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Perpetual Pets, Via Cloning

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TIMES STAFF WRITER

Lisa Johnson laid her cat to rest near some alder trees in the backyard, marking his grave with a ring of stones. Then she heard about Richard Denniston and his effort to create the first-ever cat by cloning. Soon, she was back at the grave with a shovel.

And so, three days after his death beneath the wheels of a car, Johnson’s much-loved Cowcat underwent a resurrection of sorts. Johnson took his body from the ground, sped it to a veterinarian and had some skin removed. She sent the tissue to Denniston, who induced the cells to multiply.

Now millions of Cowcat’s cells live on, frozen in liquid nitrogen and waiting for scientists to do with the cat what has already been done with the cow, pig, goat, mouse--and of course with Dolly, the famously cloned sheep.

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While no one has cloned a cat yet, three top-notch U.S. teams are racing for what is the next big trophy in the burgeoning field of cloning. Experts say the first one could be born this year, with the first cloned dog probably coming later, its arrival hampered by the peculiar hurdles of the canine reproductive system.

Even before the first copied cat arrives, companies connected to each research team are already running a test of what happens when cloning is offered as a consumer product. The looming question is whether cloning, if ever perfected, will win acceptance as a way to produce children. So far, the idea has provoked more outrage than approval, with scientists and ethicists last week condemning an Italian doctor, Severino Antinori, for announcing plans to try to help infertile couples through cloning.

But when it comes to animals, at least, Johnson and hundreds of other pet owners are proving that many people will set aside any fears about the technology and embrace it wholeheartedly.

“If they said it was available, I would say, ‘Don’t wait for my check. Let me give you the number of my Visa card right now,’ ” said Phyllis Sherman Raschke, a retired probation officer from Sylmar, Calif., who paid Denniston $700 to preserve cells from her cat, Sammy. “I am generally not a dingbat,” Raschke added, defending her enthusiasm. “I have my PhD. I’m not a funny lady with 93 cats in my house and one litter box.”

Debbie Thieme, an emergency room nurse near Pittsburgh, paid $1,500 to preserve cells from three of her dogs, who are fighting various forms of cancer. “I’ll clone them all. I’ll have my pack back together again, someday.”

“We were in such agony when Cowcat died. I couldn’t sleep. I couldn’t eat. It was hard to function,” said Johnson, a Seattle-area homemaker who had named her pet for his spotted black-and-white coat. “Some people may think it’s blasphemous to dig up a grave, but I just love the cat.”

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Obtaining cells is a required step in cloning, which uses the DNA within the cells to produce a new organism with the same genetic makeup as the original. The old and new animals are thought to be something like identical twins--very close in appearance but not necessarily in personality or behavior.

In the four years since Dolly’s birth, several companies have made a business of cloning cows for farmers, who want to copy the genes of their most productive animals in order to boost milk and meat yields. Specialists say that several hundred cloned cows have been produced in this country alone.

Now cloning is on the verge of moving from the farm to the living room, and the ramifications could be large. If companies like Denniston’s Lazaron BioTechnologies LLC make people more comfortable with cloning, they may also pave the way for its use in creating children.

“This will be a test bed for human cloning,” said Ronald M. Green, a Dartmouth College ethics professor. If proved safe in pets, “it will accustom us to cloning as a form of reproduction and will make it more likely that people will accept human cloning somewhere down the line.”

In addition to Lazaron of Baton Rouge, La., companies preserving animal cells for eventual cloning include Genetic Savings & Clone of College Station, Texas; PerPETuate Inc. of Sturbridge, Mass.; and Advanced Cell Technology Inc. of Worcester, Mass. Tissue processing fees range from $600 to nearly $1,400, and the companies charge a monthly storage fee of about $10. None has set a price for the cloning itself, but the cost could top $20,000, at least initially.

Nearly all samples come from live pets; some companies say they can take cells from animals that have been kept cool, but not frozen, for up to a week after death. None of the companies is accepting human tissue for storage.

