On the high school practice field, a strapping teenage quarterback fades back to pass, then falters, falls to his knees and collapses. Half an hour later, the ostensibly healthy youth is pronounced dead.
Across town a pet owner frantically rushes her cat to the veterinarian. Howling in pain, the cat has no use of its hind legs.
What do the cat and the quarterback have in common? Both were felled by a cardiac disease called "hypertrophic cardiomyopathy" in which the heart muscle grows too thick. In humans, this abnormality is often caused by mutations in a gene that produces a protein crucial for contraction of heart muscle. The heart tries to compensate for the abnormal protein by growing more muscle. But the muscle grows inward filling the chamber with tissue, rather than blood. In cats, this process slows blood flow, creating blood clots. Blood supply to the thickened muscle is inadequate, causing abnormal heart rhythms that sometime lead to sudden death in humans and cats.
A UC Davis veterinary cardiologist and a human cardiologist have teamed up to study the genetic basis of the ailment in cats, hoping their research will yield clues for diagnosis and treatment of both humans and cats. Such veterinarian/physician partnerships are becoming surprisingly common. With increasing frequency, doctors from both human and veterinary medicine are finding their research paths intersecting. By combining the talents and resources from both of their professions, they can solve medical mysteries that might have continued to baffle them individually. In fact, some researchers would say the two professions in reality are "one medicine."
"If you were to walk through the veterinary medical teaching hospital, I would bet you would find very few faculty members who have not collaborated with physicians at some time during their research careers," said Mark Kittleson, the UC Davis professor and veterinary cardiologist who continues to unravel the secrets of hypertrophic cardiomyopathy.
A mouthful to pronounce, the disease is the most common heart ailment in cats and is fairly common in humans.
"It's a terrible, lousy, nasty disease," said Kittleson. "The first symptom for human patients might be shortness of breath and abnormal heart rhythm. Eventually, these patients may experience heart failure.
"In cats, it often results in sudden death, heart failure or a blood clot blocking the aorta and causing terrible pain and paralysis of the hind legs," he said.
With the help of two cat owners and a breeder, Kittleson discovered that hypertrophic cardiomyopathy occurs quite frequently in a long-haired domestic cat breed known as the Maine coon cat. Establishing a breeding colony of Maine coon cats in 1992, Kittleson began exploring the genetic basis of hypertrophic cardiomyopathy in the breed, looking for specific genes and gene mutations associated with the ailment.
In the course of his research, he encountered Kate Meurs, a veterinarian working on her Ph.D. with Jeffrey Towbin, a pediatric cardiologist at Baylor University in Texas. Towbin, who treats infants with heart disease so severe that they require transplants, is interested in the molecular biology of cardiac disease. One of Towbin's areas of expertise is identifying genetic mutations in patients. The three struck up a working partnership, with Meurs doing the genetic screening of Kittleson's cats, including the Main coon cats, American shorthairs and domestic shorthairs.
The researchers are trying to determine whether the genetic irregularity that causes hypertrophic cardiomyopathy in humans also causes the disease in cats.
"The hope for the cat world is that we can find the mutation, develop a screening test and then encourage breeders to breed only those cats without the mutation that causes the disease," explained Kittleson.
For human medicine, gene therapy--insertion of genes to correct the flaw in the protein production--may eventually be the long-term solution to the problem.
The linkages of human and veterinary medicine in research partnerships are usually marriages of convenience, to which each side brings a dowry of resources. As in Kittleson's case, the availability of a nonhuman species for research is often the attraction for researchers from the human medicine side. And veterinary researchers are drawn to the relatively rich supply of financial resources available in human medicine.
Much of the funding for veterinary research is made available in hopes that studies will yield developments for human medicine. Techniques and drugs tested on research animals are usually developed first for humans, but eventually those therapies are made available to veterinary patients.
"The wheel goes around," said Clare Gregory, a UC Davis veterinary professor who, with the help of other faculty and residents, has developed the nation's leading kidney transplant program for cats and dogs.
Gregory has seen the money and the efforts poured into human medical research cycle back to veterinary medicine.
"For example, immunosuppressive drugs would never be developed for transplants in cats and dogs, simply because there just isn't as much demand for transplants in pets as there is in humans," said Gregory. "But research directed toward human medicine gives us the money to develop therapies for things in veterinary medicine that we normally couldn't treat."
Finding that existing kidney transplant treatments for dogs just weren't working, Gregory and Gary Gourley, now a professor emeritus, initiated a transplant program for dogs at UC Davis about 15 years ago. In the process, he contacted Randall Morris, an authority on immunosuppressive drugs at Stanford University. Gregory wound up spending a year-and-a-half sabbatic leave at Stanford, working with Morris and colleagues on research projects related to immunosuppressive drugs and transplant-related medical problems.
Gregory's Stanford studies yielded a better understanding of a transplant-related human ailment known as graft vascular disease and a new combination of immunosuppressive drugs that he is using experimentally on dogs to prevent rejection of transplanted kidneys. He expects the drugs will be available in two years to make possible kidney transplants between unrelated dogs. While such transplants are currently possible between unrelated cats, the genetic diversity of dogs has until now blocked such surgeries.
The Stanford collaboration also produced a lasting relationship between the participating researchers. All of Gregory's major research projects are now funded by grants awarded jointly to him and the Stanford researchers. But the intangible rewards of the collaboration far outweigh the monetary benefits, Gregory stressed.
"Money is the least of what I gain from my colleagues at Stanford," he said. "It's more the intellectual stimulation of a focused research group. The Stanford group knows the immunosuppressive drugs down to the last molecule."
Photos by Neil Michel/Illustration by David Scott Meier
