Cat on the Cutting Edge

Pet medicine is a booming business. It’s also a proving ground for science that could save your life. In full scrubs and armed with a scalpel, Clare Gregory hovers over an anesthetized light-brown tabby named Wink. He cuts through the vessels connecting the cat’s kidney to its circulatory system and drops the walnut-sized organ in […]

Pet medicine is a booming business. It's also a proving ground for science that could save your life.

In full scrubs and armed with a scalpel, Clare Gregory hovers over an anesthetized light-brown tabby named Wink. He cuts through the vessels connecting the cat's kidney to its circulatory system and drops the walnut-sized organ in a dish of ice. A nurse sets the hands of a large timer on the wall of the operating room, which begins the countdown from 60 minutes. That's the amount of time the vets have to connect Wink's kidney inside Binky, a very sick kitty, whose own kidneys have failed.

Joe Toreno
Joe Toreno
Forget lab rats: Household pets are being used to refine advanced cloning and surgical techniques, and to pinpoint our DNA trouble spots.
In the operating room, the two cats are tied down on adjacent tables, paws taped back in spread-eagle fashion. Breathing tubes are stuck down their throats, and drip tubes deliver anesthesia through veins in their wrists. Their tongues hang out of their mouths, and their eyes are open and glassy. They seem dead except for their opened chests, which move up and down in a slow rhythm controlled by expensive machinery. They look nearly identical.

In fact, though, they're quite different. With Binky's kidneys failing, his blood chemistry has gone haywire. At 11 years old, he's highly anemic and unable to flush his own blood of nitrogen, urea, and other respiration by-products. His emaciated and shaved body looks more like a skinned rabbit than a cat that once weighed a hefty 14 pounds - he's now shrunk to 8. Wink, on the other hand, is downright porky. Just 2 years old, he's spent his entire life as a research animal in a nutrition study at the UC Davis School of Veterinary Medicine, where he did nothing but eat and sleep. Now he's been selected to donate an organ. The deal is that in exchange for one kidney, the recipient's owner must adopt donor pet Wink, liberating him from the lab. So to save one cat, you get two.

Now, sitting over Binky's draped body, Gregory and fellow surgeon Lynda Bernsteen peer into the patient's abdominal cavity through a giant microscope built for two. Gregory asks that no one bump the table as he begins cutting into the aorta and vena cava to plug in the new organ. "Time?" Bernsteen asks between careful incisions and minute sutures. She moves so quickly it almost looks easy. A quick cut here, an expert stitch there. The doctors work the miracle of modern surgery, and it's hard to remember that the patient is a cat. After what seems like only moments, a nurse reports that 32 minutes have passed. That leaves only 28 to finish.

All this energy to save poor Binky might seem a gross indulgence. But Binky's owner, Gayle Roberts, a vet herself, would willingly part with one of her own kidneys for any member of her family. That clan - in addition to Binky, a husband, and two kids - includes Blackjack, Bedbug, Dark Crystal, Penelope, Helen, Kiwi, and Lucifer. It's hard to remember who is who. Is Dusty her son or the Australian shepherd? Although Binky's kidney transplant will set Roberts back $9,000 for surgery, drugs, and post-op care (for canines, the cost runs upwards of 15 grand), when it's close kin, it's hard to say no. Forced to choose between Binky and mortgage payments, Roberts chose her cat. Since then, her bank has threatened to foreclose on the house.

One hundred years ago, Americans considered cats little more than rat catchers and gave even beloved dogs almost no medical treatment. But as the the middle class grew wealthy enough to include animals in their families, and as the automobile displaced the horse in the early 20th century, urban veterinarians began looking for new markets. They gradually found work spaying, neutering, and fixing the broken bones of a growing population of household pets: cats and dogs. The growth proved contagious. In 1950, there were roughly 9,000 members of the American Veterinary Medical Association; that figure is now 70,000.

