Animals —Mirror into Human Health, Pt I: Heart Disease, Cancer, & More
HHN: You say there is an "astonishing connection between human and animal health." What, as a practitioner of human medicine, have you found astonishing?
BNH: I’ve had a cascade of astonishments, starting about 10 years ago, when the Los Angeles Zoo called me to come over to weigh in on a case of heart failure in a tamarin.
Not long after, I was crouching close and widening my eyes to warmly connect with this sweet, tiny monkey named Spitzbuben when one of the zoo veterinarian advised, "Stop making eye contact with Spitzbuben; you might give her ‘capture myopathy.'"
What was capture myopathy? I’d never heard of it.
Broadly defined, I learned it is any adverse clinical event that happens during an animal’s capture. Wildlife biologists, who capture animals in order to take blood samples or attach a tracking device before releasing them back into the wild,"Wildlife biologists report that the process of capturing animals can sometimes kill them."report that the process of capturing, handling, and/or transporting them can injure the animals; sometimes it even kills them. In South Africa, where animals often need to be moved because of national park boundaries and humans taking over the land, capture myopathy is a major cause of animal death.
It turned out that capture myopathy was resulting in heart failure: Upon capture, certain animals had such extreme surges of adrenaline, their pumping chambers were weakened to the point of being unable to function efficiently. Deer and birds, who are particularly high-strung, were especially vulnerable to death. And during sensitive capture periods, loud noises, such as the whirring of a nearby helicopter, were contributing to deaths of shorebirds and undulates.
Evolutionarily, at first this sounded paradoxical. Natural selection is incredibly powerful process; why wouldn’t it have weeded out animals that could die in the presence of danger? But after I applied a fundamental evolutionary principle called "life history trade-off," which basically means the conferring of benefit most of the time, but risk at other times, the extreme stress response began to make more sense. The theory is, prey animals that must make instantaneous escapes benefit from a robust adrenological response to stress that kicks them into high gear for the getaway. Yet there’s a cost: in certain individual animals, that likely have a lower stress threshold, the adrenaline burst leads directly to cardiac arrhythmia.
So, astonishment #1 for me was that I, a heart specialist, had never learned what was standard veterinary knowledge regarding cardiology in non-human animals. Nor, I would soon learn, had any of my physician colleagues ever been exposed to veterinary literature or gone to a veterinary conference.
The second astonishment was realizing capture myopathy’s incredible similarities to a heart condition I had treated in human patients undergoing severe stress.
HHN: What heart condition in humans results from extreme stress?
BNH: After highly stressful events, such as being left on your wedding day or seeing a loved one die, some people experience severe chest pain. All the signs indicate that they’ve had a heart attack. They’re rushed to an ER, taken to a cath lab, given a coronary angiogram, and the results come in: the coronary arteries are completely clean.
Years ago, doctors didn’t know what to make of this. But around 2001, we started to understand it. And so, doctors now do what’s called a ventriculargram, injecting dye into the left ventricle, and the answer emerges: The shape of the ventricle, the pumping engine for the circulatory system, is abnormal; the apex, the bottom part, is bulging out. The overall shape resembles a takotsubo, the pot in which Japanese fishermen capture octopus, which is how the condition, takotsubo cardiomyopathy, got its name.
Just like in animals, a human being’s overactive central nervous system has released an outpouring of stress hormones which can damage heart muscles, create perilous arrhythmias, and, in about 5% of the time, trigger a fatal heart attack.
Sometimes takotsubo cardiomyopathy strikes a populace at once. The New England Journal of Medicine reported that on January 17, 1994, when a big earthquake shook LA, nearly five times as many residents had cardiac events compared to that same day a year earlier, when there was no unusual occurrence."On January 17, 1994, when a big earthquake shook LA, nearly five times as many residents had cardiac events compared to that same day a year earlier, when there was no unusual occurrence."Even a placebo event such as voodoo can lead to death. If the person being "hexed" believes the person delivering it, that’s enough for the hex to come true: the resulting hormonal overload can trigger cardiac death.
Well, when 15 years ago cardiologists confirmed these insights, the story made headlines all over the world as "Stress Can Kill." But now, I realized, this massive headline about sudden stress killing human animals was essentially what veterinarians had been describing happening to non-human animals since the early 1970s.
Then I thought: If animal doctors have long known something we human doctors didn’t know existed, what else might they know about so-called "human diseases"?
I started researching veterinary databases and journals to find out, and discovered to my surprise just how many diseases animals and humans have in common.
HHN: What diseases do animals and humans share?
