other chemicals in the estuary may be posing problems, perhaps contributing to a rise of parasitic and bacterial infectious disease in young whales as well as deaths of baby belugas.

Pollution off the Pacific coast also may be weakening the sea lions’ immune systems, possibly explaining how a virus carried in their bodies could take hold and develop into cancer.

“We want to know if contaminants—PCBs and DDTs—are suppressing the sea lions’ response, and allowing the herpesvirus to colonize. We think that the contaminants decrease the ability of the immune system to function well. If you have a healthy immune system, you should be able to fight off disease,” Gulland says.

Sea lions with carcinomas had higher concentrations of PCBs and DDTs in blubber than sea lions without carcinoma, according to one study conducted a decade ago.

The new Sea Lion Cancer Consortium, which Gulland coordinates, is trying to determine how viruses pave the way for cancer in the animals, which would provide information on human cancers, too. Viral infections may contribute to 15 to 20 percent of cancers in humans and animals. Viruses are suspected of causing gastric papillomas in beluga whales as well as skin papillomas in Florida manatees and harbor porpoises. Malignant lymphoma in Atlantic bottlenose dolphins also may stem from a virus.

In Australia, study of a contagious, fastly metastasizing cancer spread by biting among Tasmanian devils also led to new knowledge. This is a cancer not transmitted by a virus but from the transfer of living cancer cells, reports Elizabeth Murchison, now at University of Cambridge, who studies the taz’s DNA.

A wildlife photographer first reported the tumors in the animals. Field biologists started to see a sharp decline in their numbers. Then scientists discovered something that is not supposed to happen: All of the tumors shared the same chromosomes and likely stemmed from an original single cancer.

The fact that the tumors had identical chromosomes meant they were physically implanted into each animal, sort of like a graft, evading the immune system. This type of transmissible cancer has been seen only in two other species—dogs contacting venereal tumors and soft shell clams from Maryland to Prince Edward Island that get a leukemia-like disease.

“If we could only understand how the cancer is able to escape detection and rejection, then we might get some insights into immunotherapies that would help save the Tasmanian devil from extinction and might also have applications in human immunotherapy,” Murchison says.

“We hope in years to come we understand more. We have a long way to go.”

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