Issue Date: May 7, 2012
Marine Mammal Health
On a pier jutting into the San Diego Bay, a team of people—some in cargo shorts, some in wet suits, and others in camouflage uniforms—stand attentively around a square netted enclosure in the water. All eyes are focused on the movements of a young dolphin below as the animal glides through the water, dipping up and down in his watery quarters.
One woman begins to call out orders, and a few team members spring into action, working in concert to evenly haul up the net with boat hooks. Others kneel on the deck, holding a stretcher in the water.
These are established signals telling the dolphin to hop onto the stretcher, explains Mark J. Xitco Jr., watching from a planked walkway overlooking the scene.
“Chances are,” he adds, “this guy’s going to be like my kid when he’s at the doctor’s office to get a shot.”
In other words, the team is going to be waiting awhile for the reluctant dolphin, who isn’t feeling well today, to get on the stretcher and see the veterinarian. “When you’re least likely to cooperate is when you’re not feeling well,” adds Xitco, who is the head of the Marine Mammal Scientific & Veterinary Support Branch at this Navy base, home to a fleet of dolphins and sea lions.
The dolphin getting all the care and attention is part of an elite marine mammal force mostly housed at the Pacific branch of the Space & Naval Warfare Systems Center and trained by the Navy to help its sailors carry out missions. The Navy deploys its dolphins and sea lions around the world to protect harbors by locating enemy swimmers, recover abandoned or lost equipment from the seafloor, and detect and mark mines for sailors needing to navigate around the explosives.
The marine mammals are ideal for these tasks because of their ability to repeatedly dive to great depths and their sensitive sensory systems. For instance, dolphins use sonar to locate objects and people, and sea lions have excellent low-light vision.
Back on the pier, as Xitco predicted, the dolphin still hasn’t decided to cooperate. Three wet-suited teammates ease into the chilly bay water and gently carry him in the direction of the stretcher. Once the animal is secure, a veterinarian will take a look at him and try to figure out the cause of his illness.
All this attention—an entire team of people examining a single dolphin—reflects the importance the Navy places on the health of its marine mammals. Like human sailors, the Navy’s dolphins and sea lions are considered to be war fighters: The military invests a lot of time and money in training them, and it wants them to be in tip-top shape when called on to deploy to places such as Iraq or Korea.
For this reason, the Navy has established the Marine Mammal Health Program to focus on protecting the health of its treasured fleet. “We’re interested in maintaining the health and fitness of the animals,” says Laura Kienker, program manager at the Office of Naval Research (ONR), which supports the work. “But the research doesn’t help only the Navy,” she emphasizes.
Studies on how the animals age and projects that develop analytical techniques to detect why they’re sick will also aid other marine mammals, whether they reside at SeaWorld or out in the wild. Furthermore, investigations of the marine mammals’ wound-healing abilities, as well as unique metabolic diseases they’re afflicted with and novel ocean pathogens they pick up, could eventually benefit human health.
“We’re finding incredible opportunities to learn from these animals,” says Stephanie K. Venn-Watson, who has been a contractor with the Navy studying its animals for the past 10 years.
One particularly fertile area has been studies on how the marine mammals age. “The animals in the Navy are getting older,” says Venn-Watson, who is also the director of clinical research for the National Marine Mammal Foundation. Because of the care they receive, Navy dolphins are living, on average, into their late 20s and early 30s, with an increasing number of them reaching 40 to 50 years of age. In contrast, Xitco says, dolphins in the wild typically make it only to their late teens and early 20s. And the same is true for Navy sea lions: They’re living two and three times as long as those in the wild.
“So the Navy’s been challenged with a wonderful problem,” Venn-Watson says. The researchers involved with the military branch’s program will need to figure out what special requirements geriatric marine mammals have—and learn to fulfill them—to improve the quality of the animals’ lives.
So far, Venn-Watson and others at the National Marine Mammal Foundation have discovered that the physiology of aging dolphins is similar to that of aging humans. By studying blood samples from a group of dolphins as the animals went from 30 to 50 years of age, the researchers found that, like humans, geriatric dolphins are more likely to have high cholesterol, high levels of triglycerides, and chronic inflammation (J. Comp. Physiol. B, DOI: 10.1007/s00360-011-0549-3).
The question now is how to treat these conditions when they become a problem. The research team, in collaboration with Andrew Dillin, a specialist on aging at the Salk Institute for Biological Studies, is planning to test whether human medicines, such as cholesterol-lowering statins, might help.