BNH: Lions, tigers, jaguars, and other big cats in captivity get breast cancer. English springer spaniels from Sweden carry the BRCA 1 and BRCA 2 mutations, and have higher breast cancer rates; Argentinian and Venezuelan jaguars may also carry the BRCA 1 mutation, though this hasn’t yet been confirmed."Lions, tigers, jaguars, and other big cats in captivity get breast cancer."In the wild, necropsies (another term for autopsies) of Canadian beluga whales found dead floating in the water have revealed breast and other carcinomas.
Rhinos get leukemia. Buffaloes, penguins, and dogs, among other animals, get melanoma, and in fact canine melanoma is extremely similar to human melanoma. And canine osteosarcoma is basically identical to the bone cancer human osteosarcoma.
There is extreme overlap between the diseases of non-human animals and humans. Indeed, an entire parallel universe of medicine is happening that most of us—and that includes us physicians—know little about.
And this parallel universe is not only happening in our time; some of these diseases date back millions of years.
HHN: Which human diseases date back millions of years?
BNH: Cancer, for certain. From fossils there is evidence that cancer existed in animals living at least 70 million years ago. The skull of a dinosaur, a Gorgosaurus, showed that this relative of Tyrannosaurus rex had a brain tumor.
It’s noteworthy, this fact that cancer is not unique to our modern times. We’ve grown accustomed to a much narrower view: that cancer as a disease of civilization, something that happens to us because of our bad habits."Cancer is not unique to our times. A dinosaur from 70 million years ago had a brain tumor."Today, people with cancer try to answer why it happened: "I lived in the wrong place," "I ate the wrong things," "It was the stress from my divorce." This discussion can be tricky, because humans do all kinds of things that can increase our cancer risk.
Then there’s the prevention side of the equation. Whether we realize it or not, some of us think about cancer prevention all day long. I slather sunscreen on my kids before they go out; I just gave my son a blueberry smoothie. All these actions we take also reinforce the notion that cancer is in our control.
But the fact is, what we do either amplifies or lessens a cancer risk that has long been embedded into our DNA.
HHN: Has studying human and animal cancer together yielded insights and applications in contemporary medicine?
BNH: Yes. One synergy grew out of a spontaneous dinner table exchange during a meeting of human cancer specialists at New York’s Princeton Club. The one veterinary clinician attending Dr. Philip Bergman. Sitting near him was physician Dr. Jedd Wolchok of Memorial Sloan-Kettering Cancer Center, who turned to him and asked, "Do dogs get melanoma?"
Soon, upon discovering that in both human and canine, melanomas are highly similar, Drs. Bergman and Wolchok decided to work together." In both human and canine, melanomas are highly similar."They gave 350 dogs with melanoma a DNA vaccine which has a very small piece of human DNA encoding. This vaccine was what’s called "xenogeneic," meaning a different—in this case, human—species of DNA was given to trick the other species' immune systems into mounting an attack on its own cells to destroy the invader. Dr. Bergman notes that xenogeneic vaccines tend to work for nearly every target tried, whereas syngenic vaccines, those from the same species, don’t work in the vast majority of instances.
In this case, the dogs' muscles were injected with human tyrosinase DNA, an enzyme which catalyzes melanin or black pigment production. All of the dogs' muscle cells then made the human tyrosinase protein, and, not recognizing the proteins, their immune system fighter cells, called T cells, attacked the proteins. In about half the dogs, their immune systems responded by making a specific anti-tyrosinase—in effect, anti-melanoma—antibody."Dogs with melanoma who were given human DNA had a significant 70% increase in long-term survival."Notably, ~70% of the dogs— all in stage II or III with malignant melanoma who had surgery and/or radiation followed by this vaccine—had a significant 70% increase in long-term survival. As reported in the American Journal of Veterinary Research (2011), up to 75% of these dogs were alive 2−3 years later, the maximum time period followed by the researchers, whereas more than 50% of a control group of dogs with the same condition who had surgery and/or radiation without the vaccine died of the melanoma within a year.
HHN: Has this successful study been replicated and shown to extend other dogs' lives?
BNH: Three other groups have since reported outcomes in dogs treated with the same Oncept vaccine, all without success. Dr. Bergman questions the methodology in those three studies, none of which were published in a top veterinary journal. He notes the other studies had very small numbers of patients—15 or fewer dogs in the vaccine group per study—and studies with small numbers of subjects are much less reliable. In addition, he says, all reported on retrospective data, meaning the information was collected from past records rather than following up with the patients after the intervention, and retrospective studies are much more poorly controlled.
