Authors: Barbara Natterson-Horowitz
Zoobiquity (9 page)
The way German families from the Black Forest region are susceptible to kidney and retinal cancers, or Ashkenazi Jews to breast, ovarian, and colon cancers, certain dog breeds are prone to certain cancers.
German shepherds, for example, can develop a kind of heritable kidney tumor. As the veterinary oncologists Melissa Paoloni and Chand Khanna explain in a review published in
Nature Reviews Cancer
, the genetic mutation that causes the dog cancer is similar to the one that leads to Birt-Hogg-Dubé syndrome in people—which makes them vulnerable to kidney cancer, too. Salukis, descended from the royal dogs of ancient Egypt, are among the oldest breeds. Their chromosomal legacy codes for their lean, regal elegance but also for a one-in-three chance of developing hemangiosarcoma, a highly aggressive tumor of the heart, liver, and spleen occasionally seen by human cardiologists, hepatologists, and oncologists.
‖
Paoloni and Khanna note that chow chows have higher-than-usual rates of gastric carcinoma and melanoma. Boxers lead the list for developing mast-cell cancer as well as brain tumors. Bladder cancer disproportionately strikes Scottish terriers. Histiocytic sarcoma (an extremely
complicated cancer that hides out in locations like the spleen) favors flat-coated retrievers and Bernese mountain dogs.
But noticing where cancer
isn’t
can be as instructive as noticing where it
is
. As Paoloni and Khanna point out, remarkably (although so far still inexplicably), two breeds of dogs seem to get cancer less often than the others: beagles and dachsunds. Like the professional lactators who rarely get breast cancer, these extra-healthy dog breeds may point to behaviors or physiology that offer cancer protection.
Despite all the possibilities that lie in comparative oncology, only a fraction of human doctors ever think beyond the mouse. As a UCLA oncologist colleague confirmed to me, even the smartest human cancer researchers
never
talk about naturally occurring animal cancers.
And while initiatives like the COP are slowly changing that, zoobiquitous collaborations between physicians and veterinarians are, at present, all too rare. If we could change this, the world of cancer care and cancer research might look quite different. I learned this for myself when I heard the story of a fortuitous meeting of two oncologists, one a physician, the other a veterinarian, that resulted in a radical new treatment for melanoma.
In many ways, the dinner crowd at New York’s Princeton Club that autumn evening in 1999 was like any other. Blue blazers and regimental ties. Silvering temples. Smart skirts and pearls and pumps. Conversation probably tumbled around the Y2K bug, an exciting new HBO series called
The Sopranos
, and gas prices that were climbing to a steep $1.40 per gallon after hovering below the dollar mark for most of the preceding summer. Silently surveying it all, as it had for decades, was the cold metal eye of a bronze tiger on the wall.
But at one table, the banter was anything but ordinary. Around the starched white tablecloth, ice clinking in the water glasses, sat a dozen or so scientists intently strategizing about lymphoma. With one exception, they were all human cancer experts.
Listening quietly at first was the sole outlier, Philip Bergman. Bergman, who is tall, with thick, wavy dark hair and a groomed Van Dyke beard, is a veterinarian. He has the calm, measured voice and lack of extraneous movement that mark nearly every animal doc I’ve met. That night, though, he was feeling a little out of his element. As he told me a
few years later, he kept thinking: “
This is the
Princeton
Club. I’m a veterinarian. I don’t really belong here.” (Never mind that he spent years training at the M. D. Anderson Cancer Center and holds multiple degrees, including a Ph.D. in human cancer biology.)
Near Bergman sat Jedd Wolchok, an M.D. and Ph.D. with board certifications in human internal medicine and oncology. Wolchok was a rising star at Memorial Sloan-Kettering, one of the leading cancer research hospitals in the world. Suddenly Wolchok turned to Bergman. And out of his mouth came a most zoobiquitous question.
“
Do dogs,” he asked, “get melanoma?”
It was the right question, the right person, the right moment. Bergman happened to be one of the world’s few experts in how this difficult, aggressive form of cancer attacks dogs. And he was looking for his next big project.