Another area of marine mammal research in which the Navy is taking cues from human medicine is disease detection. For years, researchers have been trying to develop methods to analyze exhaled breath from humans to diagnose health problems (C&EN, April 2, page 34). The Navy wants to piggyback on that work to give its animals noninvasive checkups.
“As we exhale, we’re breathing out a lot of information about what’s going on in our bodies,” says Laura C. Yeates, a marine mammal physiologist with the National Marine Mammal Foundation. An exhaled breath contains both volatile small molecules and fine liquid droplets filled with macromolecules such as peptides and antibodies. Some of those compounds could be biomarkers for disease: A change in their levels might indicate a sick animal.
“Dolphins and sea lions are incredibly good at masking illness,” Yeates explains. “You don’t know they’re sick until they stop eating,” and by then, veterinarians have to take an aggressive treatment approach.
To avoid these drastic measures, says Sam H. Ridgway, the Navy’s senior scientist for animal care and president of the National Marine Mammal Foundation, “we’d like the animals to be able to come over every morning when the trainers give them their vitamins” and breathe into a collection device. The trainers could then look at a readout from the analyzed breath to determine whether the animal is healthy or is beginning to come down with something, Ridgway explains.
As a first step toward that vision becoming reality, Ridgway and Yeates have teamed with Cristina Davis, an associate professor of engineering at the University of California, Davis, to build a breath collection device fit for a dolphin. “Dolphins are built differently than we are,” Yeates explains, so apparatuses already being used to collect human breath samples wouldn’t work for the animals.
What Yeates and the others have come up with is a device that fits over the animal’s blowhole and condenses its exhaled breath into a liquid plug. At this point, Davis says, the team has collected a multitude of liquid samples and is using various types of mass spectrometry to establish baseline biomarker values for healthy animals. A lot of the exhaled compounds they’ve detected are similar to those breathed out by humans. “But there’s also some unique stuff in there not found in humans,” Davis says.
The next step will be to identify which molecules are disease indicators. So far, Yeates and Ridgway have demonstrated that, like humans, dolphins with inflamed lungs exhale an increased amount of nitric oxide. Specifically, the researchers observed this phenomenon for a dolphin with pneumonia.
But increased nitric oxide doesn’t indicate exactly what kind of pulmonary disease the marine mammals might have, Davis says. Whenever a Navy animal gets sick, Davis and crew will take the opportunity to collect some of its exhaled breath and then hunt for alternative markers of specific diseases. “This work is really exciting for my group,” she says. “It gives a voice to an animal that doesn’t have a way of telling you it’s not feeling well.”
The Navy isn’t just taking ideas from human medicine to benefit its dolphins and sea lions. The military branch is also hoping that research on its fleet of about 120 animals will one day benefit humans. For instance, Venn-Watson and Ridgway, who’s been around since the Navy acquired its first dolphin and is commonly referred to as the “father of marine mammal medicine,” hope dolphins might teach them ways to control diabetes in humans.
“It turns out that dolphins have diabetes,” Venn-Watson says. By studying blood profiles, she and Ridgway have determined that after dolphins eat either sugar or high doses of protein, their blood sugar skyrockets for hours, a hallmark of diabetes (Gen. Comp. Endocrinol., DOI: 10.1016/j.ygcen.2010.10.005). Not only that, but during the morning, after the animals have fasted overnight, their bodies also appear to be in a type 2 diabetes-like state. Later in the day, Venn-Watson says, their hyperglycemia disappears.
“So they seem to switch their diabetes on and off,” Venn-Watson says. If the researchers can figure out the mechanism that triggers that switch, it could mean treatments down the road for humans with type 2 diabetes.
Venn-Watson thinks the switch probably has a genetic basis and is likely associated with the liver. That’s because insulin resistance can throw the liver, which normally helps regulate glucose levels in the body, out of whack.
Although dolphins live in a diabetes-like state part of the time, “it’s not killing them,” Venn-Watson says. But they do show other signs of metabolic dysfunction. Venn-Watson and Ridgway have identified dolphins with fatty-liver disease and hemochromatosis, or iron overload—conditions also associated with type 2 diabetes in humans. So locating the on-off switch for diabetes might also help treat these diseases in the animals.
Stem cell research is another area of marine mammal study that could benefit both animal and human health. “When you get a cut and the cut stays wet, it seems as though the wound never heals,” says Shawn Johnson, a veterinarian who works with the Navy’s fleet. “Dolphins live in water, but we know that they heal, heal really quickly, and usually do it with minimal scarring.”
