Heal: The Vital Role of Dogs in the Search for Cancer Cures

Heal

The Vital Role of Dogs in the

Search for Cancer Cures

Arlene Weintraub

ECW Press

Beth and Spot, the fox terrier mix, circa 1973

For My Family

In Loving Memory of

Beth Ellen Weintraub Schoenfeld,

1962–2010

Prologue

206 Dogs

In February 2012, I flew to San Francisco, rented a tiny Suzuki four-door sedan, and drove 120 miles southeast in search of inspiration from dogs. I headed for Los Banos, California, home of retired schoolteachers Alan and Kathy Wilber, whose golden retriever, Basil, had been diagnosed with cancer in 2001 at the age of two. In a last-ditch attempt to save their young dog’s life, the Wilbers entered Basil into an experimental drug trial.

This trial was part of a growing international effort to recruit dogs with cancer for research designed to yield new and vastly improved treatments — for both man and man’s best friend. The scientists who invented that drug were also developing a version of it for people, and using what they learned from the dog trial to improve their efforts.

I had been working as a science reporter when I first learned about this initiative, which is called comparative oncology. Fascinated, I set out to learn as much as I could about the dogs contributing to the search for cancer cures.

My interest was not just professional, nor was it entirely driven by my lifelong love of dogs. Two years before I met Basil’s family, I lost my sister, Beth, to gastric cancer. Witnessing her brutal battle against a disease that was ultimately unconquerable left me feeling empty and hopeless. So after she died, I sought comfort in the stories of the dogs whose own cancer battles were inspiring new treatments.

As I dug deeper into the topic, I learned that one of the first big comparative oncology projects was a trial at the University of California at Davis — the trial that offered Basil a second chance at life. That research resulted in Palladia, the first-ever product approved by the Food and Drug Administration (FDA) to treat cancer in dogs,[ 1 ] and a similar drug for people called Sutent.

A young veterinary oncologist at UC Davis named Cheryl London conceived of and managed the two clinical trials that the FDA required before it would approve Palladia. The first trial started in 2001 and enrolled fifty-seven dogs whose owners were willing to try the little-understood new drug.[ 2 ] That trial was a success and led to a second, more complex research project, involving ten veterinary clinics and 149 dogs.[ 3 ]

Among the 206 dogs that nudged Palladia to market were purebreds and mixed breeds, giant dogs and tiny lapdogs. They had one thing in common: their owners were willing to advance the search for a cure in return for the slim chance that they would get to spend more time with their beloved pets.

Ten years later, I wanted to learn more about those 206 dogs and their owners. I knew the dogs were gone, whether they had lost their battle against cancer, or had won it and ended up dying of old age. But I needed to hear their stories and see their photos. I needed to tell their owners that their contribution to cancer research was making a difference for millions of patients and pets around the world. Most of all, I needed to see how the trailblazing research that they had participated in had given rise to other studies that were yielding new therapies for dogs and people with cancer.

I needed 206 reasons to believe there was hope for a cure.

I soon realized, however, that uncovering all 206 stories would not be easy. When I reached London by phone to tell her about my book project, she explained that clinical trial records in veterinary medicine are often thrown out a few years after they’re published, which would make it difficult for me to locate the names and contact information for the participants in those trials. Furthermore, many pet owners lose touch with their veterinary oncologists after their dog’s treatment has finished — either because the dog survives and returns to a normal, healthy life, or doesn’t, and the owner moves on, eager to put the whole cancer nightmare behind them. London simply no longer knew where most of the Palladia trial participants were.

I was undeterred.

My mission turned into a much broader journey, during which I learned about hundreds of research programs aimed at finding new cures for cancers that are the same in dogs and people. As I met the dogs and their owners who were participating in this research, I became more and more curious about exactly how veterinary medicine is helping uncover innovative new pathways in the search for those elusive cures.

So I broadened the boundaries of my research even further. I looked into newly released reports about the dogs’ remarkable ability to sniff out cancer and the efforts underway to translate that talent into devices that might be able to detect some cancers in humans before they produce symptoms. Even our feline friends, I learned, are becoming allies in the war on cancer (see Chapter 8).