Bergman and Wolchok started comparing human and canine melanoma. They quickly learned, as Bergman put it, that “
the diseases are essentially one and the same.” In humans as in dogs, malignant melanomas often show up in the mouth, on foot pads, and under finger- and toenails. In both species, it metastasizes to the same “weird spots,” favoring the adrenal glands, heart, liver, brain membranes, and lungs. In humans, melanoma resists chemotherapy. Surgery and radiation often don’t keep it from spreading. It has a nasty trait of recurring, even after treatment. Same thing in dogs. Sadly, both humans and dogs have a very low survival rate with this cancer. Once diagnosed with advanced canine malignant melanoma, dogs can have as little as four and a half months to live. Human patients with metastatic melanoma often live less than one year. Wolchok and Bergman both knew that, for the sake of patients of both species, new approaches to malignant melanoma were “desperately needed.”
Wolchok confided to Bergman that he was on the trail of a novel therapy, one that would trick a patient’s immune system into attacking its own cancer.
a
His team at Sloan-Kettering had had some early success
with mice. But they needed to know how the remedy might fare in animals with spontaneously occurring tumors, intact immune systems, and longer life spans. Bergman realized instantly that dogs could be that animal.
In three short months, Bergman had a trial up and running. He recruited nine pet dogs: a Siberian husky, a Lhasa apso, a bichon frise, and a German shepherd, as well as two cocker spaniels and three mixed breeds. All had been diagnosed with various stages of melanoma. For most of these pets, the experimental treatment was their last chance—and it was eagerly embraced by their grateful owners.
The therapy—which involved injecting
human
DNA into the dogs’ thigh muscles
b
—worked even better than Bergman and Wolchok expected. Overall, the dogs’ tumors shrank. Their survival rates soared. When the news of the success got out, Bergman started getting calls and e-mails from desperate dog owners all over the world. One client flew to New York from Napa Valley every two weeks so his dog could receive the injections. Another moved from Hong Kong with her pet and took up residence near Bergman’s New York office. Before long, Bergman had more volunteers for the new therapy than he could handle. With financial support from the drug company Merial and help from Sloan-Kettering to produce the drug, Bergman launched another round of trials. And even when the spots were filled, the owners of canine cancer patients kept calling.
The treatment was ultimately tested in more than 350 pet dogs—and prolonged life so well that more than half the animals who got the injections exceeded their cancer-shortened life expectancies.
In 2009, Merial released the vaccine to veterinary oncologists, under the name Oncept, making the treatment available to thousands of family pets stricken with cancer.
Wolchok’s four zoobiquitous words—“Do dogs get melanoma?”—sparked an intense collaboration, one that may have permanently changed the way veterinarians treat the disease in canine patients. And the translational potential is enormous. Bergman and Wolchok’s success is inspiring work on a similar vaccine for melanoma in humans.
c
Yet Bergman knows that, even with the success of Oncept, human medicine may still take a while to wake up to the possibilities of interspecies collaboration.
“
Almost without fail, when I tell this story to groups of human doctors,” he said to me—adding politely yet pointedly, “no offense to your colleagues”—“someone will come up to me afterward and ask, ‘How did you convince those dog owners to let you give their pets cancer?’ ” Bergman chuckled. “I have to explain. These are not lab dogs. We didn’t ‘give’ them cancer.”
What he actually gave them was another shot at life.
*
Sadly, Linda Munson, the U.C. Davis veterinary pathologist leading the research, died before the jaguar genome was fully sequenced and scanned for clues to BRCA1 relevance, although her early research pointed to a connection.
†
Here I should pause to dispel the myth—often repeated—that sharks “don’t get cancer.” Tumors of many kinds, some metastatic, have been found in numerous species of sharks. Rumors to the contrary are likely promulgated by those hawking alternative remedies at the expense of wild species.
‡
According to the WHO, “a region that extends from West to East Africa between the 10th degree north and 10th degree south of the equator and continues south down the Eastern coast of Africa.”
§
Cats have served as sentinels, too: one study linked oral cancer in cats to environmental tobacco smoke.
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When certain populations show the same mutation, it’s usually a result of the “founder effect.” That’s when a long line of descendants arises from a very few progenitors and for some reason—geographic, cultural—remains isolated. The founder effect has been noticed in populations from microbes and plants to animals, including humans. The mutation that causes cystic fibrosis, for example, can be traced to one person. The founding individual who first carried the BRCA1 mutation in Ashkenazi Jewish families is thought to have lived more than two thousand years ago.