As pet owners pour more and more money into advanced treatments, it's not just the Binkys who are benefiting. Animal medical procedures are pushing vets into the most experimental regions of science. Demand for sophisticated pet care has brought terms like gene therapy and MRI into the vet lexicon. Surgeons at UC Davis now complete 25 kidney transplants a year and are trying out experimental drugs on pets with terminal brain tumors. At Iowa State, dogs are getting artificial elbows, and at the University of Illinois at Urbana-Champaign, vets are saving damaged limbs by implanting the bones of dead animals. Over the years, the passion of pet owners has created a discipline poised to inform medicine as a whole.

"Our pets have this huge veterinary profession scrutinizing them, with thousands of observers of disease graduating from veterinary schools each year," says Stephen O'Brien, chief scientific officer at the National Cancer Institute's Laboratory of Genomic Diversity.

All this data provides a window into human medicine that researchers otherwise wouldn't have. For starters, vet science gathers information that policy or mores make inaccessible in human science. Advanced cloning technologies, for instance, have allowed vets to begin using embryonic stem cells in ways that are against the law in human medicine.

Then there's the quality that drew humans to these animals in the first place - their emotional dimension. Drugs and other therapies affect moods in cats and dogs much as they do in humans. "The dog can look at you, and you can see if he's anxious or uncomfortable," says Stanford medical researcher Emmanuel Mignot. "You can see the side effect of a drug immediately. You can't see that in a mouse."

But a happy patient's wagging tail reveals only a fraction of what pets' congenital health problems can teach medicine in general. In our carefully propagated companions, there's a huge reservoir of diseases and mutations that result from efforts to breed the most skin folds in a shar-pei, the best eye color in a Siamese, perfect contours in a boxer, and herding qualities in a border collie. Generations of refinements have created extremely inbred populations, much more distinct than any found in the human species. Which means: Doberman pinschers get heart disease, schnauzers develop cataracts, and English bulldogs suffer from sleep apnea. By linking mutations in pets to their breed-specific ailments, scientists can find out which genes are active in certain disorders and apply that knowledge to the human model. Animals also share many of humanity's more common ills: Cats suffer from diabetes, hemophilia, retinal degeneration, and more than 250 other human diseases. Veterinary medicine has been cataloging these ailments for decades, creating a massive library of data that's applicable to people.

When it comes to the study of genetics in particular, vet knowledge of animal diseases and inherited traits is invaluable. For O'Brien and other medical researchers, every disease, every autopsy, every breed-specific disorder might be a clue to pinpointing a gene responsible for similar diseases in people and even to finding a cure.

It took completing the sequencing of the human genome to fuel cross-species genetic research. Suddenly, the costly labs and equipment designed for decoding human DNA were out of work, and scientists began proposing all types of organisms to be next in line - the dog, the chimp, the cow, the honeybee. This emerging field, which promises everything from better tasting chicken to the end of incurable diseases, is called comparative genomics. By contrasting the DNA of various species and then locating mutations among 3.2 billion base pairs that make up the genome of most advanced organisms, geneticists can directly increase their understanding of human genes.

That's where Stephen O'Brien comes in. Think of him as the publicly funded Craig Venter of kitties. O'Brien, 58, started paying serious attention to cats 30 years ago when he began decoding the feline genome, which, in some ways, is closer to the genome of humans than to that of other nonprimate mammals like mice, elephants, and dogs. (Cats and humans each have roughly 35,000 genes, long segments of which are in the exact same order for both species.) O'Brien looked at a family of 37 feline species - including lions, tigers, cheetahs, leopards, ocelots, margays, and the common house cat. Because these lean predators are on display in almost every zoo in the country, it was easy for O'Brien to get the samples he needed to build a complete record of feline DNA. So far, he has collected blood and tissue from 10,000 cats. His team has already identified 1,881 genes, half of them with direct human parallels.