My story includes information I gathered during visits to eight universities over the course of two years, along with additional details I learned during in-person and telephone interviews with people who participate in comparative oncology research. All of the anecdotes and quotes in this book come from my interviews with veterinarians, oncologists, scientists, drug company executives, and pet owners, unless otherwise noted.

The recollections of the people I talked with are not perfect. But with the help of many experts who are leading the comparative oncology movement, I have done my best to present the events that occurred and the dialogue that was spoken as accurately as possible.

What follows is a story of the quest for healing — of dogs and people suffering from cancer, and of one bereaved sister looking for hope in cancer research.

After Beth began chemotherapy, the basic chores that came with caring for her family’s dog, Honey — even the simple act of opening the screen door to let the dog into the backyard — became too much for her. Now, when I let my dog into the backyard I often think about Beth’s fight with cancer. With each step toward the back door comes a sad memory, or a twinge of guilt, or a question. How does cancer strike down one member of a family that has virtually no history of the disease? How can a patient who survives a brutal chemo regimen end up dying of the disease anyway? Why can’t we spot cancer early, when it’s still possible to cure it?

Man’s best friend might help us find the answer to those questions, and more.

Chapter 1

We Believe in Science

From the moment Alan and Kathy Wilber brought home their new golden retriever, Basil, in October 2000, they knew the dog would fit right in to the menagerie of pets they had been assembling since their three daughters had grown up and moved away. Basil became fast friends with the Wilbers’ other two dogs, a petite shepherd mix named Friday and an aging chocolate lab, Chauni, whom Basil doted over like a protective dad.

Basil spent his days romping with Chauni and Friday in the yard of the Wilbers’ home in Los Banos, California, and trotting from room to room carrying his favorite toy, a life-sized stuffed duck. Basil stood twenty-nine inches from paws to forehead — six inches taller than the average golden — but he regarded his size as neither an obstacle nor an advantage. Often when Alan sat in his recliner, the dog would join him, hauling his huge body onto the chair, oblivious to the fact that he was far too big to be a lapdog.

Just after New Year’s in 2001, the Wilbers noticed a bump on Basil’s right hind leg, below his knee. Their vet told them it was probably nothing more than a bruise, but they were worried. Their previous golden retriever, Teddy, had died of cancer, and they couldn’t bear the thought of losing another dog to the disease. By that spring the bump had grown, so Kathy brought Basil back to the vet for a biopsy. A few days later, their fears were realized. The two-year-old dog had cancer.

The Wilbers, both schoolteachers, didn’t have a lot of extra money to spend on Basil’s medical care, but they wanted to give him the best chance of survival. So they set out on a 140-mile drive to the University of California at Davis, home to one of the most advanced veterinary cancer centers in the country. Veterinarians there discovered that the lump was a sarcoma wrapped around the tibia bone. They amputated the leg, and the Wilbers took Basil back to Davis four times over the next six months for infusions of doxorubicin, a standard chemotherapy drug.

Basil quickly adapted to his new life as an amputee. To compensate for the lost leg, he curled his tail around his body as an anchor. He learned to walk effortlessly, centering his left hind leg beneath his body to distribute his seventy-­five pounds comfortably across his slender frame. The Wilbers bought a Roadtrek camper, because Basil could jump into it without having to climb any stairs. They carried a small rug with them wherever they went, so the dog could always sit comfortably.

In November 2001, the Wilbers went back to UC Davis for what they believed would be a routine checkup. When they pulled up in front of Davis’s veterinary complex, Basil hopped out of the camper and bounded toward the door. His tail wagging, he greeted everyone with an exuberance that belied the seriousness of his disease. He sat calmly through blood tests and CT scans.

After the tests, veterinarian Gillian Dank called the Wilbers into an exam room and delivered the sobering news: Basil’s cancer had spread to his lungs. The Wilbers knew that many dog owners in this situation would opt for euthanasia.

