By Rick Weiss
Washington Post Staff Writer
Thursday, August 4, 2005
South Korean researchers said yesterday that they have created the world's first cloned dog: a playful black, tan and white Afghan hound named Snuppy.
The puppy, grown from a single cell taken from the ear of a 3-year-old male Afghan, marks a milestone in the race to fabricate genetically identical dogs for research and as companion animals.
The process of dog cloning remains highly inefficient, a reflection of how much scientists still have to learn about how to make mammalian offspring from single parents and without the help of sperm. Multiple surgeries on more than 100 anesthetized dogs and the painstaking creation of more than 1,000 laboratory-grown embryos led to the birth of just two cloned puppies -- one of which died after three weeks.
But the feat suggests that a market in cloned dogs, through which people grieving the loss of their favorite pets could order genetic duplicates, may not be as futuristic as some had thought. And by leapfrogging a seven-year-old, multimillion-dollar U.S. effort, the success has clinched South Korea's quickly growing reputation as a premier center for cloning and stem cell research.
Cloned dog embryos could make available the first canine versions of embryonic stem cells. Researchers could then test stem cell therapies that have been proposed for people and, perhaps, cure some dog diseases along the way.
"Wouldn't it be great if the first beneficiaries of stem cell medicine were our best friends?" asked Gerald P. Schatten, a reproductive scientist at the University of Pittsburgh School of Medicine who served as a consultant for the Korean team.
Snuppy's birth announcement, published in today's issue of Nature, was greeted with scorn by some animal care activists, who decried the work as inhumane and wasteful, given the global glut of unwanted dogs.
"The cruelty and the body count outweighs any benefit that can be gained from this," said Mary Beth Sweetland, a vice president at People for the Ethical Treatment of Animals in Norfolk.
Others expressed concern that publication of the team's advanced techniques may help rogue scientists create the first human clone.
But the researchers and others defended the achievement as an important step toward boosting the usefulness of dogs as biomedical research tools.
From dachshunds to Great Danes, dogs are extremely diverse, and many of the more than 400 breeds are predisposed to particular diseases. Scientists hope clones with propensities for specific illnesses will help them decipher the molecular underpinnings of those syndromes and develop treatments for the human diseases that those dog ailments mimic.
"Dogs are really good models for biomedical research," said Mark E. Westhusin, a researcher at Texas A&M University who a few years ago abandoned a costly effort to be the first to clone a canine.
Scientists have cloned mice, cows, sheep, goats, rabbits, cats and a few other mammals since Dolly the sheep -- the first cloned mammal -- was born in 1996. But dog cloning has proved a formidable challenge, largely because of inefficiencies that result from the dog's quirky reproductive physiology, Westhusin said.
"It's an incredible logistical nightmare," he said. "You must have access to hundreds and hundreds of dogs. We were never able to handle that many dogs at one time."
Cloning starts with the creation of an embryo in a laboratory dish. Scientists take a cell from the animal to be duplicated -- typically a skin cell -- and fuse it to an egg cell whose own DNA has been removed. Fluids in the egg "reprogram" the skin cell's genes, prompting that most ordinary cell to grow into an embryo.
In the new study, a team led by Woo Suk Hwang of Seoul National University fused individual cells from an adult hound's ear to eggs painstakingly obtained from fertile female dogs.
This required a staggering amount of work because, in contrast to women, dogs cannot be prompted to produce ripe eggs with hormone injections. Instead, the researchers had to monitor the dogs daily for signs of natural egg ripening -- estrus, or "heat," which occurs about twice a year. Then they measured the dogs' blood hormone levels daily.
Within hours after a blood test confirmed that a batch of ripe eggs had been released from a dog's ovaries, Korean veterinarians anesthetized the dog, surgically exposed her reproductive tract and flushed the barely visible eggs into laboratory dishes.
Then began the exquisitely delicate task of extracting the DNA from those eggs. Many eggs are inadvertently destroyed in this process, but Hwang's team is world-renowned for its manual dexterity under the microscope -- a skill Hwang has credited to the Korean tradition of eating food with difficult-to-master steel chopsticks.
Of about 1,400 embryos created by fusing those eggs to skin cells with an electrical shock, 1,095 were deemed healthy enough to be transferred to the reproductive tracts of surrogate mother dogs -- each of which also had to be in heat, to support the growth of those embryos into fetuses. That required more surgeries, with five to 12 embryos transferred to each of 123 surrogates.
The breed of the egg donors and the surrogate mothers varied and were irrelevant because they did not contribute any DNA to the clones.
As is typical for cloned embryos, very few survived their time in the womb, perhaps because of abnormalities induced by the process. Follow-up sonograms later indicated thatthree of the 123 surrogate mothers were pregnant. One miscarried, and the other two delivered puppies after full-term pregnancies. One newborn died from pneumonia after 22 days, a common but still inexplicable fate for young cloned mammals. The survivor is Snuppy, for "Seoul National University puppy."
The work drew congratulations from Genetic Savings & Clone, a Sausalito, Calif.-based company that offers cat-cloning services and hopes to clone dogs soon.
The American Anti-Vivisection Society, which recently failed to force the Food and Drug Administration to regulate pet cloning, renewed its call for limits. "Using 123 dogs to obtain one cloned puppy is absurd," said Crystal Miller-Spiegel, the group's senior policy analyst.
Jorge A. Piedrahita, a professor of genomics at North Carolina State University's College of Veterinary Medicine in Raleigh, said people hoping to get their old pets back through cloning are likely to be disappointed.
In studies he conducted, pigs that were clones of each other were no more alike than were conventional pigs with regard to food preferences, sleep habits or levels of aggressiveness. "What was most fascinating is how important the environment is -- that it really overrides the genetic similarities," Piedrahita said.
Ian Wilmut of the University of Edinburgh in Scotland, who led the effort to clone Dolly, said in an e-mail that the success in dogs should motivate legislators to enact bans on the creation of cloned babies.
"Successful cloning of an increasing number of species confirms the general impression that it would be possible to clone any mammalian species, including humans, given an optimized method," Wilmut wrote.