Scientists Investigate a Mysterious Cancer Plaguing California Sea Lions

“This one might be a little stinky,” says Tenaya Norris, a scientist at The Marine Mammal Center in Sausalito. Research assistant Barbie Halaska carries a limp, sodden carcass into the room and drapes it across a gleaming steel table.

Even before the researchers slice into the tiny, brown California sea lion pup and remove its internal organs, the animal is mostly skin and bones. The young male was less than a year old when he arrived. He hung on for ten days, but was already suffering the effects of severe malnourishment when he arrived — he was about one-quarter the size of a healthy pup—and the staff were unable to save him.

Norris stretches out the subject’s flippers. Picking up a scalpel, she gets ready to open the animal from chin to tail. The pup occupies just one narrow corner of a table large enough for an animal many times this size. And the center has seen its fair share of those. The facility takes in several hundred distressed animals each year, from sea lions to elephant seals to the occasional dolphin or sea turtle. Scientists and volunteers do their best to rehabilitate the sick animals and return them to the ocean. But about half will end up on the metal table instead. Each death is a loss — and an opportunity.

Every animal that dies here is studied exhaustively. Researchers carve the bodies into samples for dozens of ongoing studies. They’re especially interested in the carcasses of California sea lions, which are helping them study a mysterious and aggressive cancer that’s plaguing the species.

The disease starts in the reproductive organs of adult males and females. By the time they die, tumors have sometimes infiltrated their backbones and turned vertebrae to “mush,” Norris says. She describes examining one dead animal whose spine she could simply slice through.

More than a quarter of the adult California sea lions that die at the Marine Mammal Center suffer from cancer, says director of veterinary science Shawn Johnson. That’s one of the highest cancer rates seen in any wild animal, which is why the center’s scientists have made the disease a research priority. This emphasis has led to some promising discoveries, including the identification of a virus that is likely transmitted sexually and that seems to trigger the cancer.

If researchers can piece together the full story of the California sea lions’ disease, it may help explain how some cancers develop in other animals—including humans. After all, cancer-causing viruses strike people too. At the same time, our understanding of disease susceptibility in humans — in particular, how environmental stressors can turn relatively minor infections into life-threatening disease — is helping scientists understand the role the environment might play in sea lion cancer. In other words, we may not be able to fully understand the set of threats to either species’ health without understanding the other.

Under Pressure

When a sick or injured marine mammal washes up anywhere along 600 miles of the Pacific coastline, volunteers send word to The Marine Mammal Center. If the center decides a rescue is necessary and feasible, it sends a truck. The vehicles carry vanity plates like PINNIPD (for pinniped, a shorthand name for a seal, sea lion, or walrus) or BG ELIE (for elephant seal, a species that’s also represented by a life-sized sculpture at the center). Volunteers use nets and wooden boards to maneuver each sickly or injured creature into an animal crate and onto the truck for its journey to the Marin Headlands — a hilly peninsula separated from San Francisco by the Golden Gate Bridge.

The center sits high above the ocean, perched on a dry brown hillside dotted with scrubby manzanita. Its remote location is a reminder of the site’s former life as a missile silo during the Cold War. On a beach visible from the center, rolling Pacific waves crest and break against tall humps of rock. In normal years, 600 to 800 different animals come through the center’s doors. But these aren’t normal years. There’s been a surge of sick animals, especially California sea lions (Zalophus californianus), which live up and down the west coast of North America. The center took in 1,800 animals last year, 1,300 of which were California sea lions. Both numbers were records in the center’s four decades of operation.

A variety of environmental conditions has led to the surge. A patch of freakishly warm water nicknamed “the blob” sat in the northeastern Pacific from 2013 to 2015. The year 2015 also brought a massive bloom of the algae Pseudonitzschia. These microscopic plants produce domoic acid, a toxin that travels up the food chain and concentrates in top predators like sea lions, in some cases causing seizures and brain damage.