How does that happen? One hypothesis is that the animals’ stem cells might aid the healing process. To test this idea, the Navy contacted San Diego-based Vet-Stem—a firm that provides stem cell therapy to horses, dogs, and cats—to determine whether it is possible to extract stem cells from dolphins and culture them.
The Navy researchers started with stem cells extracted from body fat, which scientists know have promise for tissue regeneration. They developed an ultrasound-guided liposuction technique to locate the cells in dolphins and collect them. Unlike human liposuction, this method doesn’t involve an aspirator, just some local anesthesia and a syringelike device that penetrates the dolphins’ unique blubber layer, Johnson says.
So far, Vet-Stem, Johnson, and the other researchers have used this method to isolate small quantities of fat stem cells from dolphins. They’ve amassed frozen samples and are analyzing whether the cells can help heal wounds for the same dolphin from which they were extracted. “We haven’t published yet,” Johnson says, “but it does seem like the stem-cell-treated wounds heal faster and better” than wounds left to heal on their own. It also seems like the stem cells decrease wound inflammation and signal to other cells in the vicinity to help with the healing process, he says.
In the future, Johnson adds, the team will study whether stem cells from one dolphin can be used to treat wounds on another dolphin. But first, “we want to make sure that when we mix these cells there’s no adverse reaction or tumor development.”
If that test is successful, “it would revolutionize stem cell treatments for us,” Johnson says. “We could have a whole bunch of stem cells on a shelf in the freezer and thaw them out and use them to treat any animal we have.” In the far future, he adds, cells might even help treat wounded sailors or people who frequently work in the water.
If stem cell research on the Navy’s animals is still in its infancy, pathogen detection is well into adulthood. And it could also eventually save human lives.
Much less is known about pathogens in the ocean than those on land, Xitco says. “We want to know more about the potential microbe- or virus-filled environments that our animals might be traveling to,” he says. Not only does the Navy not want their animals contracting anything, but it also doesn’t want the dolphins and sea lions introducing any new pathogens into the environments where they travel.
“Over the past five or six years,” Venn-Watson says, “what we’ve found is that once you start looking for viruses, you’ll find them.” So far, her team, working with outside researchers such as Jim Wellehan, a veterinary bioscientist at the University of Florida, Gainesville, has identified more than 50 new viruses picked up by the Navy’s marine mammals.
Mainly, the pathogens the scientists have identified are innocuous, but some—such as influenza or cold viruses—can cause illness. Wellehan and others most recently identified in two of the Navy’s sea lions a novel papillomavirus, which belongs to a family of viruses that can lead to cervical cancer (Vet. Microbiol., DOI: 10.1016/j.vetmic.2011.09.027).
It’s great that the Navy is being proactive in looking for potential pathogens, Wellehan says, because it’s a way of staying ahead of a pandemic. “Unfortunately what we do in human medicine is wait for a disease to come along and kill a whole bunch of people and then deal with the consequences afterward,” he says. For example, “until AIDS came along, no one really cared about retroviruses.”
For this reason, Venn-Watson thinks the Navy’s marine mammals might benefit human health by acting as sentinels of potential new infectious diseases originating in a marine environment. As a case in point, Wellehan recently identified a new astrovirus in a sea lion that he says is clearly a recombinant version of both a sea lion virus and a human virus (J. Gen. Virol., DOI: 10.1099/vir.0.015222-0). That means that at some point, both of those diarrheal-disease-linked viruses infected the same host. The ocean is a major reservoir of biodiversity, Venn-Watson says, and right now there aren’t many scientists searching there for potential pathogens.
The Navy’s virus discovery research will also one day help the military’s own animals, such as the dolphin reluctant to get into the stretcher. The crew of scientists and trainers in San Diego knew the dolphin was sick because the youngster had stopped accepting meals. He was one of several dolphins exhibiting that behavior over several days, Xitco says, and “we suspected a contagious illness might be working its way through our group.”
Fortunately, the dolphin and his companions perked up shortly after his exam. The veterinarian found no serious cause for concern after checking him, and the team now suspects a coldlike virus of causing all the trouble. It’ll take some time, Xitco says, but the Navy will eventually identify the pathogen culprit.
In the meantime, Xitco adds, the Navy will continue to develop the tools needed to make an earlier diagnosis for its marine mammal patients. “We’re always trying to push the envelope on the level of care we provide.”
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