S. Korean Researchers Create World's First Cloned Dog
RICK WEISS / Washington Post 3aug2005
[More articles below]
South Korean stem cell researcher Hwang Woo-suk, left, and Gerald Schatten of the University of Pittsburgh School of Medicine, look at Snuppy, the first successfully cloned dog, after a news conference at the Seoul National University Wednesday, Aug. 3, 2005.
AP Photo/Ahn Young-joon
South Korean researchers today said 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 three-year-old male Afghan, marks a milestone in the race to fabricate genetically identical dogs for research and as companion animals.
The achievement required a staggering amount of work. 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.
The researchers said canine cloning will allow them to test stem cell therapies under development 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 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 the Thursday issue of the journal 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, Va.
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 those dog ailments mimic.
"Dogs are really good models for biomedical research," said Mark 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 proven a formidable challenge, largely because of the dog's quirky reproductive physiology, Westhusin said.
"It's an incredible logistical nightmare. 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. In contrast to women, dogs cannot be made to produce ripe eggs with hormone injections. So the dogs had to be monitored daily for signs of natural egg ripening — estrus, or "heat" — an event that occurs about twice a year, and then have their blood hormone levels monitored 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.
Follow-up sonograms later indicated that three 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."
Scientists attributed the success to the large number of dogs and dog eggs available to the team and technical improvements, including a decision to use only very fresh eggs.
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.
Jorges 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, who led the effort to clone Dolly, said in an e-mail that the success in dogs should motivate legislators around the world 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 optimised method," Wilmut wrote.
source: http://www.washingtonpost.com/wp-dyn/content/article/2005/08/03/AR2005080301145_pf.html 3aug2005
Korean First to Successfully Clone a Dog
JOSEPH B. VERRENGIA / AP 3aug2005
Scientists for the first time have cloned a dog. But don't count on a better world populated by identical and resourceful Lassies just yet.
That's because the dog duplicated by South Korea's cloning pioneer, Hwang Woo-suk, is an Afghan hound, a resplendent supermodel in a world of mutts, but ranked by dog trainers as the least companionable and most indifferent among the hundreds of canine breeds.
The experiment extends the remarkable string of laboratory successes by Hwang, but also reignites a fierce ethical and scientific debate about the rapidly advancing technology.
Last year, Hwang's team created the world's first cloned human embryos. In May, they created the first embryonic stem cells that genetically match injured or sick patients.
Researchers nicknamed their cloned pal Snuppy, which is shorthand for "Seoul National University puppy." One of the dog's co-creators, Gerald Schatten of the University of Pittsburgh School of Medicine, describes their creation, now 14 weeks old, as "a frisky, healthy, normal, rambunctious puppy."
Researchers congratulated the Korean team on improving techniques that might someday be medically useful. Others, including the cloner of Dolly the sheep, renewed their demand for a worldwide ban on human reproductive cloning.
"Successful cloning of an increasing number of species confirms the general impression that it would be possible to clone any mammalian species, including humans," said Ian Wilmut, a reproductive biologist at the University of Edinburgh, who produced Dolly nearly a decade ago.
Since then, researchers have cloned cats, goats, cows, mice, pigs, rabbits, horses, deer, mules and gaur, a large wild ox of Southeast Asia. Uncertainties about the health and life span of cloned animals persist; Dolly died prematurely in 2003 after developing cancer and arthritis.
"The ability to use the underlying technology in developing research models and eventually therapies is incredibly promising," said Robert Schenken, president of the American Society for Reproductive Medicine. "However, the paper also points out that in dogs as in most species, cloning for reproductive purposes is unsafe."
The experiment's outcome only seems to buoy the commercial pet-cloning industry, which has charged up to $50,000 per animal. The first cloned-to-order pet sold in the United States was a 9-week-old kitten produced by the biotech firm, Genetic Savings & Clone Inc. of Sausalito, Calif.
Company officials said they expect to commercially clone a dog within a year using eggs collected from spaying procedures at veterinary clinics. The South Korean researchers can surgically remove eggs from research animals with fewer regulations than in the United States.
"This justifies our investment in the field," said spokesman Ben Carlson. "We've long suspected that if anyone beat us to this milestone, it would be Dr. Hwang's team _ due partly to their scientific prowess, and partly to the greater availability of canine surrogates and ova in South Korea."
But the dog cloning team tried to distance its work from commercial cloning. "This is to advance stem cell science and medicine, not to make dogs by this unnatural method," Schatten said.
On scientific terms, the experiment's success was mixed. More than 1,000 cloned embryos were implanted into surrogate mothers and just three pregnancies resulted. That's a cloning efficiency rate lower than experiments with cloned cats and horses. Details appear in Thursday's issue of the journal Nature.
Like Dolly and other predecessors, Snuppy was created using a method called somatic cell nuclear transfer, or SCNT.
Scientists transfer genetic material from the nucleus of a donor adult cell to an egg whose nucleus _ with its genetic material _ has been removed. The reconstructed egg holding the DNA from the donor cell is treated with chemicals or electric current to stimulate cell division.