“Off the California coast, the ecosystem is really under stress,” says Johnson. That stress is hitting California sea lions particularly hard. Amid these challenging environmental conditions, “The females are having a really, really hard time even finding enough food to produce milk for their pups,” he says. With their mothers struggling to feed them, pups may strike out on their own too soon. They’re landing on shore starving and emaciated — like the one on Norris’s autopsy table. Over the past three years, Johnson says, 80 to 90 percent of all California sea lion pups have died. The National Oceanic and Atmospheric Administration (NOAA) has dubbed it an “unusual mortality event.”

Then there’s the cancer. Scientists first noticed it in California in the 1970s, and they now know it affects Z. californianus along the entire western U.S. coastline.

Between the 1980s and mid-90s, researchers at the Marine Mammal Center saw cancer in 18 percent of adult California sea lions they examined after death. From 1998 through 2012, that number increased to 26 percent. This may mean the rate of cancer is increasing in the wild, or simply that researchers are paying better attention. Now that they know what to look for, they can spot early-stage cancer in animals without obvious tumors. The toxic algal bloom is also sending young adult animals to the center that might not otherwise have required rehabilitation.

Right now, the California sea lion population is large enough that it can absorb the losses from cancer, Johnson says. But if starving pups and other challenges cause the population to plunge, cancer’s relative influence could increase dramatically. And whether or not the disease is becoming more common or simply holding steady, Johnson says he knows one thing for certain: “It’s not declining.”

The disease rates researchers are seeing among sea lions are far from normal, and they want to know why. “Wild populations shouldn’t have cancers like this,” Johnson says.

Viral Discovery

In the center’s outdoor pens, patients swim in pools or loll like dogs on sunny patches of concrete. Elephant seal pups with identifying yellow “hat” tags stuck on the tops of their heads watch the goings-on with bulging, Disney-esque eyes. Workers and visitors don rubber boots and step into disinfecting footbaths to avoid cross-contamination among species.

Some animals in the pens are starving sea lion pups that volunteers are fattening up with a diet of thick, pink “fish milkshakes.” Others have infections, wounds from boat strikes, or brain damage from domoic acid poisoning. If the animals recover, the staff happily sends them splashing back into the surf. While about half of all patients here make it, sea lions don’t fare as well. Last year, only about 35 percent survived to be released.

The first cancerous California sea lion — a male that staff members nicknamed “Bobby” — showed up among the center’s patients in 1978. During the 1980s and early 1990s, dozens more died during rehabilitation, and researchers found the same types of tumors in the reproductive tracts of all of them.

Tumors first form in the cervix or penis, then spread, often metastasizing to the lymph nodes and spine. Sick animals typically have swollen genitals and hind flippers. If the cancer has infiltrated the spine, causing partial paralysis, they may have to drag their hind flippers behind them. Inside a stricken animal, “there’s just masses of yellow, cancerous tissue,” says Frances Gulland, senior scientist at the Marine Mammal Center.

“Sea lions themselves are affectionate animals. They’re nice to each other. They’re very endearing,” Gulland says. “When you see a sea lion coming in with cancer and they’re in pain… it’s not only distressing but it also compels you to understand why it’s happening.”

Over the past two decades, the center has intensified its work on cancer research. Scientists have largely focused on causes of the disease and why and how it spreads, Gulland says. When she started working at the center in the mid-1990s, scientists were beginning to suspect that the culprit might be a virus.

It wasn’t a crazy idea. Creatures throughout the animal kingdom suffer from cancers that begin as viral infections. In humans, viruses have been linked to as many as 15 to 20 percent of cancers, including cervical cancer, Hodgkin’s disease, lymphomas, and liver cancer.

Gulland and others scoured the DNA of cancerous tissues taken from dead sea lions and discovered a previously unknown herpesvirus. The virus appears in the tumors and reproductive tracts of all cancerous sea lions, but is scarce in other parts of the body, and is rarely found in healthy sea lions. While the scientists haven’t proven definitively that the virus causes cancer, evidence is piling up.

Although that evidence hasn’t yet gotten them closer to curing the cancer-stricken animals, understanding the disease could lead to earlier diagnoses and the development of measures to help prevent its spread. Right now, California sea lions that arrive at the center with suspicious symptoms receive an ultrasound and other tests for cancer. If an animal tests positive, it is euthanized, Gulland says regretfully; there’s nothing else to be done. “We know [the disease] progresses, it’s painful, and it’s not curable.”