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Its sheer novelty aside, cloning might offer a variety of benefits. Owners could spay and neuter their pets, as vets and others forcefully recommend, and still breed their favorite animals. In a nation that destroys 5 million or so cats and dogs at shelters each year, cloning would produce a single pup or kitten instead of a litter.

But there are many unknowns. Some critics fear it would demean the individuality of a pet to know that DNA is already in the freezer, ready to grow into a replacement.

“I’m stumped on that one, myself,” said James Serpell, director of the Center for the Interaction of Animals and Society at the University of Pennsylvania. “It might kind of denigrate the individual to have it constantly reproduced.

“But in a curious way, it might also increase its value, like fine wine. You could have whole generations of the same dog within a family--or at least people seeing it as the same dog, a copy of the dog that their grandfathers and parents had.”

Critics also say the companies are selling a fantasy that they can’t possibly fulfill: the notion that an old friend will rise from the dead. “It’s the idea that we’re also cloning personalities, and that’s where I think this is snake oil,” said Alan Beck of the Center for the Human-Animal Bond at Purdue University.

No one knows, in fact, whether a cloned cat would retain that funny meow of the original or perform the same parlor tricks that thrilled its owner. Some aspects of personality are partly based on genes, and perhaps those can be reproduced, said Lou Hawthorne, chief executive of Genetic Savings & Clone. But at the same time, Hawthorne said, “we bend over backwards” to explain that cloning cannot copy the animal’s experience in the uterus or in the wider world, which also shape appearance and behavior.

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There is another caution for pet owners and cloners. In the lingo of the field, cloning is “inefficient”: It produces many stillborn or deformed animals for each live cow, sheep or goat. Before creating Dolly, scientists tried their technique on 276 other sheep cells, producing 28 embryos that failed to develop normally.

In fact, spokesmen for the National Conference of Catholic Bishops and the American Society for the Prevention of Cruelty to Animals say they see nothing wrong with cloning pets in itself, but they ask whether it can be done without producing damaged animals.

“Given the enormously high rate of miscarriages and birth defects, one wonders whether someone who really loves a pet would want to subject that pet’s genetic twin to such travail,” said Richard Doerflinger of the bishops’ group.

Egg Is ‘Factory’ for Cloning a Being

No one knows why cloning goes awry. But that question was on the minds of scientists scrubbing up one recent day in a New Orleans surgical suite at the Audubon Center for Research of Endangered Species.

As veterinarians slipped on hairnets and surgical masks, technician Barbara Vincent reached into a pet carrier and gently pulled out Cassandra, one of 150 cats who live in the research colony here. The 6-pound tabby had spiked a slight temperature, the result of nerves. This was her first trip to the surgical suite, and the sight was unfamiliar: coiled oxygen tubes, doctors in green scrubs, a cold, metal operating table.

Soon, the year-old cat was drifting away under anesthetic as Vincent cooed, “Think good thoughts. . . . Think good thoughts.” Researcher Earle Pope and two veterinarians quickly made small incisions in Cassandra’s shaved belly, inserted a tiny camera and guided their instruments to her left ovary.

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Watching their work on a video monitor, the vets poked a thin tube again and again into the fleshy orb of the ovary, sucking out the egg cells that had grown inside.

It took seven people and thousands of dollars in equipment to harvest Cassandra’s eggs, a process from which she would quickly recover. But for this team, the effort was worthwhile. “It all starts with the egg,” Pope said. “That’s the factory for producing a new cloned being.”

Cloning relies on the egg’s ability to divide and grow into a whole organism. What kind of organism is dictated by the DNA within the cell, which acts like a blueprint.

Traditionally, the DNA comes from a mother and father--from the egg itself and from a male’s sperm. In cloning, by contrast, DNA is removed from the egg and replaced with genetic material from an entirely different animal--an animal like Cowcat, who has donated a cell sample in order to be copied.

