Heal: The Vital Role of Dogs in the Search for Cancer Cures240
Heal: The Vital Role of Dogs in the Search for Cancer Cures240
“This book is science, emotion, and love of dogs all mixed together.” — Chicago Tribune
How man’s best friend could help cure man’s greatest scourge
Drawn from extensive research, on-the-ground reporting, and personal experience, this book explores the fascinating role dogs (and cats) are playing in the search for cures for cancer. Learn how veterinarians and oncologists are working together to discover new treatments — cutting-edge therapies designed to help both animals and people suffering from cancer. Heal introduces readers to the field of comparative oncology by describing several research projects aimed at finding new therapies for cancers that are similar in dogs and people, including lymphoma, osteosarcoma, breast cancer, melanoma, and gastric cancer.
Weintraub, who lost her sister to gastric cancer, also writes about the emerging science behind the remarkable ability of dogs to sniff out early stage cancer and the efforts underway to translate that talent into diagnostic devices for early detection of the disease.
In the course of bringing these dogs and their human companions to life, Arlene Weintraub takes her own personal journey from grief to healing, as she shows how man’s best friend might be the key to unlocking the mysteries of cancer.
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The Vital Role of Dogs in the Search for Cancer Cures
By Arlene Weintraub
ECW PRESSCopyright © 2015 Arlene Weintraub
All rights reserved.
"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.
* * *
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. 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."
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.
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. All told, less than 1 percent of all animals used in medical experiments today are primates.
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. 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 topnotch 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. 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," LindbladToh 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. 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 dog's potential to further the war on cancer. Our companion dogs live in our homes, breathe our air, and eat food grown on our farms and made in our factories, making them susceptible to the same environmental risk factors that contribute to human disease. They bond so closely with us that even though they can't use words to tell us how they're feeling, we know anyway. My dog, Molly, smiles when she's basking in the sun or chomping on her favorite pumpkin chew. And when she needs to expel that gross object she ate off the sidewalk, she freezes, her lips curl, and her eyes take on a glassy gaze. Her expression is exactly what a dog trainer I know calls "barf face."
Our ability to decipher our dogs' emotions and physical well-being is a godsend for veterinary oncologists. They know they can count on pet owners to tell them when the symptoms that alerted them to the cancer go away and their dog starts acting normally again, or when the side effects of a new drug are so harsh he turns his nose up at a favorite treat. Such clues, which are nearly impossible to glean from a mouse in a cage, can help a scientist who has spent years perfecting an experimental treatment to better predict whether it's going to be the next cancer blockbuster or just the latest new idea to bomb in human trials.
Although the Wilbers didn't know it when they enrolled Basil in Cheryl London's trial at UC Davis, their new vet was one of a handful of scientists who were pioneering the field of comparative oncology. After earning her veterinary degree from Tufts University in 1990, London went to Harvard, where in 1999 she earned a Ph.D. in immunology. Then she moved to UC Davis, where she devised trials designed to help both pets and people with cancer.
London was working on Palladia alongside a San Francisco biotechnology start-up called Sugen, which was helping to develop a new class of drugs known as tyrosine kinase inhibitors. These powerful drugs use many different modes of attack against cancer cells. They block a lethal protein produced by a mutation in a gene called c-kit — a gene that had been implicated in some human cancers, including gastrointestinal stromal tumors (GISTs), which originate in the tissue that surrounds the stomach and intestines. That c-kit mutation was also found in some dogs with mast cell tumors, a common form of skin cancer.
In addition to blocking the mutant c-kit protein, Sugen's experimental drugs cut off the blood supply to tumors and slowed down the proliferation of cancer cells by inhibiting two other proteins: vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF).
The effort to develop Palladia began around 2000, when London read a journal article co-written by Gerald McMahon, Sugen's head of drug discovery. London cold-called McMahon and explained to him that the c-kit mutation occurs in some dogs with cancer. She asked him if she could study some of Sugen's tyrosine kinase inhibitors in dogs.
McMahon didn't need much convincing. Two of Sugen's previous tyrosine kinase inhibitors had made tumors shrivel in lab mice, but then failed to produce any meaningful results in human trials. One of the drugs increased the median survival rate of mice with colon cancer by 58 percent — an unqualified success. But when Sugen's scientists tried the same drug in people, it was so poorly absorbed by the body it was bound to have little effect against tumors. McMahon and his colleagues were desperate for a fresh perspective and an opportunity to try the next generation of the drug in something more realistic than a mouse.
Excerpted from Heal by Arlene Weintraub. Copyright © 2015 Arlene Weintraub. Excerpted by permission of ECW PRESS.
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