Geneticists frequently see founder effects in bottleneck populations. These are groups where certain factors mean that many descendants come from few ancestors. Cheetahs are a natural bottleneck population. As their numbers dwindle, they rely on the genes of fewer and fewer breeding members to keep their species alive. This is an issue for many endangered species. With domesticated dogs, we humans create bottleneck populations on purpose: by breeding all future descendants from a set number of progenitors, we limit the genes in that pool, including the mutated ones.
a
It’s called
xenogeneic plasmid DNA vaccination. Essentially, it “hides” proteins from a foreign species within the cells of a patient with cancer. When these foreign proteins circulate through the blood and lymph, the immune system senses the alien proteins. It thinks there’s an invader afoot, and mounts an attack on its own cells. Getting the immune system to attack itself is called “breaking tolerance”—and it’s so hard, said Bergman, that it’s the “holy grail of cancer immunotherapy.”
b
From a
human
melanoma cell donated by an anonymous patient, the gene jocks at Sloan-Kettering extracted human tyrosinase cDNA. They shaped each strand into a ring and cloned it millions of times. Then Bergman injected these tiny doughnuts of DNA, called plasmids, into the dogs’ thigh muscles, using a high-pressure, needle-free delivery system sort of like a high-tech air gun.
Deep inside the dogs’ muscle and white blood cells, the plasmids started making
human
tyrosinase. Then the cells released the human proteins into the dogs’ blood and lymph … which is where they encountered the immune system’s fighter cells, called T cells. Not recognizing the human tyrosinase, the dogs’ T cells attacked it. This immune response sparked the T cells to go after canine tyrosinase in the dogs’ tumor cells as well.
c
For the time being mice, not dogs, are providing the foreign tyrosinase.
Roar-gasm
An Animal Guide to Human Sexuality
Lancelot
*
was having a rough morning. He kicked puffs of dirt up from the barn floor and snorted. A handful of students hovered around him warily, gauging his movements. He froze for a moment, standing tall on his dark brown legs and shifting his muscular haunches.
“Urine!” shouted Joel Viloria, the barn supervisor. In an instant, a student appeared with a plastic pouch of “liquid gold,” urine that had been collected from a mare in heat and then frozen. Joel wafted the urinary ice cube under Lancelot’s velvety nose. Clearly stimulated by the aroma, the stallion flared his nostrils, and his head reared back.
“Give him another look at the mare,” Viloria commanded tensely. The thousand-pound stallion was led past a stall at the side of the barn. There, bathed in streaks of February sunlight, stood a pale young horse, her tail raised obligingly and receptively in a classic equine come-hither stance. Lancelot beelined for her.
“Okay, go!” urged Viloria, his voice firm but calm. Quickly, the stallion was steered away from the mare. But one of Lancelot’s big eyes remained
on her, rolling sideways in the socket, as he was led away. “That’s right, good,” encouraged Viloria when Lancelot mounted one end of the padded metal breeding apparatus horsemen call a phantom mare.
The stallion struggled, his sleek forelegs gripping the sides of the metallic mare as though he were copulating with a real horse. But he slipped off. A student gently guided him to remount. Distracted, he tried. But again he slid back. This time, when the student tried to return his attention to the phantom, Lancelot pulled away and refused to get back on.
“All right, that’s three—he’s not in the mood. Take him back,” said Viloria. The stallion was led away to his corral, his dark chocolate tail swishing across his flanks.
As Viloria later explained to me, the University of California, Davis, horse barn he oversees abides by a strict three-mount rule. When producing semen for breeding, each stallion is given three chances to accomplish what in nature seems like a very straightforward task. But this is not nature. First, the horse must become aroused and erect. He must next mount the metal-and-vinyl phantom. Then he must insert his penis into a lubricated, warmed metal tube underneath the phantom, thrust a few times, and ejaculate into the one-gallon plastic condom lining the tube. If on the third attempt he still hasn’t produced a specimen, he’s declared done for the day and led back to his corral for a restful (though possibly frustrating) afternoon and night.