He says: "How some people can take these data to supposedly definitively prove the vaccine doesn’t work as they assert is mind-boggling to me as a clinician scientist."
HHN: Has the initial success of giving dogs the Oncept vaccine prompting other animal trials?
BNH: Currently, trials are in progress on horses. Dr. Bergman says that some horse owners giving the animals Oncept have told him that the tumors have started to respond after 5 — 9 months, which he believes is in line with the science, as it takes DNA vaccines months to make enough target-specific T cells to attack literally billions of cancer cells."The tips of our human pinky fingers have about 1.5 billion cells."As a point of reference, he notes that the tips of our human pinky fingers have about 1.5 billion cells, so killing multiple billions of cells is a tall order. But in horses the disease grows considerably more slowly, giving scientists potentially much more time to grow the target-specific T cells to tackle many billions of cancer cells.
Right now, there aren’t good melanoma treatment options for horses. Melanoma is not very radiation sensitive, and because most horse melanomas are extremely large, surgical resection is not usually possible. So if the results pan out, it could make a significant difference in treatment.
HHN: Have any studies using dog proteins been conducted on human patients?
BNH: Not with dogs. Because dog protein wasn’t available at the time, whereas both mouse and human DNA was, Dr. Wolchok and his team gave 18 human patients with melanoma a mouse tyrosinase DNA vaccine. This was, however, a Phase I study, which doesn’t measure treatment effectiveness—that begins in Phase II—but instead evaluates treatment safety and identifies side effects. As reported in Molecular Therapy, the vaccine was found safe and induced T-cell fighting responses in 7 of the 18 patients. We’ll need a Phase II study to learn more.
HHN: What kind of animal-human synergistic research do you wish was happening now?
BNH: I’d love to look differently at breast cancer. I spoke earlier of many animals getting breast cancer— well, besides lions, tigers, jaguars, and beluga whales, so do leopards, cougars, kangaroos, llama, and sea lions."Notably absent from the list of the many animals which get breast cancer are dairy cows and goats that regularly make milk."Notably absent from this list are animals that veterinarians call "professional lactators": dairy cows and goats that regularly make milk. Their rates of mammary cancer are so low, they’re considered statistically insignificant.
In humans, too, breast-feeding has been associated with a lowered breast cancer risk. So, what is it about lactating that offers protection in in both humans and animals? What if lactation, induced a few times a year, could significantly reduce breast cancer risk? Might something as natural and as simple as breastfeeding change the treatment of the most common cancer in women in America?
HHN: Have humans and animals benefited from similar treatment for other medical conditions?
BNH: Yes. We’re restoring healthy bacterial and viral flora in both non-human and human animals through fecal therapy. Notably, this therapy is another example of veterinary medicine being many decades ahead of human medicine."Fecal therapy is another example of veterinary medicine being many decades ahead of human medicine."Essentially, fecal therapy enables us to restore a human or a non-human animal with a diverse ecology of bacteria and viruses. In human patients, it first emerged in the 1950s, but only became a widely used treatment in the last 10 years or so. It’s typically given to patients who develop a condition called C. difficile colitis after taking antibiotic therapy. Broad-spectrum antibiotics can also wipe out a lot of healthy bacteria living in the gut, and sometimes the C. difficile bacteria take over and create colitis, inflammation. This presents as infectious diarrhea. The condition can be very serious, sometimes fatal.
The pathogen causing C. difficile colitis emerged because it could withstand the broad-spectrum antibiotics that killed all of its competitors. We can try another antibiotic to treat it… or, better yet, find another way to recolonize the patient’s GI tract with a healthy, diverse population of bacteria and viruses.
Fecal therapy has emerged as a way to do just that: Doctors colonize the patient with an infusion of another person’s healthy fecal bacteria via enema, a tube, or orally in the form of a capsule containing freeze-dried material.
In contrast to human practitioners, animal experts have been practicing fecal therapy for more than 100 years. They give ruminant animals such as cows and sheep the healthy rumen of another individual of the same species, who is called a rumen donator. After the animal swallows the rumen, it’s brought back to its herd mates in the fields. Then the process continues naturally. Since these animals are grazing and defecating in the same general area of the fields, just grazing there re-exposes the treated animal to the healthy flora of its mates.
Today, human fecal therapy is also being used experimentally to treat multiple sclerosis, Parkinson’s, irritable bowel syndrome, and constipation. It holds considerable promise for human medicine.
And these are just the medical models we know of that demonstrate animal-human synergy!
In Part II of this two-part series, read about animals who deal with drug addiction and overeating. These findings shed light on who we are as human animals and how we might cope with our natural, animalistic behaviors.