Zoobiquity Read online

  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 musclesb—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 rele
vance, 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.

  ‖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.

  aIt’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.”

  bFrom 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.

  cFor the time being mice, not dogs, are providing the foreign tyrosinase.

  FOUR

  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.

  Experienced horse breeders like Viloria know that even very practiced stallions sometimes can’t perform sexually. As one website counsels, “Most people think of stallions as being big and tough, but they actually are quite sensitive. Circumstances have to be to their liking for them to feel comfortable with breeding.”

  Even when copulating with a live mare instead of producing a semen sample for artificial insemination, stallions can suffer from stage fright, intimidation, distraction, and inexperience. Male horses who are punished for sexual behaviors by rough handlers or mean mares in their youth may develop inhibitions around mounting and copulation as adults.† Some stallions show sexual interest in mares but will not mount. Some will mount but will not penetrate. Others get through the first two stages but cannot ejaculate. And there are stallions who will mount mares only when another particular horse is present or watching. Among some social animals, including horses, the highest-ranking males dominate mating. The runners-up are deprived of most sexual opportunities. Their lower status and forced celibacy put them at risk for what veterinarians call “psychological castration,” the eventual inability to have sex at all.

  As Jessica Jahiel, an author and expert in the fields of horses and horsemanship, writes, “Pain, fear, and confusion can all lead to vastly decreased libido and sometimes an inability to breed.”

  Like veterinarians, human physicians also encounter patients in whom fear, pain, and confusion (and many other factors) interfere with the ability to have erections. As medical students we’re taught to ask every patient about their sexual function and satisfaction, and we know we should because sexual performance is a useful measure of cardiovascular fitness. But the truth is that many doctors find it easier to ask Mr. Green whether he can walk up two flights of stairs without symptoms than whether he has chest pain during intercourse. Unless a patient brings up a specific sexual problem during a visit, physicians aren’t likely to inquire about the quality and frequency of a patient’s erections, ejaculations, and orgasms.

  Cultural barriers, time constraints, and even prudishness get in the way of in-depth discussions about sex between physicians and patients. So, while a patient’s sex life contains key information about his or her overall health, most physicians will address only those sexual problems that a patient feels need fixing.

  Veterinarians, on the other hand, see and deal with sex much more as a normal part of their patients’ lives. The firs
t time I attended morning rounds at the Los Angeles Zoo, I was surprised by the careful attention the vets and keepers paid to the sexual activity of the animals in their care. How much, how often, and with whom—it was all valuable information relating to the physical and mental well-being of their patients. And the discussions proceeded without the uncomfortable silences and flushed faces I’ve seen in human exam rooms.

  Spend any time around animals and you’ll notice that sex comes in many forms. Some species commit to monogamous lifelong partnerships. Others are outrageously promiscuous and spread sexually transmitted diseases (STDs). There are species that engage in heterosexual behavior at one phase of their life and homosexuality during another. There are animals who rape, animals who trick partners into sex, animals who force themselves on their young. There are also animals who engage in what appears to be lengthy foreplay. Animals who fellate their partners. Animals who secure a form of consent before engaging in intercourse.

  Careful scientific scrutiny of the shared biology and behavior of animal sex sheds light on the evolutionary background of human sexuality. A zoobiquitous survey of animal erections, copulations, ejaculations, and even orgasms could advance the treatment of human sexual dysfunction. And it might even uncover ways to enhance our sexual pleasures.

  In this chapter we’ll journey through a world of insect foreplay, comparative clitorology, and the shared pleasure of orgasm. But there’s no better place to start this tour of the sex lives of animals, both human and nonhuman, than with the extraordinary feat of biomechanical engineering called the male penile erection.

  Not surprisingly, when physicians study penises, we tend to focus on the human variety. But our world is abristle with phalluses and has been for at least half a billion years. Today and every day since at least the early Paleozoic era, in meadows, oceans, streams, and the air, many trillions of erections preceded trillions of copulations, which preceded trillions of ejaculations. Some erections sprouted readily and penetrated easily. Others flickered to life and abruptly terminated. Some were measurable in yards. Others were microscopic. Some were stiffened by blood; others by a similar fluid called hemolymph; others by skeletal supports made of cartilage or bone. Some erections culminated in mere seconds; others lasted hours.