But in death, Gulland says, the animals provide a goldmine of information. “Because we have them in hand, we can obtain a lot of very fresh samples.”

Causes of Death

Norris, it turns out, is right about the smell. The sea lion pup she’s now dissecting on the metal table has been frozen and thawed, making its odor reminiscent of roadkill. She says fresh carcasses have more of a musty, sometimes fishy aroma. An open door lets in air, along with barks and chirps that drift in from the outdoor pens.

Norris and Halaska begin to remove and sort through the sea lion’s organs. They pull out fistfuls of intestines in long, pink loops. Halaska dons goggles and turns on a buzzing electric saw to cut through the skull and get at the animal’s brain.

Researchers at the Marine Mammal Center must determine a cause of death for every animal that reaches this metal table. And each one—fur seal, harbor seal, pregnant female, unborn fetus—surrenders its own set of scientific samples. It may be swabbed for flu viruses; its urine or milk or bile or body lice may be carefully saved. These samples will go to labs all over the country, and some will travel the world. Researchers at the center are participating in 40 different collaborative research projects at the moment, Johnson says. And he estimates that a third of those have to do with the cancer that’s afflicting the California sea lion.

The tiny sea lion whose blood is now pooling at the edge of the rimmed table was not a cancer victim, and his autopsy is comparatively short. Cancerous sea lions, in contrast, as well as a select few adult “controls” that died of other causes, undergo a much more involved “cancer protocol.” For these, researchers must take extensive samples. Skin. Blood. Brain. Tumor. Norris holds a kidney sample in her gloved palm that looks like a slice of beet—she will send tissue slices like this one to a pathologist, who will scrutinize them under a microscope for cancerous cells. Some of the “control” samples have, when observed more closely, revealed very early signs of cancer.

So far, scientists have learned a few things for certain about the disease. They know animals with cancer carry the herpesvirus. The cancerous animals all have a specific genotype that may help the disease spread. They are also more inbred than other sea lions. Finally, animals with cancer have more pollutants—specifically PCBs and DDT—stored in their blubber than individuals that die of other causes. Research on other marine mammals has linked these ocean contaminants to suppressed immunity.

How these pieces of knowledge all fit together, however, isn’t yet clear. The scientists’ best guess, Gulland says, is that exposure to pollutants makes a sea lion more susceptible to a herpesvirus infection. When the virus takes hold, it triggers cancer—somehow.

To learn more, researchers are studying the DNA of cancerous tissues in the lab, focusing on changes at the level of the chromosome. They’re measuring the concentrations of contaminants like DDT and PCBs in sea lions’ blubber to find out whether these might make the animals more susceptible to a virus. Alissa Deming, a veterinarian and University of Florida PhD student, is looking at the genetics of the sea lion herpesvirus. She wants to prove that the virus indeed causes sea lion cells to turn cancerous. The next question will be how.

“Herpesviruses are one of the oldest classes of viruses,” says University of Florida geneticist Rolf Renne, who studies the human herpesvirus that causes Kaposi’s sarcoma. “They’re pretty much in all mammals, and even in sea urchins.” Humans alone can be infected by eight different herpesviruses.

These viruses have spent a long time evolving alongside their animal hosts, and they’re usually well-adapted to do little harm, because a dead host is not much good to a virus. Infections can be quite common, and typically lead to cancer or other serious illness only when something suppresses the host’s immune response. “If your immune system craps out on you, then a herpesvirus can take control,” Deming says.

The human Epstein-Barr virus, for example, is a herpesvirus that infects about 90 percent of adults. It commonly causes mononucleosis, but if its host has an impaired immune system, the virus can lead to lymphomas or other cancers. Another human herpesvirus causes Kaposi’s sarcoma, a disease best known in the U.S. for affecting immune-suppressed AIDS patients. According to Renne, in sub-Saharan Africa, where malaria and other infections compromise people’s immune systems, Kaposi’s sarcoma is much more common—the most common cancer among men, in fact. Ocean contaminants like PCBs and DDT might compromise the immune systems of California sea lions in similar way.