Then Dank told them that her colleague, a young veterinary oncologist named Cheryl London, was looking for pet dogs to take part in an innovative study of a powerful experimental drug — a medicine that would come to be called Palladia. Dog owners who enrolled in the study, Dank said, would get the drug at no charge, as well as complimentary veterinary care throughout.

What’s more, Basil’s cancer — spindle cell sarcoma — was similar to a tumor type found in humans. The research, the Wilbers learned, might benefit people, even if the drug didn’t help Basil.

The Wilbers signed Basil up for London’s study that day.

12

It was early morning when I set out for Los Banos to visit the Wilbers. As I drove, I thought about the personal tragedy that had sent me on a quest to find hope in the story of Basil. It had been just over two years since I’d lost my sister, Beth, to gastric cancer. She was forty-seven when she died, after a painful and fruitless year of chemotherapy and surgery. Beth left behind a husband, four children, our parents and older brother — and me, the little sister who had idolized her for as long as I could remember.

My shock and sorrow had barely diminished. One day, Beth was an energetic mom, juggling four children’s busy schedules while starting her own home-based business, pausing occasionally to sweep the ever-present crumbs and dog hair off the kitchen floor. The next, she was checking in to the hospital with extreme stomach pain, facing a diagnosis that was as baffling as it was tragic. I still could not grasp how my vibrant sister could be struck down so swiftly by a cancer that had never appeared in our family before, and that was exceedingly rare in someone so young.

From the moment Beth was diagnosed, I tried my best to give her hope. It was an unsettling role reversal. After all, she was my big sister, five years my senior. She was the one who had dried my tears at summer camp when I got homesick, entertained my friends at my birthday parties, and offered me advice, whether I asked for it or not. Now I was expected to be the cheerleader. I did not like this new role, but I had to embrace it. So whenever we spoke on the phone or I visited Beth during her treatments, I tried to convince her that she could beat this disease because she was young and strong.

I knew the odds were not in her favor. So did she. And then she was gone.

For me, that last year of Beth’s life was a blur of depressing hospital visits, support group meetings, and awkward phone calls from friends who struggled to make sense of this unspeakable tragedy. I diligently showed up to my job as a magazine science reporter but quickly lost all my passion for the latest medical research. Science, after all, had failed my sister. Writing about it had become little more than a sad obligation.

Then two veterinarians from Texas A&M University came to my office to publicize their new, state-of-the-art cancer center, which was designed to find new cures, not just for animals, but for people too. I was surprised to learn that dogs get many of the same cancers we do, including lymphoma, melanoma, breast cancer, bone cancer, and gastric cancer. Texas A&M, they explained, was part of a rapidly expanding network of academic veterinary centers that recruit pets with cancer for translational research — studies that have the potential to speed up the search for a cure for humans.

I became enthralled by the idea that research with pet dogs might spare other families from suffering a tragedy like ours. This felt natural. After all, Beth and I were born into a family of dog fanatics. I loved all of them, from Spot, the fox terrier mix who never minded when my sister and I tugged on her tail or tried to dress her in doll clothes, to my treat-loving terrier mix, Molly, whom I nicknamed my midlife crisis dog when I adopted her just after I turned forty. I even bonded with Honey, the lanky, standoffish mutt Beth’s family rescued from a shelter when their eldest son turned thirteen.

The veterinarians leading this branch of cancer research work in an emerging field called comparative oncology. The premise of comparative oncology is simple but powerful: Dogs make ideal models for studying human cancer because, like us, they develop cancer naturally. That makes them much more realistic models for human cancers than the rodents that are most commonly used in the discovery and development of new therapies.

Mice and rats rarely develop cancer, so they have to be manipulated in some way to mirror the human cancer experience. Some have tumors implanted under their skin, while others are genetically engineered to be prone to certain types of cancer. Research rodents are often genetic clones whose immune systems are no longer intact. What’s more, their diets are tightly controlled, and they live in clean rooms that are scrubbed of all the pathogens that we encounter every day.