Brett Reggio of Lazaron, who is a research partner of the Audubon center, showed how it works.

In his lab at Louisiana State University, Reggio placed a cat’s egg cell under a microscope. It came up big and silvery on the attached video monitor, like a ball bearing trapped in a glob of jelly.

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Toward one end was some dark material--the cell’s DNA. “That’s what I’m going to remove,” Reggio said, maneuvering a tiny pipette, thinner than a human hair, next to the egg. With a flick of his wrist, he pushed the pipette into the cell, then sucked out the DNA.

Next, Reggio placed some cat skin cells on the microscope stage. They looked like tiny gnats, buzzing around the giant sunflower of the egg. “Each one of these skin cells has a nucleus, and in the nucleus is all the DNA needed to make a whole cat,” Reggio said.

He drew one of the skin cells into his pipette, punctured the egg again and released the skin cell inside.

With a tiny zap of electricity from a nearby machine, Reggio fused the skin and egg cells. They were now one--an egg from one cat containing DNA from another. The whole process took less than 10 minutes.

What Reggio had just done has been accomplished hundreds of times with cat and dog cells. If all worked properly, the egg would grow in a laboratory dish for a few days before researchers transferred it to a surrogate mother, who would carry it to term.

And yet, no one has succeeded with cats or dogs. Cassandra’s eggs were being used to tweak the process so that it might work.

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At the Audubon center, scientist Martha Gomez put some of Cassandra’s eggs in a chemical bath designed to encourage them to start dividing into an embryo. Then she put the eggs in a second bath designed to temporarily stop the cell division. Researchers think that hitting the pause button this way might help the embryo grow properly. They believe it gives the egg time to “reprogram” its new DNA, telling it to act like the fresh DNA of an embryo instead of the genetic material that operates a mature skin cell.

By testing different types of these baths, Gomez hoped to find which combination would produce the healthiest embryos. “And this is just one tiny part of the cloning process,” she said. “There are so many other problems.”

One is proving especially nettlesome in dogs, said Mark Westhusin, an associate professor of veterinary physiology at Texas A&M; University and principal scientist on a dog-cloning project.

Dogs come into heat only once or twice a year, and that is the only time they are able to become surrogate mothers.

Cats come into heat more frequently. Even when Westhusin produces dog embryos, it is hard to time their transfer to a surrogate mother. This requires him to keep more than 40 dogs on hand to act as surrogates and egg donors.

While several teams are working on the cat, Westhusin’s group is the only one with a comprehensive program to clone the dog. Called the Missyplicity Project, it is funded by an anonymous donor who has put up $3.7 million in hopes of cloning his own dog, Missy.

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Cloning researchers say their work will bring corollary breakthroughs in dog and cat contraception and in agriculture.

The Audubon research center, whose primary goal is to aid endangered species, believes that cloning could be one of the lifelines to save mountain gorillas, pandas, pygmy chimpanzees and other animals whose numbers are dwindling.

But not everyone believes cloning will catch on among the nation’s 90 million dog and cat owners. Kathleen Revelt, a veterinarian in Jeannette, Pa., said, “Around here, it’s economically depressed enough that it’s a struggle to vaccinate and provide basic care.”

But one of her own clients is dreaming of the possibilities. Thieme, the emergency room nurse, is a self-described “wolf freak” who decorates her home with wolf sculptures and wolf clocks. Her four dogs look something like wolves as well.

Three of the dogs are fighting cancer, and Thieme has preserved cells from each of them. Nikki, age 7, just had surgery to remove part of her palate.

Eight-year-old Diamond receives radiation therapy for a soft-tissue cancer. Wolf, 13, is largely immobile, his hind legs dragging behind him as a result of liver cancer.

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“I think there’s one mistake God made. He didn’t let animals live a little longer,” Thieme said. “I’d like to see them live to 20 or 30. You just want them to live a little longer.”

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