Issue 11.04 | April 2003
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Cat on the Cutting Edge (continued)
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.