That may explain why an estimated nine out of ten experimental drugs that cure lab rodents of their cancers fail miserably in human trials.[ 1 ] As Richard Klausner, former director of the National Cancer Institute, told the Los Angeles Times in 1998, We have cured mice of cancer for decades — and it simply didn’t work in humans.[ 2 ]

Our closest animal cousins, non-human primates, are rarely useful in cancer research either. Even though we share more than 90 percent of our genes with them, we are far more susceptible to cancer than they are. Cancers of the breast, prostate, and lung, for example, cause more than 20 percent of human deaths, but occur in less than 2 percent of great apes.[ 3 ]

Because of growing international concerns about the ethics of keeping wild animals in captivity purely for medical research, the scientific world has been moving away from primate studies. In June 2013, the National Institutes of Health announced that it would retire most of its laboratory chimpanzees to wildlife sanctuaries.[ 4 ] All told, less than 1 percent of all animals used in medical experiments today are primates.[ 5 ]

Pet dogs who are stricken with cancer can help fill this void in medical research. About six million dogs are diagnosed with cancer every year in the United States alone.[ 6 ] Many of them have forms of the disease that are so similar to ours that even the most eagle-eyed cancer specialists would struggle to tell them apart. As Texas A&M veterinarian Theresa Fossum put it that day she came to my office, We have access to companion animals with diseases that are genetically identical to their human counterparts.

In comparative oncology, researchers at biotechnology companies team up with veterinary oncologists and with physicians who treat people at cancer centers around the world. They work together to translate discoveries they make in dogs with cancer — perhaps about cancer-causing mutations and how they might be corrected, or new surgical methods for removing tricky tumors — into treatments for people. As they test new drugs or devices or techniques in both dogs and people, they trade insights, with the aim of improving promising treatments and moving them as quickly as possible to the market.

This isn’t animal experimentation. Comparative oncology isn’t about breeding colonies of cancer-ridden dogs in the lab, and then giving them unproven medications to see how they’ll react. The number-one goal of comparative trials, as it is in human clinical trials, is to improve the prognoses for the patients who participate. Fossum explained that the dogs who take part in this research get access to leading-edge treatments and top-notch follow-up care that’s often entirely paid for by the companies or research groups funding the trials. Throughout their treatments, the dogs are regarded as valuable members of the scientific team, whose experiences in the trials could pave the way to new cures for cancer.

Scientists working in comparative oncology have been helped by emerging research suggesting that, genetically speaking, our canine companions are more closely related to us than we realize. In 2005, scientists at the Broad Institute, which is co-managed by Harvard University and the Massachusetts Institute of Technology, sequenced the genome of a female boxer named Tasha.[ 7 ] They discovered that dogs and people have about 85 percent of the same nucleotides — the molecules that link together to form DNA.

This means the genetic commonalities between dogs and humans are far greater than they are between mice and humans, explained Kerstin Lindblad-Toh, who is the scientific director of vertebrate genome biology at the Broad Institute and one of the co-authors of the paper describing Tasha’s genome. Most mammals have about twenty thousand genes, and most of these are similar across species, she said when I reached her by phone to talk about comparative oncology, but it is the nucleotide overlap that’s key to determining how closely related one creature is to another. And when it comes to providing a good model for the human experience, dogs rule.

The regulation of genes — when and how they are turned on and off, what they produce, and so forth — is overall more similar between dogs and humans than it is between mice and humans, Lindblad-Toh said. That’s important for clinical trials. Say you have a drug that’s supposed to interact with a certain portion of a protein. It’s likely that protein will have the same structure and composition in dogs as it does in humans. Exactly the same. That means the dog is more likely than the mouse to provide an accurate picture of how that drug will work in people.

In addition to sequencing Tasha’s genome, the Broad team studied the DNA from ten other dog breeds and compiled a database of millions of genetic components that differ from one breed to another. Since then, scientists there and at other institutions have identified unique genetic markers for dozens of breeds.[ 8 ] The result is a treasure trove of genomic data that scientists can use not only to determine what makes some dogs more susceptible to disease than others, but also to better understand the illnesses they share with people and to improve treatments for everyone.

The more I learned about comparative oncology, the more convinced I became of the