Once the cloned embryo reaches a suitable stage, it is transferred to the uterus of a surrogate where it continues to develop until birth.
Dog eggs are problematic because they are released from the ovary earlier than in other mammals. This time, the researchers waited and collected more mature unfertilized eggs from the donors' fallopian tubes.
They used DNA from skin cells taken from the ear of a 3-year-old male Afghan hound to replace the nucleus of the eggs. Of the three pregnancies that resulted, there was one miscarried fetus and one puppy that died of pneumonia 22 days after birth.
That left Snuppy as the sole survivor. He was delivered by Caesarean section from his surrogate mother, a yellow Labrador retriever.
Researchers determined that both of the puppies that initially survived were genetically identical to the donor dog.
Schatten said the Afghan hound's genetic profile is relatively pure and easy to distinguish compared to dogs with more muddled backgrounds. But dog experts said the researchers' choice of breed choice was disquieting.
"The Afghan hound is not a particularly intelligent dog, but it is beautiful," said psychologist Stanley Coren, author of the best-selling manual "The Intelligence of Dogs." He ranked the Afghan hound last among 119 breeds in temperament and trainability.
"Many people who opt for the cloning technique are more interested in fashionable looks," he said. "Whenever we breed dogs for looks and ignore behavior, we have suffered."
source: http://www.washingtonpost.com/wp-dyn/content/article/2005/08/03/AR2005080301149.html 3aug2005
Give a Dog a Clone
MARK HENDERSON / The Times (UK) 3aug2005
Where man has led, man’s best friend has followed: a dog has been cloned for the first time, by the same team of scientists that first achieved the feat with human embryos.
The birth of Snuppy, an Afghan hound named after the Seoul National University (SNU) in South Korea where it was created, promises to advance both human and veterinary medicine by providing a new model species for research into therapeutic cloning.
The success also raises the prospect that dog owners could one day clone their favourite pets. Though the scientists who created Snuppy are opposed to this and pledged today never to attempt it, their work could help others attempting commercial canine cloning.
An American company, Genetic Savings & Clone, already offers cat lovers the opportunity to clone their pets at a cost of $50,000 (£26,000) a time, and last year produced the first made-to-order kitten, Little Nicky, for a Texan woman. It is also engaged in dog cloning research: it was established with the support of John Sperling, a billionaire who has invested millions of dollars in the company’s "Missyplicity Project" to clone his deceased pet, Missy.
Freda Scott-Park, the president-elect of the British Veterinary Association, said pet cloning was likely to remain ethically questionable for some time, chiefly because of concerns about the health of the animals and the inefficiency of the cloning process.
"No one can deny that techniques that advance our understanding of diseases and their therapy are to be encouraged but cloning of animals raises many ethical and moral issues that have still to be properly debated within the profession," she said.
Pet owners may also be disappointed by clones of their animals: while Snuppy has the same markings as his father, Tai, the first cloned cat, CC or Copy Cat, looked very different from its mother. There is no guarantee that cloning will produce an animal of similar temperament or personality.
Professor Gerald Schatten of the University of Pittsburgh, a member of the team that created Snuppy, said the nuclear transfer technique used in cloning was no more appropriate for making pets than it is for human reproduction.
"We are not in the business of cloning pets," he said. "Nuclear transfer is an extraordinary tool for scientific and medical research. It has never been about reproductive medicine or making any members of our family - even our pets."
While many animals, including sheep, mice, cows, goats, pigs, cats, mules and horses, have been successfully cloned, dogs have proved one of the most challenging species to reproduce in this manner. One of the chief problems is that dog eggs are released earlier than those of most other mammals, and are much harder to work with in the laboratory.
The Korean team, led by Professor Woo-Suk Hwang, which leads the world in cloning human embryos, has now overcome the technical hurdles. Professor Hwang created the first cloned human embryos last year, and in May announced the production of 11 batches of stem cells derived from clones of human patients.
In the new research, which is published in the journal Nature, cells were taken from the ear of an adult Afghan hound named Tai, and the genetic material was injected into eggs from which the nucleus had been removed. Three viable cloned embryos were produced from 123 attempts and implanted into the womb of a female labrador that acted as a surrogate mother. While one miscarried, two puppies were born - Snuppy and his brother, named only NT-2 as the second nuclear transfer dog. NT-2 was born with respiratory problems and though he seemed to recover he died 22 days after birth after contracting pneumonia. Snuppy, however, remains healthy and has his father’s black-and-tan colouring.
The team now plans to clone further dog embryos from which stem cells can be extracted, to learn more about these master cells that can form any type of tissue in the body.
Stem cells could eventually be taken from cloned embryos that are genetically identical to patients with conditions such as diabetes and Parkinson’s, and grown into replacements for damaged tissue. These cells would carry the patient’s genes and could be transplanted without risk of rejection by the immune system.
Professor Schatten said this technology, known as therapeutic cloning, might now be tested in dogs, both to provide new treatments for canine illnesses and to test techniques that could help people.