O'Brien's biggest payoff has been his work on feline immunodeficiency virus, the first cousin of HIV. Discovered in 1988 by a veterinarian in Petaluma, California, FIV is transferred through saliva, bite wounds, and at birth from mother to offspring, and it appears in roughly 10 percent of domestic cats. What O'Brien found - that wild cats are resistant to the virus - could have profound implications for HIV research. Although they can get infected, they don't get sick. Once O'Brien and his colleagues identified the mechanism that made the wild animals immune, they began looking for genes that would predispose people to similar resistance. That's when they found CCR5, the gene that codes for proteins residing on the surface of cell membranes. HIV uses this protein, like a key in a lock, to gain access to cells. When a person has two mutated CCR5 genes, the cell can't create the protein, and HIV basically bounces right off.

A similar comparison of genomes led to breakthroughs in the treatment of narcolepsy, which affects more than 150,000 people in the US; those who suffer from it can fall asleep at inopportune moments. Some patients experience a condition called cataplexy where extreme states of emotion make them instantly fall into a deep REM sleep and collapse.

In the 1970s, William Dement at Stanford found that dogs too suffered from the disease. He visited veterinary schools throughout the US to learn more. In 1999, the Stanford group then led by Emmanual Mignot found that narcoleptic Labradors and Dobermans have a mutated gene that produces damaged receptors for hypocretin, a chemical that tells the brain to stay awake. When they looked for a similar problem in humans, they came across a logical variation on the theme: In people, rather than damaged receptors, there's a lack of hypocretin itself. "The beauty of it," says Mignot, "is that when we found the gene in canine narcolepsy, it led us directly to the cause of human narcolepsy." Without the study of dogs, researchers would have had little idea where to look.

Mignot sees his 10 years of work on a single gene as a small triumph presaging great advances to come: "Vet science is a huge field where there are tons of animals with various diseases and disorders that could be used for the common good - to find new treatments, to cure disease."

After a three-hour procedure to put in a kidney, surgeons Gregory and Bernsteen felt Binky's prognosis was excellent. His blood-urea-nitrogen levels were good, and the kidney appeared to be working. In fact, his doctors recommended he go home early. When Roberts took Binky back to Southern California in a carrying box, wedged under her airplane seat, the cat still had a feeding tube in his side.

Two weeks later, Binky took a turn for the worse. He was rejecting the organ. His doctors shifted him from oral to intravenous cyclosporine, the immunosuppressive drug that helps the body accept transplanted organs. But something was going wrong, and the vets weren't sure if it was a reaction to the drugs, an infection resulting from the cat's drug-compromised immune system, or something else entirely.

As Binky convalesced at home, the catheters and continual blood tests took their toll. Like a heroin addict's veins, Binky's blood vessels were hardening and closing, and there were barely any more to tap. Several days after his arrival, Binky's gums turned blue, and he became heavily congested. That evening, Roberts rushed him to the local emergency clinic. At 1:30 am, he went into cardiac arrest. The medics spent 20 minutes fighting to keep him alive, and then his heart stopped again, and they let Binky go.

The night he died, Roberts had Binky's body put in a freezer. Then she packed him in a Styrofoam box and sent him by US mail to Davis. The results from Binky's autopsy will be added to the growing encyclopedia of data created by vets and pet lovers everywhere.

Sitting on her sofa days later, Roberts reflects on the loss. The room is a study in anthropomorphism: On one wall is a painting of cats as cowboys, complete with bandanas, guns, and 10-gallon hats. It's titled The Magnificent Seven. The ashes of Roberts' late dog, Lucy, fill a cedar box above the wet bar.

Then Roberts picks up Wink, the one-kidneyed tabby who has become the newest member of the menagerie of humans and animals she calls her family. Wink's body hangs from her hands, which are wedged into what on a human would be armpits. The long incision down his stomach is healing nicely, and he seems to have found his place in the Roberts' home. Blackjack, the Australian shepherd, has decided to terrorize him all through the house, and the racket is incredible. But for Bedbug, the suddenly lonely littermate of the late Binky, Wink is a new companion.

Wink, for his part, got a great deal. He's a $9,000 alley cat who's totally unaware that he's been sprung from the lab in a failed attempt to give another kitty a second chance. And Roberts, who is well aware of the cost and the failure, has no regrets. It was, she says, the least she could do.