posted August 06, 2005 12:28 AM         

August 4, 2005
Beating Hurdles, Scientists Clone a Dog for a First
By GINA KOLATA

South Korean researchers are reporting today that they have cloned what scientists deem the most difficult animal, the dog.

The group worked for nearly three years, seven days a week, 365 days a year and used 1,095 eggs from 122 dogs before finally succeeding with the birth of a cloned male Afghan hound. The surrogate mother was a yellow Labrador retriever.

Dogs have such an unusual reproductive biology, far more so than humans, scientists say, that the methods that allowed cloning of sheep, mice, cows, goats, pigs, rabbits, cats, a mule, a horse and three rats, and creation of cloned human embryos for stem cells, simply do not work with them.

Woo Suk Hwang, the principal author of the dog cloning paper, being published in the journal Nature, wrote that the puppy, an identical twin of the adult Afghan but born years later, was delivered by Caesarean section on April 24. The pregnancy lasted a normal 60 days and the newborn pup weighed 1 pound 3.4 ounces and was named Snuppy.

Not Snoopy. The scientists named him for Seoul National University puppy.

Cloning researchers were awed at the achievement, but not everyone shared their admiration.

Nigel Cameron, a bioethicist at Chicago-Kent College of Law and director of its Institute on Biotechnology and the Human Future, noted some people see dogs as members of the family. "There's sort of a dry run here for the human cloning debate," he said. "What we do with dogs we may well end up doing with our kids."

Dr. Cameron said he objected to cloning dogs, but not farm animals or laboratory rodents. He said he did, however, oppose all human cloning, including cloning human embryos for stem cells.

The reason that other researchers are so impressed, said Mark E. Westhusin, a cloning researcher at Texas A&M University, is that with dogs, "their reproductive biology makes them a nightmare." Cats, in what might seem a turnabout, are biologically much less finicky.

Dr. Westhusin cloned the first cat, in 2002, on his second try. But, he said, after trying for a few years to clone a dog, "I quit."

His work with cats and dogs was sponsored by a private company, Genetic Savings & Clone of Sausalito, Calif. Its chief executive, Lou Hawthorne, said the company had spent seven years and more than $19 million in its attempts to clone a dog. It just opened a lab in Madison, Wis., with 50 employees. But, so far, no dogs have been cloned.

Other researchers say dog cloning is so hard, they will not try it. George E. Seidel Jr. of Colorado State said Genetic Savings & Clone approached him and "I refused." As for the South Koreans, who succeeded in what is the Mount Everest of cloning, it was "simply a heroic effort, a brute force heroic effort," Dr. Seidel said.

Snuppy is the second coup this year for the Seoul researchers. In May, Dr. Hwang's lab announced that it had created cloned human embryos and extracted stem cells from them. The dog project is separate, and its goal, Dr. Hwang explained in an e-mail message, is to use dogs to study the causes and treatment of human diseases.

Dogs have long been used to study human diseases. Rabies, in fact, was first discovered in dogs, insulin was discovered in dogs, and the first open heart surgery was in dogs. Eventually, the team hopes to make dog embryonic stem cells and test them in the animals as treatments.

Dogs presented a number of challenges to the researchers. Ovulation is once or twice a year, but not predictable, and no one has found a way to induce ovulation by giving dogs hormones.

Eventually, the South Koreans discovered, through trial and error, a signature spike in the hormone progesterone that signaled ovulation.

With other animals, scientists collect mature eggs from ovaries, but the eggs dogs ovulate are immature. They mature in the oviduct and so far it has proved impossible to extract eggs from a dog's ovary and mature them in the laboratory.

So the researchers had to pinpoint when to pluck a mature egg from the oviduct, and needed surgery to retrieve it, instead of the kind of needle suctioning used in other animals.

The next step in cloning of any other animal is to replace the egg's genes with those of an adult and let the cloned embryo grow in the lab for several days.

But no one has been able to grow dog embryos in the lab. So the South Koreans quickly started the cloning. They removed the genetic material from the eggs and replaced it with skin cells from the ears of Afghan hounds. When the altered eggs were starting to develop into embryos, the researchers anesthetized a female dog, slipped the eggs into the animal's oviduct, and hoped the eggs would grow into early embryos, drift into the uterus, and survive. They found they had less than four hours after starting the process to get the eggs into the female dogs.

Ordinarily, researchers give hormones to female animals that are to serve as surrogate mothers, preparing them to become pregnant with a cloned embryo. Not so with dogs. No one knows how to prepare a dog for pregnancy, so the researchers used the same dogs for egg donors and for surrogate mothers, 123 dogs in all.

In the end, three pregnancies resulted. One ended in a miscarriage, one was carried to term but the puppy died a few weeks later of respiratory failure, and one resulted in Snuppy.

Until dog cloning becomes a lot more efficient, few people will be able to afford to clone their pets. Mr. Hawthorne estimated that it would cost more than $1 million to repeat what the South Koreans have done.

The market among dog owners might not be much, in any case. Apart from ethical issues, Dr. Cameron said, dogs are like family members. "My dog is now deceased," he said. "But I wouldn't want to clone Charlie. It would be disrespectful to Charlie and to Charlie II."

Tina Vogel, an Afghan breeder in Norwalk, Ohio, agreed that cloning a dog "would be like cloning a person." And she is opposed to that. "If it was meant to be, God would have done it," she said.

She said Afghans have a reputation as the dumbest dogs around, but that is just because they are "very aloof," more like a cat than a dog. "They are sweet and affectionate. If you have one you can never go back."