The finding that cancer-stricken sea lions have more pollutants in their blubber has caught researchers’ attention. “That’s really important for the human health perspective as well,” Gulland says. “These are contaminants the sea lions are acquiring from their prey. And the fish they eat are the same fish that we eat.”

Their environment is our environment, in other words. And what scientists can learn about cancer in each species might help the other.

The Messy World

Flies circle as Norris and Halaska scoop up and discard what’s left of the young sea lion. Its stripped-down carcass goes into a barrel, which will be picked up and taken to a rendering plant. The carefully collected slices and scraps of its body—anything the researchers aren’t immediately shipping on ice to other scientists—go into vials and plastic baggies, and then into freezers for storage.

Most of those freezers are in the basement, where Cold War missiles were once stored. The freezers stand at attention in a long white row, drawers stuffed with thousands of samples for future research. Frost crackles as Halaska opens the door to one of them. She points out a baggie holding a whale eyeball as big as an apple.

Scientists who study cancer particularly value samples like these, which come from animals that lived not in the sterile confines of a lab but in the complicated, messy, germy natural world. These marine mammals’ diseases almost certainly arose from a collision of many factors: genes, environment, other animals and parasites with which they crossed paths. Complex as their stories are, in many ways these specimens are far better than specially bred, genetically identical lab rats for helping scientists understand how cancer develops in humans and other animals living in the real world.

“How can we look at diseases in our marine mammals and translate what we are learning from that to human medicine, and vice versa?” Johnson asks. To him, this cross-species exploration is the most exciting research underway at the center.

The idea that human and veterinary medicine can inform each other is part of a philosophy known as “One Health,” which says that we need to consider the health of people, animals, and the environment simultaneously if want to truly understand each of them. Human diseases don’t exist in isolation and, Deming says, “people are animals too.” This philosophy isn’t yet widespread in the medical world, where doctors tend to be highly specialized. But the National Institutes of Health is starting to embrace the idea. It held a workshop in 2015 on incorporating One Health into its own research; its program for “comparative biomedical scientists” trains new researchers in both human and animal health at once.

Using such an approach, the research on sea lion cancer can help answer big-picture questions about cancer in other species—humans included—and the viruses that may cause it. One place it’s already revealing connections to human cancer-causing viruses is in Renne’s work on Kaposi’s sarcoma.

Studying the herpesvirus that causes Kaposi’s sarcoma in the lab is difficult. “There’s not an animal model that’s very close,” Renne says. That’s why his interest was piqued when Deming approached him about working together on her PhD research: The sea lions and their resident herpesvirus are turning out to be a great model for humans and our own viruses.

Deming’s investigation into the genome of the sea lion herpesvirus has already shown it to have striking similarities to both the Epstein-Barr and Kaposi’s sarcoma viruses. The three belong to the same subfamily, and the sea lion virus has genes that seem equivalent to two cancer-triggering genes in the human herpesviruses. These genes help push a host cell into an immortal, constantly dividing state—a strong hint that the sea lion virus not only causes cancer in its hosts, but does so using similar mechanisms to human viruses.

Now, Renne and Deming are looking into whether the virus targets sea lion genes using microRNAs, tiny bits of genetic material that regulate gene activity. Renne has found this to be the case with the Kaposi’s sarcoma virus. If this is also true of the sea lion virus, Renne says, then the researchers will have solid evidence that there are general mechanisms by which this type of herpesvirus causes cancer across very different mammalian species.

Before she began her PhD research, Deming worked as a clinical veterinarian at SeaWorld in San Diego. She used to get discouraged when she saw cancerous sea lions and could do nothing but euthanize them. But now, her work at the Marine Mammal Center is turning the deaths of these animals into research opportunities. “[It] gives us something productive to do,” she says.

In a way, the center itself is also turning death into opportunity. Today the deadly missiles are gone, and the walls that once protected them now hold countless samples of animals that lost their lives on this coast. Armed with those bits of blood and bone, scientists hope to protect the health of this ecosystem and the animals—all the animals—that share it.

This story comes from Biographic, an online magazine published by San Francisco’s California Academy of Sciences.