"Once embryonic stem cells are established from dogs, veterinary applications of stem cell transplantations for the various diseases and disorders that occur in dogs might well be the first clinical uses of therapeutic cloning," he said.
Professor Hwang said: "Our research goal is to produce cloned dogs for studying disease models, not only for humans, but also for animals."
Professor Ian Wilmut of the Roslin Institute near Edinburgh, the scientist who created Dolly the sheep, the first cloned mammal, congratulated the Koreans on their achievement. He said the work had succeeded in part because of the team’s use of fresh, high-quality eggs, which underlines the need to collect eggs from dedicated donors if the technique is also to work in humans. Professor Wilmut recently applied for permission to do this, instead of using eggs left over after IVF treatment, for his cloning research into motor neuron disease.
source: http://www.timesonline.co.uk/article/0,,3-1720006,00.html 3aug2005
South Koreans Clone Dog Without Even the Slightest Trace of Irony
The Inquirer (UK) 3aug2005
NEWS WIRES have gone nuts in May after a Korean boffin told Nature magazine he's managed to clone a dog.
Many of the wires are describing copying doggies as a breakthrough for the pet cloning market, so that when your favourite animal dies you can rest assured it will rise from the grave.
That's even though common sense tells human beings that while identical twins are, er, identical, their personalities don't have to mirror their genes. But then maybe pets don't have personalities. But if they don't, why bother clone them?
The boffins at Seoul University deny that they're trying to make money out of grief-stricken pet owners but to further medical research. But the dog they've cloned is called Snuppy and doesn't have any kind of scientific nomenclature attached to it in the press release.
This is in fine contradistinction to workers at certain fabs in South Korea. The people don't have names like Snuppy, but have photographs on their ID bearing their number. Last time we were there, many of them lived in dormitories which also had numbers, so you could describe yourself as worker 4321 at dormitory 65, and that would locate you perfectly.
The story - about Snuppy, not the numbered people - will be related in this week's edition of magazine Nature.
Snuppy, unlike Patrick McGowan in popular cult series The Prisoner, has a name and not a number.
source: http://www.theinquirer.net/?article=25125 3aug2005
Snuppy Rewards Dogged Approach
EMMA MARRIS / Nature 3aug2005
Canine eggs are tough to crack, but clone finally survives.
The first duplicate pooch ambles on to the world stage today. His birth was a feat of ingenuity and perseverance, but some scientists question the value of the exercise.
The Afghan hound puppy has been hidden from the world at the Seoul National University in South Korea for the nine weeks since his birth from a yellow Labrador retriever. He bears exactly the same DNA as an older hound who lent a few ear cells to the researchers.
He's also quite a survivor, being the only one of 1,095 cloned embryos implanted in 123 dogs to survive to healthy puppyhood.
Since Dolly the cloned sheep made her appearance nearly a decade ago, the field has not advanced as much as was expected at first.
Cloning animals has proven difficult and every species presents its own problems. Even when everything seems to be going right, the majority of cloned embryos fail because their genes are expressed in abnormal ways.
For dogs, the main challenge lies in harvesting the eggs. Canine eggs leave the ovary at a very early stage of development and then mature as they travel towards the uterus in the oviducts.
Harvesting the eggs at the point of ovulation and trying to mature them in a test tube failed. So the research team had to wait and remove the eggs by flushing them out of the oviducts using a custom-made solution.
The nucleus of each of these egg was removed and replaced with a nucleus from an ear cell. Successfully fused cells were then implanted in female dogs.
The painstaking work was completed by the lab of Woo Suk Hwang, the South Korean researcher who is famous for creating a cloned human embryo and deriving stem cells. The lab's dog work is reported in this week's Nature2.
It took a team of about 15 people two-and-a-half years to produce the dog, whose name 'Snuppy' is short for Seoul National University puppy.
"He is very cute. If you come here, if you meet him, you may fall in love with him," says Hwang, who adds that while the puppy looks exactly like the somatic cell donor, it's still unclear whether their personalities are similar.
The donor dog belongs to a professor of internal veterinary medicine at the university, but the puppy "belongs to all human beings, not to myself or the somatic-cell-donor owner", says Hwang.
Barking up the wrong tree?
Hwang says the point of bringing Snuppy into the world is to pave the way for a line of dogs that could model certain human illnesses. But cloning a kennel of diseased canines is a long way off, according to Mark Westhusin, a reproductive biologist at Texas A&M University, College Station, who is famous for cloning a cat2.
Westhusin and his team spent three years trying to clone a dog before they threw in the towel. He says the Korean success, while wonderful, may not have been worth it.
"It's a logistical nightmare to work with this species. We've known and predicted for years that it was feasible. It's just, how much time and money and effort do you want to devote to the project?"
Westhusin would like to see work done that would make the process easier, such as the development of a hormone treatment to induce canine ovulation, or a method for maturing eggs in a test tube.
The current work impresses him more for its single-minded tenacity than for its novelty. "They're an outstanding lab and I'm happy for them, but all this says is that you can clone a dog, which we've basically known for some time."
source: http://www.nature.com/news/2005/050801/full/050801-7.html 3aug2005